La Tests Introductory

5-HIAA 1
ACE 3
ACTH 6
AFB Culture 10
AFP Tumor Markers 13
Albumin 15
Aldolase 17
Aldosterone and Renin 17
Allergies 20
ALP 23
Alpha-1 An trypsin 24
ALT (GPT) 28
AMA 29
Ammonia 31
Amylase 34
ANA 35
Antibody Tests 38
Apo A 41
Apo B 43
ApoE Genotyping 46
ASMA 49
ASO 51
AST(GOT) 53
Autoantibodies 55
Vitamin B12 & Folate 58
BMP 61
Bilirubin 63
Blood Culture 65
Blood Gases 68
Blood Smear 71
BNP and NT-proBNP 78
Bone Markers 80
Bone Marrow Aspiration and Biopsy 82
BRCA-1 and BRCA-2 87
BUN 90
Clostridium difficile toxin 92
CA-125 95
CA 15-3 96
CA 19-9 98
Calcium 99
Cardiac Biomarkers 104
Cardiac Risk Assessment 106
Catecholamines, Plasma and Urine 108
CCP 112
CD4 Count 114
CEA 115
Celiac Disease Tests 116
CF Gene Mutation Testing 121
Chemistry Panels 124
Chlamydia 125
Chloride 127
CK 128
CK-MB 131
CMV 132
CO2 138
Coagulation Factors 139
Complement Levels 143
Comprehensive Metabolic Panel 146
Cortisol 148
Creatinine 152
Creatinine Clearance 154
C-Reactive Protein 156
Cyclosporine 158
Cystatin C 161
DHEAS 163
Diabetes-related Autoantibodies 166
Digoxin 169
Direct Antiglobulin Test (Direct Coomb’s test) 171
DLDL 173
Testing for Drugs of Abuse 175
Epstein-Barr Virus Antibodies 178
Epidermal Growth Factor Receptor 183
Electrolytes 184
Ethanol 187
Protein Electrophoresis Immunofixation Electrophoresis 190
Estrogen 194
Factor V Leiden and PT 20210 197
Fecal Occult Blood Test 200
Fetal fibronectin 203
Fructosamine 206
FSH 208
GFR and EGFR 212

GGT 214
Gonorrhea 216
Gram Stain 218
Growth Hormone 219
HCG 224
Hepatitis A 227
Hepatitis B 228
Hepatitis C 231
Her-2/neu 234
Herpes 236
HIV Antibody 240
HIV Genotypic Resistance Testing 242
HIV Viral Load 244
HLA-B27 245
Homocysteine 248
Hormone Receptor Status 251
HPV 252
hs-CRP 256
IGF-1 258
IMA 262
Indirect Antiglobulin Test 265
Influenza Tests 268
Lactate 273
LDH 276
Lead 278
LH 285
Lipase 289
Lipoprotein Subfraction Testing 291

Lithium 293
Liver Panel 296
Lipoprotein little a 297
Lyme Disease 299
Magnesium 301
Mercury 303
Methylmalonic Acid 306
Mono 308
Myoglobin 311
Ova and Parasite Exam 313
Osmolality 316
p24 An gen 321
Pap Smear 322
Phosphorus 325
Plasma Free Metanephrine 327
Platelet Count 330
Porphyrin Tests 332
Potassium 336
Prealbumin 339
Progesterone 342
Prolactin 344
Protein C and Protein S 347
PSA 350
PSEN1 354
PTH 356
Rheumatoid Factor 359
Respiratory Syncytial Virus 361
Rubella 363
Semen Analysis 367
SHBG 369
Sickle Cell 372
Sodium 374
Stool Culture 376
Strep Throat 380
Susceptibility Testing 383
Sweat Test 386
Syphilis 388
Tau/A?42 390
TB Skin Test 392
Testosterone 395
Therapeutic Drug Monitoring 398
TORCH 401
Total Protein and A/G Ratio 403
TPMT 405
Trichomonas 406
Triple Screen 408
Troponin 410
Trypsin 413
Trypsinogen 414
Tumor Markers 416
Uric Acid 419
Urine Culture 422
Urine Metanephrines 425
Urine Protein 428
Vancomycin 432
Vitamin D 435
West Nile Virus 437
White Blood Cell Count 441
Zinc Protoporphyrin 443

5-HIAA
Also known as: 5-hydroxyindoleacetic acid, HIAA, Serotonin metabolite
Formal name: 5-hydroxyindoleacetic acid
Related tests: Serotonin, Chromogranin A
Why get tested?
To help diagnose and monitor treatment for a serotonin-secreting carcinoid tumor
When to get tested?
When you have symptoms suggestive of a carcinoid tumor such as flushing, diarrhea,
and/or wheezing, and at intervals following treatment
Sample required(A 24-hour urine sample; rarely a random urine sample).
What is being tested?
This test measures the amount of 5-hydroxyindoleacetic acid (5-HIAA) in the urine.
5-HIAA is a muscle stimulant and the primary metabolite of serotonin, a hormone
derived from the amino acid tryptophan. Serotonin is produced as needed by the
nervous system, mainly the brain, but also special cells in the bronchial tubes (lungs)
and gastrointestinal tract. It helps transmit nerve impulses and constrict blood vessels,
participates in the wake-sleep cycle, and affects mood. After it is used by the body,
serotonin is broken down in the liver, and its metabolites, including 5-HIAA, are
excreted in the urine.
Ordinarily, only small varying amounts of 5-HIAA are present in the urine. Large
quantities of serotonin and 5-HIAA may be produced, however, by some carcinoid
tumors. Carcinoid tumors are slow-growing masses that can form in the
gastrointestinal tract, on the appendix, and in the lungs. According to the American
Cancer Society, there are about 5,000 carcinoid tumors diagnosed each year in United
States. Many more of these tumors may exist, but most remain small and do not cause
any symptoms. When carcinoid tumors are discovered in asymptomatic patients
during surgical procedures performed for other reasons, they are called "incidental"
tumors. A small percentage of these tumors may eventually grow large enough to
cause obstructions in the intestines or bronchial tubes of the lungs.
About 10% of carcinoid tumors, primarily those found in the gastrointestinal tract,
will produce enough serotonin to cause symptoms such as flushing of the face,
diarrhea, a rapid heart rate, and wheezing, usually only after the tumor has spread to
the liver. These symptoms are referred to as carcinoid syndrome. The serotonin that
causes carcinoid syndrome may be released continuously or intermittently and can
lead to significantly increased quantities of 5-HIAA in the urine.
How is the sample collected for testing?

For the 24-hour urine collection, all of the urine should be saved for a 24-hour period.
It is better to keep sample in cool, dark place, such as a refrigerator. Pre-sample
preparation is important for accurate 5-HIAA test results. For more information, see Is
there anything else I should know and talk to your doctor.
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How is it used?
5-HIAA may be ordered by itself or along with a blood serotonin level to help
diagnose and monitor carcinoid tumors. A 24-hour urine sample is preferred for the 5-
HIAA test because the metabolite level in the urine can vary during the day. A
random urine sample is sometimes tested, usually along with a urine creatinine level,
when a 24-hour sample is not feasible. The random sample is not as accurate,
however, and if the excess 5-HIAA is released intermittently, then it may be missed.
When is it ordered?
This test is primarily ordered when a patient has symptoms suggestive of a carcinoid
tumor. It may also be ordered at intervals to help monitor the effectiveness of
treatment in patients who have been diagnosed with and treated for a serotonin-
secreting carcinoid tumor.
What does the test result mean?
A significantly increased level of 5-HIAA in a 24-hour urine sample in a patient with
carcinoid syndrome symptoms is suggestive but not diagnostic of a carcinoid tumor.
In order to diagnose the condition, the tumor itself must be located and a sample of it
examined. The doctor will frequently follow an abnormal test result with an order for
an imaging scan to help locate any tumor(s) that may be present.
A patient with symptoms may still have a carcinoid tumor even if the concentration of
5-HIAA is normal. The patient may have a tumor that does not secrete serotonin or
one that secretes it intermittently. A patient with no symptoms and normal levels of 5-
HIAA is unlikely to have a serotonin-secreting carcinoid tumor.
In patients who are being monitored following treatment for carcinoid tumor,
decreasing levels of 5-HIAA indicate a response to treatment, while increasing or
continued excessive concentrations indicate that the treatment has not been
successful.
Is there anything else I should know?
Foods such as avocados, bananas, pineapples, plums, walnuts, tomatoes, kiwi fruit,
and eggplant can interfere with 5-HIAA measurement and should be avoided for three
days prior to and during urine collection.
There are also a variety of drugs that can affect the 5-HIAA test. Medications that can
increase 5-HIAA include acetaminophen, caffeine, ephedrine, diazepam (Valium),
nicotine, glyceryl guaiacolate (an ingredient found in some cough medicines), and
phenobarbital. Medications that can decrease 5-HIAA include aspirin, ethyl alcohol,
imipramine, levodopa, MAO inhibitors, heparin, isoniazid, methyldopa, and tricyclic
antidepressants. Patients should talk to their doctor before decreasing or discontinuing
any medications.
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1. Are there other metabolites of serotonin?
Yes, the other major metabolite is 5-hydroxytryptphol (5-HTOL). This substance is
not routinely tested for but may sometimes be performed in a ratio with the 5-HIAA
test to evaluate ethyl alcohol ingestion. An increased ratio of 5-HTOL/5-HIAA can be
indicative of alcohol consumption in both living people and postmortem.
2. Can I do the 5-HIAA urine test at home?

No, this test requires specialized equipment and must be performed in a laboratory.
Not every laboratory will perform this assay; in some cases, your sample will need to
be sent to a reference laboratory.
3. Will my results be accurate if I must continue to take my medication?

If the drug is one that can increase or decrease the amount of serotonin and 5-HIAA,
then your results may be affected. However, it is up to your doctor and you to decide
whether or not your medication can be safely stopped prior to and during the test
collection. If your drugs must be taken, then your doctor will interpret the test results
with this in mind.
4. Are some people at a higher risk for developing a carcinoid tumor?
Anyone at any age can develop a carcinoid tumor but, according to the American
Cancer Society, the average age at diagnosis is usually about 55 to 65. Patients with a
family history of multiple endocrine neoplasia (MEN1), a genetic condition that
increases a patient's risk of developing tumors in the endocrine system glands, may be
at higher risk for developing a carcinoid tumor.
ACE
Also known as: SACE (Serum Angiotensin Converting Enzyme)
Formal name: Angiotensin Converting Enzyme.
Why get tested?
To help diagnose and monitor sarcoidosis. To help differentiate this systemic
condition from other disorders causing similar symptoms.
When to get tested?
When you have granulomas (masses of inflammatory cells) that create small bumps
under the skin, a lingering cough, red watery eyes and/or other symptoms suggestive
of sarcoidosis. Regularly when you have active sarcoidosis to monitor its course.
Sample required (blood sample).
Angiotensin converting enzyme (ACE) is an enzyme produced by endothelial cells to
help regulate blood pressure. It catalyzes the conversion of angiotensin I (an inactive
protein) to angiotensin II. Angiotensin II functions as a strong vasopressor – it causes
arteries to contract, making them temporarily narrower and increasing the pressure of
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the blood flowing through them. ACE is produced throughout the body, but is
especially concentrated in the lungs. It is normally found in high levels in the blood in
those less than 20 years of age, but then drops to a relatively stable lower level in
healthy adults.
Increased amounts of ACE are sometimes secreted by cells found at the margins
(outside borders) of granulomas. Granulomas are small tumor-like masses of immune
and inflammatory cells and fibrous tissue that create bumps under the skin and
throughout the body. They are a classic feature of sarcoidosis, a systemic disorder of
unknown cause that often affects the lungs but may also affect many other body
organs including the eyes, skin, nerves, liver, and heart. ACE levels often increase
when granulomas are developed. About 50-80% of patients with active sarcoidosis
will have elevated levels of ACE – levels that will rise and fall with disease activity.
Granulomas, fibrosis, and elevated ACE levels may also be seen with infectious
disorders such as leprosy and tuberculosis (the granulomas form around the invading
mycobacteria) and with exposure to irritant particle poisons such as beryllium,
asbestos, and silicon (with current worker protection, these causes relatively rare).
How is it used?
ACE is primarily ordered to help diagnose and monitor sarcoidosis. It is often ordered
as part of an investigation into the cause of a group of troubling chronic symptoms
that may or may not be due to sarcoidosis. ACE will be elevated in 50-80% of
patients with active sarcoidosis. If it is initially elevated in someone with sarcoidosis,
ACE can be ordered at regular intervals to monitor the course of the disease and the
effectiveness of corticosteroid treatment.
When is it ordered?
ACE is ordered when you have signs or symptoms such as granulomas, a chronic
cough or shortness of breath, red watery eyes, and/or joint pain that may be due to
sarcoidosis or to another disorder. This is especially true if you are between 20 and 40
years of age, when sarcoidosis is most frequently seen. Your doctor may order ACE,
along with other tests such as an AFB culture or sputum culture (tests that can detect
mycobacterial and fungal infections), when he wants to differentiate between
sarcoidosis and another granulomatous condition.
If you have been diagnosed with sarcoidosis, and your initial ACE levels were
elevated, your doctor may order ACE testing at regular intervals to monitor their
change over time
If someone is under 20 years of age, then high ACE levels are usually normal, not
significant. For those over 20 years of age, ACE blood levels are a nonspecific
indicator. They do not tell you why the levels are elevated, what organs and/or body
systems are involved, or to what degree. ACE does not cause granulomas but it often
reflects their presence.
If ACE levels are high, other diseases have been ruled out, and you have clinical
findings consistent with sarcoidosis, then it is likely that you have an active case of
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sarcoidosis. About 20-50% of the time, however, sarcoidosis can be present without
elevated ACE levels. This may be due to the disease being in an inactive state, due to
an early detection of sarcoidosis – the levels have not risen yet, or due to the fact that
the cells are just not excreting increased amounts of ACE. ACE levels are also less
likely to be elevated in those with chronic sarcoidosis.
What is often important with sarcoidosis is initially high levels of ACE, then
decreasing levels, indicating spontaneous or therapy induced remission. Falling levels
usually indicate a favorable prognosis. Rising levels of ACE on the other hand, may
indicate either an early disease process, or disease activity that is not responding to
therapy.
ACE conversion of angiotensin I to angiotensin II is a normal regulatory process in
the body. This process has been targeted by the development of drugs called ACE
inhibitors that are commonly used in treating hypertension and diabetes. These drugs
inhibit the conversion process, keeping the blood vessels more dilated and the blood
pressure lower. ACE inhibitors are useful in managing hypertension but they are not
monitored with ACE blood tests. They may however interfere with ACE
measurements ordered for other reasons.
Hemolysis (broken red blood cells) and hyperlipidemia (excess fats) in the blood
sample may falsely decrease ACE levels. Decreased ACE levels may also be seen in
patients with:
 Chronic obstructive pulmonary disease (COPD)

 Cystic fibrosis
 Emphysema
 Lung cancer
 Starvation
 Steroid drug therapy
 Hyperthyroidism
ACE has been found in moderately increased levels in a variety of diseases and
disorders such as:
 HIV
 Certain fungal diseases
 Diabetes mellitus
 Hyperthyroidism
 Lymphoma
 Alcoholic cirrhosis
 Gaucher’s disease (a rare inherited lipid metabolism disorder).
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The ACE test, however, is not routinely used to diagnose or monitor these conditions
(it had not been shown to be clinically useful).
1. What other tests are used to diagnose sarcoidosis?
A variety of tests may be ordered, both to help diagnose sarcoidosis and to determine
the degree of organ involvement. Laboratory tests may include: a liver panel, CBC,
and calcium (blood and urine – they tend to be elevated). Other tests may include a:
physical exam (for skin lesions) pulmonary function test (about 90% of the time there
will be some amount of lung involvement with sarcoidosis), bronchoscopy (passing a
flexible tube that is used to look at the lining of the airway and to biopsy the lung),
chest x-ray, gallium screening (radioactive gallium is used to evaluate inflammation).
Biopsies of the skin, lungs, lymph nodes and sometimes liver may also be needed, as
may a thorough eye exam (a test called a slit-lamp examination may be used).
2. What causes sarcoidosis?
The cause is not well understood. It is not contagious. It is inflammatory and involves
the immune system. It appears to have a genetic component, as well as an
environmental one. It has been been reported both in related and unrelated individuals
living in the same area. About 10 – 40 people per 100,000 are affected in the U.S., the
majority of them between 20 and 40 years old. In the U.S. and in the Caribbean
sarcoidosis is more common in those of African descent, but worldwide about 80% of
those with sarcoidosis are white. It is relatively common in Scandinavia and Northern
Ireland, but rare in China, Japan, and Africa. For some reason, those who have moved
from a part of the world where the prevalence is low to a part of the world where it is
high tend to take on the risk of the higher prevalence area.
3. What is the long-term prognosis for sarcoidosis?
The majority of those with sarcoidosis recover from this disease over a period of
several months to a couple of years, but some may suffer permanent scarring in their
lungs. Early detection can help better manage the disease although many cases resolve
themselves without any treatment.
ACTH
Also known as: Corticotropin
Formal name: Adrenocorticotropic hormone.
Why get tested?
To help diagnose adrenal and pituitary diseases such as Cushing’s syndrome,
Cushing’s disease, Addison’s disease, adrenal tumors, and pituitary tumors
When to get tested?
When you have symptoms associated with excess or deficient cortisol production;
when your doctor suspects that you have a hormone imbalance that could be caused
by a problem in your pituitary or adrenal glands
Sample required (Blood sample).
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This test measures the amount of adrenocorticotropic hormone (ACTH) in the blood.
ACTH is a hormone produced by the pituitary gland. The pituitary gland is located
below the brain in the center of the head. It is part of the endocrine system, a network
of glands that produce hormones that act on organs, tissues, and other glands and that
help to regulate systems throughout the body. The pituitary creates ACTH and
releases it to stimulate the production of cortisol by the adrenal glands (small organs
located at the top of each kidney). Cortisol is important for regulating glucose,
protein, and lipid metabolism; suppressing the immune system’s response; and
maintaining blood pressure. Normally, ACTH increases when cortisol is low and falls
when cortisol is high.
How is it used?
ACTH levels in the blood are measured to help detect, diagnose, and monitor
conditions associated with excessive or deficient cortisol in the body. These
conditions include:
 Cushing’s disease: excess cortisol that is due to an ACTH-producing tumor in the
pituitary gland (usually a benign tumor)
 Cushing's syndrome: refers to the symptoms and signs associated with excess
exposure to cortisol. In addition to Cushing’s disease, Cushing’s syndrome may be
due to an adrenal tumor, adrenal hyperplasia (increased adrenal cell growth), the use
of steroid medications, or due to an ACTH-producing tumor that is located outside the
pituitary (such as in the lungs).
 Addison's disease, primary adrenal insufficiency: decreased cortisol production due
to adrenal gland damage
 Secondary adrenal insufficiency: decreased cortisol production because of pituitary
dysfunction
 Hypotituitarism: pituitary dysfunction or damage that leads to decreased (or no)
hormone production by the pituitary – including ACTH production
Measuring both ACTH and cortisol can help to differentiate among some of these
conditions. Because the level of ACTH normally changes in the opposite direction to
the level of cortisol, your doctor can learn much by identifying an imbalance in this
relationship and the direction in which the imbalance occurs. The table below
indicates the common patterns of ACTH and cortisol seen with different diseases
involving the adrenal and pituitary glands.
Disease Cortisol ACTH

Cushing's disease (pituitary tumor making ACTH) High High
Adrenal tumor High Low
"Ectopic" ACTH (ACTH made by a tumor outside the pituitary, High High
usually in the lung)
Addison's disease (adrenal damage) Low High
Hypopituitarism Low Low
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When is it ordered?
This test is ordered when a patient has signs or symptoms associated with excess or
deficient cortisol.
Too much cortisol often causes symptoms such as obesity (especially if it spares the
arms and legs), a rounded face, fragile and thin skin, purple lines on the abdomen,
muscle weakness, acne, and increased body hair. It is often accompanied by findings
such as high blood pressure, low potassium, high bicarbonate, and high glucose (or
even diabetes).
Patients with insufficient cortisol production may exhibit symptoms such as muscle
weakness, fatigue, weight loss, increased skin pigmentation (even in areas not
exposed to the sun), and loss of appetite. This is often accompanied by findings such
as low blood pressure, low blood glucose, low sodium, high potassium, and high
calcium.
Symptoms suggestive of hypopituitarism include loss of appetite, fatigue, irregular

menstrual cycle, hypogonadism (lower levels of sex hormones in males), decreased
sex drive, frequent nighttime urination, and weight loss. When the condition is due to
a pituitary tumor (usually benign), the patient may also have symptoms associated
with the compression of nearby cells and nerves. The tumor can affect the nerves
controlling vision, causing symptoms such as "tunnel vision" (inability to see things
off to the side), loss of vision to some localized areas, and double vision, and can
cause a change in a pattern of headaches.

Changes in ACTH and cortisol are usually evaluated together, as shown in the table
above.
An increased ACTH result can mean that a patient has Cushing's disease, Addison's
disease, or ectopic ACTH-producing tumors. A decreased ACTH result can be due to
an adrenal tumor, steroid medication, or hypopituitarism.
In some cases, the interpretation of the results can be complex. Concentrations of both
ACTH and cortisol vary throughout the day. Normally, ACTH will be at its highest
level in the morning and lowest at night. It will stimulate cortisol production, which
will follow the same pattern but will rise after ACTH does and fall to its lowest level
very late in the evening. Conditions that affect the production of ACTH and cortisol
often disrupt this diurnal variation (daily pattern).

Testing the change in cortisol when certain drugs are given often helps to clarify the
picture and allows the doctor to make the right diagnosis. The most commonly used
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drugs are cortrosyn (cosyntropin, a drug form of ACTH) for an ACTH stimulation test
and dexamethasone for a dexamethasone suppression test.
 Cortrosyn, like ACTH, stimulates the adrenal glands to make cortisol. If cortisol
levels don't rise after cortrosyn is given, this indicates adrenal failure as can occur in
Addison's disease or hypopituitarism.
 Dexamethasone is a very potent drug that acts like cortisol. In normal people, it
should stop ACTH production. By testing the ability of different doses of
dexamethasone to stop ACTH production, it is often possible to tell if the patient has
Cushing's syndrome and help determine its cause.
A number of other drugs are sometimes used, including insulin, corticotropin
releasing hormone, and metyrapone (metapyrone).
Some drugs and conditions can cause ACTH levels to rise, including amphetamines,
insulin, levodopa, metoclopramide, and RU 486.
Drugs that cause ACTH to fall include dexamethasone and other drugs that act like
cortisol (including prednisone, hydrocortisone, prednisolone, and
methylprednisolone), and megestrol acetate.
Secretion of ACTH may be increased by stress.
ACTH has also been used as a drug to treat Multiple Sclerosis.
1. What is the difference between Cushing’s disease and Cushing’s syndrome?

Cushing’s disease is the overstimulation of the adrenal gland by ACTH because of a
tumor (usually benign) of the pituitary gland. Cushing’s syndrome refers to the same
symptoms regardless of the cause. It also can be caused by taking steroid hormones
(often used to treat cancer or autoimmune diseases), by tumors of the adrenal glands,
and by ACTH-producing tumors outside the pituitary gland (usually in the lungs).
2. What is Addison's disease?
Addison's disease is another name for primary adrenocortical insufficiency, which

happens when the adrenal cortex is damaged or destroyed and there is a lack of
cortisol and other adrenal steroids, especially aldosterone.
3. My doctor told me that my extra ACTH is not produced in my pituitary gland.

What is going on?
Another way your body can make ACTH is called ectopic production of ACTH. This
means that ACTH is made from tumors elsewhere in the body, usually (but not
always) in the lungs. This causes Cushing’s syndrome and may alert your doctor to
the presence of a tumor.
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AFB Culture
Why get tested?
To help identify a mycobacterial infection; to diagnose tuberculosis (TB); to monitor
the effectiveness of treatment
When to get tested?
If you have symptoms, such as a chronic cough, weight loss, fever, chills, and
weakness, that may be due to TB or another mycobacterial infection; if your doctor
suspects that you have active TB; if your doctor wants to monitor the effectiveness of
TB treatment
Sample required?
Usually, three sputum samples are collected early in the morning on different days. If
the patient is unable to produce sputum samples, a bronchoscope may be used to
collect fluid during a procedure called a bronchoscopy. In children, gastric
washings/aspirates may be collected. Depending on symptoms, urine, cerebral spinal
fluid (CSF), other body fluids, or biopsied tissue samples are sometimes tested.
Acid-fast bacillus (AFB) are rod shaped bacteria that can be seen and counted under
the microscope on a specially stained sample on a glass slide, called an AFB smear.
The most common acid-fast bacilli are members of the genus Mycobacterium.
Mycobacterium tuberculosis is the most prevalent mycobacteria, and the most

infectious. Most samples that are submitted for AFB smears and cultures are collected
because the doctor suspects that the patient has TB. Only a few of the more than 60
species of mycobacteria that have been identified cause infections in humans. They
include:
 M. africanum, causes a disease similar to TB in other parts of the world

 Mycobacteria avium-intracellulare complex (MAC), can cause a lung
infection in immunosuppressed patients, such as the elderly and those with
AIDS; this infection is not contagious, but it can be difficult to treat as it tends
to be highly resistant to antibiotics
 Other mycobacterial species grow in water, such as fish tanks, and can cause
skin infections, while others can infect wounds and artificial body parts.
 A few mycobacteria, such as M. bovis, can sometimes be transferred from
animal to human.
Several AFB smears, from different samples, are frequently evaluated. If acid-fast
bacilli are present on any of the smears, a mycobacterial infection is likely. Since
TB is the most common cause, a presumptive diagnosis of TB can be made but
other follow-up testing must be done to positively identify the acid-fast bacilli as
either M. tuberculosis, or as another mycobacteria.
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AFB cultures are the next step; they are used to grow acid-fast bacilli in the
laboratory. Body fluid or tissue samples are decontaminated, digested, and
concentrated before being introduced into a nutrient environment and incubated.
Since mycobacteria grow slowly, positive identification of the species that is/are
present may take days to several weeks, while negative results (no mycobacterial
growth) can take up to 6 to 8 weeks to confirm.

Since TB (and M. avium) most frequently infects the lungs (pulmonary), sputum is the
most commonly tested sample. Sputum is phlegm, thick mucous that is coughed up
from the lungs. Usually, three to five early morning samples are collected (on
consecutive days) in individual sterile cups.
If you are unable to produce sputum samples, your doctor may collect respiratory
samples using a procedure called a bronchoscopy. Bronchoscopy allows your doctor
to look at, and collect samples from, your bronchi and bronchioles. These branching
tubes connect the trachea in your throat to your lungs, providing a pathway for air to
enter your lungs. Once a local anaesthetic has been sprayed onto the trachea, your
doctor can insert a tube into your bronchi and smaller bronchioles and aspirate fluid
samples for testing. Sometimes, they will introduce a small amount of saline through
the tubing and into the bronchi and then aspriate it to collect a bronchial washing.
In children, gastric washings/aspirates may be done. This involves introducing saline

into the stomach through a tube, followed by fluid aspiration.
If your doctor suspects extrapulmonary TB (outside of the lungs, fairly common in

AIDS patients), he may test the body fluids and tissues most likely affected. For
instance, you may collect one or more urine samples if he suspects TB has infected
your kidneys. Or a needle may used to collect fluid from your joints or from other
body cavities, such as the pericardium (lining around the heart) or abdomen.
Occasionally, your doctor may need to use a needle to collect a sample of cerebral
spinal fluid (CSF) or do a minor surgical procedure to obtain a tissue biopsy. A blood
culture may be done if your doctor suspects that the infection has spread through the
blood.
How is it used?
AFB smears and cultures are used to determine whether you have an active M.
tuberculosis infection, an infection due to another member of the Mycobacterium
family, or TB-like symptoms due to another cause. They are used to help determine
whether the TB is confined to the lungs (pulmonary) or has spread to organs outside
the lungs (extrapulmonary). They are ordered to identify TB and multi-drug resistant
TB, as well as to grow pure cultures for drug sensitivity testing. They can be used to
monitor the effectiveness of treatment and can help determine when a patient is no
longer infectious.
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Since TB is airborne and infectious - spread through respiratory secretions - it is a
public health risk. It can spread in confined populations, such as correctional
facilities, nursing homes, and schools; those who are very young, elderly, or have
diseases and conditions that compromise their immune systems tend to be especially
vulnerable. AFB smears and cultures can help track and minimize the spread of TB in
these populations.
When is it ordered?
AFB testing is ordered when:
 you have symptoms that suggest pulmonary TB, such as a lingering cough that
may include streaks of blood
 you have a positive TB skin test and have characteristic lung involvement (as
shown by X-ray)
 someone you are in close contact with, usually a family member or co-worker,
has been diagnosed with TB and you either have symptoms or you have a
condition or disease that puts you at a much higher risk of contracting the
disease, such as HIV (those with AIDS are more likely to have
extrapulmonary TB with few and vague symptoms)
 you are being treated for TB; AFB smears and cultures are usually ordered at
intervals, both when your doctor is evaluating the effectiveness of treatment
and when they are attempting to determine whether or not you are still
infectious

Positive AFB smears indicate a likely mycobacterial infection. Positive AFB cultures
identify the particular mycobacteria causing your symptoms and give your doctor
information about how resistant it may be to treatment.
A positive AFB smear or culture several weeks after drug treatment has started may
mean that your treatment regimen is not effective and needs to be changed. It also
means that you are likely still infectious and can pass the mycobacteria to others
through coughing or sneezing.
Negative results mean that you do not have an AFB infection or that the mycobacteria
was not present in that particular specimen (which is why multiple samples are often
collected). If you have TB, the infection may be in another part of your body and a
different type of body sample may need to be collected. Negative results several
weeks after treatment most likely mean that your TB is responding to drug treatment
and that you are no longer infectious.

Sometimes, young children may be treated based on the culture results and
sensitivities of the TB source (the adult infected). This is because the child's AFB
smear and culture results may be more likely to be negative.
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Several other testing methods, based on genetic components of mycobacteria, have
been developed to help decrease the amount of time necessary to diagnose
tuberculosis. These include genetic probes and molecular TB testing. They
amplify/replicate pieces of the microorganisms genetic code to detect mycobacteria in
body samples in less than 24 hours and can narrow the identification to a complex of
mycobacteria (a combination, of which M. tuberculosis is the most common). They
are fairly sensitive and specific when they are paired with positive AFB smears; but
when they are done on samples that are AFB negative by smear, they tend to be less
accurate. These methods are approved for respiratory samples and must be confirmed
with an AFB culture, but they do provide the doctor with a quick answer, allowing
him to isolate potentially infectious patients and minimize the spread of the disease.
1. Can I be infected with TB and not be sick?
Yes. There are about 10 to 15 million people in the United States, and many more
world wide, who have a latent form of TB infection. They have been exposed to the
bacteria and their body's immune system has confined it to a few of their cells, in an
inactive form. Patients with latent TB infections are not sick and they are not
infectious, but the TB bacteria is still there and still alive and, if they were tested,
most would have a positive TB skin test. The majority of those with latent TB
infection, about 90%, will never progress to active tuberculosis disease.
Those who do have active TB may not feel ill at first. Early symptoms may be subtle
and, if the TB is extrapulmonary (outside of the lungs in organs such as the kidney
and bone), the tuberculosis may be fairly advanced by the time it is causing noticeable
symptoms.
AFP Tumor Markers
Also known as: AFP, Total AFP, AFP-L3%
Formal name: Alpha-fetoprotein, Alpha-fetoprotein-L3%
Why get tested?
To screen for and monitor therapy for certain cancers of the liver, testes, or ovaries
When to get tested?
If your doctor suspects that you have certain cancers of the liver, testes, or ovaries,
have previously been treated for one of these cancers, or are under treatment for them,
or if you have chronic hepatitis or cirrhosis
AFP is a protein produced by fetal tissue (especially the liver) and by tumors.
Increased amounts of AFP are found in the vast majority of patients with a type of
liver cancer called hepatocellular carcinoma. They are also found in some patients
with cancer of the testes and ovaries.
AFP exists in several different variants. Traditionally when a doctor orders an AFP
test, he is ordering a total AFP, one that measures all of the AFP variants together.
This is the primary AFP test in the United States.
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One of the variants is called L3 because of its ability, in the laboratory, to bind to a
particular protein called Lens culinaris agglutinin. The AFP-L3% test is a new test
that compares the amount of total AFP to the amount of AFP-L3. An increase in the
percentage of L3 to total AFP is associated with increased risk of developing
hepatocellular carcinoma in the near future and of having a poorer prognosis, as the
L3-related cancers tend to be more aggressive. The AFP-L3% test is being ordered by
a few doctors in the U.S. and is in wider use in some other countries, such as Japan.
How is it used?
AFP is used to detect tumors that mark cancers of the liver, testes, and ovaries.
Patients with chronic liver diseases such as cirrhosis or chronic hepatitis B must be
monitored at regular intervals because they have a lifetime risk of developing liver
cancer. A doctor may order an AFP test, along with imaging studies, to try to detect
liver cancer when it is in its earliest, and most treatable, stages. An AFP-L3% test
may be ordered by some doctors to help further evaluate the risk of patients with
chronic liver disease developing hepatocellular carcinoma in the near future.
If a patient has been diagnosed with hepatocellular carcinoma or another form of

cancer, an AFP test may be ordered periodically to help monitor a patient’s response
to therapy.
When is it ordered?
Your physician may order an AFP blood test when he:

 suspects that a patient has liver cancer or certain cancers of the testes or ovaries.
 is monitoring a patient with chronic liver disease for the emergence of
hepatocellular carcinoma or another type of liver cancer.
 is monitoring the effectiveness of treatment in a patient who has been diagnosed
with and treated for a cancer of the liver, testes, or ovaries.
An AFP-L3% may be ordered to help evaluate the risk of hepatocellular carcinoma

when a patient has chronic liver disease. This new test, however, is not widely used
and its ultimate clinical utility has yet to be established.

Increased AFP levels can mean liver cancer, cancer of the ovary, germ cell tumor of
the testes, cirrhosis, hepatitis, or other cancers (stomach, colon, lung, breast,
lymphoma).
With an AFP-L3%, the doctor receives both a total AFP result and the percentage of
AFP that is L3. If a patient has chronic liver disease and their AFP and L3% are
significantly elevated, then the patient has an increased risk of having or developing
hepatocellular carcinoma in the next year or two. Both AFP and AFP-L3%
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concentrations can be elevated, and fluctuate, in patients with chronic hepatitis and
cirrhosis. In these patients, a significant increase in AFP is more important than the
actual numerical value of the test result.

In general, the higher the AFP level in patients with cancer, the bigger the tumor. AFP
decreases when your body responds to anti-cancer therapy. If AFP does not return to
normal within about one month after cancer therapy, some of the tumor may still be
present.
Not every patient with increased AFP and AFP-L3% test results has cancer or will
develop liver cancer. The AFP and AFP-L3% tests are not diagnostic; they are
indicators. They must be used in conjunction with imaging studies to look for
malignant tumors when monitoring the patient, or when a doctor suspects that a
cancer is present. The tests can provide useful information, but they are not as specific
or sensitive as doctors would wish. They should not be used to screen the general
population for cancer.
Note that AFP is not always a tumor marker. Because AFP is produced by the fetus,
levels are normally higher in pregnant women and in their newborns. For more
information on AFP testing during pregnancy, see Triple Screen.
1. What are the risk factors for hepatocellular carcinoma?

This cancer usually occurs in people who have chronic scarring of the liver, called
cirrhosis. Most commonly, this is caused by chronic infection from one of two
viruses: hepatitis B and hepatitis C. Alcohol abuse also increases the risk of
developing cirrhosis. Some inherited diseases, especially a disorder called
hemochromatosis (in which the body absorbs too much iron), can cause cirrhosis and
later hepatocellular carcinoma.
2. If my AFP is normal/abnormal, do I need other tests?
If you have chronic liver infection or damage, a high AFP could simply be due to the
disease itself. If your AFP suddenly rises, or if it is very elevated, your doctor will
usually ask for a study to look at your liver, such as an ultrasound exam, a CT scan, or
an MRI scan. These scans can often spot liver cancers if they are present.
Albumin
Why get tested?

To screen for a liver disorder or kidney disease or to evaluate nutritional status,
especially in hospitalized patients (prealbumin is sometimes used instead of albumin
in this situation)
15
When to get tested?
If your doctor thinks you have symptoms of a liver disorder or kidney disease, if you
have a recent, rapid weight change or prior to a planned surgery
Albumin is the most abundant protein in the blood plasma. It keeps fluid from leaking
out of blood vessels; nourishes tissues; and transports hormones, vitamins, drugs, and
ions like calcium throughout the body. Albumin is made in the liver and is extremely
sensitive to liver damage. The concentration of albumin drops when the liver is
damaged, with kidney disease (nephrotic syndrome), when a person is
malnourished, if a person experiences inflammation in the body, or with shock.
Albumin increases when a person is dehydrated.
How is it used?
Since albumin is low in many different diseases and disorders, albumin testing is used
in a variety of settings to help diagnose disease, to monitor changes in health status
with treatment or with disease progression, and as a screen that may serve as an
indicator for other kinds of testing.
When is it ordered?
A physician orders a blood albumin test (usually along with several other tests) if a
person seems to have symptoms of a liver disorder or nephrotic syndrome.
Doctors may also order blood albumin tests when they want to check a person’s
nutritional status, for example, when someone has lost a lot of weight.

Low albumin levels can suggest liver disease. Other liver enzyme tests are ordered to
determine exactly which type of liver disease.
Low albumin levels can reflect diseases in which the kidneys cannot prevent albumin
from leaking from the blood into the urine and being lost. In this case, the amount of
albumin (or protein) in the urine also may be measured.
Low albumin levels can also be seen in inflammation, shock, and malnutrition.
Low albumin levels may also suggest conditions in which your body does not
properly absorb and digest protein (like Crohn’s disease or sprue) or in which large
volumes of protein are lost from the intestines.
High albumin levels usually reflect dehydration.

Certain drugs increase albumin in your blood, including anabolic steroids, androgens,
growth hormones, and insulin.
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If you are receiving large amounts of intravenous fluids, the results of this test may be
inaccurate.
1. Is anyone at high risk for abnormal albumin levels?

Individuals who have chronic liver disease and kidney disorders are at highest risk for
developing abnormal albumin levels. In addition, individuals whose GI tract doesn’t
absorb nutrients properly and individuals who have prolonged diarrhea can develop
abnormal albumin levels.
2. Is there a home test for albumin levels?

No, not for blood albumin. You can test for high albumin levels in urine with a
dipstick purchased in a drug store.
3. What is the difference between albumin, prealbumin, and microalbumin tests?

Albumin and microalbumin are the same molecule while prealbumin, despite the
similar-sounding name, is a completely unrelated molecule. The prealbumin test
measures a protein that reflects your nutritional status, particularly before and after
surgery, or if you are hospitalized or taking nutritional supplements. Albumin testing
is more often used to test for liver or kidney disease or to learn if your body is not
absorbing enough amino acids. Albumin can also be used to monitor nutritional
status. However, prealbumin changes more quickly, making it more useful for
detecting changes in short-term nutritional status than albumin. The microalbumin test
measures very small levels of albumin in your urine and may indicate whether you are
at risk for developing kidney disease.
Aldolase
Aldolase is an enzyme that helps convert glucose into energy. It is found throughout
the body and is elevated in the bloodstream when a patient has muscle or liver
damage or disease. In the past, the aldolase blood test was ordered to diagnose and
monitor certain conditions related to skeletal muscle and/or liver disease. It largely
has been replaced by other enzyme tests such as CK (creatine kinase), ALT (alanine
aminotransferase), and AST (aspartate aminotransferase), which are more specific
indicators of muscle or liver damage. The aldolase test still receives some use in the
monitoring of patients with muscular dystrophy.
Aldosterone and Renin
Why get tested?
To determine if your aldosterone or renin levels are abnormal; to detect
hyperaldosteronism (overproduction of aldosterone) or hypoaldosteronism
(underproduction of aldosterone)
When to get tested?
If you develop findings associated with hyperaldosteronism, such as elevated blood
pressure, muscle weakness, and low potassium
Sample required (blood sample or a 24-hour urine sample).
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Aldosterone is a mineral (salt)-retaining steroid, a hormone that directly regulates the
retention of sodium (salt) by the kidneys and indirectly regulates the excretion of
potassium. It plays an important role in the control of blood volume and blood
pressure. Aldosterone is produced by the adrenal cortex, the outer portion of the two
adrenal glands that are located at the top of each kidney. It usually takes a chain of
events to stimulate the production of aldosterone. The enzyme renin is released by the
kidneys when potassium is increased in the blood, sodium is decreased, there is a
decrease in the volume of blood in circulation, low blood pressure, and/or when there
is decreased blood flow to the kidneys. Renin splits angiotensinogen (a protein
created by the liver) to form angiotensin I. Angiotensin-converting enzyme then acts
on angiotensin I to form angiotensin II. Angiotensin II constricts blood vessels and
stimulates the production of aldosterone. In normal healthy people, when renin
increases aldosterone increases; when renin is low, aldosterone decreases.

A blood sample is taken by needle from a vein in the arm to measure plasma
aldosterone and/or renin. A 24-hour urine collection for aldosterone is preferred by
some physicians since plasma aldosterone levels are variable – they vary throughout
the day and are affected by position. Discuss sample collection with your doctor. For
a plasma aldosterone, your doctor may ask you to be upright or lying down for a
couple of hours prior to the blood draw.
How is it used?
Although some doctors measure either plasma or urine aldosterone by itself, in most
cases it is necessary to measure both renin and aldosterone (and occasionally cortisol)
to get a complete picture of what is happening with hormone production. These tests
may be ordered to help diagnose and to monitor conditions associated with
aldosterone excess or deficiency. The table below indicates the changes in renin,
aldosterone, and cortisol that occur with different disorders.
Disorder Aldosterone Cortisol Renin

Primary hyperaldosteronism High Normal Low
(Conn’s syndrome)
Secondary High Normal High
hyperaldosteronism
Cushing’s syndrome Low-normal High Low
Adrenal insufficiency Low Low High
(Addison's disease)
Pituitary disease Normal Low Normal
Primary hyperaldosteronism is caused by the overproduction of aldosterone by the

adrenal glands, usually by a benign tumor of one of the glands. The high aldosterone
level increases reabsorption of sodium (salt) and loss of potassium by the kidneys,
resulting in an electrolyte imbalance. Primary hyperaldosteronism is sometimes called
18
Conn's syndrome. Symptoms are not typically present, although muscle weakness can
occur if potassium levels are very low. The presence of hypokalemia (low potassium)
in a person with hypertension suggests the need to look for hyperaldosteronism.
Secondary hyperaldosteronism, which is more common, can occur as a result of

anything that decreases blood flow to the kidneys, decreases blood pressure, or lowers
sodium levels. The most important cause is narrowing of the blood vessels that supply
the kidney, termed renal artery stenosis. This causes high blood pressure due to high
renin and aldosterone, that may be cured by surgery or angioplasty (using a catheter
put into the groin to open up blocked vessels). Sometimes, to see if only one kidney is
affected, a catheter is inserted through the groin and blood is collected directly from
the veins draining the kidney (renal vein renin levels); if the value is significantly
higher in one side, this indicates where the narrowing of the artery is present.
Similarly, blood may sometimes be taken from both of the adrenal veins to determine
whether there is a difference in the amount of aldosterone (and sometimes cortisol)
produced by each of the adrenal glands. Secondary hyperaldosteronism may also be
seen with congestive heart failure, cirrhosis, kidney disease, and toxemia of
pregnancy.
Hypoaldosteronism (decreased production) usually occurs as part of adrenal

insufficiency; it causes dehydration, low blood pressure, hyperkalemia (high
potassium), and hyponatremia (low sodium).
When is it ordered?
A plasma and/or 24-hour urine aldosterone and a plasma renin may be ordered when a
patient has high blood pressure and a low potassium. Aldosterone levels are
sometimes ordered, along with other tests, when a doctor suspects that a patient has
adrenal insufficiency. Since primary aldosteronism is a potentially curable cause of
hypertension, and because it is often resistant to conventional treatment for high blood
pressure, some doctors order aldosterone and renin levels when they want to help
clarify the treatments that are likely to be effective in patients with high blood
pressure.
The changes in plasma aldosterone, cortisol, and renin are summarized in the table
earlier on the page. High levels of serum and urine aldosterone, along with a low
plasma renin, indicate primary aldosteronism. Secondary aldosteronism, on the other
hand, is characterized by an increase in both aldosterone and renin.
A low aldosterone is usually part of adrenal insufficiency or Addison's disease. In
infants with congenital adrenal hyperplasia, the infant lacks an enzyme needed to
make cortisol; in some cases, this also decreases production of aldosterone. This is a
rare cause of low aldosterone.
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The amount of salt in the diet and medications, such as over-the-counter pain relievers
of the non-steroid class (such as Motrin and Advil), diuretics (water pills), beta
blockers, steroids, angiotensin-converting enzyme (ACE) inhibitors, and oral
contraceptives can affect the test results. Many of these drugs are used to treat high
blood pressure. Your doctor will tell you if you should change the amount of sodium
(salt) you ingest in your diet, your use of diuretics or other medications, or your
exercise routine for aldosterone testing.
Aldosterone levels fall to very low levels with severe illness, so testing should not be
done at times when a person is very ill. Stress and strenuous exercise can temporarily
increase aldosterone results.
1. Are there any other precautions I should take before the test?
Licorice may mimic aldosterone properties and should be avoided for at least two
weeks before the test because it can decrease aldosterone results. This refers only to
the actual products of the licorice plant (hard licorice); most soft licorice and other
forms of licorice sold in North America do not actually contain licorice. Check the
package label if you are not certain, or bring a package with you to ask your doctor.
2. If my posture is important in the outcome of the results, how can I control it?
You may be asked to arrive well before your testing time so you can remain in a lying
or upright position long enough to establish that as your baseline testing position.
3. Are there any other conditions associated with abnormal aldosterone levels?
Prolonged use of steroids, a diet high in salt, some blood pressure medications, and
Addison's disease can cause decreased aldosterone levels.
Allergies
Also known as: RAST test, allergy screen
Formal name: Allergen-specific IgE antibody test
Why get tested?
To screen for allergies, to identify particular allergens, and, sometimes, to monitor the
effectiveness of immunotherapy (desensitization) treatment
When to get tested?
When you have symptoms such as hives, dermatitis, rhinitis (nasal congestion), red
itchy eyes, asthma, or abdominal pain that your doctor suspects may be caused by an
allergy
Immunoglobulin E (IgE) is a protein associated with allergic reactions; it is normally
found in very small amounts in the blood. IgE is created as needed; it functions as part
of the body’s immune system, its defense against “intruders.” When someone with a
genetic predisposition to allergies is exposed to a potential allergen (such as food,
grass, or animal dander, something that does not cause a reaction in a non-allergic
20
person) for the first time, they become sensitized. Their body perceives the potential
allergen as a threat and creates a specific IgE protein, an IgE antibody that binds to
mast cells (specialized cells in your tissues), and basophils (a type of white blood cell)
in your blood stream. The mast cells are found in tissues throughout your body but are
highest in concentration in your skin, respiratory system, and gastrointestinal tract.
With the next exposure, these attached IgE antibodies recognize the allergen and
cause the mast and basophil cells to release histamine and other chemicals, resulting
in an allergic reaction that begins at the exposure site.
The allergen-specific IgE antibody test is used to screen for an allergy to a specific
allergen. It measures the amount of that suspected IgE antibody in the blood. Each
selection is one separate test, and the tests are very specific: honeybee versus
bumblebee, egg white versus egg yolk, giant ragweed versus western ragweed.
Groupings of these tests, such as food panels or regional weed, grass, and mold
panels, can be done. Alternatively, you and your doctor may pick and choose
selectively from a long list of individual allergens suspected of causing your allergies.
The allergen-specific IgE test can be done using a variety of methods. The method
that has been used and studied for the longest time is the RAST (radioallergosorbent
test). Some doctors refer to all IgE allergy tests as RAST even though this is a specific
methodology and may not be the exact test that the lab at their institution is using.
How is it used?
The allergen-specific IgE antigen test is done to screen for an allergy (a type I
hypersensitivity) to a specific substance or substances in response to acute or chronic
allergy-like symptoms in the patient.
The allergen-specific IgE antibody test may be done (instead of other medically
supervised allergy testing) when the patient has significant dermatitis or eczema, is
taking necessary histamines or anti-depressants that would make other testing more
difficult, or if a dangerous allergic reaction could be expected to follow another test.
The allergen-specific IgE antibody test may also be done to monitor immunotherapy
or to see if a child has outgrown an allergy, although it can only be used in a general
way; the level of IgE present does not correlate to the severity of an allergic reaction,
and someone who has outgrown an allergy may have a positive IgE for many years
afterward.
When is it ordered?
The allergen-specific IgE antibody test is usually ordered when you have signs or
symptoms that suggest that you have an allergy to one or more substances or foods.
Normal negative results indicate that you probably do not have a “true allergy,” an
IgE-mediated response to that specific allergen, but the results of allergen-specific IgE
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antibody tests must always be interpreted and used with caution and the advice of
your doctor. Even if your IgE test is negative, there is still a small chance that you do
have an allergy.
Elevated results usually indicate an allergy, but even if your specific IgE test was
positive, you may or may not ever have an actual physical allergic reaction when
exposed to that substance. And the amount of specific IgE present does not
necessarily predict the potential severity of a reaction. Your clinical history and other
allergy tests, done under close medical supervision, may be necessary to confirm an
allergy diagnosis.
Sometimes your doctor will look at other blood tests for an indirect indication of an
ongoing allergic process, including your total IgE level or your complete blood count
(CBC) and white blood cell differential (specifically at your eosinophils and
basophils). Elevations in these tests may suggest an allergy, but they may also be
elevated for other reasons.
1. What other tests are available for allergy testing?
Skin prick or scratch tests, patch tests, and oral food challenges are usually done by an
allergist or dermatologist. Your doctor may also try eliminating foods from your diet
and then reintroducing them to find out what you are allergic to. It is important that
these tests be done under close medical supervision, as a life threatening anaphylactic
reaction is possible.
2. My allergy test was negative, but I am having symptoms. What else could it
be?
You could have a genetic hypersensitivity problem, like Celiac disease’s sensitivity to
gluten, or an enzyme deficiency, such as lactase deficiency causing lactose
intolerance. It could also be an allergy-like condition that is not mediated by IgE for
which there are no specific laboratory tests. Or it could be another disease that is
causing allergy-like symptoms. It is important to investigate your individual situation
with your doctor’s assistance.
3. My allergy symptoms are generally mild. How serious is this really?

Allergic reactions are very individual. They can be mild or severe, vary from
exposure to exposure, get worse over time (or may not), involve the whole body, and
can sometimes be fatal.
4. Will my allergies ever go away?

Although children do outgrow some allergies, adults usually do not. Allergies that
cause the worst reactions, such as anaphylaxis caused by peanuts, do not usually go
away. Avoidance of the allergen and advance preparation for accidental exposure, in
the form of medications such as antihistamines and portable epinephrine injections, is
the safest course. Immunotherapy can help decrease symptoms for some unavoidable
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allergies, but they won’t work for food and the treatment, which usually consists of
years of regular injections, may need to be continued indefinitely.
5. Why am I told to avoid fresh fruit when my allergy is to tree pollen?

There are cross-reactions between some airborne allergens and fruit proteins. Your
body thinks it is detecting tree pollen and creates an allergic reaction to the fruit. It is,
however, a relatively rare occurrence.
ALP
Why get tested?
To screen for or monitor treatment for a liver or bone disorder
When to get tested?

As part of a routine liver panel or when a person has symptoms of a liver or bone
disorder
Alkaline phosphatase is an enzyme, a protein that helps cells work. You find alkaline
phosphatase in high concentrations in the cells that make bone and in the liver. In the
liver, it is found on the edges of cells that join to form bile ducts (tiny tubes that drain
bile from the liver to the bowels where it is needed to help digest fat in the diet).
Smaller amounts of ALP are found in the placenta (afterbirth) of women who are
pregnant, and in the bowel. Each of these body parts makes different forms of ALP.
The different forms are called isoenzymes.
How is it used?
When a person has evidence of liver disease, very high ALP levels can tell the doctor
that the person’s bile ducts are somehow blocked. Often, ALP is high in persons who
have cancer that has spread to the liver or the bones, and doctors can do further testing
to see if this has happened. If a person with bone or liver cancer responds to
treatment, ALP levels will decrease. When a person has high levels of ALP, and the
doctor is not sure why, s/he may also order ALP isoenzyme tests to try to determine
the cause.
When is it ordered?
ALP is generally part of a routine lab testing profile, often with a group of other tests
called a liver panel. It is also usually ordered along with several other tests if a patient
seems to have symptoms of a liver or bone disorder.
High ALP usually means that the bone or liver has been damaged. If other liver tests
such as bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase
(ALT) are also high, usually the ALP is coming from the liver. If calcium and
phosphate measurements are abnormal, usually the ALP is coming from bone.
In some forms of liver disease, such as hepatitis, ALP is usually much less elevated
than AST and ALT. When the bile ducts are blocked (usually by gallstones, scars
from previous gallstones or surgery, or by cancers), ALP and bilirubin may be
23
increased much more than AST or ALT. In a few liver diseases, ALP may be the only
test that is high.
In some bone diseases, such as a disorder called Paget’s disease (where bones become
enlarged and deformed), or in certain cancers that spread to bone, ALP may be the
only test result that is high.
Sometimes doctors don’t know why ALP is high, and they need to order other tests to
determine the exact cause. In such cases, your doctor may order another enzyme,
GGT, that is made by the liver in the same places as is ALP, but which is not made by
bone.
Pregnancy can increase ALP levels. Children have higher ALP levels because their
bones are growing, and ALP is often very high during the “growth spurt,” which
occurs at different ages in males and females. Eating a meal can increase the ALP
level slightly for a few hours in some people. It is usually better to do the test after
fasting overnight. Some drugs may increase ALP levels, especially some of the drugs
used to treat psychiatric problems, but this is rare. Fasting is preferred but not required
for this test.
1. What other tests are used to evaluate liver disorders?
Other commonly used liver tests include more enzymes found in liver cells, such as
alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and bilirubin
(a yellow pigment removed from the body by the liver).
2. Who is at risk for a liver disorder?
While many things could harm the liver, the major causes of liver disease are
infection by viruses and the drinking of too much alcohol. In rare cases, some
medicines can damage the liver; your doctor may suggest liver tests from time to time
if you are taking one of these drugs. Some diseases that are inherited from your
parents can also occasionally damage the liver.
3. What signs should make me aware of a liver disorder?

In many cases, liver disease has few symptoms. When the liver is damaged rapidly (a
disease called acute hepatitis), the skin and the whites of the eyes often turn yellow,
the urine turns brown, and bowel movements lose their color. In its late stages, liver
disease may cause confusion, easy bruising, swelling in your abdomen, and the
vomiting of blood.
Alpha-1 Antitrypsin
Why get tested?
To help diagnose the cause of early onset emphysema and/or liver dysfunction. To
establish the risk of developing alpha-1 antitrypsin-related emphysema and/or liver
disease and the likelihood that children might inherit the risk.
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When to get tested?
When you show signs of liver disease as an infant or young child, when you develop
emphysema (a disease that damages the lungs) before age 40, or when you have a
close relative with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin (AAT) is a protein that is produced in the liver and released into
the bloodstream. AAT helps to inactivate several enzymes but primarily works to
protect the lungs from elastase. Elastase is an enzyme produced by neutrophils (a type
of white blood cell) and it is part of the body’s normal response to injury and
inflammation. Elastase breaks down proteins so that they can be removed and
recycled by the body but, if its action is not regulated by AAT, elastase will also begin
to break down and damage lung tissue.
AAT is produced at the direction of two copies of a protease inhibitor (Pi) gene. This
gene is co-dominant, which means that each Pi gene copy is responsible for producing
half of the body’s AAT. If there is a change or mutation in one or both of the gene
copies, then less AAT and/or dysfunctional AAT is produced. If the resulting AAT
production drops down to 30% of normal or less, then the affected patient will
experience a disorder called alpha-1 antitrypsin deficiency. Patients with this disorder
are at a considerable risk of developing emphysema (a progressive lung disease) in
early adulthood. If they smoke, or are exposed to occupational dust or fumes, the lung
damage tends to occur sooner and be more severe.
If the AAT produced is dysfunctional it tends to accumulate in the liver cells that
produce it. As it builds up in these cells, the AAT forms abnormal protein chains, and
begins to destroy the cells and damage the liver. About 10% of those affected with
AAT deficiency will be jaundiced as a newborn. Many improve on their own but in
severe cases these infants may require a liver transplant to survive. AAT deficiency is
currently the most common reason for a liver transplant in the pediatric population.
The amount and function of the AAT created depends on the mutation inherited.
While there are more than 70 different alleles (variations) in the Pi gene, only a few
are common. Most people in the U.S., about 90%, have two copies of the normal M
gene (MM). The most common of the abnormal forms are S and Z. Those people
with:
 One copy of M and one of S or Z (MS or MZ) will produce reduced amounts
of AAT but should have enough to protect themselves. They will be carriers of
the condition, however, and can pass it on to their children.
 Two copies of S (SS) may be asymptomatic or moderately affected (they
produce about 60% of the required AAT)
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 One copy of S and one of Z (SZ) are at an increased risk of developing
emphysema (they produce about 40% of normal AAT)
 Two copies of Z (ZZ) are the most severely affected (they only produce about
10% of the required AAT) along with those who have one or two copies of
rare forms of the Pi gene which are “null” (they do not produce any AAT).
Types of AAT tests

Different AAT tests can be used to measure the amount of AAT, determine which
types and concentrations of AAT protein are present, and determine which Pi gene
alleles a patient has.
 Alpha-1 Antitrypsin, this test measures the concentration of AAT present

 Alpha-1 Antitrypsin Phenotype, separates out the different variants of alpha-1
protein being produced and compares them to known patterns. It also allows
an estimation of the amount of each type present. Since AAT is an alpha1
globulin type of protein a regular protein electrophoresis test can be used to
screen for a severe AAT deficiency
 Alpha-1 Antitrypsin DNA testing, genetic testing can be done to identify which
protease inhibitor gene mutations (Pi gene alleles) are present. Only the most
common mutations are usually evaluated (M, S, Z). This test can be used to
help evaluate affected patients and their family members.
How is it used?
An alpha-1 antitrypsin concentration is ordered to help diagnose the cause of early
onset emphysema, especially when a person does not have obvious risk factors such
as smoking or exposure to lung irritants such as dust and fumes.
Alpha-1 antitrypsin is also ordered to help diagnose the cause of persistent jaundice
and other signs of liver dysfunction. This is done primarily in infants and young
children but may also be done in patients of any age.
Alpha-1 antitrypsin phenotype testing may be ordered if the alpha-1 antitrypsin

concentration is lower than normal. It looks at the amount and type of AAT being
produced and compares it to normal patterns.
DNA testing may be done as a follow-up to an alpha-1 antitrypsin level and

phenotype. Once it has been established that an abnormality exists, then the DNA
genetic testing can be ordered to establish which Pi gene alleles are present. This test
does not test for every variant, just the most common ones (M, S, and Z, as well as
any that may be common in a particular geographical area or family). Once the
affected person’s Pi gene alleles have been determined, other family members may be
tested to establish their own possible risk of developing emphysema and/or liver
involvement as well as the likelihood that their children might inherit it.
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When is it ordered?
Alpha-1 antitrypsin testing may be ordered when a newborn or infant has jaundice
that lasts for an extended period of time (more than a week or two), an enlarged
spleen, ascites (fluid accumulation in the abdominal cavity), pruritus (itching), and
other signs of liver injury. It may be ordered when a person under 40 years of age
develops wheezing, a chronic cough or bronchitis, is short of breath after exertion
and/or shows other signs of emphysema. This is especially true when the patient is not
a smoker, has not been exposed to known lung irritants, and when the lung damage
appears to be located low in the lungs. AAT testing may also be done when you have
a close relative with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin phenotype testing is ordered when a patient has a decreased level
of AAT. DNA testing is performed when the AAT test indicates that the patient has
lower than normal level of AAT and when the alpha-1 antitrypsin phenotype test
indicates that some or all of the AAT protein being produced appears to be a variant.
It may also be ordered in the rare case when no AAT is being produced. AAT DNA
testing may be done on close relatives when there is an affected family member, and
when a patient wants to determine their risk of having an affected child.
AAT concentrations are primarily important when they are lower than normal and/or
indicate that the AAT being produced is abnormal. The lower the level of normal
AAT, the greater the risk of developing emphysema.
With abnormal AAT it depends on how much is produced and how abnormal it is.
Low concentrations of abnormal AAT in the blood may lead to both emphysema
(because of the lack of lung protection) and to liver disease because of the buildup of
dysfunctional AAT inside the liver cells producing it.
When DNA testing indicates the presence of one or two abnormal copies of the Pi
gene, less AAT and/or abnormal AAT will be produced and the variant copies can be
passed on to the patient’s children. The degree of AAT deficiency and the degree of
lung and/or liver damage experienced is very variable. Two people with the same
gene copies may have very different disease courses.
AAT is an acute phase reactant. This means that it will be elevated in acute and
chronic inflammatory conditions, infections, and with some cancers. Increased levels
of AAT may also be seen with infections, oral contraceptives, pregnancy, stress, and
thyroid infections. Although an increased amount of AAT may be present, this test is
not usually measured or used as a monitoring tool in these situations. This may cause
levels to be "normal" in persons with mild to moderate AAT deficiency when they
also have another condition that increases AAT.
AAT concentrations may be decreased with neonatal respiratory distress syndrome,

27
and with conditions that decrease serum proteins such as kidney disease (nephrotic
syndrome), malnutrition, and some cancers.
1. What can I do to take care of myself if I have alpha-1 antitrypsin deficiency?
Don’t smoke. Quitting smoking can increase your lifespan and delay the onset of
emphysema. Take care of your lungs – avoid lung irritants such as dust and fumes, get
regular pneumonia shots and an annual influenza shot, get prompt medical attention
for lung infections, and get regular exercise to help maintain lung function.
2. How common is alpha-1 antitrypsin deficiency?

It is thought to be one of the most frequent genetic deficiencies in Caucasians. In the
U.S. about 1 in 2,000 have some degree of AAT deficiency.
ALT (GPT)
Why get tested?
To screen for liver damage
When to get tested?
If your doctor thinks that you have symptoms of a liver disorder
ALT is an enzyme found mostly in the liver; smaller amounts of it are also in the
kidneys, heart, and muscles. Under normal conditions, ALT levels in the blood are
low. When the liver is damaged, ALT is released into the blood stream, usually before
more obvious symptoms of liver damage occur, such as jaundice (yellowing of the
eyes and skin).
How is it used?
The ALT test detects liver injury. ALT values are usually compared to the levels of
other enzymes, such as alkaline phosphatase (ALP) and aspartate aminotransferase
(AST), to help determine which form of liver disease is present.
When is it ordered?
A physician usually orders an ALT test (and several others) to evaluate a patient who
has symptoms of a liver disorder. Some of these symptoms include jaundice, dark
urine, nausea, vomiting, abdominal swelling, unusual weight gain, and abdominal
pain. ALT can also be ordered, either by itself or with other tests, for:
 persons who have a history of known or possible exposure to hepatitis

viruses,
 those who drink too much alcohol,
 individuals whose families have a history of liver disease, or
 persons who take drugs that might occasionally damage the liver.
In persons with mild symptoms, such as fatigue or loss of energy, ALT may be tested
to make sure they do not have chronic liver disease. ALT is often used to monitor the
treatment of persons who have liver disease, to see if the treatment is working, and
may be ordered either by itself or along with other tests.
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Very high levels of ALT (more than 10 times the highest normal level) are usually
due to acute hepatitis, often due to a virus infection. In acute hepatitis, ALT levels
usually stay high for about 1–2 months, but can take as long as 3–6 months to come
back to normal.
ALT levels are usually not as high in chronic hepatitis, often less than 4 times the
highest normal level: in this case, ALT levels often vary between normal and slightly
increased, so doctors typically will order the test frequently to see if there is a pattern.
In some liver diseases, especially when the bile ducts are blocked, when a person has
cirrhosis, and when other types of liver cancer are present, ALT may be close to
normal levels.

A shot or injection of medicine into the muscle tissue, or strenuous exercise, may
increase ALT levels.
Many drugs may raise ALT levels by causing liver damage in a very small percentage
of patients taking the drug. This is true of both prescription drugs and some “natural”
health products. If your doctor finds that you have a high ALT, tell him or her about
all the drugs and health products you are taking.
1. What is hepatitis?
Hepatitis is an inflammation of the liver. There are two major forms: acute and
chronic. Acute hepatitis typically makes affected persons feel sick, as if they have the
flu, often with loss of appetite and sometimes diarrhea and vomiting. In many cases,
acute hepatitis turns urine brown, makes stools pale, and colors the skin and eyes
yellow. Most affected individuals eventually recover completely. Chronic hepatitis
usually causes no symptoms, or causes only loss of energy and tiredness; most people
don’t know that they have it. In some people, chronic hepatitis can gradually damage
the liver and, after many years, cause it to fail.
2. What are the other liver tests?

aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and bilirubin (a
yellow pigment removed from the body by the liver).
AMA
Also known as: Mitochondrial Antibody
Formal name: Antimitochondrial Antibody and Antimitochondrial M2 Antibody.
Why get tested?
To help diagnose primary biliary cirrhosis (PBC)
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When to get tested?
When a doctor suspects that a patient may have PBC
This test measures the amount of antimitochondrial antibodies (AMA) in the blood.
The production of AMA is strongly associated with primary biliary cirrhosis (PBC).
PBC is an autoimmune disorder that causes inflammation and scarring of the bile
ducts inside the liver. It is found most frequently in women between the ages of 35
and 60. PBC blocks the flow of bile (a fluid produced in the liver that helps digest
fats) and causes progressive liver damage. About 94% of those affected by PBC will
have significant concentrations of antimitochondrial antibodies.
There are several types of AMA designated as M1, M2, M3, M5, and M6. The M2
type has been found to be the most strongly associated with PBC, while the others
may also be found in other conditions. Some laboratories have started to offer the
AMA-M2 instead of the AMA, which tests for all types together.
How is it used?
The AMA test is ordered to help diagnose primary biliary cirrhosis (PBC). It may be
ordered by itself or along with other autoantibodies such as anti-nuclear antibodies
(ANA) and anti-smooth muscle antibodies (ASMA) to help detect PBC and
distinguish it from other conditions that may be causing autoimmune-related liver
damage. The AMA-M2 test is being offered by some laboratories instead of the AMA
test. In most cases, the laboratory will have one test or the other but not both.
When is it ordered?
The AMA or AMA-M2 test is ordered when a doctor suspects that the patient has
PBC. The patient may have symptoms such as an enlarged liver and spleen, fatigue,
jaundice (yellowing of the skin and eyes), and itchiness, but many patients affected
with early PBC do not have any symptoms. The condition is often initially identified
because a patient has elevated liver enzymes (especially alkaline phosphatase (ALP))
that are found during routine blood tests.
AMA or AMA-M2 tests may be ordered along with or following a variety of tests that
are used to help diagnose and/or rule out other causes of liver disease or injury. These
causes can include infections (such as viral hepatitis), drugs, alcohol abuse, toxins,
genetic conditions, metabolic conditions, and autoimmune hepatitis.

When significant amounts of AMA or AMA-M2 are present in the blood, the most
likely cause is PBC. Small concentrations of AMA may also be present in patients
with chronic active hepatitis, autoimmune hepatitis, liver or bile obstruction, and with
infections such as syphilis or acute infectious hepatitis. It may also be present in
patients with other autoimmune disorders such as systemic lupus erythematosus,
30
rheumatoid arthritis, and thyroiditis. The AMA test is not used to diagnose these other
conditions, but its presence does indicate some degree of autoimmune activity. A
small number of patients will have PBC even though they are negative for AMA.
Concentrations of AMA may be lower in children and in those with compromised
immune systems.

AMA and AMA-M2 are not diagnostic of PBC. When significant concentrations of
AMA or AMA-M2 are present, and the doctor suspects PBC, a liver biopsy may be
performed to look for characteristic signs of primary biliary cirrhosis in the liver
tissue. Imaging scans of the liver may also be ordered to look for bile duct
obstructions.
About 50% of the cases of PBC will be discovered before the patient has noticeable
symptoms.
1. What causes PBC?

The cause is currently not known. It is not infectious and not inherited, although an
increased susceptibility to develop autoimmune disorders may occur in some families.
It can occur in anyone at any age, but it is primarily seen in middle-aged women.
2. How fast does PBC progress?
The course and severity of PBC is difficult to predict. Many patients will have no or
few symptoms for many years. For more information, consult with your doctor and
see the related links.
Ammonia
Why get tested?
To detect elevated levels of ammonia in the blood, to evaluate changes in
consciousness, or to help diagnose hepatic encephalopathy and Reye’s syndrome
When to get tested?
If a patient experiences mental changes or lapses into a coma of unknown origin; if an
infant or child experiences frequent vomiting and increased lethargy as a newborn or
about a week after a viral illness
This test measures the amount of ammonia in the blood. Ammonia is a compound
produced by intestinal bacteria and by cells in the body during the digestion of
protein. A waste product, ammonia is normally transported to the liver, where it is
converted into urea and glutamine. The urea is then carried by the blood to the
kidneys, where it is excreted in the urine. If this “urea cycle” does not complete,
ammonia builds up in the blood and passes through the blood/brain barrier.
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In the brain, ammonia and other compounds metabolized by the liver can cause
hepatic encephalopathy – mental and neurological changes that can lead to confusion,
disorientation, sleepiness, and eventually to coma and even death. Infants and children
with increased ammonia levels may vomit frequently, be irritable, and be increasingly
lethargic. Left untreated, they may experience seizures, respiratory difficulty, and may
lapse into a coma.
Problems with ammonia processing can arise from several sources, including:
 Rare inherited defects in the urea cycle – a deficiency or defect in one or more of
the enzymes necessary to complete the conversion of ammonia to urea.
 Severe liver disease – damage limits the ability of the liver to metabolize ammonia.
Acute increases in ammonia may be seen in patients with stable liver disease,
especially following a triggering event such as gastrointestinal bleeding or an
electrolyte imbalance.
 Decreased blood flow to liver – ammonia is less able to get to the liver.
 Reye’s syndrome – an acute condition that affects the blood, brain, and liver. It is
characterized by a rise in ammonia levels and a fall in glucose and affects children
and young adults. In most cases, it follows and appears to be triggered by a viral
infection. Children who use aspirin are at an increased risk.
 Renal failure – the kidneys are unable to effectively rid the body of urea, leading to
a build-up of ammonia in the blood.
How is it used?
The ammonia test is primarily used to help investigate the cause of changes in
behavior and consciousness. It may be ordered, along with other tests (such as
glucose, electrolytes, and kidney and liver function tests), to help diagnose the cause
of a coma of unknown origin or to help support the diagnosis of Reye’s syndrome or
hepatic encephalopathy. An ammonia level may also be ordered to help detect and
evaluate the severity of a urea cycle defect.
Some doctors use the ammonia test to monitor the effectiveness of treatment of
hepatic encephalopathy, but there is not widespread agreement on its clinical utility.
Since hepatic encephalopathy can be caused by the build-up of a variety of toxins in
the blood and brain, blood ammonia levels correlate poorly with the degree of
impairment.
When is it ordered?
An ammonia test may be ordered on a newborn when symptoms such as irritability,

vomiting, lethargy, and seizures arise in the first few days after birth. It may be
performed when a child develops these symptoms about a week following a viral
illness such as influenza or a cold and the doctor suspects that the child may have
Reye’s syndrome.
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When adults experience mental changes, disorientation, sleepiness, or lapse into a
coma, an ammonia level may be ordered to help evaluate the cause of the change in
consciousness. In patients with stable liver disease, an ammonia level may be ordered,
along with other liver function tests, when a patient suddenly “takes a turn for the
worse” and becomes more acutely ill.

Significantly increased concentrations of ammonia in the blood indicate that the body
is not effectively metabolizing and eliminating ammonia but do not indicate the cause.
In infants, extremely high levels are associated with an inherited urea cycle enzyme
deficiency or defect but may also be seen with hemolytic disease of the newborn
(where the baby’s red blood cells are destroyed). Moderate short-lived increases in
ammonia are relatively common in newborns, where the levels may rise and fall
without causing detectible symptoms.
Increased ammonia levels and decreased glucose levels may indicate the presence of
Reye’s syndrome in symptomatic children and adolescents. Increased concentrations
may also indicate a previously undiagnosed enzymatic defect of the urea cycle. In
children and adults, elevated ammonia levels may also indicate liver or kidney
damage. Frequently, an acute or chronic illness will act as a trigger, increasing
ammonia levels to the point that an affected patient has difficulty clearing them.
Normal concentrations of ammonia do not rule out hepatic encephalopathy. Not only
do other wastes contribute to the changes in mental function and consciousness, but
brain levels of ammonia may be much higher than blood levels, making correlation of
symptoms to blood levels of ammonia difficult.
Increased levels of ammonia may also be seen with:

 Gastrointestinal bleeding – blood cells are hemolyzed (broken apart) in the
intestines, releasing protein.
 Muscular exertion – muscles produce ammonia when active and absorb it when
resting.
 Tourniquet use – ammonia levels can be increased in the blood sample collected.
 Drugs that can increase ammonia include: alcohol, barbiturates, diuretics, and
narcotics
 Smoking
Decreased levels of ammonia may be seen with hypertension and the use of some
antibiotics (such as neomycin).
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Ammonia tests can also be performed on arterial blood, but this method is much less
frequently used. Some doctors feel that arterial ammonia measurements are more
clinically useful and guidelines suggest that they are helpful for recognizing hepatic
encephalopathy, but there is not widespread agreement on this.
1. Is ammonia testing used to detect or monitor ammonia poisoning?
No, it is not considered clinically useful. In most cases, ammonia acts locally, burning
or irritating whatever it comes in contact with but, according to the Agency for Toxic
Substances and Disease Registry (ATSDR), it does not usually act as a systemic
poison. Concentrated commercial ammonia, in a liquid or vapor form, causes more
severe burns than the more dilute liquid household ammonia, but both can cause
damage to the eyes, skin, respiratory tract, and to the mouth, throat, and stomach if
swallowed.
Amylase
Why get tested?

To diagnose pancreatitis or other pancreatic diseases
When to get tested?
If you have symptoms of a pancreatic disorder, such as severe abdominal pain, fever,
loss of appetite, or nausea

The sample is analyzed for amylase, an enzyme manufactured primarily by the
pancreas. Amylase is released into the digestive tract to help digest starch and
glycogen.
How is it used?
The blood test for amylase is used to diagnose pancreatitis (swelling of the pancreas)
and other pancreatic diseases. The near-immediate rise of amylase at the beginning of
a pancreatitis attack, and its fall after about 2 days, helps to pinpoint this diagnosis.
Amylase is also used (to a lesser extent) in the diagnosis and follow-up of cancer of
the pancreas, ovaries, or lungs; gallbladder attack; and mumps.
When is it ordered?
An amylase test may be ordered if you show symptoms of a pancreatic disorder, such
as severe abdominal pain, fever, loss of appetite, or nausea.
Normal values for amylase depend on the method used to test it. In pancreatitis,
amylase levels are very high, often 5 - 10 times normal levels. Increased amylase
levels may also indicate cancer of the pancreas, ovaries, or lungs; tubal pregnancy;
gallbladder attack; mumps; intestinal obstruction; or perforated ulcer. Decreased
34
amylase levels may indicate damage to the pancreas, pancreatic cancer, kidney
disease, and toxemia of pregnancy.

In acute pancreatitis, elevated amylase levels usually parallel levels of another
enzyme called lipase. Both amylase and lipase are usually ordered together to
diagnose acute pancreatitis.
Chronic pancreatitis is often associated with alcoholism. It may also be caused by
trauma; pancreatic duct obstruction; and associated with genetic abnormalities such as
cystic fibrosis. Amylase levels may be moderately elevated with chronic pancreatitis
or may be decreased when the cells that produce amylase in the pancreas become
damaged or destroyed.
1. What are the treatment options for pancreatitis?
Treatment depends upon the symptoms. If they are absent or mild, there may be no
treatment; if they are more severe, your doctor may suggest "resting the pancreas" by
a spectrum of options ranging from not eating solid foods to fasting combined with IV
(intravenous) fluid replacement for several days to a few weeks (usually requiring
hospitalization). Medication and possible surgery may also be considered for patients
with severe symptoms. Sometimes you may need pain management medications.
Nutritional support, such as low-fat diets and frequent small meals, may help relieve
symptoms. Oral pancreatic enzyme replacement is another possible choice.
2. Can medications that I am taking affect the amylase level?

Yes. Some drugs that may cause amylase to rise include aspirin, diuretics, oral
contraceptives, corticosteroids, indomethacin, and opiates.
3. How does amylase work?

Amylase is an enzyme found in plants and animals. It is found in pancreatic fluids in
the small intestine, where it digests a variety of sugars and starches. When the
pancreas is diseased or inflamed, amylase escapes into the blood.
ANA
Why get tested?
To help diagnose systemic lupus erythematosus (SLE) and drug-induced lupus and
rule out certain other autoimmune diseases
When to get tested?
If your doctor thinks that you have symptoms of SLE or drug-induced lupus
The ANA test identifies the presence of antinuclear antibodies (ANA) in blood.
Sometimes the immune system malfunctions and produces substances that attack your
body's own cells and tissues instead of foreign substances. These substances, called
autoantibodies, are produced by the body's immune system – the body's defense
system against invasion by foreign substances such as viruses and bacteria. When this
35
happens, the resulting disease is termed an autoimmune disease (autoimmunity means
immunity to self). The presence of ANA is a marker of an autoimmune process and is
associated with several autoimmune diseases but is most commonly seen in systemic
lupus erythematosus (SLE).
How is it used?
The test is used to help diagnose systemic lupus erythematosus (SLE) and drug-
induced lupus, but may also be positive in cases of scleroderma, Sj?gren’s syndrome,
Raynaud’s disease, juvenile chronic arthritis, rheumatoid arthritis, antiphospholipid
antibody syndrome, autoimmune hepatitis, and many other autoimmune and non-
autoimmune diseases. For this reason, SLE, which is commonly known as lupus, can
be tricky to diagnose correctly. Because the ANA test result may be positive in a
number of these other diseases, additional testing can help to establish a diagnosis of
SLE. Your doctor may run other tests that are considered subsets of the general ANA
test and that are used in conjunction with patient symptoms and clinical history to rule
out a diagnosis of other autoimmune diseases.
When is it ordered?
Because autoimmune diseases can be difficult to diagnose, this test offers a reliable
first step for identifying SLE and some other autoimmune disorders with a wide
variety of symptoms. These symptoms, including painful or swollen joints,
unexplained fever, extreme fatigue, and a red rash, may come and go over time and
may be mild or severe. It may take months or years for these symptoms to show a
pattern that might suggest SLE or any of the other autoimmune diseases.
A positive test result may suggest an autoimmune disease, but further specific testing
is required to assist in making a final diagnosis. ANA test results can be positive in
people without any known autoimmune disease. While this is not common, the
frequency of a false positive ANA result increases as people get older.
About 95% of SLE patients have a positive ANA test result. If a patient has symptoms
of SLE, such as arthritis, a rash, and autoimmune thrombocytopenia (a low number of
blood platelets), then s/he probably has SLE. In these cases, a positive ANA result can
be useful to support SLE diagnosis. If needed, two subset tests, anti-dsDNA and anti-
SM, can help to show that the condition is SLE. If anti-dsDNA autoantibodies are
found, this supports the diagnosis of SLE. Higher amounts of anti-Sm are more
specific for SLE.
A positive ANA can also mean that the patient has drug-induced lupus. This condition
is associated with the development of autoantibodies to histones. An anti-histone test
can be given to support the diagnosis of drug-induced lupus.
Other conditions in which a positive ANA test result man be seen include:
 Sj?gren’s syndrome: Between 40% and 70% of patients with this condition
have a positive ANA test result. While this finding supports the diagnosis, it is
not required for diagnosis. Again, your doctor may want to test for two subsets
36
of ANA, the ribonucleoproteins SSA and SSB. The frequency
of autoantibodies to SSA in patients with Sj?gren’s can be 90% or greater if
the test is done by enzyme immunoassay.
 Scleroderma: About 60% to 90% of patients with scleroderma have a positive
ANA finding. In patients who may have this condition, the subset tests can
help distinguished two forms of the disease, limited versus diffuse. The diffuse
form is more severe. Limited disease is most closely associated with the
anticentromere pattern of ANA staining (anticentromere test), while the
diffuse form is associated with autoantibodies to the anti–Scl-70.
 A positive result on the ANA also may show up in patients with Raynaud’s
disease, juvenile chronic arthritis, or antiphospholipid antibody syndrome, but
a doctor needs to rely on clinical symptoms and history for diagnosis.
A negative ANA result makes SLE an unlikely diagnosis. Unless an error in the
testing is suspected, it is not necessary to immediately repeat a negative ANA test.
However, because autoimmune diseases change over time, it may be worthwhile to
repeat the ANA test in the future.
Aside from rare cases, further autoantibody (subset) testing is not necessary if a
patient has a negative ANA result.

More specific subsets of the general ANA test are used to help pinpoint the specific
autoimmune disease; these autoantibody tests include anti-dsDNA, anti-Sm, Sj?gren’s
syndrome antigen (SSA, SSB), Scl-70 antibodies, anti-centromere, anti-histone, and
anti-RN.
Some drugs and infections as well as other conditions mentioned above can give a
false positive result for the ANA test. These drugs may bring on a condition that
includes SLE symptoms, called drug-induced lupus. When the drugs are stopped, the
symptoms usually go away. Although many medications have been reported to cause
drug-induced lupus, those most closely associated with this syndrome include
hydralazine, isoniazid, procainamide, and several anticonvulsants.
1. Why is it called “anti-nuclear” antibody?
ANA are gamma-globulins (types of antibodies) found in patients with certain
autoimmune diseases. ANAs are directed against certain components found in the
center, or nucleus, of a cell in the body.
2. If I have a negative ANA test, will my doctor order any other antibody tests?
Tests for specific autoantibodies are almost never positive in patients who get a
negative ANA result. These tests generally should not be ordered in patients with
negative ANA test results.
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3. My doctor told me my ANA test is positive but he isn’t sure if I have lupus.
How can this be?
The body’s immune system normally produces antibodies that are designed to fight
off diseases and infections. In an autoimmune disease, something goes wrong with
this system and the person’s body begins producing autoantibodies -- antibodies that
attack their own tissues. Antinuclear antibodies are autoantibodies that go against the
cell nucleus, or central controlling part of the cell. The ANA test looks at the
concentration of antinuclear antibodies in a person’s blood. A positive result means
that you have a higher than “normal” concentration of these antibodies. This is one of
the tools in diagnosing lupus as well as several other autoimmune diseases, so a
positive result may be related to lupus or another disease. Or, you may simply have a
higher than normal concentration of these autoantibodies just as some people’s
normal body temperature is higher or lower than 98.6°. Even among people with
lupus, these results can vary widely – one person can be in remission at a certain level
of ANA while another can be extremely ill at the same level. Interpreting what these
results mean for you is the work of your doctor. And, your doctor may need to
compare your test results as well as the severity of your symptoms over a period of
time in order to make a definitive diagnosis. This additional time may also allow your
doctor the opportunity to eliminate other possible causes for your symptoms.
4. Is SLE the same thing as lupus?

There are actually several forms of lupus. SLE is the form that is most commonly
referred to when someone mentions “lupus.” Systemic lupus means that it can attack
almost any organ or system in your body. This is the form with the most severe
effects on the body. There are other forms of lupus that are primarily limited to skin
and their symptoms include rashes that may be found in many shapes and many
locations on the body. The symptoms of lupus differ greatly among different
individuals. There is also a condition called drug-induced lupus, which occurs in some
people when they take certain drugs. The symptoms usually fade when the drug use
stops. This form of lupus happens only to an extremely small percentage of patients
taking such drugs.
Antibody Tests
What are they?
Antibodies are part of the body's immune system. They are immunoglobulin proteins
that help protect us against microscopic invaders such as viruses, bacteria, chemicals,
or toxins.
There are five different classes of immunoglobulins (IgM, IgG, IgE, IgA, and IgD).
The three most frequently measured are IgM antibodies, which are produced early in
an infection; IgG antibodies, which are created later and can remain in the
bloodstream for decades; and IgE antibodies, which are primarily associated with
allergies.
Each antibody produced is unique. It is created to recognize a specific chemical
structure on the invader cell or particle. This target structure is called an antigen. Once
38
the antibody attaches to the invader, it serves as a flag for the rest of the immune
system, making it a target for destruction..
The first time someone is exposed to a particular antigen it may take the immune
system up to two weeks to make an antibody blueprint and to produce enough of that
specific antibody (primarily IgM at this point) to fight the initial infection. After the
immediate threat has passed, the body saves the blueprint along with a small supply of
the antibody (a mixture of IgM and IgG). This supply, which helps the immune
system "remember," can be measured in the blood (or sometimes in the CSF -
cerebral spinal fluid) as an IgG antibody titer. The next time the body is exposed to
the same antigen it will respond much more strongly and quickly, to provide primarily
IgG antibody protection.
Vaccines are useful because they eliminate the normal time delay in initial antibody
production. Using either a weakened microorganism, or a protein that the body
recognizes as the same antigen, vaccines provide a "safe" initial exposure to the
microorganisms that cause common diseases in humans. Vaccines provoke an
immune response to create antibodies against these diseases and to stockpile enough
of them to provide long-term protection (termed immunity). Additional booster
vaccinations are sometimes used to raise the concentration of antibodies in the blood
to a level where they are considered to be sufficiently protective. Since antibody
concentrations tend to fall over time, boosters may be given several years to decades
later to maintain protection. In some infections, antibodies do not destroy the
infection, such as HIV or hepatitis C.
Appropriate antibody creation and targeting depends on the body's ability to

distinguish between itself and "others" and to correctly identify threats. Sometimes a
person's immune system may build IgE antibodies against foreign substances that do
not usually cause a response in most people, leading to food, respiratory, or animal
allergies. In addition, their system may react to antigens in donated blood that is given
during a blood transfusion, or to antigens on transplanted body organs resulting in
rejection.
Normally, a person's immune system learns to identify and ignore the antigens on
their own organs, tissues, and cells but sometimes it may mistakenly identify a part of
its own body as foreign and create autoantibodies. This autoimmune response can
affect a single organ (like the thyroid) or be systemic and it can lead to an
autoimmune disorder.
Why are they done?
The main reasons that antibody concentrations are measured is to:
 Document exposure to an infectious or foreign agent

 Evaluate protection level (immune status) against a particular microorganism
 Diagnose an autoimmune condition
39
 Diagnose the reason for a transfusion reaction or a rejection of a transplanted
organ
 Diagnose an allergy
 Monitor the course of an infection or autoimmune process
There is not a single "umbrella" test that will determine all of your various antibody
levels; antibodies are as individual as the diseases they target. Antibody tests are
ordered singly or in combinations, depending on your symptoms, and on what
information your doctor is trying to gather. If he suspects a current infection, two
samples (called acute and convalescent samples) may be taken (a few weeks apart) to
look for rising antibody levels.
Testing may involve the measurement of individual antibody IgM and/or IgG
concentrations. In the case of allergies, individual IgE antibody levels are measured
(such as an IgE test for a peanut allergy or a ragweed allergy) to determine whether or
not you are allergic to that substance.
There really isn't a "normal" antibody concentration. People produce antibodies at

different rates, and may store them at variable levels for decades. The result that is
reported out and its interpretation by your doctor depends on the particular antibody
being tested and your specific circumstances. Results may be reported as "detected"
or "not-detected" in the case of antibodies causing chronic infections (such as HIV),
where any amount of antibody is considered meaningful. They may be reported out as
"greater than" a particular cutoff level if immunity is being checked (above that level -
which varies depending on the microorganism involved - a person is usually
considered to be protected), or as "immune" or "non-immune". Or they may be
reported out as a number, a concentration that may indicate a current or previous
infection. High amounts of IgM and low amounts of IgG indicate recent exposure to
infection whereas low IgM and high IgG indicate exposure some time ago.
Antibody titers are sometimes used to determine how significant a positive antibody
level is. These titers involve increasing (serial) dilutions of the sample being tested.
The highest dilution that is still positive is reported out as a "1 to dilution rate" ratio
(for instance 1:40 or 1:320, etc.). This is still used to report out some antibody levels,
especially in the case of autoimmune conditions. ["Antibody titer" is a term that is
also sometimes used generically to refer to antibody concentrations.]
High levels of individual IgE antibodies may help diagnose an allergy but they do not
necessarily correlate to the severity of the symptoms the patient may be experiencing.
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Antibody Tests on This Site
Antibody Test Why Tested When/How used
Allergy Test Allergy Detect allergy
ANA (antinuclear Autoimmune Diagnose autoimmune conditions
antibody)
Hepatitis A Virus Infection Diagnose current or past infection
Hepatitis B Virus Infection or Immunity Diagnose current or past infection,
Determine immunity
Hepatitis C Virus Infection Diagnose current or past infection
HIV Antibody Test Infection Diagnose infection
Helicobacter Pylori Test Infection Diagnose current or past infection
(H-pylori antibody test)
Lyme Disease Test (Anti- Infection Diagnose current or past infection
borrelia burgdorferi
IgM/IgG)
Rheumatoid Factor Autoimmune Diagnose autoimmune
Rubella Test (German Infection Diagnose current or past infection,
measles) Determine immunity
Syphilis Test (VDRL, Infection Diagnose infection
RPR)
TORCH test Infection Diagnose current or past infection
(Toxoplasma, Rubella,
CMV, and HSV)
Apo A
Formal name: Apolipoprotein A-I
Why get tested?
To determine whether or not you have adequate levels of Apo A-I, and to help
determine your risk of developing coronary artery disease (CAD)
When to get tested?
When you have hyperlipidemia and/or a family history of CAD or peripheral vascular
disease; when your doctor is trying to assess your risk of developing heart disease;
when you are monitoring the effectiveness of lipid treatment and/or lifestyle changes
Sample required (Blood samole).
Apolipoproteins are the protein component of lipoproteins – complexes that transport
lipids throughout the bloodstream. Apolipoproteins provide structural integrity to
lipoproteins and shield the hydrophobic (water repellent) lipids at their center.
Most lipoproteins are cholesterol- or triglyceride-rich and carry lipids throughout the
body, for uptake by cells. High-density lipoprotein (HDL – the “good” cholesterol),
however, is like an empty taxi. It goes out to the tissues and picks up excess
cholesterol, then transports it back to the liver. In the liver the cholesterol is either
recycled for future use or excreted into bile. HDL’s reverse transport is the only way
that cells can get rid of excess cholesterol. It helps protect the arteries and if there is
enough HDL present, it can even reverse the build up of fatty plaques in the arteries
(deposits that lead to atherosclerosis and coronary artery disease).
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Apolipoprotein A is the taxi driver. It activates the enzymes that load cholesterol from
the tissues into HDL and allows HDL to be recognized and bound by receptors in the
liver at the end of the transport. There are two forms of apolipoprotein A, Apo A-I
and Apo A-II. Apo A-I is found in greater proportion than Apo A-II (about 3 to 1).
The concentration of Apo A-I can be measured directly and tends to rise and fall with
HDL levels. This has led some experts to think that Apo A-I may be a better indicator
of atherogenic risk than the HDL test.
Deficiencies in Apo A-I appear to correlate well with an increased risk of developing
coronary artery disease (CAD) and peripheral vascular disease.
How is it used?
Apo A-I may be ordered, along with other lipid tests, as part of a profile to help
determine your risk of CAD. While it is not ordered routinely, it may be helpful in
patients who have a personal or family history of heart disease and/or hyperlipidemia.
Apo A-I levels may also be ordered to help diagnose conditions that cause Apo A-I
deficiencies, and may be used to monitor the effectiveness of lifestyle changes and
lipid treatments.
When is it ordered?
Apo A-I may be measured in patients with a personal or family history of
hyperlipidemia and/or premature CAD. It may be ordered when your doctor is trying
to determine the cause of your hyperlipidemia and/or suspects it may be due to a
disorder that is causing a deficiency in Apo A-I.
Apo A-I may be ordered along with Apo B-100 when your doctor wants to check
your Apo A/Apo B ratio (sometimes used as a CAD risk indicator, - basically
showing the ratio of “good” to “bad” cholesterol.)
When you have undergone lipid lowering treatment or lifestyle changes (decreased
the fat in your diet and increased your regular exercise), your doctor may order an
Apo A-I, along with other tests, to monitor the effectiveness of the changes.

An increase of Apo-I is usually not a problem, but decreased levels are associated
with low levels of HDL and decreased clearance of excess cholesterol from the body.
Decreased levels of Apo A-I, along with increased concentrations of Apo B-100 (Apo
B), are associated with an increased risk of coronary artery disease.
There are some genetic disorders that lead to deficiencies in Apo A-I (and therefore to
low levels of HDL). People with these disorders tend to have hyperlipidemia and
higher levels of low-density lipoprotein (LDL – the “bad” cholesterol). Frequently,
they have accelerated rates of atherosclerosis (the build up of fat plaques and
hardened tissue in the arteries that can lead to heart attacks, heart disease, and
strokes).
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Apo A-I may be increased with:
 Drugs such as: carbamazepine, estrogens, ethanol, lovastatin, niacin, oral

contraceptives, phenobarbital, pravastatin, and simvastatin
 Familial hyperalphalipoproteinemia (a rare genetic disorder)
 Physical exercise
 Pregnancy
 Weight reduction
Apo A-I may be decreased with:
 Chronic renal failure

 Coronary artery disease
 Drugs such as: androgens, beta blockers, diuretics, and progestins.
 Familial hypoalphalipoproteinemia (a rare genetic disorder)
 Smoking
 Uncontrolled diabetes

The concentration of Apo A-I reflects the amount of HDL in the serum. Since women
tend to have higher HDL, they also have higher levels of Apo A-I.
The Apo A-I test is not routinely ordered. Doctors still have to determine the best uses
for Apo A-I and other emerging cardiac risk markers (such as Apo B-100, hs-CRP,
and Lp(a)). They offer the doctor additional information in specific situations but are
not meant to replace the lipid tests already available.
1. What can I do to raise my Apo A-I?

Regular exercise is one of the best ways to raise HDL and Apo A-I. By decreasing the
fat in your diet, maintaining a healthy weight, and exercising you can help decrease
your risk of developing heart disease.
Apo B
Formal name: Apolipoprotein B-100
Why get tested?
To help evaluate your risk of developing atherosclerotic heart disease.
When to get tested?
When you have a personal or family history of heart disease and/or hyperlipidemia
and your doctor is trying to determine your risk of developing cardiovascular disease.
Sometimes measured to help monitor treatment for hyperlipidemia, or to help
diagnose a rare Apo B deficiency.
Apolipoproteins are an essential part of lipid metabolism. They are component parts
of lipoproteins - molecules that the body uses to transport lipids from ingested food in
43
the intestines, throughout the bloodstream, to the liver, and to the body's cells.
Apolipoproteins provide structural integrity to lipoproteins and protect the
hydrophobic lipids (non-water absorbing lipids) at their center. They are recognized
by receptors found on the surface of many of the body's cells and help bind
lipoproteins to those cells to allow the transfer (uptake) of cholesterol and triglyceride
from the lipoprotein into the cells.
There are two forms of Apolipoprotein B, Apo B-100 and Apo B-48. Apo B-48 is
created in the intestines. It is an integral part of the structure of chylomicrons, large
lipoproteins that are responsible for the initial transport of lipids to the liver. In the
liver the body repackages the lipids and combines them with Apo B-100 (made in the
liver) to form triglyceride-rich very low-density lipoproteins (VLDL). In the
bloodstream an enzyme called lipoprotein lipase (LPL) removes triglycerides from
VLDL to create first, intermediate density lipoproteins (IDL) and then, low density
lipoproteins (LDL, - the "bad" cholesterol). Each VLDL particle contains one
molecule of Apo B-100, which is retained as VLDL shrinks to become the more
cholesterol-rich, LDL.
LDL is an essential part of lipid metabolism; the cholesterol that it transports is vital
for cell membrane integrity, sex hormone production, and steroid production. In
excess, however, LDL can lead to fatty deposits in artery walls and lead to hardening
and scarring of the blood vessels. This atherosclerosis narrows the vessels and
increases the risk of heart attack. LDL is routinely ordered as part of a lipid profile. It
is usually calculated from the total cholesterol level and tends to be less reliable as
triglyceride levels rise. Some labs will directly measure LDL levels.
Apo B-100 levels tend to mirror LDL levels, but unlike calculated LDL, Apo B-100
levels can be measured directly. Many experts think that Apo B-100 levels may
eventually prove to be a better indicator of risk of atherosclerotic heart disease than
LDL. Others disagree but feel that Apo B-100 and other emerging cardiac risk
markers such as Apo A-I, Lp(a), and hs-CRP may offer valuable additional
information.
How is it used?
Apo B-100 levels are used, along with other lipid tests, to help determine an
individual's risk of developing atherosclerotic heart disease and CAD. It is not used as
a general population screen but may be ordered when a patient has a family history of
heart disease and/or hyperlipidemia. It may be used, along with other tests, to help
diagnose the cause of hyperlipidemia, especially when someone has elevated
triglyceride levels (preventing accurate LDL calculations).
Sometimes doctors will order both Apo A-I (associated with high-density lipoprotein
(HDL) -- the "good" cholesterol) and Apo B-100 levels to get a ratio of A/B, - to
obtain additional risk information.
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Occasionally Apo B-100 levels may be ordered to monitor the effectiveness of lipid
treatment. In rare cases, they may be measured to help diagnose a genetic problem
that causes over- or under-production of Apo B-100.
When is it ordered?
Apo B-100 may be measured, along with other lipid tests, when your doctor is trying
to evaluate your risk of developing atherosclerotic heart disease and when you have a
personal or family history of heart disease and/or hyperlipidemia, especially when you
have significantly elevated triglyceride levels. Sometimes Apo B-100 is monitored
when you are undergoing treatment for hyperlipidemia.
Elevated levels of Apo B-100 correspond to elevated levels of LDL and are associated
with an increased risk of CAD. Elevations may be due to a high fat diet and/or
decreased clearing of LDL from the blood. Increased levels of Apo B-100 are seen
with hyperlipidemia and in those patients with:
 Biliary obstruction
 Diabetes
 Drugs such as: androgens, beta blockers, diuretics, progestins
 Familial combined hyperlipidemia
 Hypothyroidism
 Nephrotic syndrome
 Pregnancy
Apo B-100 levels may be decreased with any condition that affects lipoprotein
production, or affects its synthesis and packaging in the liver. Lower levels are seen
with:
 Chronic anemia
 Chronic pulmonary disease
 Drugs such as: estrogen ( in post menopausal women), lovastatin, simvastatin,
niacin, and thyroxine
 Hyperthyroidism
 Malnutrition
 Reye syndrome
 Weight reduction
 Severe illness
 Surgery

Some doctors are ordering this combination Apo A-I (associated with HDL, the
"good" cholesterol) along with Apo B-100 because a low ratio of A/B may indicate a
higher risk of developing coronary artery disease.
Some elevations of Apo B-100 (and LDL) are due to mutations in the Apo B gene that
45
cause it to produce Apo B-100 that is not recognized as easily by LDL receptors. This
slows the clearing of LDL from the blood and increases the risk of heart disease.
1. Should my doctor be measuring Apo B-48?
While researchers are looking into the role of chylomicrons (the lipoprotein that
contains Apo B-48), there is currently no reason to measure Apo B-48.
2. What can I do to lower my Apo B-100?

Diet and exercise changes that lower LDL levels (and increase HDL – the good
cholesterol) will lower your Apo B-100 levels and decrease your risk of heart disease.
ApoE Genotyping
Formal name: Apolipoprotein E genotyping

Why get tested?
 To evaluate a possible genetic component to atherosclerosis,
 to help make treatment decisions for individuals with cardiovascular disease,
 as an aid in the diagnosis of probable late onset Alzheimer's disease in a
symptomatic adult, or
 to help confirm a diagnosis of Type III hyperlipoproteinemia (also known as
familial dysbetalipoproteinemia)
When to get tested?
 If your doctor suspects that you have an inherited component to your high
cholesterol and triglyceride levels or if you have xanthomas (yellowish lesions) on
your skin
 if you have progressive symptoms of dementia and your doctor wants to determine
the likelihood that this is due to Alzheimer’s disease
The test looks at a patient’s DNA to determine what combination of Apo E gene
alleles (copies) he or she has. The ApoE gene exists in three different forms – e2, e3,
and e4 – with e3 considered to be the normal form. Everyone has a pair of ApoE
genes that is some combination of these three.
Apolipoprotein (Apo) E is produced under the direction of the ApoE gene and is one
of five main types of blood lipoproteins (A-E). It is created primarily in the liver and
brain and has two primary metabolic roles: 1) transport of lipids from their site of
synthesis, or absorption, to the tissues where lipids are stored or excreted, and 2)
transport of lipids, in particular cholesterol, from the peripheral organs to the liver for
excretion. Apo E also modulates the activity of enzymes involved in lipid and
lipoprotein metabolism.
ApoE e3/e3 is the normal genotype (62% of population) without significant

cardiovascular disease-environment association. ApoE e4 (e4/e4 and e4/e3, 25% of
population) is associated with increased risk of atherosclerosis. These patients are
46
predisposed to an exaggerated elevation of LDL-C when their diet is high in saturated
fat. Patients with the ApoE e2 isoform tend to have lower LDL-C levels, while ApoE
e2 and ApoE e4 are both associated with elevated triglyceride levels. If someone has
an e2/e2 combination, they may clear dietary fat from their body at a slower rate and
be at a higher risk for early vascular disease. If they have an e4/e4, they may be at
higher risk of developing atherosclerosis. It is not a straightforward diagnosis,
however, as other factors, such as obesity, diabetes, and hypothyroidism, may play a
role in whether a patient actually develops disease.
ApoE e4 has also been associated with an increased risk of late onset Alzheimer’s
disease (AD) (developing after the age of 65). This effect is additive in that one copy
of e4 (e2/e4 or e3/e4) carries some increased risk and two copies of e4 (e4/e4) are
associated with an even greater risk of developing AD. It must be remembered,
however, that this risk is only relative. Most individuals with ApoE4 will never
develop AD and there are many AD patients who are e4 negative.
How is it used?
In Cardiovascular Disease
ApoE genotyping is sometimes used as part of follow-up testing if high cholesterol
and triglyceride levels are found, to check for and help diagnose a genetic component
to a lipid abnormality. It is not widely used but, when it is ordered, it may be in
combination with other tests, such as lipoprotein electrophoresis.
In cases of high cholesterol and triglyceride levels, statins are usually considered the
treatment of choice for cardiovascular disease (CVD). Statins, however, are not
sufficient therapy in some susceptible individuals due to a wide variability in lipid-
lowering drug response, in part related to Apo E genotype influence. Genetic variation
affecting plasma lipoprotein concentrations predicts a therapeutic response that can be
used to drive personalized dietary recommendations. Though appropriately responsive
to a low fat diet, ApoE e4 individuals are less likely to respond to statins with a
commensurate LDL-C lowering effect, unlike ApoE e2 individuals, who have a better
therapeutic response to statins. In this light, Apo E genotyping can drive a
personalized drug-responsive therapeutic decision tree for CVD.
In Alzheimer's Disease
ApoE genotyping is also sometimes used as an adjunct test to help in the diagnosis of
probable late onset Alzheimer’s disease (AD) in symptomatic adults. It is called
susceptibility or risk factor testing because it indicates whether there is an increased
risk of AD but is not specifically diagnostic of AD. Therefore, if a patient has
dementia, the presence of ApoE4 increases the likelihood that the dementia is due to
AD. There are no clear-cut tests to diagnose Alzheimer’s disease during life.
Physicians can, however, make a reasonably accurate clinical diagnosis of AD by
47
ruling out other potential causes of dementia and checking for a genetic predisposition
to AD (with ApoE genotyping, perhaps in conjunction with Tau/A?42 testing).
When is it ordered?
 ApoE genotyping is sometimes ordered when a patient has significantly elevated
cholesterol and triglyceride levels that do not respond to changes in the patient’s
lifestyle (dietary and exercise patterns);
 when family members have ApoE e2/e2 and a doctor wants to see if the patient
may be at a higher risk for early heart disease; or
 when a patient presents with xanthomas (yellowish lesions) on their skin and the
doctor suspects Type III hyperlipoproteinemia.
ApoE genotyping is also sometimes ordered as an adjunct test when patients have
symptoms of progressive dementia, such as decreasing intellectual ability and
language and speech skills, memory loss, and personality and behavioral changes that
are starting to interfere with daily living. After non-AD causes, such as
overmedication, vascular dementia (caused by strokes), and thyroid disease, have
been ruled out, ApoE genotyping may help determine the probability that dementia is
due to Alzheimer’s disease.

Patients with ApoE e2/e2 alleles are at a higher risk of premature vascular disease, but
they may never develop disease. Likewise, they may have the disease and not have
e2/e2 alleles because it is only one of the factors involved. ApoE genotyping adds
additional information and, if symptoms are present, e2/e2 is diagnostic of Type III
hyperlipoproteinemia (also known as familial dysbetalipoproteinemia), although
diagnosis must be made in conjunction with other test results and the patient’s clinical
history.
Patients who have ApoE e4/e4 are more likely to have atherosclerosis. Patients who
have symptoms of late onset Alzheimer’s disease (AD) AND have one or more ApoE
e4 copies of the e4 gene are more likely to have AD. It is not diagnostic of AD,
though, and should NOT be used to screen asymptomatic patients or their family
members. Many people will have e4 alleles and never develop AD. Even in
symptomatic patients, only about 60% of those with late onset AD will have ApoE e4
alleles.
ApoE e3 has “normal” lipid metabolism, thus no genotype impact.

Although ApoE genotyping is being used clinically by Alzheimer’s experts, the most
it can provide at this time is additional information about a patient with dementia. A
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definite diagnosis of Alzheimer’s disease can only be made by examining a patient’s
brain tissue after their death.
ApoE genotyping is not available in every laboratory. If your doctor recommends this
test, your specimen will need to be sent to a reference lab and results may take longer
to return than they would from other labs.
1. My father has been diagnosed with probable late onset AD and his ApoE test
is negative for e4 alleles. Should his doctor be doing other genetic testing?
No, not at this time. Forty percent of those who do have late onset AD are negative
for ApoE e4 alleles. While genetic mutations of the PSEN1, PSEN2, and APP genes
are associated with AD in a very small number of specific family lines, they are
associated with early onset AD, not late onset. If your father did not show signs of AD
until after the age of 65, then this other genetic testing is not indicated. (If you have a
very strong family history of AD, several family members over several generations
have had AD, you may want to talk to your father’s doctor about family risk factors).
ASMA
Also known as: Smooth Muscle Antibody (SMA), F-Actin Antibody

Formal name: Anti-Smooth Muscle Antibody and Anti-Actin Antibody
Why get tested?
To help diagnose autoimmune hepatitis and distinguish it from other causes of liver
injury
When to get tested?
When a patient has hepatitis that the doctor suspects may be due to an autoimmune-
related process
This test measures the amount of anti-smooth muscle antibodies (ASMA) in the
blood. ASMA are proteins produced by the body’s immune system to work against its
own cytoskeletal proteins. The production of ASMA is strongly associated with
chronic autoimmune hepatitis but may also be seen in other forms of liver disease and
with other autoimmune disorders such as primary biliary cirrhosis. Autoimmune
hepatitis presents as an acute or chronic inflammation of the liver that is not caused by
another discernable cause (such as a viral infection, drug, toxin, hereditary disorder,
or alcohol abuse). It can lead to cirrhosis (liver damage and scarring) and, in some
cases, to liver failure.
Autoimmune hepatitis can be found in anyone at any age, but about 80% of those
affected are women. In the United States, more than 80% of patients with this disorder
will have ASMA, either alone or along with ANA (antinuclear antibodies). Anti-actin
is an antibody targeted at actin, a specific cytoskeletal protein. Some recent studies
49
suggest that it is a more specific test than ASMA for diagnosing autoimmune liver
disease, with about 52% to 85% of those affected having the anti-actin antibody.
How is it used?
The ASMA test is primarily ordered along with antinuclear antibodies (ANA) to help
diagnose autoimmune hepatitis. Other autoantibodies, such as liver-kidney
microsomal type 1 (LKM1) antibodies and antimitochondrial antibodies (AMA), may
also be ordered to help diagnose autoimmune hepatitis and distinguish it from other
causes of liver disease or injury.
The anti-actin test may be ordered as an initial screening test for autoimmune hepatitis
instead of the ASMA test. If it is positive, it may be followed by the ASMA to
confirm the finding.
When is it ordered?
This test and the ANA test are ordered when a doctor suspects that the patient has
autoimmune hepatitis. They are usually ordered when a patient presents with
symptoms such as fatigue and jaundice (yellowing of the skin and eyes) along with
abnormal findings on liver tests (such as aspartate aminotransferase (AST) and/or
bilirubin), results that may be found during routine blood tests.
ASMA and ANA are usually ordered following or sometimes with a variety of tests
that are used to help diagnose and/or rule out other causes of liver injury. These
causes can include infections (such as viral hepatitis), drugs, alcohol abuse, toxins,
genetic conditions, metabolic conditions, and primary biliary cirrhosis.
An anti-actin test may be ordered instead of the ASMA when the doctor wants to
screen for autoimmune hepatitis. This test is relatively new. In some cases, it is taking
the place of the ASMA test; in others it may be followed by an ASMA for
confirmation. The ultimate clinical utility of the anti-actin test has yet to be
established.

When significant amounts of ASMA and ANA are present in the blood, the most
likely cause is autoimmune hepatitis. When both are present, then systemic lupus
erythematosus can be essentially ruled out (ANA will be positive with lupus, but
ASMA will not).
When anti-actin antibodies are present in significant quantities in a patient with

clinical signs of autoimmune hepatitis, then it is likely that the patient has the
condition. In most cases, if the anti-actin is positive, the ASMA will also be positive.
Since actin is only one of several cytoskeleton proteins, it is possible for a person to
have anti-smooth muscle antibodies even when the anti-actin test is negative.
50
Concentrations of ASMA may be lower in children and in those with compromised
immune systems, and levels may vary over the course of the disease. Up to 20% of
patients with autoimmune hepatitis will not be positive for ASMA, ANA, or LKM1
antibodies.
Small amounts of ASMA may be present, along with AMA, in up to 50% of patients
with primary biliary cirrhosis and may be found in other conditions such as infectious
mononucleosis and some cancers. Anti-actin antibodies may be present in about 22%
of patients with primary biliary cirrhosis
The presence of ASMA, anti-actin antibodies, and ANA are highly suggestive of
autoimmune hepatitis but not diagnostic. When significant concentrations of both are
present and the doctor suspects autoimmune hepatitis, then a liver biopsy may be
performed to look for characteristic signs of damage and scarring in the liver tissue.
1. Will ASMA ever go away?

If it is due to a temporary condition, such as infectious mononucleosis, ASMA may
drop below detectible levels once the condition has resolved. If ASMA is produced
because of autoimmune hepatitis, then it will be present throughout the patient’s life,
although levels may vary over time.
2. Can I have more than one cause of hepatitis?

Yes. For instance, autoimmune hepatitis can co-exist with a viral hepatitis (such as
hepatitis C) and can be exacerbated by liver damage caused by alcohol abuse. Since
the treatment of hepatitis depends on the cause, it is very important that your doctor
understand the underlying cause(s) of your condition.
3. How fast does autoimmune hepatitis progress?

The course and severity of autoimmune hepatitis is hard to predict. It may be acute or
chronic. Many patients will have no or few symptoms for many years and are
diagnosed when routine liver tests are abnormal. For more information, consult with
your doctor and see the related links.
ASO
Why get tested?
To help determine whether a person has had a recent Group A streptococcal infection;
to help diagnose post-streptococcal sequelae of rheumatic fever and
glomerulonephritis
When to get tested?
When a person has symptoms of rheumatic fever (cardiac function abnormalities) or
glomerulonephritis (kidney function abnormalities) or other symptoms suggestive of a
streptococcal infection but no culture was done to confirm a Group A strep infection.
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This test measures the amount of antibody produced in response to a recent
streptococcal infection. Streptolysin O is a toxin made by the Group A streptococcus
bacteria (Streptococcus pyogenes). Antibodies made against this foreign toxin are
known as antistreptolysin O (ASO) antibodies, which appear in the blood following
infection.
How is it used?
The ASO test is primarily ordered to help determine whether a patient has had a
recent streptococcal infection. In most cases, strep infections are identified and treated
with antibiotics, and the infections resolve. In cases where they do not cause
identifiable symptoms and/or go untreated, however, post-streptococcal sequelae,
namely rheumatic fever and glomerulonephritis, can develop in some patients,
especially young children. The test, therefore, is ordered if a patient presents with
symptoms suggesting either of these conditions. Since the incidence of post-
streptococcal complications has dropped in the U.S., so has the use of the ASO test.
When is it ordered?
The ASO test is ordered when a patient has symptoms that the doctor suspects may be
due to an illness caused by a previous streptococcal infection. It is ordered when the
symptoms emerge, usually in the weeks following a sore throat or skin infection. The
test may be ordered twice over a period of 10-14 days to determine if the antibody
level is rising, falling, or remaining the same.
ASO test results can be reported in several different ways; however, the interpretation
is generally the same: the higher the result is, the more antibody that is present in the
blood (unless a titer is performed, which is a ratio and therefore is interpreted
differently).
The ASO antibody is either absent or present in very low concentrations in patients
who have not had a recent streptococcal (strep) infection. Antibodies are produced
about a week to a month after the initial strep infection. ASO levels peak at about 4 to
6 weeks after the illness and then taper off but may remain at detectible levels for
several months after the strep infection has resolved.
If the test is negative or if ASO is present in very low concentrations, then the patient
most likely has not had a recent strep infection. This is especially true if a sample
taken 10 to 14 days later is also negative or minimal.
If the ASO level is high or is rising, then it is likely that a recent strep infection has
occurred. ASO levels that are initially high and then decline suggest that an infection
has occurred and may be resolving.
The ASO test does not predict if complications will occur following a streptococcal
infection, nor do they predict the severity of the disease. If symptoms of rheumatic
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fever or glomerulonephritis are present, an elevated ASO level may be used to
confirm the diagnosis.
Some antibiotics and corticosteroids may decrease ASO antibody levels.
1. Can ASO be used to diagnose strep throat?

A throat culture or a rapid strep test is the best method to diagnose streptococcal
pharyngitis. It is important that strep throat be promptly identified and treated to avoid
complications and to avoid passing the infection on to others. Since detectible ASO
levels do not appear for at least a week, they are not used to diagnose an acute
infection.
2. If I am diagnosed with strep, will an ASO always be performed?
No. In general, the ASO test is only performed when a patient has symptoms
suggesting that a post-streptococcal complication may have developed and no culture
was done to confirm a previous infection with this bacterium. Most people do not
experience these complications, so the ASO test is not routinely done.
AST(GOT)
Why get tested?
To detect liver damage
When to get tested?
If your doctor thinks that you have symptoms of a liver disorder
AST is an enzyme found mostly in the heart and liver, and to a lesser extent in other
muscles. When liver or muscle cells are injured, they release AST into the blood.
How is it used?
Testing for AST is usually used to detect liver damage.
AST levels are also often compared with levels of other liver enzymes, alkaline
phosphatase (ALP), and alanine aminotransferase (ALT), to determine which form of
liver disease is present.
Even though AST is found in heart and other muscles, another enzyme, creatine
kinase (CK), is present in much higher amounts and is usually used to detect heart or
muscle injury.
When is it ordered?
An AST test is ordered along with several other tests to evaluate a patient who seems
to have symptoms of a liver disorder. Some of these symptoms include jaundice
(yellowing of the eyes and skin), dark urine, nausea, vomiting, abdominal swelling,
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unusual weight gain, and abdominal pain. AST can also be ordered, either by itself or
with other tests, for:
 persons who might have been exposed to hepatitis viruses,

 those who drink too much alcohol,
 persons who have a history of liver disease in their family, or
 persons taking drugs that can occasionally damage the liver.
Persons who have mild symptoms, such as fatigue, may be tested for ALT to make
sure they do not have chronic liver disease. ALT is often measured to monitor
treatment of persons with liver disease, and may be ordered either by itself or along
with other tests.

Very high levels of AST (more than 10 times the highest normal level) are usually
due to acute hepatitis, often due to a virus infection. In acute hepatitis, AST levels
usually stay high for about 1–2 months, but can take as long as 3–6 months to return
to normal. In chronic hepatitis, AST levels are usually not as high, often less than 4
times the highest normal level. In chronic hepatitis, AST often varies between normal
and slightly increased, so doctors typically will order the test frequently to determine
the pattern.
In some diseases of the liver, especially when the bile ducts are blocked, or with
cirrhosis and certain cancers of the liver, AST may be close to normal, but it increases
more often than ALT. When liver damage is due to alcohol, AST often increases
much more than ALT (this is a pattern seen with few other liver diseases). AST is also
increased after heart attacks and with muscle injury, usually to a much greater degree
than is ALT.

Pregnancy may decrease AST levels. A shot or injection of medicine into muscle
tissue, or even strenuous exercise, may increase AST levels. In rare instances, some
drugs can damage the liver or muscle, increasing AST levels. This is true of both
prescription drugs and some “natural” health products. If your doctor finds that you
have high levels of AST, tell him or her about all the drugs and health products you
are taking.
1. What is hepatitis?
Hepatitis is an inflammation of the liver. There are two major forms: acute and
chronic. Acute hepatitis typically makes affected persons feel sick, as if they have the
flu, often with loss of appetite and sometimes diarrhea and vomiting. In many cases,
acute hepatitis turns urine brown, makes stools pale, and colors the skin and eyes
yellow. Most affected individuals eventually recover completely. Chronic hepatitis
usually causes no symptoms, or causes only loss of energy and tiredness; most people
54
don’t know that they have it. In some people, chronic hepatitis can gradually damage
the liver and, after many years, cause it to fail.
2. What other tests are used to evaluate liver disorders?

alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and bilirubin (a
yellow pigment removed from the body by the liver).
3. Who is at risk for a liver disorder?

While many things could harm the liver, the major causes of liver disease are
infection by viruses that target the liver and by drinking too much alcohol. In rare
cases, some medicines can damage the liver; your doctor may suggest testing your
liver from time to time if you are taking one of these. Some diseases that are inherited
from your parents can occasionally damage the liver.
4. What signs should make me aware of a liver disorder?

In many cases, liver disease is “silent.” When the liver is damaged rapidly (a disease
called acute hepatitis), the skin and the whites of the eyes often turn yellow, the urine
becomes brown, and bowel movements lose their color. In its late stages, liver
disease may produce swelling of the abdomen, vomiting of blood, confusion, and easy
bruising.
Autoantibodies
What are they?
Autoantibodies are proteins that attack specific proteins or other substances found in
specific tissues or organs of the body. They are created by the immune system when it
fails to distinguish between “self” and “non-self.” The immune system must be
discriminating. It is normally trained to recognize and ignore the body’s own cells and
to not overreact to non-threatening substances in the environment, such as foods,
plants, and animals. At the same time the immune system must be able to create
antibodies – proteins that target and fight specific foreign substances and
microorganisms that do pose a threat.
Sometimes, however, something goes wrong. For some reason the immune system
ceases to recognize one or more of the body’s normal constituents as “self,” creates
autoantibodies, and starts to attack its own cells, tissues, and/or organs, causing
inflammation and damage. The causes of this mistake are varied and are not well
understood. It is thought that some autoantibody production is due to a genetic
predisposition combined with an environmental trigger (such as a viral illness or a
prolonged exposure to certain toxic chemicals). There is generally not a direct genetic
link however. While families may be prone to develop autoimmune conditions,
individual family members may have different autoimmune disorders, or may never
develop an autoimmune condition. Researchers believe that there may also be a
55
hormonal component as many of the autoimmune conditions caused by autoantibodies
are much more prevalent in women of childbearing age.
The type of autoimmune disorder or disease that occurs and the amount of destruction
done to the body depends on which systems or organs are targeted by the
autoantibodies, and how strongly. Disorders caused by organ specific autoantibodies,
those that primarily target a single organ, such as the thyroid in Graves’ disease and
Hashimoto’s thyroiditis, are often the easiest to diagnose as they frequently present
with organ related symptoms.
Disorders due to systemic autoantibodies can be much more elusive. Although the
associated autoimmune disorders are rare, the signs and symptoms they cause are
relatively common. Symptoms may include: arthritis-type joint pain, fatigue, fever,
rashes, cold or allergy-type symptoms, weight loss, and muscular weakness.
Associated conditions include vasculitis (inflammation of blood vessels) and anemia.
Even if they are due to a particular systemic autoimmune condition, the symptoms
will vary from person to person, vary over time, vary with organ involvement, and
they may taper off or flare unexpectedly. Add to this the fact that a person may have
more than one autoantibody, have more than one autoimmune disorder, and/or have
an autoimmune disorder without a detectable level of an autoantibody and you have a
complex maze that your doctor must often take you through to arrive at a diagnosis.
The diagnosis of disorders associated with systemic autoantibodies starts with a

complete medical history and a thorough physical exam. Based on your signs and
symptoms, the doctor may request one or more diagnostic studies that will help to
identify a specific disease. These studies include:
 blood tests to detect inflammation, autoantibodies, and organ involvement

 x-rays and other imaging scans to detect changes in bones, joints, and organs
 biopsies to look for pathologic changes in tissue specimens
As a rule, information is required from multiple sources (rather than a single

laboratory test) to accurately diagnose disorders associated with systemic
autoantibodies.Some of the most common systemic autoimmune disorders include:
 Systemic Lupus Erythematosus (SLE, Lupus)

 Scleroderma (Progressive Systemic Sclerosis, PSS)
 Sj?gren's Syndrome
 Dermatomyositis (DM)
 Polymyositis (PM)
 Mixed Connective Tissue Disease (MCTD)
 Rheumatoid Arthritis (RA)
 Wegener's granulamatosis (WG)
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Why are they done?
Autoantibody tests may be ordered as part of an investigation of chronic progressive
arthritis type symptoms and/or unexplained fevers, fatigue, muscle weakness and
rashes. The Antinuclear antibody (ANA) test is often ordered first. ANA is a marker
of the autoimmune process – it is positive with a variety of different autoimmune
diseases but not specific. Consequently, if an ANA test is positive, it is often followed
up with other tests associated with arthritis and inflammation, such as an rheumatoid
factor (RF), an erythrocyte sedimentation rate (ESR), a C-Reactive Protein (CRP),
and/or complement levels.
A single autoantibody test is not diagnostic, but may give clues as to whether a
particular disorder is likely or unlikely to be present. Each autoantibody result should
be considered individually and as part of the group. Some disorders, such as SLE may
be more likely if several autoantibodies are present, while others, such as MCTD
(mixed connective tissue disease) may be more likely if a single autoantibody (RNP -
ribonucleic protein) is the only one present. Those who have more than one
autoimmune disorder may have several detectable autoantibodies.
Whether a particular autoantibody will be present is both very individual and a matter
of statistics. Each will be present in a certain percentage of people who have a
particular autoimmune disorder. For instance, up to 80% of those with SLE will have
a positive double strand anti-DNA (anti-dsDNA) autoantibody test, but only about 25-
30% will have a positive RNP. Some individuals who do have an autoimmune
disorder will have negative autoantibody test results, but at a later date – as the
disorder progresses - the autoantibodies may develop. Systemic autoantibody tests are
used to:
 Help diagnose systemic autoimmune disorders.

 Help determine the degree of organ or system involvement and damage
(Along with other tests such as a CBC or CMP)
 Monitor the course of the disorder and the effectiveness of treatments. There is
no prevention or cure for autoimmune disorders at this time. Treatment is used
to alleviate symptoms and to help maintain body function.
 Monitor remissions, flares, and relapses
Common Autoantibodies and Disease Associations

Listed below are some of the more common autoantibodies that are used to identify a
variety of systemic autoimmune disorders. These disorders cause inflammatory,
arthritis-type symptoms. We have created a table that identifies the percentage of time
that each autoantibody tests positive with each of several of these disorders.
 ANA
 ANCA
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 Anti-dsDNA
 Anti-SS-A (Ro)
 Anti-SS-B (La)
 RF
 Jo-1 Antibody
 RNP
 Anti-SM, (Smith)
 SCL-70
Vitamin B12 & Folate

Why get tested?
To help diagnose the cause of anemia or neuropathy (nerve damage), to evaluate
nutritional status in some patients, to monitor effectiveness of treatment for B12 or
folate deficiency.
When to get tested?
When you have large red blood cells, when you have symptoms of anemia and/or of
neuropathy. When you are being treated for B12 or folate deficiency.
These tests measure the concentration of folate and vitamin B12 in the serum (liquid
portion of the blood). The amount of folate inside the red blood cell (RBC) may also
be measured -- it will normally be at a higher concentration inside the cell than in the
serum.
B12 and folate are both part of the B complex of vitamins and come from food. Folate
is found in leafy green vegetables, citrus fruits, dry beans and peas, liver, and yeast;
while B12 is found in animal products such as red meat, fish, poultry, milk, and eggs.
Fortified cereals, breads, and other grain products are now also important dietary
sources of both B12 and folate (identified as “folic acid” on nutritional labels),
especially for those vegetarians who do not consume any animal products.
Both B12 and folate are necessary for normal RBC formation, tissue and cellular
repair, and DNA synthesis. B12 is also important for nerve health, while folate is
necessary for cell division such as is seen in a fetus during pregnancy. A deficiency in
either B12 or folate can lead to a form of anemia characterized by the production of
fewer, but larger, RBCs (called macrocytes). A deficiency in B12 can also result in
varying degrees of neuropathy, nerve damage that can cause tingling and numbness in
the patient’s hands and feet. A deficiency in folate can cause neural tube defects such
as spina bifida in a growing fetus.
How is it used?
B12 and folate are primarily ordered to help diagnose the cause of macrocytic anemia.
They are ordered as follow-up tests when large RBCs and a decreased hemoglobin
concentration are found during a CBC test. Folate, B12, and an assortment of other
tests may be ordered to help evaluate the general health and nutritional status of a
58
patient with signs of significant malnutrition or malabsorption. This may include
those with alcoholism and those with disorders associated with malabsorption such as
celiac disease, Crohn’s disease, and cystic fibrosis. B12 and folate may also be
ordered to help diagnose the cause of mental or behavioral changes, especially in the
elderly.
B12 may be ordered with folate, by itself, or with other screening laboratory tests –
such as a CMP (comprehensive metabolic panel) – to help diagnose the cause of
neuropathy.
In patients with known B12 and folate deficiencies, these tests may be ordered
occasionally to help monitor the effectiveness of treatment. This is especially true in
patients who cannot absorb B12 and/or folate and must have lifelong treatment.
Either a serum or RBC folate test may be used to help detect a deficiency. Some
doctors feel that the RBC folate test is more clinically relevant than serum folate but
there is not widespread agreement on this.
When is it ordered?
B12 and folate are primarily measured when a CBC, done routinely or as part of an
evaluation of anemia symptoms, indicates the presence of large RBCs.
When a person, especially an elderly person, exhibits mental or behavioral changes

such as irritability, confusion, depression and/or paranoia, B12 and folate may be
done to help diagnose the underlying cause. They may also be ordered when a patient
has physical symptoms that suggest a B12 or folate deficiency, including dizziness,
weakness, fatigue, or a sore mouth or tongue.
When a patient has symptoms suggesting nerve damage or impairment, such as,
tingling, burning, or numbness in their hands, arms, legs, and or/feet, a B12 test may
be requested to help diagnose the cause and detect the presence of a B12 deficiency.
The B12 measurement may be ordered by itself, along with a folate level, and/or in
conjunction with other tests such as a CMP.
A B12 and folate may sometimes be ordered as part of a general health evaluation
when a patient shows signs of malnutrition or malabsorption or is known to have a
disorder that affects nutrient absorption. When a breastfed infant has a B12 or folate
deficiency, then the mother may also be tested to see if she has a deficiency that is
affecting both her and her child.
When a patient is being treated for a B12 or folate deficiency, he may occasionally be
monitored to evaluate the effectiveness of the treatment. In a person with a nutritional
deficiency, this may be done as a follow-up to treatment. In a person with a condition
causing a chronic deficiency, this may be part of a long term treatment plan.
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The doctor is searching for B12 and/or folate deficiencies. If a symptomatic patient
has decreased concentrations of B12 and/or folate, then it is likely that he has some
degree of deficiency. The test results will indicate the presence of the deficiency, but
they do not necessarily reflect the severity of the anemia or neuropathy associated
with the deficiency or its underlying cause.
There are a variety of causes of B12 and/or folate deficiencies. They include:
Insufficient intake
The human body stores several years worth of B12 in the liver and it is readily
available in the food supply, so a dietary deficiency of this vitamin is extremely rare
in the U.S. It may be seen sometimes with general malnutrition, and in vegan
vegetarians - those who do not consume any animal products including milk and eggs.
It may also be seen in children of vegan vegetarians and breastfed infants. Since they
do not have the stores that adults do, deficiencies in children and infants show up
fairly quickly.
Folate used to be a common deficiency but with the advent of fortified cereals, breads,
and grain products it is less common. Since folate is stored in tissue in smaller
quantities than B12, folate must be consumed more regularly than B12.
Malabsorption
Both B12 and Folate deficiencies may be seen with conditions that interfere with their
absorption in the small intestine. These may include:
 Celiac disease (an intolerance to wheat that causes inflammation and

malabsorption)
 Bacterial overgrowth in the stomach and intestines
 Reduced stomach acid production (stomach acid is necessary tseparate B12
from the protein in food)
 Pernicious anemia, the most common cause of B12 deficiency. Normally a
molecule called intrinsic factor is made by parietal cells that line the stomach.
B12 binds tintrinsic factor in the stomach, then the resulting compound is
absorbed in the intestines. With pernicious anemia, little or no intrinsic factor
is produced, preventing the absorption of B12.
 Surgery that removes part of the stomach (and the parietal cells) or the
intestines may greatly decrease absorption
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Increased loss This may be seen with:
 Liver and kidney disease

 Alcoholism, with alcohol abuse less B12 and folate are absorbed and more are
excreted from the kidneys
 Anti-seizure medications such as dilantin and phenytoin can decrease folate as
can drugs such as metformin and methotrexate
Increased need All pregnant women need increased amounts of folate for proper fetal
development. If a woman has a folate deficiency prior tpregnancy, it will be
intensified during gestation, and may lead tpremature birth and neural tube birth
defects in the child.
If a patient with a B12 or folate deficiency is being treated with supplements (or with
B12 injections), then normal or elevated results indicate a response ttreatment.
If a patient is deficient in both B12 and folate, but only takes folic acid supplements,
the B12 deficiency may be masked. The anemia associated with both may be
resolved, but the underlying neuropathy (nerve damage) will persist.
The Schilling test was once ordered fairly routinely to confirm a diagnosis of
pernicious anemia as the cause of a B12 deficiency. It is still ordered occasionally but
has fallen from favor because it involves the administration of radioactive B12. The
Schilling test has been replaced, in part, by the measurement of intrinsic factor
binding antibodies and parietal cell antibodies.
1. Can taking too many vitamin B12 and folic acid supplements hurt me?
Not usually. Since B12 and folic are water soluble, the body will rid itself of any
excess by excreting it in the urine.
2. Is there a difference between folate or folic acid?

No, they are effectively the same.
BMP
Also known as: Chem 7, SMA 7 (somewhat outdated terms)
Formal name: Basic Metabolic Panel
The Basic Metabolic Panel (BMP) is a group of 8 specific tests that have been
approved, named, and assigned a CPT code (a Current Procedural Terminology
number) as a panel by Medicare. Since the majority of insurance companies also use
these names and CPT codes in their claim processing, this grouping of tests has
become standardized throughout the United States.
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The BMP is often ordered in the hospital emergency room setting because its
components give doctors important information about the current status of your
kidneys, electrolyte and acid/base balance, blood sugar, and calcium levels.
Significant changes in these test results can indicate acute problems, such as kidney
failure, insulin shock or diabetic coma, respiratory distress, or heart rhythm changes.
The BMP is also used to monitor hospitalized patients and to monitor patients with
some known conditions, such as hypertension and hypokalemia (low potassium level).
If your doctor is interested in following two or more individual BMP components, she
may order the entire BMP because it offers more information. Alternatively, she may
order individual tests when monitoring, such as a follow-up glucose, potassium, or
calcium, or order an electrolyte panel to monitor sodium, potassium, chloride, and
CO2. If your doctor wants more information, she may order a Complete Metabolic
Panel (CMP), a group of 14 tests that includes the BMP.
The BMP includes:
 Glucose
 Calcium
Both increased and decreased levels can be significant.
Electrolytes
 Sodium
 Potassium
 CO2 (carbon dioxide, bicarbonate)
 Chloride
The concentrations of sodium and potassium are tightly regulated by the body as is
the balance between the four tests. Electrolyte (and acid-base) imbalances can be
present with a wide variety of acute and chronic illnesses. Chloride and CO2 tests are
rarely ordered by themselves.
Kidney Tests
 BUN (blood urea nitrogen)

 Creatinine
BUN and creatinine are waste products filtered out of the blood by the kidneys.
Increased concentrations in the blood may indicate a temporary or chronic decrease in
kidney function. When not ordered as part of the BMP, they are still usually ordered
together.
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The BMP uses a tube of blood collected by inserting a needle into a vein your arm.
Ask your doctor whether you should be fasting for 10 to 12 hours prior to the blood
draw. Depending on the reason for ordering the BMP, it may be drawn after fasting or
on a random basis.
Bilirubin
Why get tested?
To screen for or monitor liver disorders
When to get tested?
If your doctor thinks you have signs or symptoms of liver damage, liver disease, bile
duct blockage, hemolytic anemia, or liver-related metabolic problem
Bilirubin is an orange-yellow pigment found in bile. Red blood cells (RBCs) normally
degrade after 120 days in the circulation. At this time, a component of the RBCs,
hemoglobin (the red-colored pigment of red blood cells that carries oxygen to tissues),
breaks down into bilirubin. Approximately 250 to 350 mg of bilirubin is produced
daily in a normal, healthy adult, of which 85% is derived from damaged or old red
cells that have died, with the remaining amount from the bone marrow or liver.
Unconjugated bilirubin is carried to the liver, where sugars are attached to it,
producing conjugated bilirubin. This conjugated bilirubin is passed to the bile by the
liver and is further broken down by bacteria in the small intestines and eventually
excreted in the feces, of which the characteristic color is due to the break down of
bilirubin. Some bile is stored in the gall bladder. As bilirubin levels increase, the
appearance of jaundice becomes more evident. Normally, almost all bilirubin in the
blood is unconjugated.
How is it used?
When bilirubin levels are high, a condition called jaundice occurs, and further testing
is needed to determine the cause. Too much bilirubin may mean that too much is
being produced (usually due to increased destruction of red blood cells (hemolysis) or
that the liver is incapable of adequately removing bilirubin in a timely manner (due to
blockage of bile ducts, liver diseases ((such as cirrhosis, acute hepatitis), or inherited
problems with bilirubin handling).
It is not uncommon to see high bilirubin levels in newborns, typically 1 to 3 days old.
This is sometimes called physiologic jaundice of the newborn. Within the first 24
hours of life, up to 50% of full-term newborns, and an even greater percentage of pre-
term babies, may have a high bilirubin level. This is because at birth, the newborn’s
liver is not fully mature and lacks the ability to process bilirubin as well as normal.
This situation usually resolves itself within a few days. In other instances, newborns’
red blood cells (RBCs) may have been destroyed because of blood incompatibilities
between the baby and its mother, called hemolytic disease of the newborn.
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In adults or older children, bilirubin is measured to diagnose and/or monitor liver
diseases, such as cirrhosis, hepatitis, or gallstones. Patients with sickle cell disease or
other causes of hemolytic anemia may have episodes where excessive RBC
destruction takes place, raising bilirubin levels.
When is it ordered?
A doctor usually orders a bilirubin test in conjunction with other laboratory tests
(alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) for a
patient who shows signs of abnormal liver function. A bilirubin level may be ordered
when a patient shows evidence of jaundice (yellowing of eyes or skin), has a history
of drinking excessive amounts of alcohol, suspected drug toxicity, or has been
exposed to hepatitis viruses. Other symptoms that may be present include dark,
amber-colored urine, nausea/vomiting, or abdominal pain and/or swelling. Fatigue
and general malaise often accompany chronic liver disease. Determining a neonatal
bilirubin level is considered standard medical care.

Newborns: Excessive bilirubin kills developing brain cells in infants and may cause
mental retardation, physical abnormalities, or blindness. It is important that bilirubin
in newborns does not get too high. When the level of bilirubin is above a critical
threshold, special treatments are initiated to lower it. An excessive bilirubin level may
result from the breakdown of red blood cells (RBCs) due to Rh blood typing
incompatibility. (Mother is Rh negative [Rh-], father is Rh positive [Rh+], and fetus is
Rh+; mother develops antibodies against the newborn’s RBCs, which are destroyed.)
Adults and children: Bilirubin levels can be used to identify liver damage/disease or
to monitor the progression of jaundice. If conjugated bilirubin is elevated, there may
be some kind of blockage of the liver or bile duct, hepatitis, trauma to the liver, a drug
reaction, or long-term alcohol abuse. Inherited disorders caused by abnormal bilirubin
metabolism (Gilbert’s, Rotor’s, Dubin-Johnson, Crigler-Najjar syndromes) may also
cause increased levels.

Although bilirubin may be toxic to brain development in newborns (up to the age of
about 2–4 weeks), high bilirubin in older children and adults does not pose the same
threat. In older children and adults, the “blood-brain barrier” is more developed and
prevents bilirubin from crossing this barrier to the brain cells. Elevated bilirubin
levels in children or adults, however, strongly suggest a medical condition that must
be evaluated and treated.
Bilirubin levels tend to be slightly higher in males than females, while African
Americans show lower values. Strenuous exercise may also increase bilirubin levels.
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1. Are some people more at genetic risk of abnormal bilirubin levels?
Several inherited chronic conditions include Gilbert’s syndrome, Dubin-Johnson
syndrome, Rotor’s syndrome, and Crigler-Najjar syndrome. Of these four syndromes,
Crigler-Najjar is the most serious and may result in death. The first three are usually
mild, chronic conditions that can be aggravated under certain conditions, but in
general cause no significant health problems.
2. How do you treat abnormal bilirubin levels and/or jaundice?

Treatment depends on the cause of the jaundice. In newborns, phototherapy (special
light therapy), blood exchange transfusion in severe cases, and certain drugs may
reduce the bilirubin level. In Gilbert’s, Rotor’s, and Dubin-Johnson, no treatment is
usually necessary. Crigler-Najjar syndrome may respond to certain enzyme drug
therapy or may require a liver transplant. Jaundice caused by an obstruction often is
resolved by surgery to remove the blockage. Jaundice due to cirrhosis is a result of
long-term alcohol abuse and may not respond well to any type of therapy, though
abstaining from alcohol and good nutrition may improve the situation if the liver has
3. Is there anything I can do to maintain healthy bilirubin levels?
While there is no one specific thing, it is clear that excessive and long- term alcohol
consumption can lead to cirrhosis and a permanently damaged liver. Avoiding alcohol
and over-use/long-term use of drugs and eating a proper diet may help to sustain a
healthy liver. Blockages due to duct stones, pancreatic cancer, or cysts may require
surgery.
Blood Culture
Why get tested?
To check for the presence of a systemic infection
When to get tested?
When you have signs or symptoms of a bacterial infection, such as fever, chills,
elevated white blood cell count, and fatigue, which also may be a sign of infection
occurring in other parts of the body, such as a urinary tract infection (UTI),
pneumonia, diarrhea, or skin infection.
Blood cultures are done to detect and identify bacteria and yeasts (a type of fungus) in
the blood. Some bacteria prefer oxygen (aerobes), while others thrive in a reduced
oxygen environment (anaerobes). Blood cultures are usually drawn into vials
containing two types of media to detect both types of bacteria. If your blood culture is
positive, the specific bacteria causing the infection will be identified and antibiotic
susceptibility testing will be done to tell your doctor which antibiotics will be
effective for treatment. If yeasts are causing the infection, antimicrobial therapy will
be given that is appropriate for fungal infections.
Infections of the bloodstream are caused most commonly by bacteria (bacteremia),
but can also be caused by a fungus (fungemia) or a virus (viremia). If your immune
65
defenses cannot contain an infection at its source, for example in the bladder for a
urinary tract infection, the infection may spread to your bloodstream and be carried
throughout your body. Endocarditis, an inflammation and infection of the lining of the
heart and/or of the heart valves, can result from a bloodstream infection. People who
have prosthetic heart valves or prosthetic joints have a higher risk of infection
following their surgery, although these infections are not common. Bacteria and
yeasts may be introduced directly into the bloodstream by intravenous drug us,
intravenous catheters, or surgical drains. Anyone with a compromised immune system
due to underlying disease (for example, leukemia) or chemotherapy (for example,
immunosuppressive agents) has a higher incidence of bloodstream infections since
their immune system cannot kill the microorganisms that occasionally enter the
bloodstream.
Multiple samples are collected and different veins are used. This is for two reasons: 1)
when multiple samples are done, you have a better chance of detecting the infection;
and 2) sometimes, despite disinfection of the skin where the blood is collected, you
can grow a skin contaminant, which will result in a positive blood culture that is not
clinically significant (a false positive). With multiple samples, you have a better
chance of ruling out a false positive and deciding what is a true bacteremia. These
multiple samples pose no additional risk to you.
Blood is obtained by inserting a needle into a vein in your arm. The drawing site will
be thoroughly cleaned, usually with an isopropyl alcohol solution, followed by an
iodine solution that is put on in a circular pattern and then allowed to dry. The
phlebotomist will then draw about 20 mls of blood and put it into two culture bottles
containing broth to grow aerobic and anaerobic microorganisms. These two bottles
constitute one blood culture set. A second set of blood cultures should be collected
from a different venipuncture site, usually immediately after the first venipuncture,
depending on the procedure being followed. Any subsequent samples may be
collected at timed intervals.
How is it used?
Blood cultures are done to detect the presence of bacteria or yeasts, which may have
spread from a specific site in the body into the bloodstream. For example, if a person
has bacterial pneumonia or bacterial meningitis, the causative organism may be
recovered from the blood and the culture results will help your physician understand
why you are not feeling well and how to treat you.
When is it ordered?
Your doctor may order blood cultures when you are having symptoms of septicemia
or sepsis, which indicates that bacteria or their products are causing harm in your
body. You may have chills, fever, nausea, rapid heartbeat, confusion, decreased urine
output, and changes in other organ systems. If you have had a recent infection,
surgical procedure, prosthetic heart valve replacement, or immunosuppressive
therapy, you are at higher risk of a systemic infection and drawing blood cultures
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would be appropriate if you have these symptoms. Blood cultures are drawn more
frequently in newborns who may have an infection but may not have the typical signs
and symptoms of sepsis. Similarly, blood cultures are collected in young children to
detect serious infections.
If your blood culture is positive, it may mean that you have a bacterial or fungal
infection in your bloodstream that needs to be treated immediately. Septicemia can be
life- threatening, especially in immunocompromised patients. Your doctor may have
started you on a broad spectrum antibiotic, often intravenous, that would be effective
against a wide range of bacteria while waiting for the test results. Your doctor may
change your antibiotic to be specific for the bacteria grown in your blood culture once
that information is available from the laboratory.
A positive result could also be a false positive caused by skin contamination. If you
have two blood culture sets positive with the same bacteria, it is more likely that the
bacteria found in the culture are causing your infection. If one set is positive and one
set is negative, it could be an infection or contamination. Your doctor will need to
evaluate your clinical status and the type of bacteria found.
If the blood culture sets are both negative, the probability that you have sepsis caused
by bacteria or yeasts is low; however, some microorganisms are more difficult to
grow in culture and more testing may be required. Your symptoms may be due to a
virus that would not grow in routine blood culture media designed to grow bacteria.
Other laboratory tests would be required to diagnose a viral infection. Your doctor
will have to evaluate your individual case.
Because septicemia means the bacteria or yeasts have spread throughout the body,
you may experience many different symptoms of illness. The immune system is
struggling to overcome the infection and produces many factors to kill the bacteria
that also make you feel sick. Septicemia can cause shock, a rapid heart rate, and can
decrease the blood flow to your brain, heart, and kidneys as well as alter your blood
clotting components, leading to disseminated intravascular coagulation (which can
cause generalized bleeding). Bacteria in your blood may attach to your heart valves
and cause damage and heart murmurs (endocarditis) or spread to your joints and cause
septic arthritis.
Symptoms such as fever, chills, muscle pains, and exhaustion may also be seen with
influenza (the flu). If you are ill during the flu season, your doctor may do an
influenza test to rule out this viral respiratory infection. Both the flu and septicemia
can be especially serious in the very young, elderly, and immunocompromised
patient. It is important to differentiate between them because while they both need to
be treated promptly, the treatments are different (antibacterial versus antiviral).
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1. Why do I have to take antibiotics for so long if I feel better already?
It is important to eliminate all of the bacteria that are causing the problem. For some
infections, several weeks of treatment are necessary. This is especially important if
you have endocarditis, which requires weeks of antibiotic therapy to cure.
Blood Gases
Why get tested?
To determine if you have an imbalance in the amount of oxygen gas (O2) or carbon
dioxide gas (CO2) in your blood or an acid-base imbalance, which may indicate a
respiratory (lung/breathing), metabolic, or kidney disorder
When to get tested?
If your doctor suspects that you have symptoms of an oxygen/carbon dioxide
imbalance or an acid-base imbalance; symptoms include difficulty breathing,
shortness of breath, or rapid breathing (hyperventilation); may also be tested to
monitor the effectiveness of ongoing oxygen therapy (used when you have a condition
that causes an acute or chronic oxygen shortage) and during certain surgeries to
monitor your blood’s oxygen and carbon dioxide levels.
Blood gas tests tell your doctor if you have enough oxygen in your blood and whether
or not your blood pH is balanced - not too acidic (acidosis) or too alkaline/basic
(alkalosis). Blood gas tests directly measure:
 pH. A measure of the level of hydrogen ion (H+), which indicates the
acid/base status of your blood.; the pH of your blood decreases (becomes more
acidic) with increased amounts of PCO2 and other acids, and the pH increases
(blood becomes more alkaline) with decreased PCO2 or increased amounts of
bases like bicarbonate (HCO3-).
 PO2. The partial pressure of O2 (the amount of oxygen gas dissolved in
blood).
 PCO2. The partial pressure of CO2 (the amount of carbon dioxide gas
dissolved in the blood); as PCO2 levels rise, blood pH levels will decrease,
becoming more acidic; as PCO2 decreases, pH levels will rise, making the
blood more alkaline.
Calculations or measurements also can be done to give other parameters, such as:
 O2 saturation. The percentage of hemoglobin saturation or how much oxygen

is bound to hemoglobin in the red blood cells and available to be carried
through the arteries to nourish the body’s cells.
 HCO3-. Bicarbonate, the main form of CO2 in the body, can be calculated
from the pH and PCO2. It is a measurement of the metabolic component of the
acid-base balance. HCO3- is excreted and reabsorbed (conserved) by the
kidneys in response to pH imbalances and is directly related to the pH level; as
the amount of HCO3- rises, so does the pH.
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 Base excess/deficit. A calculated number that represents a sum total of the
metabolic buffering agents (anions) in the blood; these anions include
hemoglobin, proteins, phosphates, and HCO3- (bicarbonate, which is the
dominant anion); these anions try to compensate for imbalances in the pH (too
acidic/acidosis or too alkaline/alkalosis) caused by diseases or conditions that
affect the lungs (respiratory acidosis/alkalosis) or kidneys (metabolic
acidosis/alkalosis); your doctor will look at the HCO3- and base excess/deficit
results to evaluate your total buffering capacity when deciding on a treatment
to correct an imbalance.

Arterial blood is almost always used for blood gas analysis, but in some cases, such as
for babies, whole blood from heelsticks is used. Since arterial blood carries oxygen to
the body and venous blood carries waste products to the lungs, the gas and pH levels
will not be the same in both.
An arterial blood sample is usually collected from the radial artery in the wrist
(located on the inside of the wrist, below the thumb, where you can feel your pulse).
A circulation test called an Allen test will be done before the collection to make sure
that you have adequate circulation in your wrist. The test involves compressing both
the radial and the ulnar wrist arteries, then releasing each in turn to watch for
“flushing” (the return of blood to your hand). If your hand does not flush, your other
wrist will be tested. Blood can also be collected from the brachial artery in your elbow
or the femoral artery in your groin (these two require special training, so they are
usually done by your doctor).
In newborns who experience difficulty in breathing right after birth, blood may be
collected from both the umbilical artery and vein and tested separately.
If you are on oxygen therapy, the O2 will either be turned off for 20 to 30 minutes
before the collection for a “Room Air” test or, if you cannot tolerate this or if the
doctor wants to check your oxygen levels with the O2 on, the amount of oxygen you
are taking will be recorded (usually expressed as fraction of inspired oxygen in
percent (e.g., 30% FIO2) or as liters of O2 flowing per minute).
After an arterial blood draw, you will be instructed to hold the site firmly for at least 5
minutes. Since blood pumps through the artery, the puncture will take awhile to stop
bleeding. If you are taking blood thinners or aspirin, it may take up to ten or fifteen
minutes to stop. The person collecting the sample will verify that the bleeding has
stopped and put a wrap around your wrist, which should be left in place for an hour or
so.
How is it used?
Blood gas measurements are used to evaluate your oxygenation and acid/base status.
Your body will try to restore any imbalance by itself, but if you have an
overwhelming acute or a chronic (long term) problem, you may need medical
intervention, such as being given concentrated, pure O2 or, in extreme cases, being
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put on a respirator to gain additional oxygen. If you are on continuing oxygen therapy,
your doctor may order blood gas tests to monitor the effectiveness of that therapy.
When is it ordered?
Blood gas tests are ordered when you have symptoms of an O2/CO2 or pH imbalance,
such as difficulty breathing or shortness of breath. Many acute and chronic conditions
can cause an imbalance and, while the blood gas tests do not tell your doctor the
direct cause of your imbalance, they will point to either a respiratory or metabolic
problem.
Blood gas measurements may be ordered if you are known to have a respiratory,
metabolic, or kidney disease and are experiencing respiratory distress to evaluate your
oxygenation and acid/base balance. Patients who are “on oxygen” (have supplemental
oxygen) may have their blood gases measured at intervals to monitor the effectiveness
of treatment. Blood gases may also be ordered for patients with head or neck trauma,
injuries that may affect breathing. Patients undergoing prolonged anesthesia –
particularly for cardiac bypass surgery or brain surgery – may have their blood gases
monitored during and for a period after the procedure.
Checking the blood gases from the umbilical cord of newborns may uncover
respiratory problems as well as determine the baby's acid/base status. Testing is
usually only done if a newborn’s condition indicates that he or she may be having
difficulty breathing.
Abnormal results of any of the blood gas components may mean that your body is not
getting enough oxygen, is not getting rid of enough carbon dioxide, or that there is a
problem with kidney function. If left untreated, these conditions create an imbalance
that could eventually be life threatening. Your doctor will provide the necessary
medical intervention to regain your body’s normal balance, but the original cause of
the imbalance must also be addressed.
A pH imbalance, blood that is either too acidic (state of acidosis) or alkaline (state of
alkalosis) will be primarily due to a condition or disease that affects either respiration
(breathing, your lungs) or your metabolic processes. Regardless of what causes the pH
imbalance, since the respiratory and metabolic systems are interrelated, one system
will compensate for the other to bring the pH back into balance.
Respiratory acidosis is characterized by a lower pH and an increased PCO2 and is due

to respiratory depression (not enough oxygen in and CO2 out). This can be caused by
many things, including pneumonia, chronic obstructive pulmonary disease (COPD),
and over-sedation from narcotics. Respiratory alkalosis, characterized by a raised pH
and a decreased PCO2, is due to over ventilation caused by hyperventilating, pain,
emotional distress, or certain lung diseases that interfere with oxygen exchange.
Metabolic acidosis is characterized by a lower pH and decreased HCO3-; the blood is

too acidic on a metabolic/kidney level. Causes include diabetes, shock, and renal
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failure. Metabolic alkalosis is characterized by an elevated pH and increased HCO3-
and is seen in hypokalemia (low blood potassium), chronic vomiting (losing acid from
the stomach), and sodium bicarbonate overdose.

Arterial blood sample collection is usually more painful than regular venipuncture.
You will experience moderate discomfort, and a compress is required for some time
to prevent any bleeding from the site.
Sometimes, mixed venous blood taken from a central line is used in particular
situations, such as in cardiac catheterisation labs and by transplant services. Careful
interpretation of the results is required. Peripheral venous blood is of no use for
oxygen status.
1. Can this test be done in a doctor’s office?
Blood gas measurements, performed by trained personnel, are usually done in a
hospital, emergency room, or large laboratory setting since the analysis should be
done immediately after sample collection and specialized equipment is required. Most
doctors do not have such capabilities in their offices.
2. I’ve had pneumonia before and currently have asthma. Why has my doctor
never ordered this test on me?
Most cases of pneumonia or asthma can be diagnosed by symptoms and monitored by
listening to your chest sounds or by examining the results of spirometry tests or chest
x-rays. Most of the time, asthma will respond to your usual medications and
pneumonia to rest and possibly antibiotics. Blood gas tests may be necessary if you
have severe or acute breathing problems or prolonged, chronic ones. In these cases,
blood gas tests are usually done in an emergency room or hospital setting.
3. Is there any other way to measure my oxygen levels?

A pulse oximeter is a noninvasive (no needlestick to obtain a blood sample is
required) way of continuously monitoring O2 saturation only. A small clip-like device
(called a sensor) is attached to the end of the finger or earlobe. The sensor reads light
that is transmitted through the skin. Pulse oximeters are useful for monitoring trends
in O2 saturation, but their accuracy can be affected by the presence of abnormal forms
of hemoglobin, like carboxyhemoglobin (present in carbon monoxide poisoning), low
pulse rate due to poor perfusion, and very low levels of hemoglobin due to severe
anemia.
Blood Smear
Also known as: Peripheral smear, Manual differential, Red blood cell morphology
Formal name: Peripheral blood smear
Why get tested?
To help evaluate how “normal” and mature red blood cells, white blood cells and
platelets are. To distinguish between different types of white blood cells and to
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determine their relative percentages in the blood. To help diagnose a range of
deficiencies, diseases and disorders involving blood cell production, function, and
destruction. To monitor cell production and cell maturity in diseases such as
leukemia.
When to get tested?
When a CBC and Differential indicates the suspicion of abnormal or immature cells.
When a doctor suspects a deficiency, disease or disorder that is affecting blood cell
production. When you are being treated or monitored for a blood cell related disease.
A blood smear allows the evaluation of white blood cells (WBCs), red blood cells
(RBCs) and platelets (special cell fragments). These cell populations are created by
and matured in the bone marrow and released into the bloodstream as required. WBCs
are used by the body to fight infection, RBCs to carry oxygen to the tissues and cells,
and platelets to help clot the blood. The number and type of each cell present in the
blood is dynamic, maintained by the body within normal ranges, but fluctuating
slightly all the time, depending on the needs of the body.
A peripheral blood smear is a snapshot of the cells that are present in the blood at the
time that the sample is obtained. To create a blood smear, a single drop of blood is
spread in a thin layer across a glass slide, dried, and then stained with a special dye.
Once the stain has dried the slide is evaluated under a microscope by a laboratorian.
The drop of blood on the slide contains thousands of red blood cells (RBCs),
hundreds of white blood cells (WBCs) and numerous platelets (cell fragments used in
blood clotting). Along the leading feathered edge of the smear the blood cells are
present on the slide in a single layer. Under the microscope they can be plainly seen,
allowing the laboratorian to roughly estimate the number of each type of cell present,
and to compare their size, shape, and general appearance to established “normal”
cells. It is possible to distinguish between the different types of WBCs and to
determine their relative percentages by counting 100 of them. The examination can
also be used to evaluate the size, shape, and hemoglobin content of the RBCs, and to
determine whether there are an adequate number of typical looking platelets present.
How is it used?
The peripheral blood smear test was once performed on nearly everyone who had a
routine physical as part of the complete blood count (CBC). At one time it was the
standard method of evaluating RBC morphology (cell size, shape, and consistency),
identifying types and percentages of WBCs, and determining whether an adequate
supply of platelets was present in the blood. This routine cell examination, however,
has been almost entirely replaced by automation.
Now, an automated blood cell counter can count and evaluate hundreds if not
thousands of blood cells within a couple of minutes -- at least when the cells present
are normal. However, when abnormalities show up on the automated blood cell
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counter, and/or when the doctor suspects abnormal WBCs, RBCs, and/or platelets are
present, a blood smear examined by a trained eye is still the best method for
evaluating and identifying immature and abnormal cells.
There are many diseases, disorders, and deficiencies that can have an effect on the
number and type of blood cells produced, their function, and their lifespan. Although
usually only normal mature cells are released into the bloodstream, circumstances can
force the bone marrow to release immature and/or malformed cells into the
circulation. When a significant number of abnormal cells are present they can suggest
an underlying condition, and prompt the doctor to do further testing.
The blood smear is ordered to help evaluate how “normal” and mature red blood cells,
white blood cells and platelets are. It can be used to distinguish between different
types of white blood cells and to determine the relative percentages of each type in the
blood. When immature WBCs are present the smear can be used to determine how
many of the WBCs are affected, which types are affected, and to determine just how
immature they are. An example of this is the variety and number of immature
lymphocytes (one type of WBC) that will be present on the blood smear of someone
with acute lymphocytic leukemia.
When is it ordered?
The blood smear is primarily ordered to evaluate blood cell populations when a CBC
with differential performed with an automated blood cell counter indicates the
presence of abnormal or immature cells. It may also be performed when a doctor
suspects a deficiency, disease or disorder that is affecting blood cell production, such
as an anemia, decreased or abnormal production of cells in the bone marrow, or
increased cell destruction. A blood smear may also be ordered when a patient is being
treated or monitored for a blood cell related disease.
Findings from the blood smear evaluation are not diagnostic in themselves. They can
indicate the presence of an underlying condition, give some information about its
possible severity, and suggest the need for further diagnostic testing. Depending on
the disorder present, and its activity there may be problems with one or more of the
blood cell populations. Blood smear findings may include:
RBC (Red Blood Cells)

Normal red blood cells are uniform in size. They are round and flattened, like a donut
with a depression on each side instead of a hole (biconcave). Due to the hemoglobin
inside the RBCs, they are a fairly uniform shade of reddish brown, slightly paler in
the center where the cell is not as thick. While not every RBC will be perfect, any
significant numbers of cells that are different indicates an abnormality. Many of the
RBC findings are graded from 1+ (a few abnormal cells) to 4+ (primarily abnormal
cells) to reflect the percentage of cells affected. There may be one or more
irregularities present. For more detail, click here.
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WBC (White Blood Cells)
White blood cells have a nucleus surrounded by cytoplasm (fluid). All WBCs are
descendants of stem cells in the bone marrow. There they differentiate into two
groups, granulocytes and nongranculocytes and then mature into five distinct types of
WBCs.
 Granulocytes – which includes neutrophils, eosinophils, and basophils - all

have granules (that look like speckles or dots) in their cytoplasm and a
segmented nucleus (like irregular beads on a string).
 Nongranulocytes – which includes lymphocytes and monocytes have a smooth
homogeneous cytoplasm and a round or rounded nucleus.
With WBCs, the blood smear is primarily used to evaluate samples with abnormalities
identified by the automated blood cell counter. Under the microscope the laboratorian
evaluates:
 How normal the cells look, their general size, shape and appearance and
whether or not there are any characteristic inclusions in the cell.
 How mature the WBCs are. If the WBCs are immature it means that there is a
problem either with the production or destruction of the cells. If the body is
using them faster than they can be created and matured then the bone marrow
will start to release immature ones into the bloodstream. If there is a problem
with production – such as is seen with leukemia where massive amounts of
one type of blood cell are made, cells of varying maturity (of that one type)
will be released into the circulation. If there are a large number of immature
cells, or very few cells and the doctor suspects an underlying bone marrow
disorder he may order an examination of the cell production in the bone
marrow.
 Whether the WBCs are intact (or if there is a significant number of smudge
cells - cells that have broken apart). This can be due to fragility in the cell or to
delayed sample processing.
Blood smear findings include the relative percentage of each type of WBC that is
present. For more detail, click here.
Platelets
These are cell fragments that the body uses to plug holes in the blood vessels during
the clotting process; they become sticky and clump together at the site of the injury.
You must have a sufficient number of platelets to control bleeding. Sometimes people
will produce too many platelets. This can, in extreme cases, interfere with the flow of
blood and increase a person’s risk of developing a blood clot. These same people may
also experience bleeding, because many of the extra platelets may be dysfunctional –
even though they appear normal.
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Platelets are usually counted by an automated blood cell counter, but sometimes giant
(large) platelets and platelet clumps are present and are incorrectly measured by the
machine. This may (or may not) indicate a platelet related deficiency or abnormality.
There are a certain number of people, for instance, that will have platelet clumping in
vitro – when the blood is drawn out of their body – but this does not cause a problem
inside their body. When a platelet count is suspiciously low, and/or the automated
blood cell counter presents with a warning, the blood smear is used to determine
whether or not there are adequate platelets present and to verify the presence of giant
platelets, and/or platelet clumps.
Since blood transfusions involve giving someone another person’s red blood cells,
white blood cells (although these are not normally functional in the recipient), and
sometimes platelets, a recent transfusion will affect both automated cell counts and
the blood smear.
1. Why hasn’t the automated blood cell counter totally replaced the blood
smear?
It has on a routine basis, but the automated blood cell counter usually evaluates the
RBCs, WBCs, and platelets based on their shape, size, and electrical properties. There
is always going to be some variation in each cell the body produces and the machines
both measure and allow for this variation. Sometimes cells will be abnormal or
immature but fall within the machines allowances, or they will not be classic
examples of immature cells that the machine recognizes. Cell fragments and platelet
clumps may also not be evaluated properly. A laboratorian can see these
abnormalities on a blood smear and has been trained to identify and classify them.
Details: Red Blood Cell Irregularities
SIZE
 Anisocytosis, this is a variation in size

 Macrocytosis, large RBCs that may be due to a vitamin B12 or folate
deficiency. They are seen in pernicious anemia.
 Microcytosis, this is the presence of small RBCs that may be due to an iron
deficiency anemia or to an inherited disorder such as thalassemia.
SHAPE
 Echinocytes (burr cells – have spiny projections), due to renal failure, iron
deficiency, or may be an artifact – something caused during sample
preparation.
 Elliptocytes, may be due to hereditary elliptocytosis
 Leptocytes, called “target cells” because they resemble a bullseye, due to
hemoglobinopathies (abnormal forms of hemoglobin) and thalassemia
 Poikilocytosis (variation in shape), several different abnormalities may be
present at the same time
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 Schistocytes (fragments– broken up pieces of RBCs), this may be due to a
disorder that is causing the red blood cells to be especially fragile or due to
mechanical hemolysis (seen sometimes with devices such as artificial heart
valves).
 Sickled (cresent shape), due to sickle cell anemia
 Spherocytosis (sphere shaped instead of flattened), may be due to hereditary
spherocytosis or to an immune hemolytic anemia
 Spicule (crenated), scalloped or serrated perimeter, may be due to loss of water
from the cell or to liver disease
 Dacrocyte (teardrop-shaped), may be due to thalassemia, iron deficiency, or
myelofibrosis
COLOR
 Hypochromasia, this may be seen in a variety of disorders including

thalassemia and iron deficiency. The RBC is pale in color due to insufficient
hemoglobin.
 Hyperchromasia, the RBC is darker in color that normal, this may be due to
dehydration
 Polychromasia, blue-staining RBCs indicating that they are immature due to
early release from the bone marrow
Intracellular Structure (nuclear material, remnants, and inclusions inside the

RBC)
 Nucleated RBCs (normoblasts), an immature form of RBCs seen with severe

anemia, myelofibrosis, in thalassemia, in miliary tuberculosis, cancers that
involve the bone marrow, and in chronic hypoxemia (low oxygen levels).
Nucleated RBCs can be normal in infants.
 Reticulocytes, a few of these young red blood cells are normal in the
circulation. Elevated numbers may be seen with acute blood loss, hypoxia,
RBC destruction, sickle cell disease, glucose-6-phosphate dehydrogenase
(G6PD) deficiency, and autoimmune hemolytic anemia
 Basophilic stippling (bodies inside RBC cause cytoplasm to stain blue), due to
myelofibrosis or lead poisoning
 Heinz bodies, granules in the RBCs, due to an enzyme (G6PD) deficiency,
unstable hemoglobin variant, thalassemia, and autoimmune hemolytic anemia
 Howell-Jolly bodies (small round remnants inside cell), due to hemolytic or
megaloblastic anemia, may be seen after a splenectomy
 Cabot’s Rings, threadlike inclusions, seen in a variety of anemias
 Malaria, this parasite lives a good portion of its life cycle inside RBCs,
breaking them as it leaves. This is not a routine finding, it would normally
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only be detected on a blood smear when an investigating doctor suspects a
patient has an active case of malaria.
Details: White Blood Cells
NEUTROPHILS, (also called segmented neutrophils, segs, polys or PMNs) engulf

and destroy invading organisms. They make up about 50 to 70% of the total WBC
count. They have two to five nuclear lobes with a thin strand connecting them in a
row. Their cytoplasm is pale pink and has evenly distributed granules of a light purple
color. Anomalies may include:
 Toxic Granulation, large dark blue granules in the cytoplasm, they are
associated with severe infection, chemical poisoning, and other toxic states.
 Vacuolization, vacuoles (that look like holes) in the cytoplasm, frequently
found in association with toxic granulation.
 D?hle bodies, irregular grayish or greenish inclusions in the periphery of
neutrophils. They are nuclear remnants that are often seen in association with
toxic granules and vacuoles. They may be present in association with burns,
trauma, acute or systemic infections, and with exposure to cytotoxic agents.
They may also be seen during a normal pregnancy
 Auer Bodies (Auer Rod), pink or red rod-shaped inclusions that are seen in
immature granulocytes in patients with acute non-lymphocytic leukemias.
 Bands, immature neutrophils with a “U” shaped nucleus, bands are normal in
the circulation in small numbers. If there is a percentage increase of them,
there is said to be a “left shift.” This may happen when an acute infection
stimulates increased neutrophils production.
 Hypersegmentation, if there are 5 or more segments to the neutrophils nucleus
it is said to be hypersegmented. This is mainly associated with B12 and Folate
deficiency.
 Pelger-Huët, neutrophils with two lobes and one connecting filament.
 Alder-Reilly granules, large dark leukocyte granules that stain purple. They
are indicative of mucopolysaccharidosis (an inherited enzyme deficiency
disorder).
 Chédiak-Higashi syndrome, big red, blue, or greenish granules of variable size
that are peroxidase positive and indicate a lethal metabolic disorder, they may
be found in granulocytes, lymphocytes, and monocytes.
EOSINOPHILS have 2 or 3 lobes to their nucleus and many reddish orange granules
in their cytoplasm. They are involved in allergic response and parasitic infections.
They may have some of the same inclusions as neutrophils. About 1 – 4% of WBCs
are eosinophils.
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BASOPHILS have a multi-lobed nucleus and many dark blue granules (which
contain histamines) in their cytoplasm. Only about 1% of WBCs are basophils. They
are involved in allergic response and can increase in cases of leukemia, and chronic
inflammation.
LYMPHOCYTES are relatively small and round in shape. The nucleus is generally
large in relation to the cytoplasm. The cytoplasm is blue and does not contain any
granules. The nucleus of most lymphocytes is dark blue. There are two major types of
lymphocytes, B cell and T-cell, but they cannot be distinguished under the
microscope. B cells create specific antibodies, while T-cells recognize and destroy
invading organisms. Lymphocytes make up about 20% to 40% of the total WBC
count.
 Lymphocyte, Reactive (atypical, activated), these cells are larger (they have
more cytoplasm) than regular lymphocytes and they tend to be variable in size
and shape. Their nucleus also varies in size and shape. They are found in viral
illnesses such as mononucleosis
 Hairy Cell, these lymphocytes have tiny projections that make them appear
hairy under the microscope. They are found in hairy cell leukemia
 Monocytes are larger than a lymphocyte, they have grey-blue cytoplasm, and a
folded nucleus. Monocytes ingest microorganisms, and respond to infection
and inflammation.
 When stimulated by cytokines, monocytes can move out of the bloodstream
and become tissue macrophages.
BNP and NT-proBNP
Also known as: b-type natriuretic peptide, proBNP

Formal name: Brain natriuretic peptide, N-terminal prohormone brain natriuretic
peptide
Why get tested?
To help diagnose the presence and severity of heart failure
When to get tested?
If you have symptoms of heart failure, such as shortness of breath and fatigue, or if
you are being treated for heart failure.
These tests measure the concentration of BNP or NT-proBNP in the blood. When the
heart is stressed, it produces a precursor, pro-BNP, which is cleaved to release the
active hormone BNP and an inactive fragment, NT-proBNP. Both BNP and NT-
proBNP are produced mainly in the heart’s left ventricle (the organ’s main pumping
chamber). Your heart releases them as a natural response to heart failure, to
hypotension (when your heart is not strong enough to pump enough oxygen-rich
blood and nutrients to meet your body's needs), when the heart itself does not get
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enough oxygen (with angina and heart attack), and when the left ventricle has been
“stretched” too much (hypertrophy) from the accumulation of blood and fluid.
How is it used?
Either BNP or NT-proBNP may be ordered to help diagnose heart failure and to grade
the severity of that heart failure. There are various causes of heart failure. Currently,
the condition is diagnosed by symptoms such as swelling in the legs (edema),
difficulty breathing, shortness of breath, and fatigue, in addition to chest X-rays and
an ultrasound test called echocardiography. Despite this information, heart failure is
still often confused with other conditions. BNP and NT-proBNP levels can help
doctors differentiate between heart failure and other problems, such as lung disease.
An accurate diagnosis is important because heart failure can be successfully managed
with various medical treatments.
Another reason for using BNP and NT-proBNP is to evaluate risk in persons who
present with chest pain. It has been found that high BNP predicts an increased risk of
death or subsequent heart attack in patients with acute coronary syndromes.
When is it ordered?
A BNP or NT-proBNP test may be ordered under these circumstances:
 In your doctor’s office, if you have symptoms that could be due to heart
failure.
 In the emergency room, if you are in crisis and doctors need to quickly
determine whether you are suffering from heart failure or some other medical
problem.
 To monitor the effects of therapy for heart failure.

Higher-than-normal results suggest that a person is in heart failure, and the level of
BNP or NT-proBNP in the blood is related to the amount or severity of heart failure.
Higher levels of BNP or NT-proBNP also may be associated with a worse outlook for
the patient.
BNP and NT-proBNP levels decrease in most patients who have been taking drug
therapies for heart failure, such as ACE inhibitors, beta-blockers, and diuretics. Levels
of both BNP and NT-proBNP tend to increase with age. Levels of NT-proBNP and, to
a lesser extent, BNP, are increased in persons with kidney disease.
While both BNP and NT-proBNP will rise with left ventricle dysfunction and either
can be measured, they are not interchangeable and the results cannot be directly
compared.
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1. How common is heart failure?
There are 5 million Americans living with the condition, and 550,000 new cases
diagnosed each year.
2. How is heart failure treated?

For information on treatment, please visit the American Heart Association’s web site.
Bone Markers
What is bone?
Bone is a living, growing tissue that turns over at a rate of about 10% a year. It is
made up largely of collagen, a protein that gives the bone its tensile strength and
framework, and calcium phosphate, a mineralized complex that hardens the
framework. This combination of collagen and calcium makes bone strong and yet
flexible enough to bear weight and to withstand stress. More than 99% of the body's
calcium is contained in the bones and teeth. The remaining 1% is found in the blood.
Throughout your lifetime, old bone is constantly being removed (resorption) and
replaced by new bone (formation). During early childhood and in the teenage years,
new bone is added faster than old bone is removed. As a result, bones become larger,
heavier, and denser. Bone formation happens faster than bone resorption until you
reach your peak bone mass (maximum bone density and strength), around age 24.
After age 24, bone resorption slowly begins to happen faster than bone formation.
Bone loss is most rapid in women in the first few years after menopause but continues
into the postmenopausal years.
What diseases affect the bone?
Osteoporosis. Osteoporosis, or porous bone, is a disease characterized by low bone

mass and structural deterioration of bone tissue. This means you may be more likely
to get fractures of the hip, spine, and wrist. Osteoporosis develops when bone
resorption occurs too rapidly and bone formation fails to keep up. It is more likely to
develop if your bones do not achieve their optimal mass during your bone-building
years. Men as well as women suffer from osteoporosis, a disease that can be
prevented and treated.
Paget’s disease. Paget's disease is a chronic disorder that typically results in enlarged
and deformed bones. In this disease, the breakdown and formation of bone tissue is
excessive. As a result, bone can weaken, resulting in bone pain, arthritis, deformities,
and fractures. This disease may be caused by a "slow virus" infection that is in your
body for many years before symptoms appear. It may also be inherited, since the
disease has been known to appear in more than one family member. Paget's disease is
rarely diagnosed in people under 40 years of age. Men and women are affected
equally.
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Bone metastasis. Cancer cells that leave the (primary) tumor and enter the
bloodstream can take up residence in nearly every tissue of the body. Bones are one of
the most common sites for these circulating cells to settle and start growing again.
Metastases can occur in bones that are near or far from the primary tumor site.
Metastatic bone disease is not the same as primary bone cancer. Primary bone cancer
refers to a cancer that starts in bone. Bone metastasis and primary bone cancer differ
in their risk factors, treatments, and outlook. Primary bone cancer is much less
common than bone metastasis. Bone metastasis is one of the most frequent causes of
pain in patients with cancer.
About half of all people who have cancer (except those with skin cancer) develop
bone metastasis at some point in the course of their disease. Breast, prostate, kidney,
lung, pancreas, colorectal, stomach, thyroid, and ovarian cancers account for most
metastases to bones. The spine is the area most often affected by bone metastasis,
followed by the pelvis, hip, upper leg bones (femurs), and the skull.
What tests are used to detect a problem with bone?
Usually, bone problems are detected by measuring bone density (mass) using special
types of X-rays. Bone problems can also be detected by ultrasound scans that use
high-frequency sound waves.
Bone markers, which are signs of the bone turnover process, are sometimes used as an
aid to bone density testing when doctors are evaluating whether or not you have a
bone disease. The process involves measuring markers of bone resorption, such as the
telopeptides, and markers of bone formation, such as bone-specific alkaline
phosphatase (ALP). Bone resorption markers can be measured in blood or urine. Bone
formation markers are measured in blood.
Most often, bone markers are used to monitor therapy for bone disease and to help
your doctor determine if your body is responding to treatment. Bone markers can
enable your doctor to tell if you are responding to bone-strengthening therapy in a
much shorter time period than the X-rays types of bone density testing. This way,
your therapy can be altered if you are not responding properly to it.
There is also some evidence that bone markers can help doctors to predict which
breast and prostate cancer patients are at high risk for bone metastases. Bone markers
may also be able to predict a patient’s response to therapy for a bone-loss condition.
When are these tests ordered?
In some cases, bone markers are ordered with other bone mineral density tests to
diagnose a bone disease. Usually, however, bone markers are ordered periodically to
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monitor patients who already have a diagnosed bone condition and who are
undergoing therapy to see how well they are responding to treatment.
FAQs
1. What are the FDA-approved medications for treating osteoporosis? Hormone

replacement therapy (HRT), alendronate, calcitonin, raloxifene, and risedronate.
2. How prevalent is osteoporosis? The condition affects more than 28 million

Americans. Of these, 80% are women.
Bone Marrow Aspiration

and Biopsy
Why get tested?
To evaluate the type, quantity, and maturity levels of the blood cells present in the
marrow; to evaluate the fibrous structure of the marrow; and sometimes to collect a
sample of marrow for more specific testing
When to get tested?
When a patient is anemic without an obvious cause and/or has a condition or cancer
that may be affecting blood cell production; sometimes when a doctor is investigating
a fever of unknown origin, often when the patient is immuno-compromised
Sample required?
A bone marrow sample collected primarily from the hip bone (pelvis) or sternum;
sometimes collected from a vertebrae or the femur (thigh bone).
There are two methods for sampling bone marrow, an aspirate and a biopsy. The bone
marrow, a soft fatty tissue found inside the body’s larger bones, is often described as
being like a honeycomb – it is a fibrous network filled with a liquid containing cells in
various stages of maturation, and “raw materials” such as iron, vitamin B12, and
folate that are required for cell production. The bone marrow aspirate provides a
liquid sample of cells that can be studied individually, and the biopsy collects a
cylindrical core that preserves the marrow’s structure and shows the relationships of
bone marrow cells to one another and the overall cellularity (relative amount of
marrow cells compared to fat).
Red blood cells (RBCs), platelets, and five different types of white blood cells
(WBCs) are produced in the marrow as needed, with the number and type of cell
being created at any one time based on the use of cells, loss, and a continual
replacement of old cells. For instance, RBCs, which carry oxygen throughout the
body, have a lifespan of about 120 days. The marrow paces RBC production at such a
rate as to replace old RBCs that are taken out of circulation and maintain a relatively
constant number in the blood. The marrow increases the rate of RBC production
whenever the patient’s number of RBCs decreases, due to such things as bleeding or
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hemolysis (RBC destruction). The increased rate of production continues until there is
a sufficient number of RBCs in the blood stream or until marrow production capacity
is reached. If the need approaches this capacity, then an increased number of
reticulocytes (immature RBCs) will be released into circulation as the marrow tries to
keep up. If the need exceeds capacity then the number of RBCs in the blood stream
will decrease and the patient will become increasingly anemic (symptoms of which
include pallor, fatigue, and shortness of breath due to decreased oxygen in the blood).
There are a variety of bone marrow disorders, cancers such as leukemia, vitamin and
mineral deficiencies, inherited conditions, and diseases such as aplastic anemia that
can affect the marrow’s ability to produce an adequate number of each of the different
blood cell types and release them into circulation. These diseases may affect the
overall number of cells produced, the proportion of cells produced, and/or the
function of the cells. Some bone marrow disorders may lead to a deficiency of one or
more cell types while others result in excess production of a specific type or of a
specific clone of a cell (a single cell that reproduces without regulation).
Leukemia, for example, is a cancer of the blood cells. It results in the excessive
production of one WBC type at the expense of other cell types, and can lead to the
release of large quantities of abnormal immature WBCs into the blood stream. These
WBCs do not fight infection as other WBCs do and they leave the patient more
vulnerable to illness. When leukemic WBCs crowd out RBC production, the patient
becomes anemic; when they decrease the number of platelets produced, they leave the
patient vulnerable to excessive bruising and bleeding. Other conditions, such as
vitamin B and folate or iron deficiency, lead to the creation of large or small or
abnormally shaped RBCs and result in specific types of anemia. Another disorder,
myelofibrosis, is characterized by the overgrowth of the fibrous network found in the
marrow, compressing cells and leading to changes in red cell shape and changes in the
cell counts..
Bone marrow aspiration and/or biopsy as a “test” includes both the collection of
marrow and bone samples and the evaluation of it under the microscope. A
pathologist or hematologist microscopically examines slides containing stained
smears of marrow samples (bone and/or fluid). The number, size, and shape of each
of the cell types present are examined, as are the proportions of mature and immature
cells. If leukemia, or another cancer that has spread to the marrow, is present, it can be
diagnosed through this examination and the type and severity of the disease (the
stage) can be established.
There are other tests that can also be ordered on the marrow sample, depending on
what the doctor requests, and what he suspects may be occurring. Additional stains to
look for things such as excess iron storage in the marrow, culturing of the marrow to
look for viral, bacterial or fungal infections that may be causing a “fever of unknown
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origin,” and tests for chromosomal abnormalities are among some of the other
analyses the physician may request. In the case of leukemia, tests to determine the
type of leukemia may be done. These include special stains or determining antigenic
markers (immunophenotype) to show just what type of leukemia is present.

The bone marrow aspiration and/or biopsy procedure is performed by a doctor or
other trained specialist. Both types of samples may be collected from the hip bone
(pelvis), and marrow aspirations may be collected from the sternum (breastbone). In
children, samples may also be collected from a vertebrae in the back or from the
femur (thigh bone).
The most common collection site is the iliac crest (top ridge) of the hip bone. Before
the procedure the patient’s blood pressure, heart rate, and temperature are measured
and evaluated to make sure that they are within normal limits and some patients are
given a mild sedative. The patient is then asked to lie down on his stomach or side for
the collection and his lower body is draped with cloths so that only the area
surrounding the site is exposed.
The site is cleaned with an antiseptic such as iodine, and injected with a local
anesthetic. When the site has numbed the doctor inserts a needle through the skin and
into the bone. For an aspiration, the doctor attaches a syringe to the needle and pulls
back on the plunger. This creates vacuum pressure and pulls a small amount of
marrow into the syringe. For a bone marrow biopsy, the doctor uses a special needle
that allows the collection of a core (a cylindrical sample) of bone and marrow.
Even though the patient’s skin has been numbed, the patient may feel brief but
uncomfortable pressure (pulling and/or pushing) sensations during these procedures.
After the needle has been withdrawn, a sterile bandage is placed over the site and
pressure is applied. The patient is then usually instructed to lie quietly until his blood
pressure, heart rate, and temperature are normal, and then to keep the collection site
dry and covered for about 48 hours.
How is it used?
The bone marrow biopsy and aspiration provide information about the status of and
capability for blood cell production. They are not routinely ordered and in fact the
majority of people will never have one done. A marrow aspiration and/or biopsy may
be ordered to help evaluate blood cell production, to help diagnose leukemia, to help
diagnose a bone marrow disorder, to help diagnose and stage a variety of other types
of cancer (to determine spread into the marrow), and to help determine whether a
severe anemia is due to decreased RBC production, increased loss, abnormal RBC
production, and/or to a vitamin or mineral deficiency or excess. Conditions that affect
the marrow can affect the number, mixture, and maturity of the cells, and can affect
its fibrous structure.
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A bone marrow sample may also be evaluated and cultured for the presence of
microorganisms such as fungi, bacteria, or mycobacteria (such as that which causes
tuberculosis) when the patient has a fever of unknown origin. Additional marrow
testing may be ordered when it is suspected that the patient has a chromosomal
abnormality and/or a disorder associated with iron storage that may cause iron to
accumulate in the marrow.
When a person is being treated for a cancer, a bone marrow aspiration and/or biopsy
may be ordered to evaluate the response to therapy to determine whether suppressed
marrow function is beginning to return to normal.
A CBC and reticulocyte count are frequently ordered along with the bone marrow
aspiration/biopsy. The results are used to help evaluate cell production in the marrow
and compare it to current cell populations in circulation.
When is it ordered?
A bone marrow aspiration and/or biopsy may be indicated as follows:
As a diagnostic procedure when one of the following is suspected:
o Aplastic Anemia
o Acute Leukemia
o Myelodysplastic Syndrome
o Chronic Myelogenous Leukemia
o Myelofibrosis and Essential Thrombocythemia
o Multiple Myeloma
o Severe Thrombocytopenia and/or Anemia and/or Neutropenia
As a staging procedure in:
o Hodgin’s and Non-Hodgkins lymphomas

o Small Cell Carcinoma of the Lung (although this not frequently done
anymore)
For culturing:
o when fever is present in HIV/AIDS or other immuno-compromised patient

o in patients suspected of having Brucellosis or Typhoid Fever
A bone marrow biopsy and aspiration may also be ordered at intervals when a person
is being treated for a cancer to evaluate whether marrow function is being suppressed
and if it is, when its function begins to recover.
With a bone marrow biopsy and aspiration the doctor is evaluating what is in the
marrow in order to determine whether the cells found are normal and present in
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typical quantities, to determine whether there are cells present that shouldn’t be there
(such as abnormal cells that are characteristic of specific cancers or disorders such as
the Gaucher cell found with Gaucher’s disease or the foamy lipid-filled Niemann-Pick
cell found with Niemann-Pick disease), and to determine what is missing.
The training and expertise of the pathologist or hematologist evaluating the marrow
samples allows him to sort through the marrow clues and tell the doctor what is
happening in the marrow. In most cases, this information can confirm or rule out a
diagnosis and bone marrow involvement, but it can also point out the need for further
investigation. For instance, if there are a decreased number of RBCs in the blood and
an increased number of reticulocytes, and a marrow evaluation shows that RBC
production appears normal but increased, then the doctor knows that marrow
production of RBCs has increased appropriately to meet a RBC demand. What she
still doesn’t know is the reason for the demand. It could be due to an acute or chronic
loss of RBCs (such as may occur with gastrointestinal bleeding) or due to acute or
chronic RBC destruction (such as sometimes occurs with an artificial heart valve).
A patient with few RBCs and no increase in reticulocytes may have aplastic anemia
(suppressed RBC production in the marrow). An evaluation of the bone marrow may
confirm this condition but it does not necessarily tell the doctor whether it is due to a
bone marrow disorder, radiation, exposure to certain chemicals, some cancers, cancer
treatment, or due to a tuberculosis infection.
The doctor takes the information that she receives from the marrow evaluation and
combines it with information from a clinical examination, blood tests, and a variety of
other tests, such as imaging scans and X-rays, to reach a final diagnosis. It can be a
straightforward process or it can be a complex diagnostic puzzle. Patients should stay
involved in this process by talking to their doctor before and after a bone marrow
biopsy and/or aspiration, asking her what her suspicions are, what kind of information
she is hoping to obtain from the evaluation, and what follow-up tests might be
indicated.

Complications from the bone marrow aspiration and/or biopsy procedure are rare, but
some patients may have excessive bleeding at the collection site or develop an
infection. Patients should tell the doctor about any allergies they have, and about any
medications or supplements they are taking prior to the procedure and should contact
their doctor promptly if they experience persistent or spreading redness or bleeding at
the site, a fever, or increasing pain.
1. Will I be put to sleep for a bone marrow aspiration and/or biopsy?
It is not usually necessary, but you may be given a sedative before the procedure.
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2. How does a bone marrow aspiration and/or biopsy compare with a bone
marrow collection for donation?
The collection process is similar, but the bone marrow donor goes through a physical,
and has blood tests done prior to the collection to make sure that he is healthy and that
his sample will be compatible with the person to whom the marrow will be donated.
The donor is usually put under general anesthesia during the collection because a
larger amount of marrow must be obtained under sterile conditions. The sample is
then processed, filtered and given to the transplant recipient through a vein. The stem
cells in the donor sample travel through the blood stream to the marrow and if all goes
right, begin to create RBCs, WBCs, and platelets.
BRCA-1 and BRCA-2
Also known as: BRACA
Formal name: Breast Cancer Gene 1 and Breast Cancer Gene 2
Why get tested?
To assess the risk of developing breast or ovarian cancer associated with inheriting
abnormalities in BRCA-1 or BRCA-2
When to get tested?
If you have a family history of breast cancer before the age of 50 or ovarian cancer at
any age
BRCA-1 and BRCA-2 are two genes that are linked with hereditary breast and
ovarian cancers. About 200,000 women are diagnosed with invasive breast cancer
each year and about 23,000 with ovarian cancer (according to the American Cancer
Society). Of these cancers, about 5% to 10% will be due to a mutation in one of the
BRCA genes. Men can also inherit an increased risk of developing breast cancer,
primarily from an alteration in the BRCA-2 gene.
Individuals with mutations in BRCA1 or BRCA2 have significantly elevated risks for
breast cancer (up to 80% lifetime risk), ovarian cancer (up to 40% lifetime risk),
bilateral breast cancer and other types of cancers. BRCA mutations are inherited and
passed from generation to generation. One half of the time, they are passed from the
father’s side of the family.
The DNA in white blood cells is used to detect mutations in the BRCA genes. While
the gene products (proteins) of the BRCA genes act only in breast and ovarian tissue,
the genes are present in every cell of the body and blood is the most easily accessible
source of that DNA.
How is it used?
The tests for BRCA-1 and BRCA-2 can tell you if you have mutations in either of
these two genes that have been connected to the development of breast and ovarian
cancer. Most people do not have a BRCA gene mutation (only about 1 in 800 people
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in the general population will have one) and the U.S. Preventive Services Task Force
has recommended (September 2005) that BRCA genetic testing not be ordered as a
screening test on women who do not have a strong family history of breast and/or
ovarian cancer.
BRCA testing should be considered for those women who do have close relatives
(male or female) who have been diagnosed with breast cancer and/or have female
relatives with ovarian cancer. This is especially true if the cancer occurred at a
relatively young age (prior to 50). A patient should also strongly consider testing if a
BRCA mutation has been identified in another family member. It is recommended
that patients be counseled by a health care provider knowledgeable in cancer genetics
both pre and post testing.
Comprehensive analysis of both genes is typically performed for referred patients. In

specific populations, such as those of Ashkenazi Jewish descent, testing may be
targeted to diagnose only those mutations known to appear in that group of people. If
a particular BRCA-1 or BRCA-2 mutation has been identified in a family member
with breast and/or ovarian cancer, then that specific mutation should be tested for in
other family members.
When is it ordered?
Individuals with a strong family history of breast cancer or ovarian cancer often want
this test performed. The test results may be used to decide whether to take steps that
may prevent breast or ovarian cancer from developing in the future. Because we don’t
know how effective the options for prevention are, people who are considering taking
this test should seek counseling by a knowledgeable health care professional. In this
way, they can be sure of learning about and understanding the implications of the test
result (see “Is there anything else I should know?” below).
Since there are hundreds of possible mutations of BRCA genes, test results must be
interpreted by taking into account a person’s family history. A genetic
counselor/trained health care professional should explain the meaning of the results
and explain treatment options for the individual to decrease risk and testing options
for other family members. Counseling on genetics should be offered both before
testing occurs and after receiving test results.
A negative result does not mean that you cannot or will not develop breast cancer. It
only means that you are not at risk for developing hereditary breast cancer related to
the BRCA mutations for which you were tested.
The presence of a BRCA mutation means that the affected person is at an increased
risk for developing breast and/or ovarian cancer. However, even within a family with
the same BRCA mutation, not everyone will develop cancer, and those that do may
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develop it at different times during their life. According to the Centers for Disease
Control and Prevention, estimates of lifetime risk for breast cancer in those with
BRCA-1 or BRCA-2 mutations can range from 36%-85% and estimates of ovarian
cancer from 16% to 60%.

Your test results may have implications for other family members. When one member
of a family is tested for BRCA mutations, issues often arise about how or whether to
share this information with other family members. Seek advice from a genetic
counselor about communication of result with your family members.
Pre and post test consultation with a health care provider knowledgeable about genetic
testing cannot be overemphasized. There are many issues to be considered when
preparing for a genetic test and upon learning the results, and a genetic counselor has
the knowledge and experience to help you sort through them.

The test for BRCA mutations is done on a blood sample collected by needle from a
vein in the arm. The test does not require surgical biopsy of breast or ovarian tissue.
1. If the BRCA test is positive, what are my options?

If the BRCA test is positive, the options include increased frequency of check-ups
(e.g., mammography, blood tests for CA-125, or transvaginal ultrasonography);
medications that could reduce risk (e.g., oral contraceptives or tamoxifen); or surgical
removal of the ovaries or breasts. There are a number of variables involved and it is
important to discuss your options with your doctor and genetic counselor.
2. If the BRCA test is negative, how likely/unlikely am I to get breast or ovarian

cancer?
Research studies have reported that for every 1000 women negative for BRCA
mutations, between 12 and 45 of them will develop breast cancer by age 50 and
between 3 and 4 will develop ovarian cancer by age 50. The risk increases with age.
3. Where can I get this test?
The test can be ordered by a doctor, preferably by one who can also offer genetic
counseling. The blood sample will be sent to a laboratory that specializes in BRCA
testing. The American Society of Clinical Oncology and the National Breast Cancer
Coalition encourage women seeking the test to participate in long-term outcome
studies to help gather information on the effectiveness of different check-up and
treatment options.
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BUN
Why get tested?
To evaluate kidney function and monitor the effectiveness of dialysis and other
treatments related to kidney disease or damage
When to get tested?
As part of a routine comprehensive or basic metabolic panel and when you are acutely
or chronically ill with a condition that may cause or be exacerbated by kidney
dysfunction
This test measures the amount of urea nitrogen in the blood. Nitrogen, in the form of
ammonia, is produced in the liver when protein is broken into its component parts
(amino acids) and metabolized. The nitrogen combines with other molecules in the
liver to form the waste product urea. The urea is then released into the bloodstream
and carried to the kidneys, where it is filtered out of the blood and excreted in the
urine. Since this is an ongoing process, there is usually a small but stable amount of
urea nitrogen in the blood.
Most diseases or conditions that affect the kidneys or liver have the potential to affect
the amount of urea present in the blood. If increased amounts of urea are produced by
the liver or decreased amounts are excreted by the kidneys, then urea concentrations
will rise. If significant liver damage or disease inhibits the production of urea, then
BUN concentrations may fall.
How is it used?
The BUN test is primarily used, along with the creatinine test, to evaluate kidney
function under a wide range of circumstances and to monitor patients with acute or
chronic kidney dysfunction or failure. It also may be used to evaluate a person’s
general health status when ordered as part of a basic metabolic panel (BMP) or
comprehensive metabolic panel (CMP).
When is it ordered?
BUN is part of both the BMP and CMP, groups of tests that are widely used:
 when someone has non-specific complaints,

 as part of a routine testing panel,
 to check how the kidneys are functioning before starting to take certain drug
therapies,
 when an acutely ill person comes to the emergency room and/or is admitted to
the hospital, or
 during a hospital stay.
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BUN is often ordered with creatinine:
 when kidney problems are suspected,

 at regular intervals to monitor kidney function in patients with chronic
diseases such as diabetes, congestive heart failure, and myocardial infarction
(heart attack),
 at regular intervals to monitor kidney function and treatment in patients with
known kidney disease,
 prior to and during certain drug treatments to monitor kidney function, or
 at regular intervals to monitor the effectiveness of dialysis.

Increased BUN levels suggest impaired kidney function. This may be due to acute or
chronic kidney disease, damage, or failure. It may also be due to a condition that
results in decreased blood flow to the kidneys, such as congestive heart failure, shock,
stress, recent heart attack, or severe burns, to conditions that cause obstruction of
urine flow, or to dehydration.
BUN concentrations may be elevated when there is excessive protein catabolism

(breakdown), significantly increased protein in the diet, or gastrointestinal bleeding
(because of the proteins present in the blood).
Low BUN levels are not common and are not usually a cause for concern. They may
be seen in severe liver disease, malnutrition, and sometimes when a patient is
overhydrated (too much fluid volume), but the BUN test is not usually used to
diagnose or monitor these conditions.
Both decreased and increased BUN concentrations may be seen during a normal
pregnancy.
If one kidney is fully functional, BUN concentrations may be normal even when
significant dysfunction is present in the other kidney.

BUN levels can increase with the amount of protein in your diet. High-protein diets
may cause abnormally high BUN levels while very low-protein diets can cause an
abnormally low BUN.
1. What other tests are used with BUN to check how my kidneys are functioning?
BUN and creatinine are the primary tests used to check how well the kidneys are able
to filter waste products from your blood. Your doctor may also order electrolyte tests
such as sodium and potassium, or calcium to help understand how your kidneys are
functioning.
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2. How does BUN change with age?
BUN levels increase with age. BUN levels in very young babies are about 2/3 of the
levels found in healthy young adults, while levels in adults over 60 years of age are
slightly higher than younger adults. Levels are also slightly higher in men than
women.
3. What is a BUN/Creatinine ratio?

Occasionally, a doctor will look at the ratio between a person’s BUN and blood
creatinine to help them determine what is causing these concentrations to be higher
than normal. The ratio of BUN to creatinine is usually between 10:1 and 20:1. An
increased ratio may be due to a condition that causes a decrease in the flow of blood
to the kidneys, such as congestive heart failure or dehydration. It may also be seen
with increased protein, from gastrointestinal bleeding, or increased protein in the diet.
The ratio may be decreased with liver disease (due to decrease in the formation of
urea) and malnutrition.
Clostridium difficile toxin
Also known as: C. difficile, C. diff
Why get tested?
To detect the presence of Clostridium difficile toxin
When to get tested?
When a patient has acute diarrhea that persists for several days, abdominal pain, fever,
and/or nausea following antibiotic therapy
Sample required?
A fresh stool sample that has not been contaminated with urine or water.
This test detects the presence of Clostridium difficile toxin A and/or B in a fresh or
frozen stool sample. C. difficile is a bacterium that is present in the intestines of up to
70% of healthy infants and 5% of healthy adults. Ordinarily, C. difficile is one of the
groups of bacteria that usually inhabit the colon, called “normal flora.” If something
happens to depress the growth of the other normal flora, such as broad-spectrum
antibiotic therapy, C. difficile may overgrow and disrupt the balance of bacteria in the
colon. About 75% of C. difficile produce two toxins, A and B. The combination of
overgrowth and toxin production can cause prolonged acute diarrhea and the toxin can
damage the lining of the colon and lead to pseudomembranous colitis, a severe
inflammation of the colon.
C. difficile is the major cause of antibiotic-associated diarrhea in the hospital,

affecting as many as 20% of those who are taking antibiotics for other infections.
While C. difficile is frequently carried by infants, it does not usually cause diarrhea in
this population. The risk of being affected increases with age and is increased in those
who are immunocompromised, have acute or chronic colon conditions, have been
previously affected by C. difficile, or who have had recent gastrointestinal surgery or
chemotherapy. About 80% of the time, C. difficile-associated diarrhea occurs in
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patients who have been taking antibiotics for several days, but it can also occur
several weeks after treatment is completed.
The severity of C. difficile diarrhea and colitis may vary greatly. Symptoms may
include frequent loose stools, abdominal pain and cramps, nausea, fever, dehydration,
and fatigue. Patients may have blood, mucous, or white blood cells (WBCs) in their
stool and frequently have leukocytosis (increased numbers of WBCs in their blood).
While some cases of C. difficile diarrhea and colitis do not require treatment, others
require specific oral antibiotic therapy. Most patients improve as the normal flora re-
establishes itself, but about 20% of patients may have one or more relapses, with
symptoms and detectible toxin levels re-emerging.

A fresh stool sample is collected in a sterile container. The stool sample should not be
contaminated with urine or water. Once it has been collected, the stool should be
taken to the laboratory within about an hour or refrigerated or frozen and taken to the
lab as soon as possible. The container should be labeled with the patient’s name and
the date and time of the stool collection.
How is it used?
The Clostridium difficile toxin test is used to diagnose antibiotic-associated diarrhea
and pseudomembranous colitis that is caused by C. difficile. It may also be ordered to
monitor the effectiveness of treatment for C. difficile diarrhea and to detect a
recurrence. Although it is possible to detect the presence of C. difficile by growing the
bacteria (stool culture), the results of the culture take several days and further testing
must be done to detect the toxin.
When is it ordered?
A C. difficile toxin test may be ordered when a hospitalized patient has frequent loose
stools, abdominal pain, fever, and/or nausea during or following a course of
antibiotics or following a recent gastrointestinal surgery. It may be ordered when an
outpatient develops these symptoms within 6-8 weeks after taking antibiotics, several
days after chemotherapy, or when a patient has a chronic gastrointestinal disorder that
the doctor suspects is being exacerbated by a C. difficile infection. The C. difficile
toxin test may be ordered to help diagnose the cause of frequent diarrhea when a
patient has leukocytosis and/or blood in the stool and no other discernable cause (such
as parasites or other pathogenic bacteria) has been detected.
If a patient treated for antibiotic-associated diarrhea or colitis relapses and symptoms

re-emerge, C. difficile toxin testing may be ordered to confirm the presence of the
toxin.
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If the C. difficile toxin test is positive, it is likely that the patient’s diarrhea and other
symptoms are being caused by an overgrowth of toxin producing C. difficile.
Occasionally, false positives may be seen with grossly (visibly) bloody stool samples.
If the test is negative but the diarrhea continues, another sample needs to be tested.
The C. difficile toxin test does not detect 100% of cases and the toxin may have been
missed the first time. Since the toxin breaks down at room temperature, a negative
result may also indicate that the sample was not processed promptly or stored
correctly prior to processing. A negative test result may also mean that the diarrhea
and other symptoms are being caused by something other than C. difficile.

Clostridium difficile can be grown and isolated on a stool culture, but its presence
does not indicate whether the strain present is a toxin producer. It also does not
distinguish between C. difficile colonization (presence in healthy individuals) and
overgrowth/infection.
1. What else can cause diarrhea?
Diarrhea can be due to a pathogenic bacterial infection, a viral infection, a parasite,
food intolerance, certain medications, chronic bowel disorders such as IBS (irritable
bowel syndrome), or malabsorption disorders (such as celiac disease). Diarrhea may
also be caused or exacerbated by psychological stresses.
2. Why must the stool sample be fresh?

For C. difficile toxin testing, the sample must be fresh because the toxin will break
down in one to two hours and may result in a false negative test.
3. Why shouldn’t I take an over the counter anti-diarrhea medicine when I have
diarrhea caused by C. difficile?
Anti-diarrhea medicine can slow down the passage of stool through the
gastrointestinal tract, increasing the length of time that the colon is exposed to the
toxin and increasing tissue damage and inflammation.
4. Once I’ve had a C. difficile infection, can I be re-infected?

Yes, but in the short-term it is generally a case of recurrence of overgrowth and toxin
production rather than re-infection; this happens because the normal flora has not
reestablished itself fully yet. A patient who has had C. difficile diarrhea may also be at
an increased risk of developing a new case of it with future courses of antibiotics.
5. Are some antibiotics more likely to cause antibiotic-related diarrhea?

Almost any antibiotic may lead to diarrhea since the drugs alter the normal population
of good bacteria in the bowel. Broad-spectrum antibiotics, which kill many different
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types of bacteria, are more likely to wipe out normal bowel flora and leave C. difficile
to overgrow and produce its toxin.
An endoscopic procedure can be used to diagnose C. difficile colitis. A specialist

(gastroenterologist) can observe and biopsy any characteristic pseudomembranous
lesions that may be present.
CA-125
Why get tested?
To monitor treatment for ovarian cancer
When to get tested?
Before starting therapy for ovarian cancer or if at high risk for developing ovarian
cancer, and at intervals during and after treatment
CA-125 is a protein often found on the surface of ovarian cancer cells and in some
normal tissues. It is one of the protein antigens that have been associated with the
presence of various cancers but is most often positive for ovarian cancer. CA-125
levels may also be high in other types of non-cancerous conditions, including
menstruation, pregnancy, and pelvic inflammatory disease.
How is it used?
CA-125 is used to monitor therapy during treatment for ovarian cancer. CA-125 is
also used to detect whether cancer has come back after treatment is complete. This
test is sometimes used to follow high-risk women who have a family history of
ovarian cancer but who do not yet have the disease.
When is it ordered?
Before a patient starts treatment for ovarian cancer, the physician may order a
baseline CA-125 to compare against future measurements. During therapy, physicians
use CA-125 testing at intervals to monitor response to therapy. CA-125 may also be
measured periodically after therapy is completed. An increase in CA-125 may
indicate that the cancer has returned.
If CA-125 levels fall during therapy, this generally indicates that the cancer is
responding to treatment. If CA-125 levels rise, the cancer may not be responding to
therapy. High CA-125 levels after treatment is complete may indicate that the cancer
has come back.
Because CA-125 can be high in many normal or benign conditions (for example,
pregnancy, menstruation, endometriosis, pelvic inflammatory disease), it is not useful
as a screening test in large populations.
1. Is CA-125 always increased in ovarian cancer?
No, not all ovarian cancers are associated with increased levels of CA-125. Elevated
levels have been found in about 80% of women with ovarian cancer.
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2. My CA-125 is elevated. Does that mean I have cancer?
No. CA-125 may be elevated in several other conditions and diseases. This means it is
not specific for ovarian cancer. CA-125 may normally be increased in early
pregnancy and during menstruation. It can also be increased in diseases such as pelvic
inflammatory disease or endometriosis and sometimes in hepatitis and cirrhosis of the
liver.
3. Does ovarian cancer run in families?
Family history is a risk factor for ovarian cancer. If you have close family members
who have had ovarian cancer, you are at higher risk than someone who has no family
history of the disease. Make sure your doctor knows about your family medical
history.
CA 15-3
Why get tested?
To monitor the response to treatment of invasive breast cancer and to watch for
recurrence of the disease
When to get tested?
When you have been or are being treated for invasive breast cancer.
Cancer antigen 15-3 (CA 15-3) is a normal product of breast cells; it is produced by
a gene that is often overexpressed (i.e., the body makes too many copies) in cancerous
breast tumors, leading to an increased production of CA 15-3 and the related Cancer
antigen 27.29. CA 15-3 does not cause cancer; rather, it is a protein that is shed by the
tumor cells, making it useful as a tumor marker to follow the course of the cancer.
CA 15-3 is elevated in about 30% of women with localized breast cancer and in about
75% of those with metastatic breast cancer (cancer that has spread to other organs).
CA 15-3 also may be elevated in healthy people and in individuals with other cancers,
conditions, or diseases, such as colorectal cancer, lung cancer, cirrhosis, hepatitis, and
benign breast disease.
How is it used?
CA 15-3 is not sensitive or specific enough to be considered useful as a tool for
cancer screening. Its main use is as a tumor marker to monitor a patient’s response to
breast cancer treatment and to watch for breast cancer recurrence. CA 15-3 can only
be used as a marker if the cancer is producing elevated amounts of it; however, since
only a small percent of women with localized breast cancer have increased CA 15-3,
it may still be able to be used later as a marker. CA 15-3 sometimes may also be used
to give a doctor a general sense of how much cancer may be present.
When is it ordered?
CA 15-3 may be ordered along with other tests, such as estrogen and progesterone
receptors, Her2/neu, and BRCA-1 and BRCA-2 genetic testing, when advanced breast
96
cancer is first diagnosed to help determine cancer characteristics and treatment
options.
If CA 15-3 is initially elevated, then it may be used to monitor treatment and, if
repeated on a regular basis, to detect recurrence. CA 15-3 is usually not done when
breast cancer is detected early, before it has metastasized, because levels will not be
elevated in the majority of early cancers.
In general, the higher the CA 15-3 level the more advanced the breast cancer and the
larger the tumor burden (amount of tumor present). The level tends to increase as the
cancer grows. In metastatic breast cancer, the highest levels of CA 15-3 often are seen
when the cancer has spread to the bones and/or the liver.
Mild to moderate elevations of CA 15-3 also are seen in a variety of conditions,
including liver and pancreatic cancer, cirrhosis, and benign breast disorders as well as
in a certain percentage of apparently healthy individuals. The CA 15-3 elevations seen
in these non-cancerous conditions tend to be stable over time.
Negative CA 15-3 levels do not ensure that a patient does not have cancer. It may be
too soon in the disease for elevated levels to be detected. In addition, 25% to 30% of
individuals with advanced breast cancer have tumors that do not shed CA 15-3.
Levels of CA 15-3 are not usually taken immediately after breast cancer treatment
begins. There have been instances of transient (temporary) increases and decreases in
CA 15-3 that do not correlate with the patient’s progress. Usually, your doctor will
wait a few weeks after starting treatment to begin monitoring CA 15-3 levels.
1. Should I have a test for CA 27.29 in addition to the CA 15-3 test?
CA 27.29 is protein that is produced by the same gene (MUC1) as CA 15-3 and is
used in the same way. It is newer than CA 15-3, but most doctors consider it
essentially equivalent to CA 15-3. It can be used instead of CA 15-3, but you usually
wouldn’t have both tests.
2. I have a strong family history of breast cancer. Shouldn’t I be screened for CA

15-3?
CA 15-3 is not recommended as a screening tool. It is not specific or sensitive enough
to detect early breast cancer. Any CA 15-3 elevations seen may be due to other
causes, and negative results do not ensure that you do not have cancer. It should only
be used after breast cancer has been diagnosed.
3. What can I do to lower my CA 15-3?

There is nothing you can do directly to lower your CA 15-3 level. It is not a risk
factor like cholesterol that can be lowered through dietary restrictions and exercise. It
is a reflection of what is going on in your body. CA 15-3 may rise with tumor growth
and fall with treatment, or it may be mildly elevated and stable in a benign condition.
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CA 19-9
Why get tested?
To help differentiate between cancer of the pancreas and bile ducts and other
conditions; to monitor response to pancreatic cancer treatment and to watch for
recurrence
When to get tested?
When your doctor suspects that you have pancreatic cancer and during or following
pancreatic cancer treatment.
Cancer antigen 19-9 (CA 19-9) is a protein that exists on the surface of certain cells.
CA 19-9 does not cause cancer; rather, it is a protein that is shed by the tumor cells,
making it useful as a tumor marker to follow the course of the cancer.
CA 19-9 is elevated in most patients with advanced pancreatic cancer, but it may also
be elevated in other cancers, conditions, and diseases such as colorectal cancer, lung
cancer, gall bladder cancer, gall stones, pancreatitis, cystic fibrosis, and liver disease.
Other causes of bile duct obstruction may also cause very high CA 19-9 levels, which
fall when the blockage is cleared. It is often a good idea, if the bile ducts are blocked,
to wait a week or two after the blockage is removed or treated to check CA 19-9
levels. If they are checked inititally, then it is a good idea to repeat the test after the
blockage is removed or treated to see if the cause of the increased CA 19-9 was the
tumor or the blockage itself. Very small amounts of CA 19-9 may also be found in
healthy patients.
How is it used?
CA 19-9 is not sensitive or specific enough to be considered useful as a tool for
cancer screening. Its main use is as a tumor marker:
 to help differentiate between cancer of the pancreas and bile ducts and other
non-cancerous conditions, such as pancreatitis;
 to monitor a patient's response to pancreatic cancer treatment; and
 to watch for pancreatic cancer recurrence.
CA 19-9 can only be used as a marker if the cancer is producing elevated amounts of
it; if CA 19-9 is not initially elevated, then it usually cannot be used later as a marker.
When is it ordered?
CA 19-9 may be ordered along with other tests, such as carcinoembryonic antigen
(CEA), bilirubin, and/or a liver panel, when a patient has symptoms that may indicate
pancreatic cancer, including abdominal pain, nausea, weight loss, and jaundice.
If CA 19-9 is initially elevated in pancreatic cancer, then it may be ordered several

times during cancer treatment to monitor response and, on a regular basis following
treatment, to help detect recurrence.
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Low amounts of CA 19-9 can be detected in a certain percentage of healthy people,
and many conditions that affect the liver or pancreas can cause temporary elevations.
Moderate to high levels are found in pancreatic cancer, other cancers, and in several
other diseases and conditions. The highest levels of CA 19-9 are seen in excretory
ductal pancreatic cancer -- cancer that is found in the pancreas tissues that produce
food-digesting enzymes and in the ducts that carry those enzymes into the small
intestine. This tissue is where 95% of pancreatic cancers are found.
Serial measurements of CA 19-9 may be useful during and following treatment
because rising or falling levels may give your doctor important information about
whether the treatment is working, whether all of the cancer was removed successfully
during surgery, and whether the cancer is likely returning.

Unfortunately, early pancreatic cancer gives few warnings. By the time a patient has
symptoms and significantly elevated levels of CA 19-9, their pancreatic cancer is
usually at an advanced stage.
. Why is my doctor not screening me for CA 19-9?
CA 19-9 is not sensitive or specific enough to be recommended as a screen for people
who do not have symptoms. There are too many false positives and false negatives
associated with it. Researchers are searching for other markers that may help detect
pancreatic cancer at an earlier stage and that may be more suitable for screening.
2. What other procedures will my doctor likely order along with my CA 19-9?
Your doctor may order a CT scan (computed tomography), an ultrasound, an MRCP
(using an MRI scan to look at the pancreatic and bile ducts), an ERCP (endoscopic
retrograde cholangiopancreatography, a procedure in which a small lighted tube is
passed through the mouth and stomach into the small intestine and then into the bile
and pancreatic ducts), and/or a biopsy to look for cancer cells under the microscope.
3. What are the main risk factors for pancreatic cancer?
Doctors still do not know what causes most cases of pancreatic cancer. Identified risk
factors include smoking, age (most are over 50 years old), gender (males are more
likely to have it than females), family history, diabetes, chronic pancreatitis, and
heavy occupational exposure to certain chemicals and dyes.
Calcium
Why get tested?
To determine if the level of calcium in your blood is at normal levels
When to get tested?
As part of a routine metabolic panel, in persons with kidney, bone, or nerve disease,
or when symptoms of abnormal calcium are present
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Sample required?
A blood sample drawn from a vein in your arm; a timed urine collection may be used
when blood calcium is abnormal; urine calcium may also be done if you have kidney
stones.
Calcium is one of the most important minerals in the body. About 99% of it is found
in the bones, and most of the rest circulates in the blood. Roughly half of the calcium
is referred to as free or ionized, and is metabolically active; the remaining half,
referred to as “bound” calcium, is attached to protein and other compounds and is
inactive.
Most commonly, doctors measure the total amount of calcium in the blood (called
total calcium); this measures both the active and inactive forms of calcium. If
measurement of the active form of calcium (ionized calcium) is needed, special
handling of the sample is required. Urine calcium tells how much calcium is being
eliminated by the kidneys.
How is it used?
Blood calcium is tested to screen for, diagnose, and monitor a range of conditions
relating to the bones, heart, nerves, kidneys, and teeth. Blood calcium levels do not
directly tell how much calcium is in the bones, but rather, how much total calcium or
ionized calcium is circulating in the blood.
Doctors can get a better picture of your health by comparing your calcium result with
the results of other tests. Calcium levels in the blood are regulated and stabilized by a
feedback loop that includes: calcium, PTH, vitamin D, phosphorus, and magnesium.
Your doctor is looking at the balance among all of these elements. Conditions and
diseases that disrupt this feedback loop can cause inappropriate elevations or
decreases in calcium and lead to symptoms of hyper- or hypocalcemia. For example,
when parathyroid hormone (PTH) from the parathyroid gland is released, PTH level
rises, calcium also rises, and phosphorus drops. In some kidney problems, a high
phosphorus level in blood can depress calcium levels. Depending on the levels you
have, these two tests can help your doctor discover whether you have a parathyroid
problem or another condition.
Directly measuring free or ionized calcium is important during major surgery
(particularly if blood or blood products are transfused), in critically ill patients, and
when protein levels are very abnormal. Large fluctuations in free calcium can cause
the heart to slow down or to beat too rapidly, can cause muscles to go into spasm
(tetany), and can cause confusion or even coma.
When is it ordered?
Calcium is often used as a screening test as part of a general medical examination. It
is typically included in the comprehensive metabolic panel.
Calcium can be used as a diagnostic test if you go to your doctor with symptoms that
suggest:
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 kidney stones,
 bone disease, or
 neurologic (nerve-related) disorders.
Your doctor also may order a calcium test if:
 you have kidney disease, because low calcium is especially common in those
with kidney failure;
 you have symptoms of too much calcium, such as fatigue, weakness, loss of
appetite, nausea, vomiting, constipation, abdominal pain, urinary frequency,
and increased thirst;
 you have symptoms of low calcium, such as cramps in your abdomen, muscle
cramps, or tingling fingers; or
 you have other diseases that can be associated with abnormal blood calcium,
such as thyroid disease, intestinal disease, cancer, or poor nutrition.
Your doctor may order an ionized calcium test if you have numbness around the
mouth and in the hands and feet and muscle spasms in the same areas, which are
symptoms of low levels of ionized calcium. If calcium levels fall slowly, however,
many people have no symptoms at all.
You may need calcium monitoring as part of your regular laboratory tests if you have
certain kinds of cancer (particularly breast, lung, head and neck, kidney, and multiple
myeloma) or kidney disease or transplant. You may need to be monitored for calcium
level also if it is clear that you have abnormal calcium levels or if you are receiving
calcium or vitamin D supplements.

A normal calcium result with other normal lab results means that you have no
problems with calcium metabolism (use by the body).
Because about half of the calcium in your blood is bound by albumin (a protein),
these two tests are usually ordered together. Calcium values must be interpreted in
combination with albumin to determine if the calcium concentration of serum is
appropriate. As albumin levels rise, calcium rises as well, and vice versa.
A high calcium level is called hypercalcemia. You have too much calcium in your
blood and will need treatment for the underlying condition. This usually is caused by:
 Hyperparathyroidism (increase in parathyroid gland function): This condition

is usually caused by a benign (not cancerous) tumor on the parathyroid gland.
This form of hypercalcemia is usually mild and can be present for many years
before being noticed.
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 Cancer: Cancer can cause hypercalcemia when it spreads to the bones, which
releases calcium into the blood, or when cancer causes a hormone similar to
PTH to increase calcium levels.
Other causes of hypercalcemia include:
 hyperthyroidism,
 sarcoidosis,
 tuberculosis,
 bone breaks combined with bed rest or not moving for a long periods of time,
 excess Vitamin D intake,
 kidney transplant, and
 high protein levels (for example, if a tourniquet is used for too long while
blood is collected). In this case, free or ionized calcium remains normal.
High levels of ionized calcium occur with all the above, except high protein
levels.
Low calcium levels, called hypocalcemia, mean that you do not have enough
calcium in your blood or that you don't have enough protein in your blood. The
most common cause of low total calcium is low protein levels, especially low
albumin. When low protein is the problem, the ionized calcium level remains
normal.
Low calcium, known as hypocalcemia, is caused by many conditions:
 low protein levels,

 underactive parathyroid gland (hypoparathyroidism),
 decreased dietary intake of calcium,
 decreased levels of vitamin D,
 magnesium deficiency,
 too much phosphorus,
 acute inflammation of the pancreas,
 chronic renal failure,
 calcium ions becoming bound to protein (alkalosis),
 bone disease,
 malnutrition, and
 alcoholism.
Causes of low ionized calcium levels include all the above, except low protein levels.

Two hormones control blood calcium within a small range of values. Parathyroid
hormone (PTH) is produced by a group of small glands in the neck (near the thyroid
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gland), stimulated by a decrease in ionized calcium. PTH causes the release of
calcium from bone and decreases calcium losses from the kidneys, so that calcium
levels rise. PTH also stimulates activation of Vitamin D by the kidneys.
Vitamin D, in turn, increases calcium absorption in the intestine, but decreases
calcium lost from the kidneys in urine. Overall, as Vitamin D levels rise, calcium
levels rise and PTH falls. In healthy people, these two hormones keep blood calcium
at normal levels, even though maintaining that balance in the blood may cause
calcium to be released from bones.
Newborns, especially premature and low birthweight infants, often are monitored
during the first few days of life for neonatal hypocalcemia. This can occur because of
an immature parathyroid gland and doesn't always cause symptoms. The condition
may resolve itself or may require treatment with supplemental calcium, given orally
or intravenously.
Blood and urine calcium measurements cannot tell how much calcium is in the bones.
A test similar to an X-ray, called a bone density or "Dexa" scan, is needed for this
purpose.
Taking thiazide diuretic drugs (drugs that encourage urination) is the most common
drug-induced reason for a high calcium level.
1. Should I be concerned if my doctor only orders a regular calcium and not free
or ionized calcium?
No. The total calcium is sufficient for most screening purposes. Free or ionized
calcium is particularly important during surgery as well in severely ill patients, when
changes in total calcium do not reliably tell how abnormal the free calcium level is.
2. What foods are high in calcium?

Dairy products are the main source of calcium, but lesser amounts are found in eggs,
green leafy vegetables, broccoli, legumes, nuts, and whole grains. Many fruit juices
are now fortified with calcium.
3. If I consume foods fortified with calcium, would it change my laboratory

results?
In general, consuming fortified foods will not affect your calcium test results.
4. Can I perform this test at home?

No. While there are hand-held instruments available, these are intended for use in a
hospital or medical office setting and must be operated by trained personnel.
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Cardiac Biomarkers
What are they?
Cardiac biomarkers are enzymes, proteins, and hormones that are associated with
heart function, damage or failure. Some of the tests are specific for the heart while
others are also elevated with skeletal muscle damage. Cardiac biomarkers are used for
diagnostic and prognostic purposes and are frequently ordered by doctors when
someone comes into the Emergency Room complaining of symptoms, such as chest
pain, pressure, nausea, and shortness of breath. These tests are ordered, along with
other laboratory and non-laboratory tests, to detect heart failure (which is often a
chronic, progressive condition affecting the ability of the heart to fill with blood and
pump efficiently) and the acute coronary syndromes (ACS) as well as to help
determine prognosis for people who have had a heart attack. ACS is a group of
symptoms that reflect a sudden decrease in the amount of blood and oxygen, also
termed ‘ischemia,’ reaching the heart. This decrease is frequently due to either a
narrowing of the coronary arteries (atherosclerosis or vessel spasm) or unstable
plaques, which can cause a blood clot (thrombus) and blockage of blood flow. If the
oxygen supply is low, it can cause angina (pain); if blood flow is reduced, it can cause
death of heart cells (called myocardial infarction or heart attack) and can lead to death
of the affected heart muscle cells and to permanent damage and scarring of the heart.
The goal with cardiac biomarkers is to be able to detect the presence and severity of
an acute heart condition as soon as possible so that appropriate treatment can be
initiated. Cardiac biomarkers must be available to the doctor 24 hours a day, 7 days a
week with a rapid turn-around-time. Different biomarkers have different times that
their levels rise, peak, and fall within the body, allowing them to be used not only to
track the progress of a heart attack but to estimate when it began and to monitor for
recurrence. There are only a few cardiac biomarkers that are being routinely used by
physicians. Some have been phased out because they are not as specific as the marker
of choice – troponin. Many other potential cardiac biomarkers are still being
researched but their clinical utility has yet to be established.
Laboratory Tests
Current Cardiac Biomarkers
 CK and CK-MB
 Troponin
 Myoglobin (not always used; sometimes ordered with troponin)
 BNP or (NT-proBNP)
Phased out Biomarkers
 AST
 LDH
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More General Tests Frequently Ordered along with Cardiac Biomarkers
 Blood Gases
 CMP
 BMP
 Electrolytes
 CBC
On the Horizon
 Ischemia modified albumin (IMA) – Test has received FDA approval for use with
troponin and electrocardiogram to rule out acute coronary syndrome (ACS) in patients
with chest pain. May become useful for identifying patients at higher risk of heart
attack and potentially could replace myoglobin one day.
Non-laboratory Tests
These tests allow doctors to look at the size, shape, and function of the heart as it is
beating. They can be used to detect changes to the rhythm of the heart as well as to
detect and evaluate damaged tissues and blocked arteries.
 EKG (ECG, electrocardiogram)
 Nuclear scan
 Coronary angiography (or arteriography)
 ECG (echocardiogram)
 Stress testing
 Chest X-ray
Summary Table
The following table summarizes currently used cardiac biomarkers.
What Where What Time to Time back When/How Used
Found Indicates Increase to Normal
Marker
CK Enzyme Heart, Injury to 4 to 6 hours Normal in 48 Being phased out,
that exists brain, and muscle cells after injury, to 72 hours, may be ordered prior
in three skeletal peaks in 18 to unless due to CK-MB
different muscle 24 hours to continuing
isoforms injury
CK-MB Heart- Heart Injury (cell 4 to 6 hrs after Returns to Not as specific as
related primarily, death) to heart attack, normal in 24 Troponin for heart
portion of but also in heart peaks in 12 to to 48 hours injury/attack, may be
total CK skeletal 20 hours unless ordered when
enzyme muscle new/continua Troponin is not
l damage available, may be
ordered to monitor
new/continuing
damage
105
Myoglobin Small Heart and Injury to Starts to rise Falls back to Ordered along with
oxygen- other heart or within 2 to 3 normal by Troponin, helps
storing muscle other hours, peaks about one diagnose heart
protein cells muscle in 8 to 12 day after injury/attack
cells. Also hours. injury
elevated occurred
with kidney
problems.
Cardiac Componen Heart Heart 4 to 8 hours Remains Ordered to help

Troponin ts of a muscle injury/dama elevated for assess prognosis and
Regulatory ge 7 to 14 days diagnose heart attack
protein
complex.
Two
cardiac
specific
isoforms: T
and I
LDH Enzyme Almost all General Phased out, not
body marker of specific
tissues injury to
cells
AST> Enzyme Heart, liver, Injury to Phased out, not

and liver, heart-specific
muscles muscle, or
heart
Hs-CRP Protein Associated Inflammator Elevated May help determine
with y process with prognosis of patients
atheroscler inflammation who’ve had heart
osis attack
BNP Hormone Heart’s left Heart failure Elevation Help diagnose and
ventricle related to evaluate heart failure,
severity prognosis, and to
monitor therapy
Cardiac Risk Assessment
What is a cardiac risk assessment?

This is a group of tests and health factors that have been proven to indicate your
chance of having a coronary event. They have been refined to indicate the degree of
risk: slight, moderate, or high.
What is included in a cardiac risk assessment?

Perhaps the most important indicators for cardiac risk are those of your personal
health history. Age, hereditary factors, weight, smoking, blood pressure, exercise
history, and diabetes are all important in determining your risk. The lipid profile is the
most important blood test for risk assessment. There are other tests, non-invasive and
invasive, which may be used in cardiac risk assessment. Non-invasive tests may
include an EKG stress test, thallium stress test, EKG, CT scan, and echocardiogram.
Invasive tests include an arteriogram and cardiac catheterization.
How is the lipid profile used?

The lipid profile measures cholesterol, triglycerides, HDL (“good” cholesterol), and
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LDL (“bad” cholesterol). Triglycerides are the major form of fat found in the body
and their function is to provide energy for the cells. Below are the desirable ranges for
the components of the lipid profile:
 Cholesterol <200 mg/dL (5.18 mmol/L)

 HDL-cholesterol > 40 mg/dL (1.04 mmol/L)
 LDL-cholesterol <100 mg/dL* (2.59 mmol/L)
 Triglycerides <150 mg/dL (1.70 mmol/L)
optimal; levels will depend on the number and type of risk factors present and whether testing is being used in primary or secondary
intervention
If any or all of your results are significantly outside these ranges, your risk of a
cardiac event is increased. If they are only slightly outside the desirable level, diet,
exercise, and/or medication may be sufficient to reduce the abnormal levels,
thereby reducing your risk.
What other tests are used to assess cardiac risk?

Another test gaining importance is serum homocysteine. Homocysteine is an
amino acid that comes from the normal breakdown of proteins in the body and
appears to be a better test than cholesterol for predicting heart disease, stroke, and
reduced blood flow to the hands and feet. Lipoprotein A, Lp(a), is a lipoprotein
consisting of an LDL molecule with another protein (Apolipoprotein (a)) attached to
it. Lp(a) is similar to LDL but does not respond to typical strategies to lower LDL
such as diet, exercise, or most lipid lowering drugs. Since the level of Lp(a) appears to
be genetically determined and not easily altered, the presence of a high level of Lp(a)
may be used to identify individuals who might benefit from more aggressive
treatment of other risk factors. A fairly new test, hsCRP may be measured on
apparently healthy patients to determine if they are at risk for a coronary event, even
if their lipid levels are normal or borderline elevated.
How is treatment determined?

Treatment will be based on many factors – including the results of the above tests and
your family and personal medical and lifestyle history.

Eating a healthy diet and exercising are important in reducing blood pressure,
cholesterol and triglycerides. There are also drugs (known as statins) that have been
effective in lipid management. There are some forms of elevated lipids that are
hereditary and cannot always be lowered sufficiently by diet and exercise. This type
of elevation usually requires treatment with lipid-lowering drugs.
FAQs
1. Are some people more at risk for a heart attack than others? Yes. Those who
are overweight, smoke, have high blood pressure or diabetes, abnormal risk test
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results, and those with a family history of heart disease are at greater risk.
2. Are there home test kits for determining if I am at risk for a heart attack? No.
The diagnosis is based on the results of any or all of the tests mentioned. The overall
assessment requires special equipment and interpretation by a trained professional.
Catecholamines, Plasma and Urine
Also known as: Dopamine, Epinephrine, Norepinephrine, Free Urine Catecholamines

Why get tested?
To help diagnose or rule out a pheochromocytoma (tumor of the adrenal gland) or
other neuroendocrine tumor
When to get tested?
If you have symptoms of persistent or episodic high blood pressure such as severe
headaches, rapid heart rate, and sweating
Sample required?
A blood sample drawn from a vein in the arm or a 24-hour urine sample.
Catecholamines are a group of similar hormones produced in the medulla (central
portion) of the adrenal glands. The adrenal glands are small, triangular organs located
on top of each kidney. The primary catecholamines are dopamine, epinephrine
(adrenaline), and norepinephrine. These hormones are released into the bloodstream
in response to physical or emotional stress. They help transmit nerve impulses in the
brain, increase glucose and fatty acid release (for energy), dilate bronchioles (small air
passages in the lungs), and dilate the pupils. Norepinephrine also constricts blood
vessels (increasing blood pressure) and epinephrine increases heart rate and
metabolism. After completing their actions, the hormones are metabolized to form
inactive compounds. Dopamine becomes homovanillic acid (HVA), norepinephrine
breaks down into normetanephrine and vanillylmandelic acid (VMA), and
epinephrine becomes metanephrine and VMA. Both the hormones and their
metabolites are excreted in the urine.
Normally, catecholamines and their metabolites are present in the body in small,
fluctuating amounts that only increase appreciably during and shortly after a bout of
stress. Pheochromocytomas (rare adrenal gland tumors) and other neuroendocrine
tumors, however, can produce large amounts of catecholamines, resulting in greatly
increased concentrations of the hormones and their metabolites in both the blood and
urine. This can cause persistent hypertension (high blood pressure) and/or bouts or
episodes of severe hypertension, resulting in symptoms such as severe headaches,
palpitations, sweating, nausea, anxiety, and tingling in the extremities.
About 90% of pheochromocytomas are located in the adrenal glands. While a few are
cancerous, most are benign - they do not spread beyond their original location -
although most do continue to grow. Left untreated, the symptoms may worsen as the
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tumor grows and, over a period of time, the hypertension that the pheochromocytoma
causes may damage body organs, such as the kidneys and heart, and raise the risk of
an affected patient having a stroke or heart attack.
Urine and plasma catecholamine testing can be used to help detect the presence of
pheochromocytomas. Although only about 800 cases a year are diagnosed in the U.S.
according to the National Cancer Institute, it is important to diagnose and treat these
rare tumors because they cause a potentially curable form of hypertension. In most
cases, the tumors can be surgically removed and/or treated to significantly reduce the
amount of catecholamines being produced and to reduce or eliminate their associated
symptoms and complications.
Catecholamine testing measures the amount of epinephrine, norepinephrine, and

dopamine in the plasma or urine. (The metabolites of these hormones may be
measured separately with a urine metanephrine and/or VMA test). The plasma
catecholamine test measures the amount of hormones present at the moment of
collection, while the urine test measures the amount excreted over a 24-hour period.

For the 24-hour urine collection, all of your urine should be saved for a 24-hour
period. It is important that the sample be refrigerated during this time period. Since
diet, exercise, and drugs may affect catecholamine levels, precautions need to be
taken to assure that the sample reflects a true metabolic condition and not an
interference or aberration. For this reason you should talk to your doctor about your
diet and any medications you are taking. Foods such as coffee (including decaf), tea,
chocolate, vanilla, bananas, oranges and other citrus fruits should be avoided for
several days prior to the test and during collection. There are also many medications
that can potentially affect test results. Talk to your doctor about the prescriptions and
over the counter drugs and supplements that you are taking. Wherever possible, those
that are known to interfere should be discontinued prior to and during sample
collection. Emotional and physical stresses and vigorous exercise should be
minimized prior to and during test collection as they can increase catecholamine
secretion.
Plasma catecholamines are collected by inserting a needle into a vein in your arm.
Although there is some disagreement over the specifics of how the sample should be
collected, you may be asked to lie down and rest quietly for 15 – 30 minutes prior to
sample collection, and your blood may be collected while you are lying down. In
other circumstances, you may just be seated upright with little or no rest time before
the sample collection.
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How is it used?
Catecholamine testing is primarily used to help detect and rule out
pheochromocytomas in symptomatic patients. It also may be ordered to help monitor
the effectiveness of treatment when a pheochromocytoma is discovered and removed
and to monitor for recurrence. The plasma test is most useful when the patient has
persistent hypertension or is currently experiencing an episode of hypertension. This
is because the hormones do not linger in the blood; they are used by the body,
metabolized, and/or excreted. Urine catecholamine testing measures the total amount
of catecholamines released in 24 hours. Since the hormone levels may fluctuate
significantly during this period, the urine test may detect excess production that is
missed with the blood test. Plasma and urine tests may be ordered together or
separately and/or along with urine and/or plasma metanephrines to look for excessive
amounts of both catecholamines and their metabolites.
Since these tests are affected by drugs, foods, and stresses, there will be a certain
number of false positives. For this reason, catecholamine testing is not recommended
as a screen for the general public. Doctors will frequently investigate a positive result
by evaluating a patient’s stresses and intake, work to alter or minimize any influences,
and then repeat the test to confirm the original findings.
Occasionally, the tests may be ordered on an asymptomatic person if an adrenal or

neuroendocrine tumor is detected during a scan that is done for another purpose or if
the patient has a strong personal or family history of pheochromocytomas (as they
may recur and there is a genetic link in some cases).
When is it ordered?
Catecholamine testing is ordered when a doctor either suspects that a patient has a
pheochromocytoma or wants to rule out the possibility. He may order it when a
patient has persistent or recurring hypertension along with symptoms such as
headaches, sweating, flushing, and rapid heart rate. It may also be ordered when a
patient has hypertension that is not responding to treatment (patients with a
pheochromocytoma are frequently resistant to conventional therapies).
Occasionally, the test may be ordered when an adrenal tumor is detected incidentally
or when a patient has a family history of pheochromocytomas. It may also be used as
a monitoring tool when a patient has been treated for a previous pheochromocytoma.

Since the catecholamine test is sensitive to many outside influences and
pheochromocytomas are rare, a doctor may see more false positives with this test than
true positives. If a symptomatic patient has large amounts of catecholamines in her
blood and/or urine, further investigation is indicated. Serious illnesses and stresses
can cause moderate to large temporary increases in catecholamine levels. Doctors
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must evaluate the patient as a whole - his physical condition, emotional state,
medications, and diet. When interfering substances and/or conditions are found and
resolved, the doctor will frequently re-test the patient to determine whether the
catecholamines are still elevated. The doctor may also order blood and/or urine
metanephrine testing to help confirm his findings and imaging tests (such as an MRI)
to help find the tumor(s).
If levels are elevated in a patient who has had a previous pheochromocytoma, then it
is likely that either treatment was not fully effective or that the tumor is recurring.
If the concentrations of catecholamines are normal in both the plasma and urine, then
it is unlikely that a patient has a pheochromocytoma. Pheochromocytomas do not
necessarily produce catecholamines at a constant rate, however. If the patient has not
had a recent paroxysm of hypertension, their plasma and urine concentrations of
catecholamines could be at normal or near normal levels even when a
pheochromocytoma is present.

While plasma and urine catecholamine testing can help detect and diagnose
pheochromocytomas, they cannot tell the doctor where the tumor is, whether there is
more than one, or whether or not the tumor is benign (although most are). The amount
of catecholamines produced does not necessarily correspond to the size of the tumor.
This is a physical characteristic of the tumor tissue. The total amount of
catecholamines produced will tend to increase, however, as the tumor increases in
size.
It is very important to talk to your doctor before discontinuing any prescribed

medications. He will work with you to identify interfering substances and drug
treatments to determine which of them can be safely interrupted and which must be
continued for your well-being. Some of the substances that can interfere with
catecholamine testing include: acetaminophen, aminophylline, amphetamines,
appetite suppressants, coffee, tea, and other forms of caffeine, chloral hydrate,
clonidine, dexamethasone, diuretics, epinephrine, ethanol (alcohol), insulin,
imipramine, lithium, methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors,
nicotine, nitroglycerine, nose drops, propafenone (Rythmol), reserpine, salicylates,
theophylline, tetracycline, tricyclic antidepressants, and vasodilators. The effects of
these drugs on catecholamine results will be different from patient to patient and are
often not predictable.
1. Is there any way to prevent a pheochromocytoma from forming?

No, they can be detected and removed but not prevented. In most cases, the tumor is
benign and, once it is removed, it will not recur.
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2. Can I test for catecholamines at home?
No, testing must be done on specialized machines in a laboratory.
3. Is it really necessary to collect urine for 24 hours?
Yes, for accurate test results it is essential that all of the urine be collected. Because
catecholamines are released at varying times, the one sample not included might be
the one with the most hormones in it.
4. Can my state of mind really affect my test results?

Yes, because catecholamines are released from the adrenal glands in response to
stress. If you are anxious or afraid, your catecholamines concentrations may be
increased.
CCP
Also known as: Citrulline antibody, Anti-citrulline antibody, anti-cyclic citrullinated

peptide antibody, anti-CCP.
Why get tested?
To help diagnose rheumatoid arthritis (RA) and differentiate it from other types of
arthritis; sometimes to help evaluate the prognosis of a patient with RA
When to get tested?
If a patient has joint inflammation and/or undiagnosed or undifferentiated
inflammatory arthritis (symptoms suggest but do not yet meet the criteria of RA) and
the doctor suspects RA
The cyclic citrullinated peptide antibody (CCP) test is a relatively new assay that
detects the presence of citrulline antibodies in the blood. These autoantibodies are
proteins produced by the immune system in response to a perceived threat from
citrulline. An unusual amino acid (protein building block), citrulline is created when
the amino acid arginine is altered. There is speculation that the conversion of arginine
to citrulline may play a role in the autoimmune inflammatory process seen in the
joints of those with rheumatoid arthritis (RA).
How is it used?
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes
inflammation, pain, stiffness, and destructive changes in the hands, feet, and other
joints throughout the body. There are a variety of treatments available to minimize the
complications of RA, but they depend on making an accurate diagnosis and on
beginning treatment before the development of significant joint damage. Rheumatoid
factor (RF) has been the primary blood test used to detect RA and distinguish it from
other types of arthritis and other inflammatory processes. However, the sensitivity and
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specificity of RF are not ideal; it can be negative in patients who have clinical signs of
RA and positive in patients who do not.
CCP can be useful in diagnosing early RA. An elevated CCP can be found in a
significant number of patients who have a negative RF, the classic test for RA, and
therefore can help to make a diagnosis. According to the American College of
Rheumatology, CCP antibodies may be detected in about 50-60% of patients with
early RA (as early as 3-6 months after the beginning of symptoms). Early detection
and diagnosis of RA allows doctors to begin aggressive treatment of the condition,
minimizing the associated complications and tissue damage.
CCP may also be ordered to help evaluate the likely development of RA in patients
with undifferentiated arthritis (those whose symptoms suggest but do not yet meet the
criteria of RA). The reason it is useful in confounding clinical presentations is that
CCP is a more specific test for RA then the traditional RF. According to American
College of Rheumatology, approximately 95% of patients with a positive CCP will
develop RA in the future.
When is it ordered?
CCP is primarily ordered along with an RF test when a patient has previously
undiagnosed inflammatory arthritis or has been diagnosed with undifferentiated
arthritis. It may be ordered as a follow-up test to a negative RF test when clinical
signs, such as symmetrical joint pain and inflammation, lead the doctor to suspect RA.
As a rule, test results outside the context of clinical symptoms and signs cannot be
judged. Nonetheless, if a patient is positive for both CCP and RF, it is very likely that
they have RA and it is likely that they may develop a more severe form of the disease.
If a patient is positive for CCP but not RF and clinical signs suggest RA, then it is
likely that they have early RA or that they will develop RA in the future.
If a patient is negative for CCP but has a positive RF, then the clinical symptoms and
signs are more vital in determining whether a patient has RA versus some other
inflammatory condition. If a patient is negative for both CCP and RF, then it is less
likely that they have RA. It must be emphasized, however, that RA is a clinical
diagnosis and may be made in the absence of positive autoantibodies.

The CCP test is promising but not yet widely used. Its ultimate clinical usefulness and
the ways in which it will be used have yet to be determined.
1. Should everyone be tested for CCP?
No. CCP is not recommended as a screening test. Like RF, it is best used for patients
whose clinical signs suggest RA or who have already been diagnosed with
undifferentiated arthritis.
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CD4 Count
Also known as: T4 count, T-helper cells
Why get tested?
To measure the strength of your immune system if you’ve been diagnosed with HIV
infection
When to get tested?
If you’ve been diagnosed with HIV, to get a baseline assessment of your immune
system; four weeks after starting anti-HIV therapy and then every three to four
months if you continue therapy.
This test measures the number of CD4 cells (also known as T-helper cells) in your
blood and assesses the status of your immune system. CD4 cells are a type of white
blood cell that fight infection, and they play an important role in your immune system.
They help to identify, attack, and destroy specific bacteria, fungi, and other germs that
affect the body. CD4 cells are made in the spleen, lymph nodes, and thymus gland,
and they circulate throughout the body in the bloodstream. CD4 cells are a major
target for HIV, which binds to the surface of CD4 cells, enters them, and either
reproduces immediately, killing them in the process, or remains in a resting state,
reproducing later. As the HIV virus gets into the cell and replicates, the number of
CD4 cells in the blood gradually declines. As HIV disease progresses, the CD4 count
will go down and as treatment reduces the progression, the CD4 count will go back
up.
How is it used?
The CD4 count tells your doctor how strong your immune system is, how far HIV
disease has advanced (the stage of the disease), and helps predict the risk of
complications and debilitating infections. The CD4 count is most useful when it is
compared with the count obtained from an earlier test.
The CD4 count is used in combination with the viral load test, which measures the
level of HIV in the blood, to determine the staging and outlook of the disease.
The CD4 count is also used to identify possible health problems for which you may
be at risk and to determine which medications might be helpful.
When is it ordered?
A CD4 count and a viral load test are ordered when a person is first diagnosed with
HIV as part of a baseline measurement. Both tests should be repeated about two to
eight weeks after starting or changing anti-HIV therapy. If treatment is maintained, a
CD4 count should be performed every three to six months thereafter.
Normal CD4 counts in adults range from 500 to 1,500 cells per cubic millimeter of
blood.
In general, the CD4 count goes down as HIV disease progresses. Any single CD4
count value may differ from the last one even though your health status has not
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changed. You should not place too much importance on any one result. What is more
important than any single value is the pattern of CD4 counts over time.
If your CD4 count declines over several months, your doctor may recommend
beginning or changing anti-HIV treatment and/or starting preventive treatment for
opportunistic infections like Pneumocystis carinii pneumonia (PCP). Your CD4 count
should increase or stabilize in response to effective combination anti-HIV therapy.
According to public health guidelines, preventive therapy should be started when an

HIV-positive person who has no symptoms registers a CD4 count under 200. Some
physicians will opt to consider treatment earlier, at 350. The Centers for Disease
Control and Prevention considers HIV-infected persons who have CD4 counts below
200 to have AIDS, regardless of whether they are sick or well.
The CD4 count tends to be lower in the morning and higher in the evening. Acute
illnesses, such as pneumonia, influenza, or herpes simplex virus infection, can cause
the CD4 count to decline temporarily. Cancer chemotherapy can dramatically lower
the CD4 count. Regardless, it can be used as an effective monitoring tool if the more
sensitive HIV viral load test is not available.
The CD4 count does not always reflect how someone with HIV disease feels and
functions. For example, some people with higher counts are ill and have frequent
complications, and some people with lower CD4 counts have few medical
complications and function well.
1. Can I check my CD4 count at home?
No, this test must be ordered by a doctor and performed in a clinic or lab.
2. What are common opportunistic infections I might get?

The Center for Disease Control (CDC) includes 26 opportunistic infections in its
definition of AIDS.
CEA
Why get tested?
To determine whether cancer is present in the body and to monitor cancer treatment
When to get tested?
When your doctor thinks your symptoms suggest the possibility of cancer and before
starting cancer treatment as well as at intervals during and after therapy.
CEA is a protein that is normally not able to be detected in the blood of a healthy
person. When the protein appears in the blood of an adult, it can indicate cancer, but it
will not indicate which kind of cancer is present. CEA is often used to monitor
patients with cancers of the gastrointestinal (GI) tract. It can also indicate benign
conditions.
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How is it used?
CEA is most useful to monitor treatment of cancer patients. It is used with patients
who have had surgery to measure response to therapy and to monitor whether the
disease is recurring. A blood test for CEA is often used as a tumor marker. Physicians
can use CEA results to determine the stage and extent of disease and the outlook in
patients with cancer, especially gastrointestinal (GI) and, in particular, colorectal
cancer. CEA is also used as a marker for other forms of cancer. It has been found
helpful in monitoring patients with cancer of the rectum, lung, breast, liver, pancreas,
stomach, and ovary. Not all cancers produce CEA; therefore, the CEA test is not used
for screening the general population.
When is it ordered?
A CEA test is ordered when the patient’s symptoms suggest the possibility of cancer.
The CEA level is also tested before treatment in cancer patients, especially patients
with GI cancers. CEA levels are monitored during therapy. It is also used to follow up
patients after therapy.
On initial testing, patients with smaller and early-stage tumors are likely to have low,
if not normal, CEA levels, while patients with more advanced tumors, or tumors that
have spread throughout the body, are likely to have initially high CEA levels. When
CEA levels decrease to “normal” levels after therapy, it means that the CEA-
producing tumor has been removed. A steadily rising CEA level is occasionally the
first sign of tumor recurrence.

CEA is a protein that is found in embryonic tissues. By the time a baby is born,
detectable levels in the blood disappear.
Increased CEA levels can indicate some non-cancer-related conditions, such as some
forms of inflammation, cirrhosis, and peptic ulcer. Also, smokers tend to have higher
CEA levels than non-smokers.When cancer spreads to other organs, CEA levels rise
and may be present in other types of bodily fluids besides blood. For example, if CEA
is detected in cerebrospinal fluid, this indicates a central nervous system metastasis.
1. If I am a smoker, does an elevated CEA level mean I have cancer?
Not necessarily. Smokers can have a higher “normal” range than non-smokers and not
have cancer.
Celiac Disease Tests
Also known as: Gluten-Sensitive Enteropathy Tests.
Why get tested?
To help determine whether you have celiac disease and to monitor compliance to and
the effectiveness of a gluten-free diet
When to get tested?
When you have symptoms suggesting celiac disease, such as chronic diarrhea,
abdominal pain, anemia, and weight loss. When an infant is chronically irritable or
fails to grow at a normal rate. Occasionally to monitor treatment of celiac disease.
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Celiac disease tests are a group of assays developed to help diagnose celiac disease
and a few other gluten-sensitive conditions. These tests detect autoantibodies that the
body creates as part of an immune response to dietary proteins (gluten and gliadin)
found in wheat, rye, and barley. These autoantibodies cause intestinal inflammation
and damage in the lining of the intestinal wall. This causes symptoms associated with
malnutrition and malabsorption, such as: diarrhea, weakness, weight loss, abdominal
pain, abdominal distention, fatigue, oral ulceration, bleeding tendency, bone and joint
pain, and anemia. Adults may also experience depression and a general feeling of
illness while children are frequently irritable and may have delayed growth and
development.
In the past the only way to diagnose celiac disease was with a biopsy of the small
intestine. While this microscopic evaluation is still considered the gold standard and is
still used to confirm a diagnosis of celiac disease, the availability of less invasive
blood tests used to screen for celiac disease have reduced the number of biopsies
needed. Autoantibody blood tests that are available include:
 Anti-tissue Transglutaminase Antibody (tTG), IgA: Tissue transglutaminase is

an enzyme responsible for crosslinking certain proteins. It has been identified
as the antigen that the body responds to when it creates Anti-EMA antibodies.
Gliadin in grains triggers the development of tTG autoantibodies. Although
“tissue” is in the name of this autoantibody, it nevertheless involves testing
blood and not tissue.
 Anti-Endomysial Antibodies (EMA), IgA: Endomysium is the thin connective
tissue layer that covers individual muscle fibers. Anti-Endomysial antibodies
are developed in reaction to the ongoing damage to the intestinal lining.
Almost 100% of patients with active celiac disease and 70% of patients with
dermatitis herpetiformis (another gluten-sensitive enteropathy that causes an
itchy burning blistering rash on the skin) will have Anti-EMA, IgA antibodies.
Anti-tTG and Anti-EMA antibodies measure the same tissue damage.
 Anti-Gliadin Antibodies (AGA), IgG and IgA: Gliadin is part of the gluten
protein found in wheat (similar proteins are found in rye, barley, and oats).
AGA is an autoantibody against the gliadin portion. It is created by those who
are sensitive to it when they are exposed to gluten over a period of time.
 Anti-Reticulin Antibodies (ARA), IgA: Anti-ARA is not ordered as frequently
as it once was as it is not as specific or sensitive as the other autoantibodies. It
is found in about 60% of celiac disease patients and about 25% of patients
with dermatitis herpetiformis. When used, ARA is ordered along with other
celiac disease tests to help diagnose celiac disease.
Each of the celiac blood tests available measures the amount of a particular
autoantibody in the blood and is available in both an IgG and an IgA version. IgG and
IgA are 2 of the five classes of antibody proteins that the immune system creates in
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response to a perceived threat.
While both IgG and IgA types of each autoantibody will be present in the blood they
are not equally specific for celiac disease. In general, the IgA forms of the tests tend
to be more specific, and in some cases are used almost exclusively. IgG versions may
be ordered either to complement the IgA testing and/or ordered because someone has
an overall deficiency in IgA. This happens about 2% of the time with celiac disease
and can lead to some false negative test results.
How is it used?
Celiac disease tests are used to screen for and help diagnose celiac disease and a few
other gluten-sensitive conditions (such as dermatitis herpetiformis). They are usually
ordered on those patients with symptoms suggesting celiac disease, but may also be
ordered to help rule out celiac disease as a cause for conditions such as anemia and
abdominal pain. Since those with celiac disease may also experience conditions such
as lactose intolerance, celiac tests may be done in conjunction with other intolerance
and allergy testing.
Sometimes celiac testing is ordered to screen for asymptomatic celiac disease in those
who have close relatives with celiac disease (about 10% of those who have close
relatives with celiac disease will develop it themselves) and/or in those who have
other autoimmune diseases (those with autoimmune diseases often have more than
one disease).
A doctor may order one or more celiac disease tests, along with tests to evaluate the
status and extent of a patient’s malnutrition and malabsorption. There are four
autoantibodies that are related to celiac disease that can be measured. The doctor will
often order an Anti-tissue Transglutaminase Antibody (tTG), IgA first to screen for
celiac disease. If this test is positive, it is likely that the patient has celiac disease. The
doctor may perform an intestinal biopsy to confirm that there is damage to the
intestine. If the Anti-tTG is negative but the physician still suspects celiac disease, he
may order other tests that include:
 Anti-Gliadin Antibodies (AGA), IgG and IgA. These tests are often useful
when testing young symptomatic children but they are found in fewer cases of
celiac disease than Anti-tTG and they can also be positive in other diseases.
AGA IgG and IgA are often ordered together so that their results can be
compared. If one is positive, both should be – unless the patient has an IgA
deficiency. They can be used to monitor dietary compliance.
 Anti-Endomysial Antibodies (EMA), IgA. This test is being replaced by the
Anti-tTG test as they both measure the autoantibodies causing the tissue
damage associated with celiac disease. Anti-EMA is, however, still being
ordered at this time by many physicians and may be used to monitor dietary
compliance.
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 Anti-Reticulin Antibodies (ARA), IgA. Anti-ARA is not ordered as frequently
as it once was as it is not as specific or sensitive as the other autoantibodies. It
is found in about 60% of celiac disease patients and about 25% of patients
with dermatitis herpetiformis.
tTG can also be used for monitoring dietary compliance.
These autoantibody tests are often ordered along with other tests to help determine the
severity of the disease and the extent of a patient’s malnutrition, malabsorption, and
organ involvement. Other tests might include a:
 CBC (complete blood count) to look for anemia

 ESR (erythrocyte sedimentation rate) to evaluate inflammation
 CRP (C-Reactive protein) to evaluate inflammation
 CMP (complete metabolic panel) to determine electrolyte, protein, and
calcium levels, and to verify the status of the kidney and liver
 Vitamin D, E, and B12 to measure vitamin deficiencies
 Stool fat, to help evaluate malabsorption
When is it ordered?
Celiac disease tests are ordered when someone has symptoms suggesting celiac
disease, malnutrition, and/or malabsorption - such as diarrhea, abdominal pain,
weakness, fatigue, weight loss, and joint pain. They may be ordered as part of an
investigation of anemia, osteoporosis, infertility, or seizures (certain types are linked
to celiac disease). In children, celiac disease tests may be ordered when a child
exhibits delayed development, short stature and/or a failure to thrive.
Asymptomatic people may be tested if they have a close relative with celiac disease,
but celiac disease testing is not recommended at this time as a screen for the general
population.
Autoantibody levels may also be ordered when a patient with celiac disease has been
on a gluten-free diet for a period of time. This is done to verify that antibody levels
have decreased and to verify that the diet has been effective in relieving symptoms
and reversing the intestinal lining damage (this is sometimes still confirmed with a
second biopsy). When a patient’s symptoms have not subsided, celiac disease tests
may be ordered to check for dietary compliance, and to help the doctor and patient
look for either hidden gluten in the patient’s diet or for other reasons for their
unrelieved symptoms.
In general, if your Anti-tTG test is positive, then it is likely that you have celiac
disease. If the Anti-tTG test is negative, then it is most likely that you do not have
celiac disease. However, your Anti-tTG levels may be very low or undetectable if you
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have been avoiding wheat, rye, and barley for a period of time or if you are one of the
small percentage of patients with celiac disease who are also deficient in IgA. This
may lead to a false negative result and may prompt your doctor to do additional
testing.
If several of the other autoantibodies are present in high concentrations but tTG is
negative, then you may have celiac disease. If only one autoantibody is high, or if one
or more are present, but only at low concentrations, then your symptoms may be due
to celiac disease or due to another cause. If any of the blood test results are positive
(or indeterminate) your doctor will usually do an intestinal biopsy to confirm or rule
out celiac disease.
If you have been diagnosed with celiac disease and have removed gluten from your
diet, then your autoantibody levels should fall. If they do not, and your symptoms do
not diminish then there may either be hidden forms of gluten in your diet that have not
been eliminated (gluten is often found in unexpected places, from salad dressings to
cough syrup) or you may have one of the rare forms of celiac disease that does not
respond to dietary changes. In most cases, when celiac disease tests are used to
monitor progress, rising levels of autoantibodies indicate some form of
noncompliance with a gluten-free diet.
If you have changed your diet, eliminating gluten days or weeks prior to visiting your
doctor, then your celiac disease may not be detectable. In this case your doctor may
do a gluten challenge – have you put gluten back into your diet for several weeks or
months to see if the symptoms return, then do a biopsy to check for villous atrophy
(damage to the villi in your intestine).

Although celiac disease is relatively common, about 1 in 300 people in the U.S. are
thought to be affected, most people who have the disease are not aware of it. This is
partly due to the fact that the symptoms are variable -- they may be mild or even
absent, even when intestinal damage is present on biopsied tissue. Since these
symptoms may also be due to a variety of other conditions a diagnosis of celiac
disease may be missed or delayed -- sometimes for years.
1. What is the difference between celiac disease and an allergy to wheat and
other grains?
Allergies involve hypersensitivity reactions and the creation of specific IgE antibodies
to grains such as wheat and rye. These antibodies may cause some symptoms similar
to those caused by celiac disease but they will only do so for a short time after you eat
the food that you are allergic to. The reaction may be mild or severe but it is limited
and does not cause damage to the lining of your intestine the way that celiac disease
does. If you feel that you may have a wheat or other grain allergy, talk to your doctor.
He can test you for these specific IgE antibodies.
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2. Can you outgrow or desensitize yourself to Celiac disease?
No. Celiac disease does not go away. Once you have been diagnosed with celiac
disease you will need to follow a gluten-free diet for life. If you start eating gluten
again you will again damage the lining of your intestines, it just may take awhile for
the symptoms to come back.
3. Do I need to follow a gluten-free diet if I have been diagnosed with Celiac

disease but have never had any symptoms?
If you do have asymptomatic celiac disease it is recommended that you follow a
gluten-free diet. You will still have damaged villi in your intestines and you may have
malabsorption problems that are causing silent conditions such as osteoporosis. If you
have doubts about the accuracy of your diagnosis you may want to work with your
doctor to verify the findings.
4. Can I have Oats in my diet?

This is somewhat controversial. Some experts feel that oats should be avoided by
those with celiac disease while others believe that most patients can tolerate small
amounts of it. They feel that the proteins found in the oats are not contributing
significantly to the celiac disease. This is something you should discuss with your
doctor and a nutritionist.
5. How do I know what to eat and where can I get help?

Your doctor will have some information for you on celiac disease. You can also visit
the links listed with this article for more information and for organizations that lead to
support groups. Since this is a fairly common (if under diagnosed) disease found
throughout the world, there is help available.
CF Gene Mutation Testing
Also known as: Cystic fibrosis (CF) genotyping, CF DNA analysis, CF gene
mutation panel, Molecular genetic testing
Formal name: Cystic Fibrosis Gene Mutation Panel.
Why get tested?
To detect cystic fibrosis (CF) genetic mutations to establish CF carrier status or to
establish the diagnosis of CF in an individual; the American College of Obstetricians
and Gynecologists recommends targeted gene screening when a couple is
contemplating pregnancy or in early pregnancy
When to get tested?
When a newborn infant has meconium ileus (no stools in the first 24 to 48 hours of
life) or when a person has symptoms of CF (salty sweat, persistent respiratory
infections, wheezing, persistent diarrhea, foul-smelling greasy stools, malnutrition,
vitamin deficiency or male infertility); if a person has a positive sweat chloride or IRT
test or a close relative who has been diagnosed with CF; when a patient is undergoing
genetic counseling for available prenatal screening tests and wants to find out if they
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are a CF carrier; or for prenatal diagnostic purposes when both parents are CF carriers
Sample required?
A blood sample drawn from an infant’s heel; a spot of blood that is put onto filter
paper; or a blood sample drawn from a vein in the arm; buccal swab specimens may
also be used.
The CF gene mutation test identifies mutations in the CFTR gene on chromosome 7.
Each cell in the human body (except sperm and eggs) has 46 chromosomes (23
inherited from the mother and 23 from the father). Genes on these chromosomes form
the body’s blueprint for producing proteins that control body functions. Cystic fibrosis
is caused by a mutation in each CFTR gene located on chromosomes 7. Both copies
(alleles) of this gene must be abnormal to cause CF. If only one copy of the gene pair
is mutated, the individual is a CF carrier. Carriers are not ill; they generally do not
have any CF symptoms, but they can pass their abnormal CF gene copy on to their
children.
To date, more than 1,000 different mutations of the chromosome 7 gene have been
identified, but only a few of the mutations are common. The majority of cystic
fibrosis in the U.S. is caused by a mutation called deltaF508 (?F508).
Recommendations by the American College of Medical Genetics and the American
College of Obstetricians and Gynecologists have led to the adoption of a standard CF
gene mutation panel. It includes 23 of the most common mutations (those with
frequencies greater than 0.1% in the general U.S. population). Some laboratories use
expanded panels of as many as 88 mutations designed to pick up more rare mutations
particular to specific ethnic populations. The vast majority of different CF mutations
are “private” and unique to a single individual or family.
In CF gene mutation testing, the laboratory specifically examines the CFTR gene on
each chromosome 7 for the 23 mutations. If the initial panel of 23 mutations
demonstrates a mutation, additional testing for other mutations may be indicated if the
individual is suspected of having the disease.
How is it used?
CF gene mutation testing can be done to screen the general population or to screen a
targeted (higher risk) subset of the population for carrier status. It can be used to
confirm the diagnosis of CF in a symptomatic patient with an elevated IRT or sweat
chloride test.
It can be used, along with genetic counseling, to establish carrier status and the risk of
an infant with CF as part of a prenatal workup. This may be done by sequential or
couple testing. In a sequential strategy, the mother is tested first. If she is not a carrier,
then any child she had would, at most, be a carrier from the father’s side. Using this
logic, the father is not tested. If she is a carrier, then the father is also tested for carrier
status. With couple testing, both parents are tested at the same time. In either case,
follow-up counseling provides couples with information on what it means to be a
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carrier, and they are informed about the residual risk of being a carrier even if their
panels were negative (e.g. there is still a slight risk that rare mutations might be
present).
CF gene mutation testing can also be used for prenatal diagnosis if both parents are
known to be carriers and if their gene mutations have been previously identified.
DNA from amniocentesis and chorionic villi procedures, although somewhat
invasive, can be used to test the fetus for the known parental mutations.
When is it ordered?
A doctor may order CF gene mutation testing to rule out CF if the patient has
symptoms such as salty sweat, persistent respiratory infections, wheezing, persistent
diarrhea, foul-smelling bulky greasy stools, malnutrition, vitamin deficiency or male
infertility.
CF gene mutation testing may also be ordered to confirm a CF diagnosis following a
positive sweat chloride or IRT test. It may also be ordered as a targeted general
population screen, as part of a genetic counseling workup prior to conceiving, or as an
“at risk” screen, if, for example, the patient has a close relative who has been
diagnosed with CF.
If the CF gene mutation test is positive - it comes back with two identified gene
mutations - then the patient has CF. The test, however, cannot tell how severe or mild
the symptoms may be. Patients with the exact same mutations may have very different
outcomes.
If the test comes back negative for mutations and the patient is asymptomatic, chances
are that they do not have CF and are not a carrier. There is still a slight risk that the
person could be a carrier of a rare mutation not identified with the standard panel.
If the CF gene mutation panel test is negative and the patient is symptomatic, further
mutation testing, a sweat chloride test, and/or other laboratory testing to check organ
function are warranted. The patient may have a more rare form of CF that has not
been identified or may have a lung or pancreatic disease or condition other than cystic
fibrosis.
If the CF gene mutation test comes back with a single identified mutation and the
patient is asymptomatic, then chances are that the person is a CF carrier. This may be
information some individuals want to know before having children. If you are
identified as a carrier, your siblings may also want to verify their carrier status.
Early detection of CF allows patients to be referred to CF centers for specialized care,
individualized treatment plans, and careful monitoring. Beginning treatments such as
taking oral enzyme supplements and fat-soluble vitamins, learning how to clear
mucous out of airways, and learning to recognize respiratory infections can improve a
patient’s quality of life and minimize CF complications.
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1. Will this CF gene mutation test pick up any other genetic diseases?
No, it is only checking for specific CF mutations. Every genetic disease requires
specific DNA testing to identify it (assuming that the gene and mutations causing it
are known).
2. What will my risk of being a carrier be if I am of mixed ethnicity?

Generally, the frequency of CF carriers is highest in Caucasians (1/25), about half that
in Hispanic Caucasians and African Americans, and about half that again in Asians.
Some ethnic groups, such as individuals of Eastern European Jewish descent, may
show CF confined to a very limited number of mutations (e.g., ?508) and elect for
testing using a limited mutation panel. Since the ethnicity of the U.S. population is
becoming increasingly blended, the historical data and statistical risks are changing.
Your risk may be an unknown mix of your inherited ethnic risk. Some families may
also carry the additional risk of specific rare mutations within their family line.
3. What are the advantages of the DNA-based blood test over other CF screening
tests?
Generally, the DNA-based mutation test is much more specific than other screening
tests, which may yield abnormal results for non-CF reasons. Also, these other
screening tests may be restricted as to when they can be applied (for example,
newborns can not be tested with sweat chloride until about two months of age).
Furthermore, DNA-based testing is the only reliable means of identifying carriers of
CF mutations, and it is in this capacity that the testing is being most widely applied.
4. Does the state require or offer newborn screening for CF? Do I need to request
it?
More than a dozen states offer CF testing as part of their newborn screening tests, but
screening requirements vary from state to state, as determined by individual state
public health departments. Most states now have their own mandatory newborn
screening program, but in some states, such as Wyoming and Maryland, the screening
is not mandatory, so you may need to request it.
Chemistry Panels
Chemistry panels are groups of tests that are routinely ordered to determine a person’s
general health status. They help evaluate the body’s electrolyte balance and/or the
status of several major body organs. The tests are performed on a blood sample,
usually drawn from a vein in the arm. Some of the number and type of tests contained
in specific panels, and the names of the panels, have been standardized nationally.
The Comprehensive Metabolic Panel (CMP) usually includes 14 tests and the Basic
Metabolic Panel (BMP) usually contains 8 tests, all of which are found in the CMP.
The Electrolyte Panel, Liver Panel, and Lipid Profile are also types of chemistry
panels. While most laboratories offer the same set of CMP and BMP tests, some of
these other panels may be tailored to meet the needs of the ordering doctor. (If a
laboratory changes the tests in a CMP or BMP, it will usually also change the name of
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the panel to avoid confusion). For a list of the tests included in each of these panels
and when they may be ordered, click on the name of the panel.
Chlamydia
Why get tested?
To screen for or diagnose chlamydia infection
When to get tested?
If you are sexually active, pregnant, have one or more risk factors for developing
chlamydia, or have a cervical infection; depending on your risk factors, may be
annually
Sample required?
A swab of cells or secretion from the infected area.
The test is looking for evidence of infection by the bacterium Chlamydia trachomatis,
the most common bacterial sexually transmitted disease (STD) in the United States.
Generally, your doctor will use a swab to take a cell sample or secretion from the
infected area, such as the cervix, urethra, penis, anus, or throat. It may be possible to
use a urine sample, but only if the particular lab where the sample is sent has a new,
very sensitive molecular technology for this purpose.
How is it used?
The test is used in two ways:
1. to diagnose the cause of symptoms, and

2. to screen sexually active people for the bacterium.
A definitive diagnosis is important because chlamydia can resemble gonorrhea, and

the two infections require different antibiotic treatment.
When is it ordered?
A doctor may order the test if you have symptoms such as vaginal discharge and
abdominal pain (for women) or unusual discharge from the penis or pain on urination
(for men). However, about 75% of infected women and 50% of infected men show no
active symptoms, so the Centers for Disease Control recommend testing in the
following cases:
 All sexually active females under 20 years of age (test at least once a year).
 Women ages 20 and older who have one or more risk factors (test annually).
Risk factors include having new or multiple sex partners, having sex with
someone who has other partners, and not using barrier contraceptives, such as
condoms.
 All women with an infection of the cervix.
 All pregnant women.
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A positive test indicates an active infection that requires treatment with a course of
antibiotics.

Chlamydia is often called “the silent epidemic” because infections are so prevalent yet
many people do not know that they are infected. An estimated 3 million cases occur
annually in the U.S. Chlamydia is especially widespread among young people under
the age of 25. It is four times as common as gonorrhea and six times as common as
herpes.
Chlamydia is easily treated, but if left untreated, it can cause severe reproductive and
other health problems. If you are infected, your sexual partner(s) should also be tested
and treated as well.
People who are infected have a higher risk of developing other sexually transmitted
diseases, including a 3 to 5 times greater risk of acquiring HIV if exposed to it.
The diagnosis of a sexually transmitted disease should not be ruled out if the test is
negative; patients' clinical symptoms and history should also be considered.
1. What are the symptoms of chlamydia?

Most infected people have no symptoms, so they do not seek treatment. For women,
symptoms (if they occur) include bleeding between menstrual periods and after sexual
intercourse, abdominal pain, painful intercourse, and an abnormal vaginal discharge.
For men, symptoms include pus or milky discharge from the penis. Both sexes can
experience painful or frequent urination.
2. What will happen if I don’t get treated?
If left untreated, women may develop pelvic inflammatory disease (PID) from lesions
that start on the cervix but that can spread to the fallopian tubes and ovaries. This can
cause infertility and increase the risk of tubal pregnancy, which is often fatal. Women
who are infected and pregnant may experience heavy bleeding before delivery and
premature rupture of the membranes. Men, too, may become sterile. Both sexes may
develop rectal itching and red, swollen, itchy eyes.
3. How is chlamydia transmitted?

It is generally transmitted through sexual contact (oral, vaginal, or anal) with an
infected partner. An infected mother can spread the disease to her baby during
childbirth. These babies are in danger of developing conjunctivitis (an inflammation
that can threatens eyesight) and pneumonia.
How is it treated?
Chlamydia can be easily treated with a course of antibiotics.
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Chloride
Why get tested?
To determine if there is a problem with your body's electrolyte or acid-base balance
and to monitor treatment
When to get tested?
As part of a standard electrolyte panel or metabolic panel or if your doctor thinks that
you have an electrolyte imbalance.
Chloride is an electrolyte, a negatively charged molecule that works with other
electrolytes, such as potassium, sodium, and total carbon dioxide (CO2), to help
regulate the amount of fluid in the body and maintain the acid-base balance. Chloride
is present in all body fluids but is found in the highest concentration in the blood and
in the fluid outside of the body’s cells. Most of the time, chloride concentrations
mirror those of sodium, increasing and decreasing for the same reasons and in direct
relationship to sodium. When there is an acid-base imbalance, however, blood
chloride levels can change independently of sodium levels as chloride acts as a buffer.
It helps to maintain electrical neutrality at the cellular level by moving into or out of
the cells as needed.
Chloride is taken into the body through food and table salt, which is made up of
sodium and chloride molecules. Most of the chloride is absorbed by the
gastrointestinal tract, and the excess is excreted in urine. The normal blood level
remains steady, with a slight drop after meals (because the stomach produces acid
after eating, using chloride from blood).
How is it used?
Blood chloride testing is frequently ordered, along with other electrolytes, as part of a
regular physical. These tests may also be ordered to evaluate symptoms such as
prolonged vomiting, diarrhea, weakness, and respiratory distress. If an electrolyte
imbalance is detected, the doctor will look for and address the disease, condition, or
medication causing the imbalance and may order electrolyte testing at regular
intervals to monitor the effectiveness of treatment. If an acid-base imbalance is
suspected, the doctor may also order blood gas tests to further evaluate the severity
and cause of the imbalance.
In persons with too much base, urine chloride measurements can tell the doctor
whether the cause is loss of salt (in cases of dehydration, vomiting, or use of diuretics,
where urine chloride would be very low) or an excess of certain hormones such as
cortisol or aldosterone (where urine chloride would be high). Urine tests for chloride
are also used, along with sodium, to monitor persons put on a low-salt diet. If sodium
and chloride levels are high, the doctor knows that the patient is not following the
diet.
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When is it ordered?
The blood chloride test is almost never ordered by itself. It is usually ordered as part
of an electrolyte panel, a basic metabolic panel, or a comprehensive metabolic panel,
which are ordered frequently as part of a routine physical or evaluation of a patient
with an acute or chronic illness. Some of these tests may be ordered at regular
intervals when a patient has a disease or condition or is taking a medication that can
cause an electrolyte imbalance. Electrolyte panels or basic metabolic panels are
commonly used to monitor treatment of certain problems, including high blood
pressure, heart failure, and liver and kidney disease.
A urine chloride test may be performed along with a blood or urine sodium when
evaluating the cause of low or high blood chloride levels. The doctor will look at
whether the chloride measurement changes mirror those of the sodium. This helps the
doctor determine if there is also an acid-base imbalance and helps to guide treatment.

Increased levels of chloride (called hyperchloremia) usually indicate dehydration, but
can also occur with any other problem that causes high blood sodium.
Hyperchloremia also occurs when too much base is lost from the body (producing
metabolic acidosis), or when a person hyperventilates (causing respiratory alkalosis).
Decreased levels of chloride (called hypochloremia) occur with any disorder that
causes low blood sodium. Hypochloremia also occurs with prolonged vomiting or
gastric suction, chronic diarrhea, emphysema, or other chronic lung disease (causing
respiratory acidosis), and with loss of acid from the body (called metabolic alkalosis).

Drugs that affect sodium blood levels will also cause changes in chloride. In addition,
swallowing large amounts of baking soda or substantially more than the
recommended dosage of antacids can also cause low chloride.
Some instructions for routine testing advise patients to stop all food and fluids for
eight hours before the test to prevent the normal drop in chloride value after eating.
CK
Why get tested?

To determine if you have had a heart attack or if other muscles in your body have
been damaged
When to get tested?
If you have signs and symptoms of a heart attack (e.g., chest pain); if you have muscle
pain or muscular weakness.
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Creatine kinase is an enzyme found in the heart, brain, skeletal muscle, and other
tissues. Enzymes are proteins that help cells to perform their normal functions. In
muscle and heart cells, most of this energy is used when muscles contract.
There are three different forms of CK in your body; they are referred to as
isoenzymes:
 CK-MM (found in your skeletal muscles and heart),

 CK-MB (found mostly in your heart),
 CK-BB (found mostly in your brain).
The small amount of CK that is normally in the blood comes mainly from your
muscles. The CK in your brain almost never gets into the blood.
How is it used?
Blood levels of CK rise when muscle or heart cells are injured. Your doctor may test
for CK if you have chest pain or other signs and symptoms of a heart attack. In the
first 4 to 6 hours after a heart attack, the concentration of CK in blood begins to rise.
It reaches its highest level in 18 to 24 hours and returns to normal within 2 to 3 days.
The amount of CK in blood also rises when skeletal muscles are damaged.
When is it ordered?
CK is ordered in patients who may have had a heart attack. The test will usually be
ordered when a patient arrives at the emergency room and again at intervals of 4-6
hours for a total of three tests. If you have muscle pain or weakness, your doctor may
also order CK to see if other muscles have been damaged.
A high CK, or one that goes up from the first to the second or later samples, generally
indicates that there has been some damage to the heart or other muscles. It can also
indicate that your muscles have experienced heavy use. If your doctor suspects a heart
attack and your CK is high, she will usually order a more specific test (troponin or
CK-MB) to see if your heart is damaged.

People who have greater muscle mass have higher CK levels than those who don’t,
and African-Americans may have higher CK levels than other ethnic groups. Very
heavy exercise (such as in weight lifting, contact sports, or long exercise sessions) can
also increase CK.
Other forms of muscle damage, such as from a fall, a car accident, surgery, or a shot,
can also increase CK. Several drugs can increase CK levels. Drinking too much
alcohol slightly increases CK. Rarely, some drugs, particularly cholesterol-lowering
drugs (statins), can damage muscle and increase CK. If you are taking one of these
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drugs, let your doctor know if you experience any muscle pain or weakness. Early
pregnancy can decrease CK levels.
1. What does heart attack mean?

Heart attack means that some of the muscle in your heart has died. A medical term for
this is myocardial infarction (MI). Most commonly, a heart attack starts with a kind of
heavy pressure or pain in the chest, often extending into the neck or left arm. You
may have trouble catching your breath, or you may feel weak and break into a cold
sweat.
A heart attack usually occurs because one of the blood vessels (called coronary
arteries) that bring blood to your heart muscle is blocked. This usually happens when
a blood clot forms in a blood vessel that is already partially blocked. The partial
blockage, which happens gradually over many years, is usually caused by too much
fat layered in the wall of the blood vessel (this is often called hardening of the
arteries—the medical term for this is atherosclerosis).
2. If I have chest pain, does that mean I am having a heart attack?

Many other problems can cause chest pain, and it is not always possible to tell just
from the type of chest pain whether or not you are having a heart attack. Many people
have chest pain from straining the muscles in their chest, and chest pain can occur
with some lung problems. Chest pain can be a warning sign of hardening of the
arteries of the heart (coronary artery disease or CAD). Chest pain that occurs during
exercise, hard work, or at times of stress, lasts for a few minutes and goes away with
rest is called angina. If the pain lasts longer than just a few minutes, especially if it
occurs when you are resting, seek immediate medical attention.
3. What are the other heart attack tests?

Doctors often use more than one test to determine if a person who has chest pain is
having a heart attack. Troponin is generally considered the most accurate test, and
CK-MB (the heart isoenzyme of CK) is also highly accurate in detecting damage to
the heart, even when there is no other evidence of a heart attack. Myoglobin and
creatine kinase almost always rise in patients with a heart attack, but they are less
specific – other conditions can also produce an increase in these two tests.
4. What if I’m not sure I’m having a heart attack?
If you have prolonged chest pain, especially if it does not go away with rest— or if
you have been told you have angina, and the drugs you were prescribed do not ease
the pain—seek immediate medical attention. Many people who have had a heart
attack die without ever having tried to call an ambulance or get to an emergency
room.
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CK-MB
Why get tested?

To determine if you have had a heart attack and whether certain clot-dissolving drugs
are working
When to get tested?
If you have chest pain or other signs and symptoms of a heart attack

CK–MB is one of three separate forms of the enzyme creatine kinase (CK). CK–MB
is found mostly in heart muscle. It rises when there is damage to heart muscle cells.
How is it used?
CK–MB levels, along with total CK, are tested in persons who have chest pain to
diagnose whether they have had a heart attack. Since a high total CK could indicate
damage to either the heart or other muscles, CK–MB helps to distinguish between
these two sources. If your doctor thinks you have had a heart attack and gives you a
“clot-dissolving” drug, CK–MB can help your doctor tell if the drug worked. When
the clot dissolves, CK–MB tends to rise and fall faster. By measuring CK–MB in
blood several times, your doctor can usually tell whether the drug has been effective.
When is it ordered?
CK-MB is usually ordered, along with total CK, in persons with chest pain to
determine whether the pain is due to a heart attack. It may also be ordered in a person
with a high CK to determine whether damage is to the heart or other muscles.
If the value of CK-MB is elevated and the ratio of CK–MB to total CK (relative
index) is more than 2.5–3, it is likely that the heart was damaged. A high CK with a
relative index below this value suggests that skeletal muscles were damaged.

Severe injury to skeletal muscle can be significant enough to raise CK–MB levels
above normal, but such injury doesn’t usually cause a high relative index. If your
doctor suspects injury to both heart muscle and skeletal muscle, troponin is a more
accurate test for identifying a heart attack.
Sometimes persons who are having trouble breathing have to use their chest muscles.
Chest muscles have more CK–MB than other muscles, which would raise the amount
of CK–MB in the blood.
Persons whose kidneys have failed can also have high CK–MB levels without having
had a heart attack. Rarely, chronic muscle disease, low thyroid hormone levels, and
alcohol abuse can increase CK–MB, producing changes similar to those seen in a
heart attack.
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this is myocardial infarction (MI). Most commonly, a heart attack starts with a kind of
sweat.

arteries of the heart (coronary artery disease or CAD). Chest pain that occurs during
exercise, hard work, or at times of stress, lasts for a few minutes and goes away with
rest is called angina. If the pain lasts longer than just a few minutes, especially if it
occurs when you are resting, seek immediate medical attention.

Doctors may use more than one test to determine if a person who has chest pain is
having a heart attack. Troponin is generally considered the most accurate test, and
CK-MB is also highly accurate in detecting damage to the heart, even when there is
no other evidence of a heart attack. Myoglobin and creatine kinase almost always rise
in patients with a heart attack, but they are less specific – other conditions can also
produce an increase in these two tests.
the pain—seek immediate medical attention. Many people who have had a heart
attack die without ever having tried to call an ambulance or get to an emergency
room.
CMV
Why get tested?
If your doctor suspects you presently have or had in the past a CMV infection, or in a
clinical situation where it is important to know your CMV status, such as before
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surgery or organ transplant
When to get tested?
If a young adult, a pregnant female, or an immune-compromised patient has flu-like
symptoms that suggest a CMV infection; if a newborn has multiple congenital
anomalies, unexplained jaundice or anemia, and/or if an infant has seizures or
developmental problems that may be due to CMV
Sample required?
A blood sample is drawn from a vein in your arm for CMV antibody testing. To
detect the virus itself, the sample may be blood, urine, or sputum, amniotic fluid,
cerebrospinal fluid, duodenal (from the intestines) fluid, or other body tissue.
Cytomegalovirus (CMV) testing is used to determine whether someone is currently,
or has recently been, infected with CMV. Testing involves either a measurement of
CMV antibodies (specific proteins created by the body’s immune system in response
to the virus) or the detection of the virus itself, through culturing and growing the
virus or by amplifying the genetic material from the virus itself.
In the United States, as many as 50% to 85% of adults have been infected with CMV.
Most people are infected as children or young adults and do not experience any
significant symptoms or health problems. During an active infection, CMV is found in
many body fluids, including saliva, urine, blood, breast milk, semen, cervical
secretions, and cerebrospinal fluid (CSF). It is easily transmitted to others through
close physical contact or by contact with infected objects, such as diapers or toys.
After the initial primary infection has resolved, CMV becomes dormant like other
members of the herpes family. Cytomegalovirus remains in a patient for the rest of
their life without causing any symptoms, unless the virus reactivates when a patient’s
immune system is compromised.
CMV causes problems in three areas:
 Primary CMV infection may cause a flu-like or mononucleosis-type illness in

young adults and some others. This condition, which causes symptoms such as
extreme fatigue, fever, chills, body aches and/or headaches, usually resolves within a
few weeks.
 Primary CMV infection may cause serious physical and developmental problems in
infants whose mothers are first infected during pregnancy and then pass the infection
to them across the placental barrier. Most fetuses (about 90%) that are infected appear
perfectly normal at birth but begin to develop problems such as hearing or vision
problems, pneumonia, seizures, and/or delayed mental development a few months
later. A few babies may be stillborn, while others may have symptoms at birth such as
jaundice, anemia, an enlarged spleen or liver, and a small head. Some of these signs
and symptoms will resolve with time but others may persist.
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 CMV may cause serious illness and death in those with compromised immune
systems. This includes those with HIV/AIDS, those who have had organ or bone
marrow transplants, and those undergoing chemotherapy treatment for cancer.
Patients with compromised immune systems who become infected for the first time
may experience more severe symptoms and the CMV infection may remain active.
Those who have been exposed to CMV previously may have their infection
reactivated acutely and/or intermittently. It may affect their eyes (retinitis – which can
lead to blindness), gastrointestinal tract (causing bloody diarrhea and abdominal pain),
lungs (causing pneumonia with a non-productive cough and shortness of breath), and
brain (encephalitis). There also can be spleen and liver involvement, and those who
have had organ or bone marrow transplants may experience some degree of rejection.
Active CMV also further depresses the immune system, allowing other secondary
infections, such as fungal infections, to occur.

The sample required varies; it depends on the testing method used (antibody or viral)
and on the health status of the patient. Antibody testing requires a blood sample,
obtained by inserting a needle into a vein in the arm. Viral detection may be done on a
variety of samples, including urine, blood, or sputum (phlegm from the lungs). Some
samples may require a special procedure performed by a doctor; for instance,
amniotic fluid (surrounding and supporting the fetus), duodenal fluid (from the
intestines), CSF (cerebrospinal fluid), and a variety of body tissue (biopsy) samples.
How is it used?
There are several methods of CMV testing:
Antibody testing
There are two types of CMV antibodies found in the blood: IgM and IgG. IgM
antibodies are the first to be produced by the body in response to a CMV infection.
They are present in most individuals within a week or two after the initial exposure.
IgM antibody production rises for a short time period and then tapers off. Eventually,
after several months, the level of CMV IgM antibody usually falls below detectible
levels. Sometimes, additional IgM is produced when latent CMV is reactivated. IgG
antibodies are produced by the body several weeks after the initial CMV infection to
provide long-term protection. Levels of IgG rise during the active infection, then
stabilize as the CMV infection resolves and the virus becomes inactive. Once a person
has been exposed to CMV, they will have some measurable amount of CMV IgG
antibody in their blood for the rest of their life. CMV IgG antibody testing can be
used, along with IgM testing, to help confirm the presence of a recent or previous
CMV infection.
CMV antibody testing may be performed prior to pregnancy, prior to organ or bone
marrow transplantation, and as a baseline in a person diagnosed with HIV/AIDS to
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determine if these patients have ever been infected by CMV. Since CMV infection is
widespread and causes few problems to those with intact immune systems, general
population screening is rarely done.
IgM and IgG antibody testing and viral CMV detection may be used to help diagnose
primary CMV infection in young adults, pregnant women, and some immune-
compromised patients with flu- or mononucleosis-like symptoms. Both antibody tests
may be ordered together to distinguish between primary, latent, and reactivated CMV
in symptomatic patients.
Viral detection
Viral detection involves finding CMV in a blood, fluid, or tissue sample. This can be
done either by culturing (growing) the virus in a supportive environment or by
identifying and measuring the virus’s genetic material.
CMV culturing is the classic method of virus detection. It involves inoculating a

culture/tube of human cells with the patient’s sample and incubating the culture in a
supportive environment. Positive cultures can often be detected in as little as 1 to 2
days, but negatives must be held for 3 weeks to confirm the absence of CMV. This is
because the virus may be present in very small numbers in the original sample and/or
the CMV strain may be a slow growing one.
Other methods may detect and measure the amount of viral DNA (genetic material) in
a patient’s sample. While these tests can specifically identify the presence of CMV,
there must be a certain amount (number of copies) of the virus present in the sample
in order to be able to detect it. Testing can be qualitative (presence or absence of
CMV) or quantitative (viral load – measures the amount of virus present).
The choice of tests and body samples collected depends on the age of the patient, their
general health status and symptoms, and on the doctor’s clinical findings and
suspicions of organ involvement. For instance, newborn’s urine may be cultured to
detect CMV virus, while a pregnant woman may have IgG and IgM blood testing to
identify the presence of antibodies and distinguish between a current primary
infection and a previous infection. A second IgG test on a new blood sample (called a
convalescent sample) may be ordered 2 to 3 weeks after initial testing is performed to
determine whether antibody levels are rising, indicating an active CMV infection.
Immune-compromised patients with active CMV may be monitored using a variety of

CMV tests. Often doctors want a quantifiable viral test to be able to track the amount
of virus present (viral load). They can use a quantitative test to monitor the patient’s
response to antiviral therapy.
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When is it ordered?
CMV tests may be ordered, along with tests for influenza, mononucleosis (mono), and
EBV (Epstein Barr virus), if you are a young adult, a pregnant female, or an immune-
compromised patient and have flu- or mononucleosis-type symptoms such as fatigue,
swollen lymph nodes, and fever. They may be performed if your doctor suspects that
you may have an active primary CMV infection or a CMV reactivation.
CMV tests may be ordered if you are immune-compromised and have inflammation
of the lungs, eyes, liver, spleen, and/or gastrointestinal tract and if your doctor
suspects that you may have active CMV. One or more CMV tests may be ordered if
your doctor is monitoring the effectiveness of antiviral therapy.
CMV testing may be done on a newborn with jaundice, anemia, an enlarged spleen
and/or liver, and a small head; or on an infant with hearing and vision problems,
pneumonia, seizures, and/or signs of delayed mental development.
If you are a candidate for an organ or bone marrow transplant, CMV IgG and IgM
antibody testing may be ordered as a screening test to determine if you have been
exposed to CMV in the past.
Care must be taken when interpreting the results of CMV testing. The doctor
evaluates the results in conjunction with clinical findings. It can sometimes be
difficult to distinguish between a latent and active CMV infection. This is due to
several reasons, including:
 A healthy patient who has been infected with CMV at one time will continue to
harbor the virus. The CMV can reactivate intermittently, often sub-clinically
(shedding small amounts of virus into body fluids but not causing symptoms).
 An infant and immune-compromised person may not have a strong antibody
response to the CMV infection – their IgM and IgG levels may be lower than
expected even though they have an active case of CMV.
 The virus may not be present in sufficient number in the particular fluid or tissue
tested to able to be detected.
Antibody testing
If both CMV IgG and IgM are present in a symptomatic patient, then it is likely that
he or she has either recently been exposed to CMV for the first time or that a previous
CMV has been reactivated. This can be confirmed by measuring IgG levels again 2 or
3 weeks later. A high level of IgG is not as important as a rising level. If there is a 4-
fold increase in IgG between the first and second sample, then the patient has an
active CMV infection (primary or reactivated).
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If only IgM is present, then the patient may have very recently been infected. If a
newborn has IgM antibodies, then they have a congenital CMV infection (infected
before birth). If a patient is symptomatic but has low or undetectable levels of IgG
and/or IgM, it may mean that they either have a condition other than CMV or that
their immune system is not responding normally – not producing an adequate amount
of antibody even if CMV is present.
Viral detection
If the patient is symptomatic and the culture is positive for cytomegalovirus, then the
patient likely has an active CMV infection. If the culture is negative, then the patient’s
symptoms may be due to another cause or the CMV virus is present in the body but
not in this sample.
If a test for CMV DNA is positive, then CMV is present. High levels of viral DNA
tend to indicate an active infection. Low levels indicate a CMV infection but may not
indicate a symptomatic condition. Decreasing concentrations (diminishing viral loads)
reflect response to antiviral treatment. Levels that do not drop in response to antiviral
treatment may reflect a resistance to the therapy being used. Negative results do not
rule out CMV infection – the virus may be present in very low numbers or may not be
present in the body sample tested.

Most AIDS patients are seropositive for CMV (have CMV-specific IgG antibodies)
even before HIV infection is diagnosed.
Some immune-compromised patients may have more than one strain of CMV at the
same time. The strains can be differentiated, if necessary, with DNA testing.
1. How can I tell if my CMV has reactivated?
If you are a reasonably healthy person, you will probably not have a symptomatic
reactivation or may have mild flu-like symptoms. If you are immune-compromised,
you may have more serious symptoms associated with your lungs, gastrointestinal
tract, or eyes. In this case, it is important to talk to your doctor about your health
concerns.
Is there any way to prevent getting CMV?

Careful hygiene can help prevent transmission of the virus. But, since CMV is very
common, is present in most body fluids, and is passed through close contact, most
people are infected when they are babies. It has been estimated that as many as 70%
of children in daycare have been exposed to CMV.
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CO2
Also known as: Total C02, TCO2, Bicarbonate

Formal name: Carbon Dioxide Content
Why get tested?

As part of an electrolyte panel to screen for an electrolyte or acid-base imbalance or to
monitor a known imbalance
When to get tested?
During a routine physical or as recommended by your doctor if you are experiencing
symptoms such as weakness, confusion, prolonged vomiting, or respiratory distress
that could indicate an electrolyte or acid-base imbalance
The CO2 test measures the total amount of carbon dioxide in the blood, mostly in the
form of bicarbonate (HCO3-). Bicarbonate is a negatively charged electrolyte that is
excreted and reabsorbed by the kidneys. It is used by the body to help maintain the
body’s acid-base balance (pH) and secondarily to work with sodium, potassium, and
chloride to maintain electrical neutrality at the cellular level. Since the CO2 test
measures all three forms of carbon dioxide in the blood (bicarbonate, H2CO3 [also
known as carbonic acid], and dissolved CO2) as a total CO2, it will give a rough
estimate but not an exact determination of the bicarbonate concentration.
How is it used?
The CO2 test is almost never ordered by itself. It is usually ordered along with
sodium, potassium, and chloride as part of an electrolyte panel. The electrolyte panel
is used to detect, evaluate, and monitor electrolyte imbalances. It may be ordered as
part of a routine exam or to help evaluate a chronic or acute illness. It may be ordered
at intervals to help monitor conditions, such as kidney disease and hypertension, and
to monitor the effectiveness of treatment for known imbalances.
When an acid-base imbalance is identified, the CO2 test (as part of the electrolyte
panel) and blood gases may be ordered to evaluate the severity of the imbalance,
determine whether it is primarily respiratory (due to an imbalance between the
amount of oxygen coming in and CO2 being released) or metabolic (due to increased
or decreased amounts of bicarbonate in the blood) in nature, and monitor its treatment
until the acid-base balance is restored.
When is it ordered?
Carbon dioxide testing may be ordered, usually as part of an electrolyte panel when:
 you are having a routine blood screen;
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 your doctor suspects that you may be retaining water or are dehydrated,
upsetting your electrolyte balance;
 your doctor wants to evaluate your body’s acid-base balance (pH);
 your doctor wants to monitor a condition or treatment that might cause an
electrolyte imbalance.

When CO2 levels are higher or lower than normal, it suggests that your body is
having trouble maintaining its acid-base balance or that you have upset your
electrolyte balance, perhaps by losing or retaining fluid. Both of these imbalances
may be due to a wide range of dysfunctions.

Some drugs may increase blood carbon dioxide levels including: fludrocortisone,
barbiturates, bicarbonates, hydrocortisone, loop diuretics, and steroids.
Drugs that may decrease blood carbon dioxide levels include methicillin,
nitrofurantoin, tetracycline, thiazide diuretics, and triamterene.
. If my doctor has done a CO2 test, why does he want to test my blood gases?
Blood gas tests, in which blood is drawn from an artery instead of a vein, can give
your doctor a better look at your pH (acid/base level). They can tell your doctor
whether your lungs are working properly to keep PO2 and PCO2 at healthy levels.
Coagulation Factors
Also known as: Blood clotting factors, clotting factors, or by the individual factor
number (Factor I, Factor II, etc.) or name (Fibrinogen, Prothrombin, etc.)
Why get tested?
To determine whether one or more of your coagulation factors is missing, deficient, or
dysfunctional.
When to get tested?
When you have unexplained or prolonged bleeding, an abnormal Prothrombin Time
(PT) or activated Partial Thromboplastin Time (aPTT) test, or have a relative with a
hereditary coagulation factor deficiency. Sometimes when your doctor wants to
monitor the severity of a factor deficiency and the effectiveness of treatment.
Coagulation factors are proteins that are essential for blood clot formation. Produced
by the liver, the coagulation factors are released into the bloodstream when an injury
occurs and are activated in a step by step process called the coagulation cascade. This
cascade has two branches: if the damage is to tissue the body responds by activating
the extrinsic pathway. If the injury is to a blood vessel wall, the intrinsic pathway is
activated. Each of these pathways utilizes different coagulation factors but both come
together to complete the clotting process in the common pathway. Normally, by the
end of the common pathway soluble fibrinogen (factor I) has been changed into
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insoluble fibrin threads. These threads have been crosslinked to make a fibrin net and
stabilized at the injury site. They adhere there, along with aggregated cell fragments
called platelets, to form a stable blood clot. This barrier prevents additional blood loss
and remains in place until the area has healed. When the clot is no longer needed
other factors are activated to dissolve and remove it.
About 12 of the 20 different factors involved in the coagulation cascade are vital to
normal blood clotting. These 12 have individual names (see table) but are often
referred to by their number, for instance Factor VIII (Factor 8). When one or more of
these factors are missing, produced in too small of a quantity, or are not functioning
correctly they can cause excessive bleeding and lead to bleeding disorders.
Deficiencies in coagulation factors may be acquired or inherited, mild or severe,

permanent or temporary. Those that are inherited are rare and tend to involve only one
factor, which may be absent, deficient, or dysfunctional. Hemophilia A and B are the
most common examples of inherited disorders. They are X-linked deficiencies
(located on an X chromosome) of Factors VIII and IX that occur almost exclusively in
men (women are usually asymptomatic carriers). Other inherited factor deficiencies,
not associated with the X chromosome, are found equally in both men and women.
The severity of symptoms experienced by a patient with an inherited factor deficiency

depends on which factor is involved, how much of it is available and whether or not it
is functioning normally. Symptoms may vary from episode to episode, from a minor
prolonged nosebleed to severe recurrent bleeding into areas such as the joints. While a
patient may not have trouble with a small puncture or cut, a surgery, dental procedure,
or trauma could put them into a bleeding crisis. Those with severe factor deficiencies
may have their first bleeding episode very early, for example a male infant with a
Factor VIII deficiency may bleed excessively after circumcision. On the other hand,
patients with mild bleeding disorders may experience few symptoms and may
discover their deficiency as an adult -- after a surgical procedure or trauma, or during
a screening that includes a PT or aPTT test.
Acquired deficiencies may be due to chronic disease, such as liver disease or cancer;
to an acute condition such as disseminated intravascular coagulation (DIC, which uses
up clotting factors at a rapid rate); or to a deficiency in Vitamin K (the production of
factors II, VII, IX, and X requires Vitamin K). They may also be due to blood
thinning drugs such as aspirin, heparin or warfarin. Acquired conditions may involve
multiple factor deficiencies that must be identified and addressed.

Typically, a blood sample is drawn from a vein in the arm. As an alternative,
particularly in pediatric care, the blood sample is drawn from the fingertip.
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How is it used?
Factor testing is usually done as a follow-up to abnormal Prothrombin Time (PT) and
activated Partial Thromboplastin Time (aPTT) testing. These tests are used as
screening tools to determine whether or not someone’s clotting cascade is functioning
normally. The PT is associated with the extrinsic pathway, the aPTT with the intrinsic
pathway. If one or both are abnormal, the suspected coagulation factor deficiencies
they suggest may then be tested for individually. Functional (activity) testing and
quantity (antigen) testing can tell your doctor which factor(s) are affected and how
severely. Antigen testing is not available for all factors.
Additional testing may be done, especially when multiple deficiencies are involved, to
look for underlying health problems that may be causing an acquired deficiency. If an
inherited deficiency is suspected, other family members may also be tested to help
confirm the patient’s diagnosis, and to establish whether they may be carriers of the
condition or have the deficiency themselves (in an asymptomatic or less severe form).
Sometimes factor testing may be done on a patient with a known deficiency to

monitor the factor deficiency, and to evaluate the effectiveness of treatment. If the
patient has an acquired condition, factors may sometimes be monitored to see if they
have worsened (with a progressive disease), or gotten better because of treatment of
the underlying condition.
When is it ordered?
Coagulation factor tests may be ordered when someone has a prolonged PT or aPTT
and/or when they are experiencing excessive bleeding or bruising. Patients may be
tested when they have a suspected acquired condition that is causing bleeding, such as
DIC, pregnancy-related eclampsia, liver disease, or a Vitamin K deficiency.
Factor testing may be done if an inherited factor deficiency is suspected, especially

when bleeding episodes begin early in life or when a close relative has an inherited
factor deficiency.
Both functional factor testing (activity) and quantity testing (antigen) may be done to
evaluate the severity of the deficiency. These may be monitored if the patient is
undergoing treatment for a severe bleeding episode or is planning a surgery or dental
procedure.
Low concentrations and/or activity of one or more coagulation factor usually means
impaired clotting ability. Each coagulation factor must be present in sufficient
quantity in order for normal clotting to occur, but the level required is different for
each factor. Results are frequently reported out as a percentage of an established
normal (considered to be 100% for that factor), for instance a Factor VIII that is 60%
of normal.
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Initial factor testing screening is accomplished by evaluating the results of a PT
(extrinsic pathway) and aPTT (intrinsic pathway) test:
 If the aPTT is abnormal and the PT is normal, you may have deficiencies of
factors VIII, IX, XI, or XII.
 If the aPTT is normal and the PT is prolonged, you may have a deficiency of
factors I, II, V, VII, or X.
 If both PT and aPTT are abnormal, you may have deficiencies in the common
pathway or to multiple factor deficiencies.
Elevated levels of several factors are seen in situations of acute illness, stress, or
inflammation. In general, they are not thought to be associated with particular disease
states although in some cases (such as elevated fibrinogen) they may raise the risk of
developing thromboses (inappropriate blood clots).
Normal coagulation factor concentrations and activity usually mean normal clotting
function. If the quantity of a factor is adequate but the activity level is low, it may
mean that the factor is dysfunctional. If the factor activity is normal, but the quantity
is low, it may mean that there is something interfering with its production. Normal
activity but low quantity may also mean that something is inhibiting the factor (such
as an antibody against the factor), or that it has been temporarily used up by the body.
If more than one clotting factor is decreased, it is usually due to an acquired

condition. Factors may be decreased because of: DIC, liver disease, uremia, some
cancers, bone marrow disorders, exposure to snake venom, a Vitamin K deficiency,
anticoagulation therapy, an accidental ingestion of the anticoagulant warfarin, or due
to blood transfusions (stored units of blood lose some of their clotting factors).
For both inherited and acquired factor deficiencies, the missing factor(s) – once
identified - can be replaced as needed. This may be done with a transfusion of fresh or
fresh frozen “normal” plasma which contains all of the missing factors, with a
concentrated cryoprecipitate, with a supplemental factor (a few such as Factor VIII
are available commercially) or with a drug treatment such as desmopressin acetate
(DDAVP) that stimulates the body to make more of Factor VIII. These treatments can
be used during a bleeding episode and as a temporary preventative, to provide
protection against excessive bleeding during an upcoming surgery or dental
procedure.
When testing coagulation factors, proper sample collection and timely processing are
essential. Some of the factors are labile, meaning their concentration will decrease in
the blood sample over time.
1. What is von Willebrand factor?
Von Willebrand factor is related to Factor VIII. It is responsible for helping platelets
stick to the injured blood vessel wall and to each other (aggregation – essential to
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normal blood clot formation). A deficiency in von Willebrand factor can cause von
Willebrand’s disease, a relatively common inherited bleeding disorder, and it can
cause a secondary decrease in Factor VIII concentrations. While von Willebrand
factor may be ordered along with coagulation factors if an inherited factor deficiency
is suspected, it is usually considered separately because it is associated with platelets
and not part of the classic coagulation cascade.
2. Why are some inherited bleeding disorders more severe than others?
The severity of bleeding depends on the individual – how low is their factor
concentration and how normally does it function - as well as which factor is deficient.
Those who have a missing factor or one with very low activity will have more severe
versions of the disease. Also, in general, those with one good gene copy and one
altered gene copy (heterozygous) will tend to have less severe bleeding than those
with two altered copies (homozygous).
If a person has a deficiency of Factor XII, they may be asymptomatic. This rare factor
deficiency causes abnormal blood sample test results but has not been associated with
excessive bleeding.
Complement Levels
Also known as: C3, C4, Total Complement (also known as CH50 or CH100), Total
Hemolytic Complement Activity
Formal name: Complement Activity, and Complement Proteins, C1 – C9
Why get tested?
To determine whether deficiencies or abnormalities in the proteins that are part of the
complement system are contributing to increased infections or increased autoimmune
activity. To monitor activity of autoimmune diseases.
When to get tested?
When you have unexplained inflammation or edema, recurrent bacterial infections, or
symptoms related to an autoimmune disorder. To help monitor an acute or chronic
condition that affects the complement system.
The complement system is a set of circulating blood proteins that act as mediators of
inflammatory response – especially in the destruction of foreign substances like
bacteria and viruses. It is part of the body’s innate immune system. It does not require
advance exposure to an invading microorganism or substance (like an antibody does)
and it does not maintain a memory of previous encounters. The complement system
has evolved to recognize antigen antibody complexes (immune complexes) as well as
certain structures and polysaccharides (complex carbohydrates) found on the outside
membranes of microorganisms and other foreign cells.
Once complement activation has been initiated, the complement proteins are
sequentially activated down one of two different pathways, the classical or the
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alternative, ending in the formation of the membrane attack complex (MAC).
Complement activation causes several things to happen:
 It kills a number of microorganisms through the action of the Membrane

Attack Complex (MAC). This is formed of activated complement proteins C5
to C9 and acts by creating a lesion (hole) in the microbial membrane, causing
lysis (rupture) of the cell.
 It increases the permeability of blood vessels, allowing white blood cells to
move out of the bloodstream and into the tissues.
 It attracts white blood cells to the site of the trouble.
 It stimulates phagocytosis (a process in which microorganisms are engulfed by
macrophages and neutrophils and killed).
 It also increases the solubility of the immune complexes and helps to clear
them out of the serum.
One important component of the complement system, however, is the membrane

attack complex (MAC). A MAC is assembled on the surface of each microorganism
or abnormal cell that has been targeted for destruction (lysis). Each activated
complement protein adds to a structure that, when finished, creates a hole (lesion) in
the cell membrane and lyses the cell (destroys it by letting the contents out, like
piercing a water filled balloon).
Complement and the regulation of its activity is an important part of the immune
system. While antibodies need time to be generated, complement is immediately
available and helps alert other parts of the immune system. Inherited or acquired
deficiencies in one or more of the complement components may adversely affect the
integrity and function of the immune system.
C3 and C4 are the most frequently measured complement components. Total

complement activity (CH50, or CH100) will be measured if your doctor suspects a
deficiency that is not measured by C3 or C4. CH50 measures the function of the
complete classical complement pathway, C1 – C9. If this measurement is outside the
normal range, then each of the 9 different complement levels can be measured
individually to look for hereditary or acquired deficiencies.
How is it used?
C3 and C4 are used to determine whether deficiencies or abnormalities in the
complement system are causing, or contributing to, a patient’s disease or condition.
Total complement activity (CH50, or CH100) may be ordered to look at the integrity
of the entire classical complement pathway. Other complement components are
ordered as needed to look for hereditary deficiencies.
Complement testing may be ordered to help diagnose the cause of recurrent microbial
infections, angioedema (which causes edema, swelling, and hives), or inflammation.
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It may be used to help diagnose and to monitor the activity of acute or chronic
autoimmune diseases such as systemic lupus erythematosus (SLE). Since complement
helps clear immune complexes from the blood it may be tested and monitored with
immune complex related diseases and conditions such as: glomerulonephritis, serum
sickness, rheumatoid arthritis, and vasculitis.
When is it ordered?
Complement testing may be ordered when you have unexplained inflammation or
edema, or symptoms of an autoimmune disorder such as SLE. It may also be ordered
when your doctor suspects that you may have an immune complex-related condition
and he wants to check the status of your complement system.
C3 and C4 levels are the most frequently ordered but others, such as C1, may be
ordered when other deficiencies are suspected. Individual complement components
may be ordered when the total complement activity is abnormal to help determine
which of the components are deficient or abnormal.
When an acute or chronic condition has been diagnosed, complement testing may be
used to help give a rough idea of the severity of the condition (with the assumption
that the severity is linked to the decrease in complement levels). Complement testing
may also be ordered occasionally when your doctor wants to monitor the current
activity of your condition.
Complement levels may be decreased due to a hereditary deficiency (relatively rare)
or due to increased consumption. Hereditary deficiency in one of the complement
proteins will usually lead to a high frequency of recurrent microbial infections or
autoimmune disease. If the deficiency is due to an underlying acute or chronic
condition, complement levels will usually return to normal if the underlying condition
can be resolved.
Decreased complement levels may be seen with:
 Recurrent microbial infections (usually bacterial)

 Autoimmune diseases, including SLE and vasculitis
 Hereditary angiodema
 Acquired angiodema
 Various types of kidney disease, including: glomerulonephritis, lupus
nephritis, membranous nephritis, IgA nephropathy
 Malnutrition
 Septicemia
 Serum sickness (immune complex disease)
Complement protein levels are usually increased, along with other unrelated proteins
called acute phase proteins, during acute or chronic inflammation. These all usually
return to normal when the underlying condition is resolved. However complement
proteins are rarely measured in these conditions, compared to the widely ordered C-
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reactive protein (CRP) and the relevance of their measurement in these situations is
not reviewed here.
Increased and decreased complement levels will not tell your doctor what is wrong,
but they will give him an indication that the immune system is involved with your
condition. Complement levels can be increased with inflammation, rising before other
markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP).
1. What are the other parts of the innate immune system?
It includes:
 The phagocytic system (macrophages, neutrophils, and monocytes) - whose

function is to ingest and digest invading microorganisms
 Inflammatory mediators produced by various cells, including basophils, mast
cells, and eosinophils
 Natural killer (NK) cells (which kill some tumors cells, microorganisms, and
cells that have been infected by viruses)
 Acute phase reactants and Cytokines (a group of soluble proteins that can
cause changes in the growth of many cells, including the white blood cells that
produce them).
Comprehensive Metabolic Panel

Also known as: Chem 12, SMA 12, SMA 20, SMAC (somewhat outdated terms)
The Comprehensive Metabolic Panel (CMP) is typically a group of 14 specific tests

that have been approved, named, and assigned a CPT code (a Current Procedural
Terminology number) as a panel by Medicare (although labs may adjust the number
of tests up or down). Since the majority of insurance companies also use these names
and CPT codes in their claim processing, this grouping of tests has become
standardized throughout the United States. The CMP is a frequently ordered panel
that gives your doctor important information about the current status of your kidneys,
liver, and electrolyte and acid/base balance as well as of your blood sugar and blood
proteins. Abnormal results, and especially combinations of abnormal results, can
indicate a problem that needs to be addressed.
The CMP is used as a broad screening tool to evaluate organ function and check for
conditions such as diabetes, liver disease, and kidney disease. The CMP may also be
ordered to monitor known conditions, such as hypertension, and to monitor patients
taking specific medications for any kidney- or liver-related side effects. If your doctor
is interested in following two or more individual CMP components, he may order the
entire CMP because it offers more information.
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The CMP is routinely ordered as part of a blood work-up for a medical exam or yearly
physical and is collected by inserting a needle into a vein in your arm. Although it
may be performed on a random basis, the CMP sample is usually collected after a 10
to 12 hour fast (no food or liquids other than water). While the individual tests are
sensitive, they do not usually tell your doctor specifically what is wrong. Abnormal
test results or groups of test results are usually followed-up with other specific tests to
confirm or rule out a suspected diagnosis.
The CMP includes:
 Glucose
 Calcium
Both increased and decreased levels can be significant.
Proteins
 Albumin
 Total Protein
Albumin, a small protein produced in the liver, is the major protein in serum. Total
protein measures albumin as well as all other proteins in serum. Both increases and
decreases in these test results can be significant.
Electrolytes
 Sodium
 Potassium
 CO2 (carbon dioxide, bicarbonate)
 Chloride
The concentrations of sodium and potassium are tightly regulated by the body as is
the balance between the four tests. Electrolyte (and acid-base) imbalances can be
present with a wide variety of acute and chronic illnesses. Chloride and CO2 tests are
rarely ordered by themselves.
Kidney Tests
 BUN (blood urea nitrogen)

 Creatinine
BUN and creatinine are waste products filtered out of the blood by the kidneys.
Increased concentrations in the blood may indicate a temporary or chronic decrease in
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kidney function. When not ordered as part of the CMP, they are still usually ordered
together.
Liver Tests
 ALP (alkaline phosphatase)

 ALT (alanine amino transferase, also called SGPT)
 AST (aspartate amino transferase, also called SGOT)
 Bilirubin
ALP, ALT, and AST are enzymes found in the liver and other tissues, while bilirubin
is a waste product of the liver. All can be found in elevated concentrations in the
blood with liver disease or dysfunction.
Cortisol
Why get tested?
To help diagnose Cushing's syndrome or Addison's disease
When to get tested?
When your doctor suspects excess or deficient cortisol production
Sample required?
A blood sample drawn from a vein in the arm or a urine sample; sometimes a saliva
sample may be used.
Cortisol is a hormone produced by the adrenal glands (small organs on top of each
kidney). Production and secretion of cortisol is stimulated by ACTH
(adrenocorticotropic hormone), a hormone produced by the pituitary gland – a tiny
organ located inside the head below the brain. Cortisol has a range of roles in the
body. It helps break down protein, glucose, and lipids, maintain blood pressure, and
regulate the immune system. Heat, cold, infection, trauma, stress, exercise, obesity,
and debilitating disease can influence cortisol concentrations. The hormone is
secreted in a daily pattern, rising in the early morning, peaking around 8 a.m., and
declining in the evening. This pattern, which is sometimes called the “diurnal
variation” or “circadian rhythm,” changes if you work irregular shifts (such as the
night shift) and sleep at different times of the day.
Inadequate amounts of cortisol can cause nonspecific symptoms such as weight loss,
muscle weakness, fatigue, low blood pressure, and abdominal pain. Sometimes
decreased production combined with a stressor can cause an adrenal crisis that
requires immediate medical attention.
Too much cortisol can cause increased blood pressure, high blood sugar, obesity,
fragile skin, purple streaks on the abdomen, muscle weakness, and osteoporosis.
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Women may have irregular menstrual periods and increased facial hair; children may
have delayed development and a short stature.

Typically, blood will be drawn from a vein in the arm, but sometimes urine or saliva
may be tested. Cortisol blood tests may be drawn at about 8 am, when cortisol should
be at its peak, and again at about 4 pm, when the level should have dropped.
Sometimes a resting sample will be obtained late in the evening to look at cortisol
when it should be at its lowest concentration in the blood (about midnight). Obtaining
more than one sample allows the doctor to evaluate the daily pattern of cortisol
secretion (the diurnal variation). This pattern may be disrupted with excess cortisol
production – the maximum amount may be at or near normal concentrations, but
levels may not fall as they should throughout the day. A single morning sample may
be sufficient to detect decreased concentrations of cortisol.
Sometimes urine is tested for cortisol; this usually requires collecting all the urine
produced during a day and night (a 24-hour urine), but sometimes may be done on a
single sample of urine collected in the morning. A 24-hour urine sample may be
ordered to measure the amount of free (not protein bound) cortisol. This sample will
show the total amount of unbound cortisol secreted in the urine but it will not allow
doctors to evaluate variations in cortisol secretion.
Cortisol testing of saliva can be performed. Although the sampling is less stressful
than a blood draw, it requires special care and the test is not yet widely available.
Saliva testing is a snapshot of the cortisol present at the time it is collected.
How is it used?
Blood and urine tests for cortisol are used to help diagnose Cushing's syndrome and
Addison's disease, two serious adrenal disorders. Some physicians are using salivary
cortisol to diagnose Cushing's syndrome as well as to evaluate possible stress-related
disorders, although these uses are not widespread.
Both the urine and saliva tests are most frequently used to evaluate excess cortisol
production.
Once an abnormal cortisol concentration has been detected, the doctor will do
additional testing to help confirm the excess or deficiency and to help determine its
cause.
Dexamethasone Suppression
If there is excess cortisol production, the doctor may perform a dexamethasone
suppression test to help determine whether the cause of the cortisol is related to excess
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ACTH production by the pituitary. This test involves giving the patient oral
dexamethasone (a synthetic glucocorticoid) and then measuring their blood and urine
cortisol levels. Dexamethasone suppresses ACTH production and should decrease
cortisol production if the source of the excess is pituitary related. There are a variety
of dosing schedules, but the medication is usually given every 6 hours for either 2 or 4
days prior to blood or urine collection. Separate 24-hour urine samples are collected
prior to and throughout the testing period and then the blood and urine samples are
measured for cortisol and evaluated.
ACTH Stimulation
If the findings of the initial blood and/or urine tests indicate insufficient cortisol
production, the doctor may order an ACTH stimulation test. This test involves
measuring the concentration of cortisol in a patient’s blood before and after an
injection of synthetic ACTH. If the adrenal glands are functioning normally, then
cortisol levels will rise with the ACTH stimulation. If they are damaged, then the
response will be limited. A longer version of this test (1-3 days) may be performed to
help distinguish between adrenal and pituitary insufficiency.
When is it ordered?
A cortisol test may be ordered when a patient has symptoms that suggest Cushing’s
syndrome (obesity, muscle wasting, and muscle weakness) or Addison’s disease
(weakness, fatigue, increased pigmentation, among others).
Suppression or stimulation testing is ordered when initial findings are abnormal.

Cortisol testing may be ordered at intervals when patients are being or have been
treated for Cushing’s syndrome or Addison’s disease to monitor the effectiveness of
treatment.

In normal people, cortisol levels are very low at bedtime and at their highest just after
waking. This pattern will change if a person works irregular shifts (such as the night
shift) and sleeps at different times of the day. With Cushing’s syndrome, this pattern
is typically lost.
Increased or normal cortisol concentrations in the morning along with levels that do
not drop in the afternoon and evening suggest an overproduction of cortisol. If this
excess cortisol is suppressed during a dexamethasone suppression test, it suggests that
the excess cortisol is due to increased pituitary ACTH production. If it is not
suppressed, then the increased cortisol could be due to an ACTH-producing tumor
outside of the pituitary, due to a problem with the adrenal gland, or due to a
medication that the patient is taking.
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If the adrenal glands are overactive, then a patient may have Cushing’s syndrome,
with symptoms and signs caused by prolonged exposure to the effects of too much
cortisol. This may be due to excess production of cortisol by the adrenal glands
(which is frequently due to a benign adrenal tumor) or excess ACTH stimulation (due
to a pituitary or other ACTH-producing tumor). It can also be seen in patients who
must take corticosteroid medications, such as those used to treat asthma. If
insufficient cortisol is present and the patient responds to an ACTH stimulation test,
then the problem is likely due to insufficient ACTH production by the pituitary. If
cortisol levels do not respond to the ACTH stimulation test, then it is more likely that
the problem is based in the adrenal glands. If the adrenal glands are underactive, due
to adrenal damage or insufficient ACTH production, then the patient is said to have
adrenal insufficiency. If decreased cortisol production is due to adrenal damage, then
the patient is said to have Addison’s disease.
Once an abnormality has been identified and associated with the pituitary gland,
adrenal glands, or other cause, then the doctor may use other testing such as CT
(computerized tomography) or MRI (magnetic resonance imaging) scans to locate the
source of the excess (such as a pituitary, adrenal, or other tumor) and to evaluate the
extent of any damage to the glands.

Pregnancy, physical and emotional stress, and illness can increase cortisol levels.
Cortisol levels may also increase as a result of hyperthyroidism or obesity. A number
of drugs can also increase levels, particularly oral contraceptives (birth control pills),
hydrocortisone (the synthetic form of cortisol), and spironolactone. Adults have
slightly higher cortisol levels than children do.
Hypothyroidism may decrease cortisol levels. Drugs that may decrease levels include
some steroid hormones.
For the blood test, you should maintain a normal salt diet (2 to 3 grams per day)
beforehand and fast and limit physical activity for 10 to 12 hours prior to the test.
Salivary cortisol testing is being used more frequently to help diagnose Cushing's
syndrome and stress-related disorders but still requires specialized expertise to
perform and is not yet widely available.
1. Do I need both tests (blood and urine) or is one better than the other?
If your doctor suspects Cushing's syndrome, usually both blood and urine are tested.
Blood cortisol is easier to collect but is affected more by stress than is the urine test.
Salivary cortisol may sometimes be tested instead of blood cortisol. However,
salivary cortisol requires specialized expertise to perform and is not yet widely
available.
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2. How do I tell if a high cortisol level isn’t just from stress?
There are several approaches that your doctor can take. The simplest involves
repeating tests at a time when you feel less stressed. Your doctor can also give you
varying doses of a medicine that replaces cortisol (usually dexamethasone) to see if
this decreases your cortisol level. Multiple tests are often needed to tell if stress or
disease is causing a high cortisol level.
Creatinine
Why get tested?

To determine if your kidneys are functioning normally and to monitor treatment for
kidney disease
When to get tested?
Routinely as part of a comprehensive or basic metabolic panel; if your doctor suspects
that you are suffering from kidney dysfunction or if you are acutely or chronically ill
with a condition that may affect your kidneys and/or be exacerbated by kidney
dysfunction; at intervals to monitor treatment for kidney disease or kidney function
while on certain medications.
This test measures the amount of creatinine in your blood and/or urine. Creatinine is a
waste product produced in your muscles from the breakdown of a compound called
creatine. Creatine is part of the cycle that produces energy needed to contract your
muscles and it as well as creatinine are produced at a relatively constant rate. Almost
all creatinine is excreted by the kidneys, so blood levels are a good measure of how
well your kidneys are working. The quantity produced depends on the size of the
person and their muscle mass. For this reason, creatinine concentrations will be
slightly higher in men than in women and children.
How is it used?
The creatinine blood test is usually ordered along with a BUN (blood urea nitrogen)
test to assess kidney function. Both are frequently ordered as part of a basic or
comprehensive metabolic panel (BMP or CMP), groups of tests that are performed to
evaluate the function of the body’s major organs. BMP or CMP tests are ordered on
healthy people during routine physical exams and on acutely or chronically ill patients
in the emergency room and/or hospital If the creatinine and BUN tests are found to be
abnormal or if the patient has an underlying disease, such as diabetes, that is known to
affect the kidneys, then these two tests may be used to monitor the progress of kidney
dysfunction and the effectiveness of treatment. Blood creatinine and BUN tests may
also be ordered to evaluate kidney function prior to some procedures, such as a CT
(computed tomography) scan, that may require the use of drugs that can damage the
kidneys.
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A combination of blood and urine creatinine levels may be used to calculate a
creatinine clearance. This measures how effectively your kidneys are filtering small
molecules like creatinine out of your blood. Urine creatinine may also be used with a
variety of other urine tests as a sort of correction factor. Since it is produced and
removed at a relatively constant rate, the amount of urine creatinine can be compared
to the amount of the other substance (such as protein) being measured.
Serum creatinine measurements (along with your age, weight, and gender) also are
used to calculate the estimated glomerular filtration rate (EGFR), which is used as a
screening test to look for evidence of kidney damage.
When is it ordered?
Creatinine may be ordered routinely as part of a comprehensive or basic metabolic
panel, when someone has non-specific health complaints, is acutely ill, and/or when a
doctor suspects kidney dysfunction. The creatinine blood test may be ordered, along
with the BUN test, at regular intervals when the patient has a known kidney disorder
or has a disease that may affect kidney function or be exacerbated by dysfunction.
Both may be ordered when a CT scan is planned, prior to and during certain drug
therapies, and before and after dialysis to monitor the effectiveness of treatments.

Increased creatinine levels in the blood suggest diseases or conditions that affect
kidney function. These can include:
 damage to or swelling of blood vessels in the kidneys (glomerulonephritis) caused

by, for example, infection or autoimmune diseases;
 bacterial infection of the kidneys (pyelonephritis);
 death of cells in the kidneys’ small tubes (acute tubular necrosis) caused, for
example, by drugs or toxins;
 prostate disease, kidney stone, or other causes of urinary tract obstruction; or
 reduced blood flow to the kidney due to shock, dehydration, congestive heart
failure, atherosclerosis, or complications of diabetes.
Creatinine can also increase temporarily as a result of muscle injury.
Low levels of creatinine are not common and are not usually a cause for concern.
They can be seen with conditions that result in decreased muscle mass.
Creatinine levels are generally slightly lower during pregnancy.
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Drugs such as aminoglycosides (gentamicin) can cause kidney damage and so
creatinine is monitored. Other drugs, such as cephalosprins (cefoxitin), may increase
creatinine concentration without reflecting kidney damage.
1. Will exercise affect my creatinine levels?
In general, moderate exercise will not affect your creatinine levels. As you continue to
exercise and build muscle mass, your creatinine levels may increase slightly, but not
to abnormal levels.
2. How does diet affect creatinine levels?

In general, creatinine levels will not vary with a normal diet. Creatinine levels may be
10%-30% higher in people who eat a diet that is very high in meat.
3. What is creatine? If I take creatine, will my creatinine levels go up?

Creatine is a compound that is made primarily in the liver and then transported to
your muscles, where it is used as an energy source for muscle activity. Once in the
muscle, some of the creatine is spontaneously converted to creatinine. The amount of
both creatine and creatinine depend on muscle mass, so men usually have higher
levels than women. Creatine is now available as a dietary supplement. If you take
creatine, your creatinine levels may be higher than when you do not take the
supplement. You should tell your doctor about all of the dietary supplements you are
taking to help her evaluate your lab results.
4. Do creatinine levels change with age?

Creatinine levels relate to both muscle mass and to kidney function. As you age, your
muscle mass decreases but your kidneys tend to function less effectively. The net
result is not much change in creatinine levels in the blood as you get older.
5. What is a BUN/Creatinine ratio?

Occasionally, a doctor will look at the ratio between a person’s BUN and blood
creatinine to help them determine what is causing these concentrations to be higher
than normal. The ratio of BUN to creatinine is usually between 10:1 and 20:1. An
increased ratio may be due to a condition that causes a decrease in the flow of blood
to the kidneys, such as congestive heart failure or dehydration. It may also be seen
with increased protein, from gastrointestinal bleeding, or increased protein in the diet.
The ratio may be decreased with liver disease (due to decrease in the formation of
urea) and malnutrition.
Creatinine Clearance
Why get tested?
To help detect and evaluate kidney dysfunction
When to get tested?
If your doctor thinks that you may have a problem affecting the function of your
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kidneys (for example, as an obstruction within the kidney or acute or chronic kidney
failure) or another disease, such as congestive heart failure.
This test measures the amount of creatinine in the blood and urine to help evaluate the
kidneys’ filtering ability. Creatinine is a waste product derived from creatine, a
nitrogen-based organic compound used by muscles to store and transfer energy. The
amount of creatinine produced in the body is dependent on muscle mass and is
constant for an individual. It is removed from the body by filtering units called
glomeruli as blood passes through the kidneys. The amount of creatinine taken from
the blood depends on the filtering ability of the glomeruli and the rate at which blood
is carried to the kidneys. If the glomeruli are damaged or diseased, or if blood
circulation is slowed, then less creatinine will be removed from the blood and released
into the urine.
The creatinine clearance is a calculation that allows a general evaluation of the

amount of blood that is being filtered in 24 hours. There are several versions of this
calculation. All of them include the measurement of the amount of creatinine in a
blood sample collected just before or after the urine collection, the amount of
creatinine in 24-hour urine sample, and the 24-hour urine volume. Since the amount
of creatinine produced depends on muscle mass, some calculations also use a
correction factor that takes into account a patient’s body surface area (their height and
weight).
How is it used?
A creatinine clearance test is used to help evaluate the rate and efficiency of kidney
filtration. It is used to help detect kidney dysfunction and/or the presence of decreased
blood flow to the kidneys. In patients with chronic kidney disease or congestive heart
failure (which decreases the rate of blood flow), the creatinine clearance test may be
ordered to help monitor the progress of the disease and evaluate its severity.
When is it ordered?
The creatinine clearance test may be ordered whenever a doctor wants to evaluate the
filtration ability of the kidneys. It may be ordered when a patient has increased blood
creatinine concentrations, a known or suspected kidney disorder, or decreased blood
flow to the kidneys due to a condition such as congestive heart failure.
Any disease or condition that affects the glomeruli can decrease the kidneys’ ability to
clear creatinine and other wastes out of the blood. When this occurs, the blood
creatinine level will be increased and the creatinine clearance will be decreased
because not as much creatinine is able to be excreted in the urine. A decreased
creatinine clearance rate may also occur when there is decreased blood flow to the
kidneys as may occur with congestive heart failure, obstruction within the kidney, or
acute or chronic kidney failure. The less effective the kidney filtration, the greater the
decrease in clearance.
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Increased creatinine clearance rates may occasionally be seen during pregnancy,
exercise, and with diets high in meat.
Patients with one dysfunctional and one normal kidney will usually have normal
creatinine clearance rates as the functional kidney will increase its rate of filtration in
compensation.
Creatinine clearance rates tend to fall later in life as the glomerular filtration rate
(GFR – the rate at which the glomeruli filter the blood) declines.
Certain drugs, such as aminoglycosides, cimetidine, cisplatin, and cephalosporins, can

decrease the creatinine clearance measurement. Diuretics can increase the result.
1. What should I do if I forget to save one urine sample during the collection?
If you do not have a complete collection, the results will not be valid. You should call
your doctor’s office or the laboratory where you obtained your container to ask if you
should discontinue the test and begin again another day.
2. Is this test extremely accurate?
There are other, more involved tests that have higher accuracy. However, these
involve injecting the patient with a tracer and are more expensive. For most clinical
purposes, the accuracy of creatinine clearance is sufficient.
3. Can I perform this test at home?
No. The test requires analysis and calculations by skilled medical professionals.
C-Reactive Protein
Why get tested?

To identify the presence of inflammation and to monitor response to treatment [Note:
to test for your risk of heart disease, a more sensitive test (hs-CRP) is used.]
When to get tested?
When your doctor suspects that you might be suffering from an inflammatory disorder
(as with certain types of arthritis and autoimmune disorders or inflammatory bowel
disease) or to check for the presence of infection (especially after surgery).

C-reactive protein (CRP) is a substance made by the liver and secreted into the
bloodstream. Its concentration increases within a few hours after the start of an
infection, making it especially valuable for monitoring infections. Its rise in the blood
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often precedes pain, fever, or other clinical indicators. The level of CRP can jump a
thousand-fold in response to inflammation. It drops relatively quickly as soon as the
inflammation passes, making it a valuable test to monitor effectiveness of treatment.
How is it used?
The CRP test is sometimes used in patients with inflammatory bowel disease and
some forms of arthritis and autoimmune diseases to assess how active the
inflammation is and to monitor the treatment. The CRP test is also used to monitor
patients after surgery or other invasive procedures to detect the presence of an
infection during the recovery period. CRP tests are not specific enough to diagnose a
particular disease. Rather, CRP is a general marker of infection and inflammation that
alerts medical professionals that further testing and treatment may be necessary.
When is it ordered?
Because CRP increases in cases of inflammation, the test is ordered when acute
inflammation is a risk (such as from an infection after surgery) or suspected based on
patient symptoms. It is also ordered to help evaluate conditions, such as rheumatoid
arthritis and lupus. The test may be repeated to determine whether treatment of an
inflammatory disease is effective since CRP levels drop as inflammation subsides.
CRP also is used to monitor wound healing and to monitor patients who have surgical
cuts (incisions), organ transplants, or burns as an early detection system for possible
infections.
A high or increasing amount of CRP in your blood suggests that you have an acute
infection or inflammation. In a healthy person, CRP is usually less than 10 mg/L.
Most infections and inflammations result in CRP levels above 100 mg/L.
If the CRP level in your blood drops, it means that you are getting better and
inflammation is being reduced.
When your results fall below 10 mg/L, you no longer have clinically active
inflammation.

Another test to monitor inflammation is called the erythrocyte sedimentation rate
(ESR). Both tests give similar information about the presence of inflammation.
However, CRP appears and then disappears sooner than changes in the ESR. Thus,
your CRP level may fall to normal if you have been treated successfully, such as for a
flare-up of arthritis, but your ESR may still be abnormal for a while longer.
1. What are chronic inflammatory diseases?
Chronic inflammatory diseases are diseases that lead to the development of long-
lasting or frequently recurring inflammation. They can be caused by a number of
different pathological conditions. Examples include arthritis, lupus, and inflammatory
bowel disease (Crohn’s disease).
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2. What is the difference between regular CRP and hs-CRP tests?
Both tests measure the same molecule in the blood. The high sensitivity CRP (hs-
CRP) test, which measures very low amounts of CRP in the blood, is ordered for
seemingly healthy people to help assess their risk for heart problems. It measures CRP
in the range from 0.5 to 10 mg/L. The regular CRP test is ordered for patients at risk
for bacterial or viral infections (such as following surgery) or patients with chronic
inflammatory diseases (such as rheumatoid arthritis). It measures CRP in the range
from 10 to 1000 mg/L.
Cyclosporine
Why get tested?
To determine the concentration of cyclosporine in your blood in order to establish a
dosing regimen, maintain therapeutic levels, and detect toxic levels
When to get tested?
As soon as cyclosporine therapy begins, usually daily or 2-3 times a week, and
periodically after that as dose is adjusted or maintained
This test measures the amount of cyclosporine in the blood. Cyclosporine is an
immunosuppressive drug used to dampen the body’s natural defenses. When patients
undergo an organ transplant, their immune system recognizes the graft as a foreign
substance and will begin to attack it just as it would any invasive bacteria or virus.
Cyclosporine affects the ability of certain white blood cells in the immune system to
respond to this foreign tissue. The transplanted organ then has a better chance of
survival and will not be as easily rejected by the patient’s system. Cyclosporine is
used routinely in the transplantation of kidney, heart, liver, and other organs.
The immunosuppressive qualities of cyclosporine have also been found to be useful in

treating symptoms of some autoimmune and other disorders. These conditions are
characterized by the immune system reacting to the body’s own cells or tissue.
Cyclosporine helps to control the immune response in these cases, decreasing the
severity of symptoms. Some examples include rheumatoid arthritis, psoriasis, aplastic
anemia, and Crohn’s disease.
When the symptoms in these cases are judged to be severe, extensive, and disabling,
cyclosporine may be prescribed. Usually, the symptoms have not responded well to
other treatments or medications. Cyclosporine is used with caution in these cases and
needs to be carefully monitored with blood tests.
Testing cyclosporine levels in the blood can help ensure that drug levels are in a range
that will be therapeutic for you. If the level is too low, organ rejection may occur (in
the case of transplantation) or symptoms may reappear (autoimmune cases). It is also
important to ensure levels are not too high and will not result in toxicity.
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How is it used?
The test for cyclosporine is ordered to measure the amount of drug in the blood to
determine whether drug concentrations have reached therapeutic levels and are not in
a toxic range. It is important to monitor levels of cyclosporine for several reasons:
 There is not a good correlation, as with some other medications, between the dose
of cyclosporine given and level of drug in the blood.
 Absorption and metabolism of oral doses of cyclosporine can vary greatly between
patients and even in the same patient depending on the time of dose and what food is
eaten.
 There can be variation in blood levels due to the brand or preparation of
cyclosporine prescribed.
 In transplant patients, it is particularly important for graft survival to ensure that
cyclosporine levels are high enough immediately following surgery to prevent
rejection of the transplanted organ.
 Blood levels need to be high enough in the case of rheumatoid arthritis or psoriasis
to begin to give relief of symptoms.
 In the case of kidney transplantation, blood levels may help to distinguish between
kidney rejection and kidney damage due to high levels of cyclosporine.
 Cyclosporine is associated with several toxic side effects that can be avoided if
blood levels are monitored and the dose adjusted if the level detected is too high.
By monitoring cyclosporine blood levels, doctors can better ensure that each
individual is receiving the right amount and formulation of drug needed to treat their
particular case.
When is it ordered?
Cyclosporine is ordered frequently at the start of therapy, often on a daily basis when
trying to establish a dosing regimen. Once an appropriate dose has been determined,
the level can be tested less frequently and may eventually be tested once every 1-2
months.
Often in transplantation, patients will begin with higher doses of cyclosporine at the
start of therapy and then decrease the dose over the course of long-term therapy. In
the cases of rheumatoid arthritis or psoriasis, if a patient appears to tolerate the drug
well, the dose may be increased to further improve symptoms. With each change in
dose, blood levels need to be measured. In addition, the frequency of testing depends
on a number of factors including type of organ transplanted, age, and general health
status of the patient. For example, a patient with a transplanted liver may need to be
monitored more regularly since cyclosporine is metabolized mainly by the liver, and
impaired function can slow clearance of cyclosporine from the blood. Tests may also
be ordered more often when organ rejection or kidney toxicity is suspected.
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The therapeutic range for cyclosporine depends on both the method used to measure
the drug and the type of transplant. Results obtained from different types of samples
and different methods are not interchangeable. Your doctor will be guided by the
laboratory that does the testing as to the appropriate therapeutic range to apply to your
test result.
A majority of institutions use whole blood samples instead of serum or plasma and
will collect samples 12 hours after the last dose or just before the next dose (trough
levels). Some laboratory methods are more specific for the cyclosporine parent drug
while others measure the parent drug plus the metabolites so their respective ranges
will differ.
If trough levels fall below the desired range, there is a risk of transplant rejection or
symptom recurrence. If levels detected are above the range, there is a risk of toxic
side effects.
Some signs or symptoms of cyclosporine toxicity are:
 kidney damage
 high blood pressure
 tremors
 bleeding, swelling, overgrowth of gums
 extra hair growth (hirsutism)
 increased lipids in the blood (hyperlipidemia)
Peak concentrations of samples collected 2 hours post dose are sometimes tested in
transplant cases. High levels of cyclosporine in peak samples are correlated with
reduced rejection rates, especially in the first year after transplant surgery.

Because cyclosporine therapeutic ranges can vary with type of assay performed by the
laboratory, it is advised that your blood samples be tested by the same institution over
the course of therapy. Results will be more consistent and will correlate better with
the reported therapeutic range.
For conditions other than transplants, cyclosporine may be prescribed with other
medications such as non-steroidal anti-inflammatory drugs (NSAIDs). In transplant
cases, other anti-rejection drugs may be used along with cyclosporine. These drugs
will work in conjunction to treat your condition. In addition, cyclosporine blood levels
can be affected by other medications you may be taking. You should notify the doctor
who is monitoring your cyclosporine levels of any additional drugs you are taking.
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Cyclosporine can cause damage to the kidneys, especially with higher blood levels
and over a longer period of time. Your doctor may want to monitor kidney function
tests. Increases in blood lipid levels have been noted in some cases and liver function
may be affected in cyclosporine therapy as well. Your doctor may order additional
laboratory tests to detect high lipid levels or to see if your liver has been affected.
. How long will I need to be on cyclosporine?

Transplant patients generally will stay on cyclosporine as long as that is the treatment
of choice for them. If there are signs of rejection, even with blood levels in the
therapeutic range, they may be switched to a different immunosuppressive drug. Also,
there is a greater chance of toxic side effects the longer a patient is on cyclosporine,
so a doctor may choose to alter drug therapy when a transplant patient has been on
cyclosporine for more than 2-3 years.
Patients with an autoimmune disorder such as rheumatoid arthritis, Crohn’s disease,

or psoriasis will be treated with cyclosporine only when their symptoms are acute and
if other treatments have not been effective. It is not advised that these patients be on
cyclosporine for more than a year due to the increase in the likelihood of toxic
symptoms the longer they are on the medication. Short-term or intermittent courses of
12 weeks at a time are more advisable.
2. Who orders cyclosporine tests?

Cyclosporine will usually be monitored by doctors who have specific knowledge of
the condition or disease for which the drug is prescribed. They tend to be very
familiar with cyclosporine and its use in therapy, and they understand the importance
of monitoring the drug. They may include your surgeon or your doctor treating you
for your arthritis or psoriasis.
3. Can I test my cyclosporine level at home?

No, cyclosporine testing involves special handling and complex procedures and
instruments for accurate results.
Cystatin C
Why get tested?
A new test for assessing kidney function that is gaining interest but is still not widely
used or available at this time in the U.S. Its usefulness is still in question, particularly
in relation to the effectiveness of EGFR.
When to get tested?
Independent guidelines for when to get tested have not yet been developed. Some
studies suggest it is effective when you have symptoms of kidney dysfunction and/or
have a disease or condition that is known to affect kidney function.
Cystatin C is a cysteine proteinase inhibitor, a small molecule that is produced by
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nucleated cells (those with chromosomes and genetic material at their center, which is
most of the body’s cells). It is produced at a constant rate and is found in a variety of
body fluids such as serum, spinal fluid, and breast milk.
Cystatin C is filtered out of the blood by the glomerulus - tiny blood vessels in the
kidneys that allow water and dissolved substances and wastes to pass through their
walls while retaining blood cells and larger proteins. What passes through the
glomerulus walls forms a filtrate fluid. The body reabsorbs Cystatin C, glucose, and
some other substances from the filtrate, while allowing the waste to be carried with
the fluid to the bladder and eventually out of the body as urine. The rate at which this
fluid is formed is called the Glomerular Filtration Rate (GFR).
The GFR can be determined in several ways and is used by your doctor as an
indication of how well your kidneys are functioning. In the past, the most common
method of determining the GFR was the creatinine clearance, a test that compared the
creatinine in your blood with the creatinine in a 24 hour urine collection. This
procedure was useful, but not as precise as it could have been. Its use is now losing
ground to other testing methods. The American Kidney Foundation recommends
using measurements of creatinine in the serum, along with other information such as
your gender, age, weight, and (in one formula) race in one of several formulas to
calculate an estimated GFR (EGFR). Cystatin C is a test that rises when your GFR
falls; high levels thus indicate a low GFR. While there is growing data and literature
supporting the use of Cystatin C, there is also a degree of controversy. Its ultimate
clinical utility remains to be seen.
How is it used?
Cystatin C may be used as an alternative to creatinine and creatinine clearance to
screen for and monitor kidney dysfunction in those with known or suspected kidney
diseases. It may be especially useful in detecting early decreases in kidney function
(as measured by EGFR) and in those for which creatinine measurement is a problem:
for instance in those who have liver cirrhosis, are very obese, malnourished or have a
very small muscle mass (creatinine is produced in the muscles).
When is it ordered?
Cystatin C is not yet widely used or accepted but it may be ordered when you have a
known or suspected disease that affects or potentially affects kidney function and
GFR. Your doctor may order Cystatin C when he wants to check for early kidney
dysfunction and/or wants to monitor known impairment over time.
Early kidney impairment may not cause elevated creatinine levels or symptoms. If
your doctor is not satisfied with your creatinine clearance test or feels that your GFR
would be better estimated by another test, he may order a Cystatin C as an alternative.
Your doctor will be checking for an elevated Cystatin C level. A high serum Cystatin
C corresponds to a low GFR and to kidney dysfunction. Since the Cystatin C is
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produced throughout the body at a constant rate and removed by glomerular filtration
(and subsequently broken down in another part of the kidney), it should remain at a
steady state in the blood if the kidneys are working efficiently and the GFR is normal.
Cystatin C levels may also be elevated in malignant and rheumatic diseases, and
levels can be affected with some drugs: corticosteroids can increase levels, while
cyclosporine can decrease them. They are not however generally affected by most
drugs, by infections, diet, inflammation or by tumor burden (amount of cancer
someone has). They also do not appear to be affected by gender, age (except very
Since Cystatin C has only been commercially available for a short period of time and
its use is still controversial it is only available in a limited number of laboratories. If
your doctor chooses to order a Cystatin C your blood will most likely need to be sent
to a reference laboratory and the results may take a few days.
1. Can Cystatin C be measured in my urine?
No. Unlike creatinine, Cystatin C is reabsorbed from the glomerular filtrate and then
metabolized in the kidneys. Under normal conditions, Cystatin C is not found in
detectable levels in excreted urine.
2. Can Cystatin C be used for anything besides a measure of GFR?

Researchers are exploring other uses of Cystatin C and the reasons for doctors
ordering it may evolve over time. So far, in addition to kidney dysfunction, it has been
associated with hyperhomocysteinemia (often found in renal transplant patients), and
has been shown to increase with the progression of liver disease. At least one study
has looked at comparing Cystatin C levels in serum with that found in pleural effusion
(fluid that builds up in the lungs in a variety of conditions) to help determine the cause
of the effusion. These associations may or may not prove clinically useful.
DHEAS
Also known as: DHEA-SO4, DHEA Sulfate

Formal name: Dehydroepiandrosterone Sulfate
Why get tested?
To determine if DHEAS concentration is normal and to help evaluate adrenal gland
function.
When to get tested?
A woman who has excess facial and body hair (hirsutism), acne, amenorrhea, or
infertility.
A male child who is undergoing precocious (very early) puberty, or a female child is
showing signs of virilism (development of physical masculine characteristics).
Dehydroepiandrosterone sulfate (DHEAS) is a sex hormone (androgen) created in
men and to a lesser extent, women. It has a role to play in developing male secondary
sexual characteristics at puberty and it can be metabolized by the body into more
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potent androgens, such as: testosterone and androstenedione, or changed into the
female hormone estrogen. DHEAS is produced primarily in the adrenal cortex - the
outer portion of the adrenal gland - with much smaller amounts coming from the
woman's ovaries and man's testes. DHEAS secretion is controlled by
adrenocorticotropic hormone (ACTH) and other pituitary factors.
Since DHEAS is primarily produced by the adrenal glands, it is useful as a marker for
adrenal function. Adrenal tumors, cancers, and hyperplasia (excess growth of
hormone producing tissue) can lead to the overproduction of DHEAS. While elevated
levels may not be noticed in adult men, they can lead to amenorrhea and visible
symptoms of virilization (development of physical masculine characteristics) in
women. These changes vary in severity and may include: a deeper voice, hirsutism -
excess hair growth on face or body, male pattern baldness, muscularity, and acne.
Excess levels of DHEAS in children can cause precocious puberty in boys; and
ambiguous external genitalia, excess body hair, and abnormal menstrual periods in
girls.
How is it used?
DHEAS levels are not routinely measured. Unless you have symptoms that warrant
its use, you will most likely never have a DHEAS test done. DHEAS, testosterone,
and several other androgens are used to evaluate adrenal function and to distinguish
between androgen secreting adrenal conditions from those that originate in the ovary
or testes. DHEAS can be measured to help diagnose adrenocortical tumors (tumor in
the cortex of the adrenal gland), adrenal cancers, and adrenal hyperplasia (which may
be congenital or adult onset) and to separate them from ovarian tumors and cancers.
Concentrations of DHEAS are often measured, along with other hormones such as
FSH, LH, prolactin, estrogen, and testosterone, to help diagnose polycystic ovarian
syndrome (PCOS) and to help rule out other causes of infertility, amenorrhea, and
hirsutism.
DHEAS levels may be ordered, along with other hormones, to investigate and
diagnose the cause of virilization in young girls and precocious puberty in young
boys.
When is it ordered?
DHEAS may be ordered, along with other hormones, whenever excess (or more rarely
deficient) androgen production is suspected and/or when your doctor wants to
evaluate your adrenal gland function.
It may be measured when a woman presents with symptoms such as: hirsutism,
alopecia (hair loss), amenorrhea, infertility, acne, increased muscularity, and
decreased breast size. It may also be ordered when a young girl shows signs of
virilization, such as hirsutism, a deep voice, or when a female infant has ambiguous
genitalia wherein the clitoris is overgrown, but the internal female organs usually
appear normal.
DHEAS may also be measured when young boys show signs of precocious puberty -
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the development of: a deeper voice, pubic hair, muscularity, and an enlarged penis
well before the age of normal puberty.
Low levels of DHEAS may be due to adrenal dysfunction or hypopituitarism - a
condition that causes decreased levels of the pituitary hormones that regulate the
production and secretion of adrenal hormones. Normal DHEAS levels, along with
other normal androgen levels, may indicate that the adrenal gland is functioning
normally, or (more rarely) that the adrenal tumor or cancer present is not secreting
hormones. Normal levels of DHEAS may be seen with PCOS, as this disorder is
usually related to ovarian androgen production (primarily testosterone).
Elevated levels of DHEAS, in conjunction with elevations in such tests as 17-
ketosteroids (which measures androgen metabolites in urine) and 17-OH progesterone
may indicate an adrenocortical tumor, adrenal cancer, or adrenal hyperplasia.
Increased levels of DHEAS usually indicate the need for further testing to pinpoint
the cause of the hormone imbalance, but do not often stand alone for diagnostic
purposes.
DHEAS levels are normally high in both male and female newborns. They drop
sharply shortly after birth, then rise again during puberty. DHEAS concentrations
peak after puberty, and then, like other male and female hormones, the levels tend to
decline as we age.
1. Does everyone with elevated DHEAS have symptoms?
Not necessarily. It may be difficult to determine when adult men have elevated levels
of DHEAS (since they already have masculine secondary sexual characteristics) and
women of some ethnic groups (for example Asian women) may have elevated levels
of testosterone and DHEAS without exhibiting symptoms such as excess hair growth
or acne. Also, it should be noted that the symptoms present, and their severity, will
vary from person to person.
2. How is excess DHEAS treated?

Increased DHEAS levels are addressed by diagnosing and treating the underlying
cause. Surgery may be necessary to remove adrenal tumors or cancers. If the affected
adrenal gland is entirely removed, the ovaries, testes, and the remaining adrenal gland
can still sufficiently produce hormones. Medications such as antiandrogens, low-dose
oral contraceptives, and fertility drugs like clomiphene citrate may be used to counter
the effects of excess androgens. Low–dose contraceptives help to balance female and
male hormones and to restore regular menstruation, while fertility drugs (ex. Clomid)
can help to induce ovulation.
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Diabetes-related Autoantibodies
Also known as: Islet autoantibodies

Formal name: Islet Cell Cytoplasmic Autoantibodies (ICA), Insulin Autoantibodies
(IAA), Glutamic Acid Decarboxylase Autoantibodies (GADA, GAD65
Autoantibodies), Insulinoma-Associated-2 Autoantibodies (IA-2A), ICA512
Autoantibodies, Protein Tyrosine Phosphatase-like Autoantibodies
Why get tested?
To help diagnose autoimmune type 1 diabetes; to help predict the development of
type 1 diabetes in family members of those affected (for research purposes only)
When to get tested?
When a patient is first diagnosed with diabetes to help determine whether their
diabetes is autoimmune-related; when a person with non-insulin-treated diabetes has
great difficulty achieving glycemic control (e.g., cannot maintain normal or near-
normal blood sugar levels)
Islet cell cytoplasmic autoantibodies (ICA), insulin autoantibodies (IAA), glutamic
acid decarboxylase antibodies (GADA), and insulinoma-associated-2 autoantibodies
(IA-2A) are a group of tests that measure diabetes-related autoantibodies. These
autoantibodies do not cause type 1 diabetes but serve as markers of the body’s
destructive immune response against its own cells that produce insulin (e.g., the beta
cells in the pancreas). When about 80-90% of the beta cells are destroyed by the
immune system, symptoms of diabetes such as frequent urination, thirst, weight loss,
and poor wound healing occur. Without sufficient insulin action, hyperglycemia (high
blood sugar) results. If the symptoms are not detected and hyperglycemia is not
treated, a diabetic medical crisis can occur that can develop over a few weeks or even
a few days.
The ICA test measures a group of islet cell autoantibodies targeted against a variety of
islet cell proteins. It is a semi-quantitative test performed by indirect
immunofluorescence. GADA and IA-2A are antibodies against two of the specific
islet cell antigens. The only antigen believed to be highly specific to beta cells is
insulin, and antibodies to insulin are abbreviated IAA. The IAA test does not
differentiate whether the body’s immune system is making autoantibodies against
insulin or if the immune system is making antibodies against insulin that has been
injected (either human or animal) in the treatment of any type of diabetes.
About 10% of all cases of diabetes are type 1 (autoimmune) in origin. Of these, about
75% are diagnosed in patients younger than 20 years old. Type 1 diabetes was
previously known as juvenile or insulin-dependent diabetes but has been re-
characterized to reflect beta cell destruction. Islet autoantibodies can be detected in
the blood stream months to years before the development of type 1 diabetes. While
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nondiabetic individuals with islet autoantibodies are at high risk for the development
of type 1 diabetes, not every person with islet autoantibodies will develop type 1
diabetes. When autoimmune type 1 diabetes is present, one or more of the diabetes
autoantibodies will be present in about 95% of patients at the time of initial diagnosis.
Testing nondiabetic individuals for islet autoantibodies is recommended only as part
of a research study.
How is it used?
In general, autoantibody testing is not required to make a diagnosis of autoimmune
type 1 diabetes. In the general population, there is no benefit to autoantibody
screening, but it can be useful in patients at high risk of diabetes (e.g. siblings of
known type 1 diabetics and offspring of diabetic parents).
Diabetes-related (islet) autoantibody testing is primarily ordered to help distinguish
between autoimmune type 1 diabetes and diabetes due to other causes (e.g., diabetes
resulting from obesity and insulin resistance). If ICA, GADA, or IA-2A are present in
an individual with diabetes, the diagnosis of type 1 diabetes has been established. IAA
testing must be performed before insulin therapy is initiated. Like ICA, GADA and
IA-2A, if IAA are present in a person with diabetes who is not insulin-treated, type 1
diabetes is the cause.
It is generally recommended that testing be done either for ICA or for the GAD/IA-
2A combination since this approach is more cost-effective. The autoantibody profile
is usually different between children and adults. IAA is usually the first marker to
appear in young children at risk of diabetes. As the disease evolves, this may
disappear and ICA, GADA and IA-2A become more important. IA-2A is less
commonly positive at the onset of type 1 diabetes than either GADA or ICA. Whereas
about 50% of children with new-onset type 1 diabetes will be IAA positive, IAA
positivity is not common in adults. Thus in younger children at risk for diabetes,
testing for IAA may also be requested.
In research settings where investigators want to predict the development of type 1
diabetes, islet autoantibody testing can be carried out. The more islet autoantibodies
that a nondiabetic person has in their blood stream, the higher their risk for later
developing type 1 diabetes.
When is it ordered?
A combination of these autoantibodies may be ordered when a patient is newly
diagnosed with diabetes and the doctor suspects that the condition may be due to an
autoimmune process. IAA testing as a marker of autoimmune type 1 diabetes must be
performed before insulin injections are begun. Insulin injections of either human or
animal insulin can stimulate insulin antibodies that will give a positive result in the
IAA assay. The IAA assay does not distinguish autoantibodies from antibodies that
form in response to insulin injections.
One or more of the autoantibodies may be ordered on the siblings of a patient
diagnosed with type 1 diabetes or on the offspring of diabetic parents. This may be
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done initially and then again at intervals recommended by the doctor in a research
setting.
Normally, nondiabetic individuals in the general population will not have any of these
islet autoantibodies. However, when islet autoantibodies are detected in individuals in
the general population or siblings of affected patients, there may be an increased risk
for type 1 diabetes since false positives are known to occur. Many of these islet
autoantibody-positive individuals will never develop diabetes, however. When type 1
diabetes does not develop, the level of the islet autoantibody in the blood is usually
low and the islet autoantibody may be transient.
Some patients who do have type 1 diabetes will never develop detectible amounts of
islet autoantibodies, although this is rare. The majority of people (95% or more) with
new-onset type 1 diabetes will have at least one islet autoantibody. Therefore, if one
or more islet autoantibody (e.g., ICA, GADA, IA-2A, and/or IAA) are present in a
patient with symptoms of diabetes, the diagnosis of type 1 diabetes is confirmed.
In nondiabetic individuals who are positive for one or more islet autoantibodies, there
is an increased risk for type 1 diabetes as mentioned above. The more islet
autoantibodies that are present, the higher is the individual’s risk for developing type
1 diabetes. However not everybody with islet autoantibodies will develop type 1
diabetes. If a non-diabetic individual with one or more islet autoantibodies has a low
insulin response to the intravenous injection of glucose, their risk for type 1 diabetes
can be very high. In first degree relatives of patients with type 1 diabetes who have
ICA and have a low insulin response to the intravenous injection of glucose, the 5-
year risk of developing type 1 diabetes is approximately 60%. Because there are no
effective therapies to prevent type 1 diabetes, general population screening for islet
autoantibodies or testing first degree relatives of patients with type 1 diabetes is not
recommended.

It is up to the doctor and patient to decide together which islet autoantibodies to test
for at any given time. Because GADA and IA-2A assays are automated, these tests are
generally more available than ICA testing, which is labor-intensive and requires
considerable expertise in interpretation.
Islet autoantibodies may also be seen in patients with other autoimmune endocrine
disorders such as Hashimoto thyroiditis or autoimmune Addison disease.
1. Do ICA, GADA, and IA-2A destroy the beta cells?

They are associated with beta cell destruction and reflect an ongoing autoimmune
process, but they are not thought to cause the damage.
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2. Does early detection of beta call destruction allow its prevention?
Not currently. What it does do is allow for diabetes to be addressed as soon as

symptoms such as frequent urination, weight loss, and hyperglycemia (high blood
sugar) appear. This can help establish diabetic glucose control and can in turn help
minimize the occurrence of complications such as the kidney and eye damage that are
seen with diabetes.
Digoxin
Why get tested?
To determine if the concentration of digoxin in your blood is at a therapeutic level or
to detect toxic levels
When to get tested?
Soon after the start of digoxin therapy and at regular intervals to ensure that drug
levels are within therapeutic range and are not low or at toxic concentrations
Digoxin is a drug used to treat heart failure and abnormal heart rhythms. This test
measures the amount of digoxin in the blood. Heart failure, including congestive heart
failure (CHF), causes the heart to become less effective at circulating blood. As a
result, blood backs up into the legs, hands, feet, lungs and liver, causing swelling,
shortness of breath, and fatigue.
Digoxin is prescribed to alleviate some symptoms of heart failure. It strengthens the

contractions of the heart and helps it to pump blood more efficiently. Digoxin also
helps control the heart rate and abnormal heart rhythms known as arrhythmias. It will
not cure heart failure or arrhythmias, which are chronic conditions, but can help to
manage the symptoms along with diet, exercise, and other medications.
Digoxin levels need to be monitored because digoxin is a drug that has a narrow
safety range. If the level in the blood is too low, symptoms may recur. If the level is
too high, toxicity may occur with possible side effects such as:
 dizziness;
 blurred vision or seeing yellow or green halos;
 vomiting;
 diarrhea;
 irregular heartbeat; or
 difficulty breathing.
Digoxin dosage may be adjusted based on levels measured.
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How is it used?
A digoxin test is ordered by your doctor to monitor the level of drug in your blood.
The dose of digoxin prescribed by your doctor may be adjusted depending on the
level measured. Your doctor will want to monitor the level of digoxin at regular
intervals to ensure that a therapeutic level is maintained and that toxic levels have not
been reached and will not produce symptoms of toxicity.
When is it ordered?
The test to measure digoxin is ordered at the beginning of drug therapy to ensure
correct dosage. Digoxin takes approximately one to two weeks to reach a steady level
in the blood and in the target organ, the heart. A test done at that time will reflect
more accurately whether you are receiving the right amount of digoxin. Digoxin
levels are monitored routinely at a frequency determined by your doctor after that to
verify correct dosage or if any changes occur in drug source, dosage, or other
medications taken at the same time. Changes in your health status can also affect
levels of digoxin and its ability to control your symptoms. Some physiologic changes
that may affect levels of digoxin in the blood are:
 kidney function
 thyroid problems
 cancer
 stomach or intestinal illness
Digoxin will not cure heart failure but will help to control it. Since digoxin is
prescribed to treat patients with a long-term, chronic condition, it is usually monitored
throughout the patient’s lifetime.
Timing of the digoxin blood test is important. The sample should be drawn at least 6-
8 hours after the last dose. Many times, the blood sample will be drawn just before the
next dose is to be taken. Timing of the sample collection is important because if the
sample is drawn too soon after dose, the results of the test may be erroneously high
and will show a toxic level when that is not the case.

The therapeutic range for digoxin has been established over time as 0.5-2.0 ng/ml for
patients being treated for heart failure. Several new studies suggest a more narrow
range, 0.5-1.0 ng/ml, may be appropriate for some some patients. The recommended
range for patients with arrhythmias is 1.5-2.0 ng/ml. Most patients find that their
symptoms improve when their digoxin levels are within these ranges.
It is important to note that each patient’s response to medications is individual and

other factors such as kidney function or concurrent medications may be involved. If
your symptoms have not improved or if you are experiencing side effects, tell your
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doctor immediately. He may need to adjust your dose according to your individual
needs.
If your result does not fall within therapeutic range but you are not experiencing
symptoms, continue to take your medication as prescribed until you consult with the
doctor who ordered the test. He will evaluate your case and decide if it is necessary to
adjust your dose. If your dose needs to be adjusted, your doctor may order additional
digoxin tests to determine the resulting blood level.

Several prescribed and over-the-counter drugs can affect the level and effectiveness of
digoxin in your system. Be sure to tell your doctor about other medications you may
be taking.
Timing of the sample for testing is important. When having your blood drawn, tell the
laboratorian when you took your last dose of digoxin. You may want to write down
the exact time at which you took your dose and when the blood was drawn. This
information will be useful if your doctor has any questions about your levels.
Digoxin is primarily cleared from your system by the kidneys. Tell your doctor if you
have or have had known kidney problems. Your doctor may want to monitor blood
potassium levels since low levels of potassium can result in symptoms of toxicity.
In cases where toxic levels of digoxin are measured, antidigoxin antisera may be
administered to reverse the effects of the drug.
1. How long will I need to be on digoxin?

Digoxin is usually taken for your lifetime. Very rarely is it ever discontinued.
2. Who orders digoxin tests?

Your primary doctor may order the test, but it also may be monitored by a
cardiologist.
3. Can I test my digoxin level at home?
No, there are no home tests developed to date. Digoxin testing requires special
handling and instruments for accurate results.
Direct Antiglobulin Test (Direct Coomb’s test)

Why get tested?
To detect the cause of hemolytic anemia, to investigate a transfusion reaction, and to
diagnose hemolytic disease of the newborn
When to get tested?
If you have symptoms suggesting hemolytic anemia, such as unusual tiredness,
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unexpected difficulty breathing when exercising, and unusually dark urine, or if your
hemoglobin and/or hematocrit are unexpectedly low, or if you have had a blood
transfusion recently and are experiencing any of the above symptoms.
The direct antiglobulin test looks for antibodies attached to your red blood cells
(RBCs). RBCs normally have structures on their surface called antigens. You have
your own individual set of antigens on your RBCs, determined by inheritance from
your parents. If you have a blood transfusion, your immune system will recognize
antigens that you do not have as foreign. Your plasma cells then may produce
antibodies to attack these foreign antigens. People who have many transfusions are
more likely to make antibodies to RBCs because they are exposed to more foreign
RBC antigens. When a baby inherits antigens from its father that are not on its
mother’s RBCs, the mother can produce antibodies against the foreign antigens on her
baby’s RBCs inside the womb. This can cause hemolytic disease of the newborn,
usually not affecting the first baby but subsequent children. In addition, some people
make antibodies to their own RBCs. These antibodies are produced in autoimmune
diseases and are called autoantibodies. In all of these situations, antibodies attach to
the RBCs and can result in their destruction.
How is it used?
The direct antiglobulin test (DAT) is used primarily to help determine the cause of
hemolytic anemia, in which red blood cells (RBCs) are being destroyed more quickly
than they can be replaced. Premature destruction also may be due other causes, such
as a mechanical problem (for example, an artificial heart valve that is altering the
shape of the RBCs as they circulate through the valve) or abnormal RBCs being
produced (such as may be seen with sickle cell anemia). If a person is experiencing
symptoms suggesting hemolytic anemia, such as fatigue, dark urine, back pain,
jaundice, paleness, or an enlarged spleen, then a doctor may order a DAT to help
determine whether an RBC antibody is present.
Immune-related hemolytic anemia may be caused when a person produces antibodies

against their own antigens. This can happen with some autoimmune disorders (such as
systemic lupus erythematosus), with malignant diseases such as chronic lymphocytic
leukemia, and with infections such as mycoplasma pneumonia and mononucleosis. It
can also occur in some people with the use of certain medications, such as penicillin,
and in rare cases can be triggered by exposure to cold.
When a baby is born, the mother may have made antibodies that react with the baby’s
RBCs. A DAT will determine if this has happened.
If you are being transfused and have a fever or other significant symptoms suggesting
a potential for a hemolytic transfusion reaction, a DAT is done to determine if you
have made an antibody to the transfused RBCs. If the antibody is found coating the
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RBCs, then the RBCs may be destroyed (hemolyzed) or be removed from your
circulation faster than normal.
When is it ordered?
The DAT is ordered when hemolytic anemia, hemolytic disease of the newborn,
and/or a transfusion reaction is suspected.
If the DAT is positive, then there is an antibody attached to the RBCs. In general, the
stronger the DAT reaction (the more positive the test), the greater the amount of
antibody bound to the RBCs. The DAT detects the presence of the antibody but it
does not tell the doctor the source or exact type of antibody. It could be due to a
transfusion reaction, autoimmune reaction, an infection, a medication, a baby-mom
Rh incompatibility, or, rarely, exposure to the cold. A small percentage of the normal
population will be DAT positive and not experience hemolytic anemia.
If a DAT is positive due to a transfusion reaction, an infection, or drug, it will remain
positive for 48 hours to 3 months. If it is positive due to an autoimmune condition, it
will often be chronically positive.
1. Can I get antibodies from donating blood?
No, you will not be exposed to anyone else’s blood while donating.
2. Do I need to tell a new doctor about an old, uneventful transfusion?
Yes. It is important for your doctor to have that information because there is a chance
that you became sensitized to one or more antigens due to that transfusion. While this
will not negatively affect your health, it will tell you doctor to be especially vigilant
with any subsequent transfusions.
DLDL
Why get tested?
To help determine your risk of developing heart disease and to monitor lipid lowering
lifestyle changes and drug therapies. To accurately determine your low-density
lipoprotein (LDL) level when you are nonfasting.
When to get tested?
As a follow-up to a lipid profile, done when your triglycerides are significantly
elevated. At regular intervals to monitor efforts to lower LDL levels.
The direct low-density lipoprotein test (DLDL or Direct LDL) provides an actual
measurement of LDL cholesterol, the “bad” cholesterol in blood. Ordinarily when a
lipid profile is ordered, LDL cholesterol is calculated using the results of the total
cholesterol, the HDL cholesterol (high-density lipoprotein – the “good” cholesterol),
and the triglycerides tests. However, calculation cannot be used if triglyceride levels
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are above 400 mg/dl or if the patient is not fasting. DLDL has now become a useful
tool in lipid management because it allows measurement of LDL cholesterol in either
of these circumstances. Since the direct measurement of LDL cholesterol is less
affected by triglyceride concentrations than the calculation of LDL cholesterol, the
DLDL test can be used when the patient is not fasting, and/or when the patient has
significantly elevated triglycerides.
How is it used?
The DLDL is primarily ordered as a follow-up to significantly elevated triglycerides
in a lipid profile and is used to accurately determine the LDL levels. The request for a
DLDL may be set up by the laboratory so that it can be ordered by the doctor as a
reflexive test. This means that the lipid profile is run first, and then if the triglycerides
are abnormal, the DLDL is automatically ordered as a follow-up test. This saves the
doctor an extra step and speeds up the test turn-around time.
DLDL may also be ordered by itself or with an HDL test to monitor the effectiveness
of lipid-lowering lifestyle changes (diet and exercise) and drug therapy. Sometimes
the DLDL test is also ordered to determine accurate LDL levels in those who are
nonfasting.
When is it ordered?
DLDL is ordered whenever calculation of LDL cholesterol will not be accurate
because the patient’s triglycerides are significantly elevated. This may occur
following a routine lipid profile, when a doctor wants to monitor the effectiveness of
therapy, or when a patient is not fasting.
Elevated levels of LDL, as measured with the DLDL, indicate a greater risk of
developing heart disease. Decreasing levels show a response to lipid-lowering
lifestyle changes and/or drug therapies and indicate a decreased risk of heart disease.
The DLDL, like the LDL, should be measured when you are healthy and
“metabolically stable.” Illness, surgery, trauma, a heart attack, sudden weight loss or
gain, and pregnancy can all temporarily affect LDL levels.
1. Why hasn’t the DLDL replaced the calculated LDL test?

The calculated LDL is still a valuable tool. It has about the same accuracy as the
DLDL if triglycerides are not elevated and since it is a calculation it can be done at no
additional cost when a lipid profile is being performed.
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Testing for Drugs of Abuse
What is it?
Testing for drugs of abuse or “drugs of abuse screening” is the detection of the
presence of both legal and illegal substances. Drug testing is used for many purposes
including clinical or medical care, workplace testing, postmortem (cause-of-death),
corrections and other law enforcement, and sports testing. Each reason for testing has
its own requirements regarding which drugs to include in the test, how fast the results
are needed, and how specific (what drugs are detected by the test) and sensitive (what
is the lowest amount detected) the test must be. In addition, for some types of testing
(for example, workplace testing of federal employees) there are many regulations that
cover the test from collection through interpretation and reporting of results. It is
important for the ordering physician, law enforcement representative, forensic
professional, government entity, insurance agent, employer, and sports organization
as well as for the person being tested to understand what exactly is included in the
testing, how it is done, and how the results may or may not be interpreted. This
process is not nearly as simple or straightforward as collecting a sample and
requesting that it be tested for “drugs.”
How is it done?
Testing for drugs of abuse (and other drugs) is done differently, depending on the
application. In workplace testing, sports testing, and some clinical testing programs, it
is important to know the actual drug or drugs present, and testing is a two-step process
consisting of a screen, followed by confirmation of any positives. Confirmation may
not be done in certain clinical situations but may be requested by the physician as
follow-up. False positive and false negative results can occur at the initial screening
stage. Therefore, taking any action based solely on a screening result may be
problematic. Most laboratories use commercially available tests that have been
developed and optimized to screen for the “major drugs of abuse.” Screen in this
context means a preliminary result. Each screen is for a different drug or drug class
such as amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates,
and phencyclidine (PCP). Patient/donor results are compared with a predetermined
cut-off. Anything below that cut-off is considered negative. Depending on the reason
for the test, specimens giving a result above the cut-off may be confirmed with a more
specific test. In the confirmation test, the exact substance present is identified with a
very sensitive and specific method, such as gas chromatography/mass spectrometry
(GC/MS).
Some of the “club drugs,” such as methylenedioxy-methamphetamine (MDMA,

Ecstasy) and flunitrazepam (rohypnol, date-rape drug) may be difficult to detect,
either because available assays do not always detect the drug (Ecstasy) or the drug
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does not remain in the body long enough to be detected (gamma-hydroxybutyrate,
GHB).
Samples Used/Drug Matrices

Urine is the most frequently tested sample, but other body samples (matrices) also
may be used for drug abuse screening. Hair, saliva, sweat, and blood are used but not
interchangeably with urine. Drug compounds in these other matrices are primarily the
parent (original) drugs, not metabolites, and they reflect a different “window” (time
period) of drug use. Urine testing shows drug use over the last 2 or 3 days for
amphetamines, cocaine, and opiates (an exception is marijuana (cannabinoids), which
may be detectable for several weeks). Hair samples, which test the root end of the
hair, reflect drug use within the last 2 to 3 months but not the most recent 2-3 weeks
(the amount of time it takes for the hair to grow). Saliva shows which drugs have been
used in the last 24 hours, and sweat, which is collected by wearing a patch, gives a
time-averaged representation. These other matrices are often used for specific
purposes. For instance, hair samples may be used as an alternative to urine testing for
pre-employment drug testing. Sweat testing may be used as a court-ordered
monitoring tool in those who have been convicted of drug use, while saliva is often
used by the insurance industry to test insurance applicants for cocaine use. Blood is
most frequently used for alcohol testing.
Why are they done?
Medical Screening
Medical drug abuse screening is primarily focused on determining what drugs or
combinations of drugs a patient may have taken so that they can receive the proper
treatment. In many cases, drugs have been combined and/or taken with ethanol
(alcohol). The overall effect on a particular person depends on the response of their
body to the drugs, on the quantity and combination they have taken, and when each
was taken. For instance, MDMA is initially a stimulant with associated psychedelic
effects, but it also causes central nervous system (CNS) depression as it is
metabolized and cleared from the body. If patients drink ethanol during this time
period, they will have two CNS depressants in their system, a potentially dangerous
combination.
Those who may be tested for drug abuse include:
 someone in the emergency room who is having acute health problems, such as
unconsciousness, nausea, delirium, panic, paranoia, increased temperature, chest pain,
respiratory failure, seizures, or headaches, that the doctor thinks may be drug-related.
 someone in the emergency room who has been in an accident, when the doctor
suspects that drugs and/or alcohol may have been involved.
 a child or adult that the doctor suspects may be using drugs.
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 those who are being monitored for known drug use. This may include both legal
and illegal drug use. It may be general testing or specific for the substance that has
been abused.
 pregnant women thought to be at risk for drug abuse or neonates exhibiting certain
characteristic behaviors.
Legal or Forensic Testing
Drug testing for legal purposes is primarily concerned with the detection of illegal or
banned drug use in a variety of situations. Sample collection procedures for this type
of testing are strictly controlled and documented to maintain a legal “chain-of-
custody.” The donor provides a sample (usually urine) that is sealed and secured with
a tamperproof seal in his or her presence. Specific chain-of-custody paperwork then
accompanies the sample throughout the testing process; each person who handles
and/or tests the sample provides their signature and the reason for the sample transfer.
This creates a permanent record of each step of the process. Examples of legal drug
abuse screening follow.
 Employment drug testing done prior to employment, on a random basis, following
an accident, or if the employer has a reasonable suspicion that their employee is using
illegal drugs. Only the major drugs of abuse are tested, and any positives are
confirmed by another method. Employment drug testing has become very common. It
is required in some industries (those that involve the U.S. Department of
Transportation), for federal employees, and has become an accepted practice in many
others.
 Court-mandated drug testing usually involves the random monitoring of someone
who has been convicted of illegal drug use. Testing may also be ordered in custody
cases to rule out drug use by one or both parents.
 Government child protective services may sometimes require extended monitoring
of a parent with a known drug problem to ensure that they have not returned to drug
use.
 Law enforcement drug testing may be done when someone has an accident that is
suspected to be alcohol- or drug-related.
 Forensic testing utilizes a variety of body fluids and tissues that may be tested for
numerous drug metabolites during a crime investigation. The goal may be to
determine whether drugs were a contributing factor to an accident or crime (such as a
DUI or rape). Testing may also be done to determine whether someone died of a drug
overdose or drug-related condition.
 Insurance companies may perform limited drug screening on their insurance
applicants. This may include a test for cocaine and a test for nicotine (even though
nicotine is a legal substance).
 Schools may have programs that incorporate random drug testing. This may include
illegal drugs of abuse and, with competitive sports, may include testing for
performance-enhancing substances.
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Sports/Athletic Screening
While conventional drug testing is performed on competitive athletes, the primary
focus is on doping - drugs and/or supplements that are taken to promote muscle
growth and/or to improve strength and endurance. On a local level, sports testing may
be limited, but on a national and international level it has become highly organized.
The World Anti-Doping Agency (WADA), U.S. Anti-Doping Agency (USADA), and
the International Association of Athletics Federations (IAAF) work together to
monitor athlete drug use on a national, international, and Olympic level. WADA has a
written code, which establishes uniform drug testing rules and sanctions for all sports
and countries, and a substantial list of prohibited substances. Athletes are responsible
for any banned substances that are found in their body during testing. Most of the
compounds tested are considered positive if they are detected in any quantity while
others, such as caffeine, are only prohibited when they are present in large amounts.
Some of the substances, such as anabolic steroids (testosterone) and peptide hormones
(such as erythropoietin, growth hormone, and IGF-1) are banned but are difficult to
measure as they are produced by the body. Testing methods must be able to
distinguish between endogenous (that produced by the athlete’s body) and
supplemented compounds.
Screening programs randomly perform out-of-competition drug tests on athletes

during the training season to look for anabolic steroids (such as testosterone) that
promote increased muscle growth. During competitions, testing is frequently done
both randomly and on all winners and includes categories such as: stimulants,
narcotics, cannabinoids, anabolic agents, and peptide hormones. Sports such as
archery, gymnastics, and shooting add additional testing for substances like beta
blockers, which are prohibited in these sports because they decrease blood pressure
and heart rate.
While professional sports organizations, such as the NFL (National Football League),
NHL (National Hockey League), and NBA (National Basketball Association), are not
covered by the WADA code, they have programs in place to test their athletes for
panels of drugs that combine aspects of sports and employment testing. Those
professional athletes that also take part in the Olympics, however, are subject to the
same out-of-competition (pre-game) and in-competition testing as other competing
athletes.
Epstein-Barr Virus Antibodies
Also known as: EBV Antibodies, EBV VCA-IgM Ab, EBV VCA-IgG Ab, EBNA-
IgG Ab, EA-D IgG Ab
Formal name: Epstein-Barr Virus Antibody to Viral Capsid Antigen, IgM; Epstein-
Barr Virus Antibody to Viral Capsid Antigen, IgG; Epstein-Barr Virus Antibody to
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Nuclear Antigen, IgG; Epstein-Barr Virus Antibody to Early D Antigen, IgG;
Heterophile Antibodies
Why get tested?

To help diagnose mononucleosis (Mono); to help evaluate susceptibility to EBV
infection; to distinguish between an EBV infection and another illness with similar
symptoms
When to get tested?
When an adolescent has symptoms of Mono but a negative Mono test; when a
pregnant woman has flu-like symptoms; sometimes when an asymptomatic person has
been exposed to Mono.

Epstein-Barr virus (EBV) antibodies are a group of tests that are ordered to help
diagnose a current, recent, or past EBV infection. EBV is a member of the herpes
virus family. Passed through the saliva, the virus causes an infection that is very
common. According to the National Center for Infectious Diseases (NCID), as many
as 95% of people in the United States will have been infected by EBV by the time
they are 40 years old. After exposure to the virus, there is an incubation period of
several weeks. EBV then causes an acute infection, followed by resolution and
dormancy. Latent EBV remains in the patient’s body for the rest of his life,
reactivating intermittently, but causing few problems unless the patient’s immune
system is significantly compromised.
Most people are infected by EBV in childhood and experience few or no symptoms,
even in the acute phase of the infection. However, when the initial infection is delayed
until adolescence, EBV causes infectious mononucleosis (Mono) in about 35 – 50%
of those infected. Mono is a condition that is associated with fatigue, fever, sore
throat, swollen lymph nodes, an enlarged spleen, and, sometimes, an enlarged liver.
Those who have it are usually symptomatic for a month or two before the initial
infection resolves.
Patients with Mono are diagnosed by their symptoms and the findings of a complete
blood count (CBC) and a Mono test (which tests for a heterophile antibody). A certain
percentage of those who have mono will have a negative mono test – this is especially
true with children. EBV antibodies can be used to determine whether or not the
symptoms these patients are experiencing are due to a current infection with the EBV
virus.
It can be important to distinguish EBV from other illnesses. For instance, the enlarged
spleen of those with a Mono infection is vulnerable to rupture. Patients who have
Mono should not be involved in contact sports for several weeks to months after
infection, as a ruptured spleen can cause a medical emergency. Also, pregnant women
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with symptoms of a viral illness need to be able to distinguish a primary EBV
infection (which has not been shown to affect the baby) from a cytomegalovirus
(CMV), herpes simplex virus or toxoplasmosis infection, as these illnesses can cause
complications during the pregnancy and damage the fetus. It can also be important to
rule out EBV and to look for other causes for the symptoms. Patients with strep throat
(a Group A streptococcus infection), for instance, need to be identified and treated
with antibiotics. A patient may have strep throat instead of Mono, or they may have
both conditions at the same time.
There are several EBV antibodies. They are proteins created by the body in an
immune response to different antigens (protein parts) of the Epstein-Barr virus. They
include IgM and IgG antibodies to the viral capsid antigen (VCA), IgG antibodies to
the D early antigen (EA-D), and antibodies to the nuclear antigen (EBNA). During a
primary EBV infection each of these EBV antibodies appears independently on its
own time schedule. The VCA-IgM antibody appears first and then tends to disappear
after about 4 to 6 weeks. The VCA-IgG antibody emerges, is at its maximum at 2 to 4
weeks, then drops slightly, stabilizes, and is present for life. The EA-D antibody
appears during the acute infection phase and then tends to disappear within 3 to 6
months, but about 20% of those infected will continue to have detectible quantities of
the EA-D antibody for several years after the EBV infection has resolved. The EBNA
antibody does not usually appear until the acute infection has resolved. It usually
develops about 2 to 4 months after the initial infection and then is present for life.
Using a combination of these EBV antibody tests, a doctor is able to detect an EBV
infection and to determine whether it is a current, recent, or past infection.
How is it used?
EBV antibodies are ordered to help diagnose Mono in patients who are symptomatic
but have a negative Mono test. NCID recommends ordering a VCA-IgM, VCA-IgG,
EA-D, and an EBNA. The VCA-IgM, VCA-IgG and EA-D are ordered to detect a
current or recent infection, the VCA-IgG and EBNA to detect a previous infection. In
pregnant women with symptoms of a viral illness, one or more of these EBV
antibodies may be ordered to help distinguish between EBV, CMV, toxoplasmosis,
and other infections that may cause similar symptoms. Occasionally, a VCA-IgG or
other EBV antibody may be repeated 2-4 weeks after the first test, either to see if a
test changes from negative to positive or to measure changes in antibody
concentrations (to see if they rise or fall).
A VCA-IgG test (and sometimes an EBNA test) may be ordered on an asymptomatic
patient to see if that person is susceptible to EBV infection or has been previously
exposed. This is not routinely done, but it may be ordered when a patient, such as an
adolescent or an immune compromised patient, has been in close contact with a
person who has Mono.
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When is it ordered?
EBV antibodies may be ordered when a patient has symptoms suggesting Mono, but a
negative Mono test and when a pregnant woman has flu-like symptoms and the doctor
wants to determine whether the symptoms are due to EBV or another microorganism.
VCA-IgG and EBNA may be ordered whenever a doctor wants to establish previous
exposure. Testing may occasionally be repeated when the doctor wants to track
antibody concentrations and/or when the first test was negative, but the doctor still
suspects that the patient’s symptoms are due to EBV.
f a patient has positive VCA-IgM antibodies, then it is likely that he has a current (or
had a very recent) EBV infection. If he also has the symptoms associated with Mono,
then it is most likely that he will be diagnosed with Mono, even if his Mono test (the
heterophile antibody) was negative. If he also has positive VCA-IgG and EA-D IgG
concentrations, then it is highly likely that he has (or recently had) an EBV infection.
If the VCA-IgM is negative but the others and an EBNA antibody are positive, then it
is likely that the person had a previous EBV infection. If an asymptomatic person is
negative for VCA-IgG, then he has not been previously exposed to EBV and is
vulnerable to infection. In general, rising VCA-IgG levels tends to indicate an active
EBV infection, while falling concentrations tend to indicate a recent EBV infection
that is resolving. However, care must be taken with interpreting EBV antibody
concentrations as the amount of antibody present does not correlate with the severity
of the infection or with the length of time it will last. High levels of VCA-IgG may be
present and may persist at that concentration for the rest of the patient’s life.
Results in table form:
Test results most likely indicate:

EBV Antibody Susceptible to Current EBV Past EBV Comments
Test EBV Infection Infection
VCA-IgM + + Appears first, gone in 4-6 weeks
VCA-IgG – + + If negative susceptible, it
appears within a week of
infection, then present for life
EBNA-IgG + Becomes positive in 2 – 4
months, then present for life
EA-D IgG + + Positive in about a week,
usually gone in 2 weeks,
persists in 20% of people
Heterophile IgM + Associated with Mono, false
(Mono test) positives with other conditions,
false negatives common in
children

There are at least two other antibodies that arise during an EBV infection -- an IgA
antibody to the EBV viral capsid antigen (EBV VCA-IgA) and an IgG antibody to the
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EBV early antigen restricted (EA-R IgG). While it is possible to test for these
antibodies as part of the EBV diagnostic workup, it is rarely necessary to do so.
The most common complication of Mono is a ruptured spleen. Other complications of

EBV infection that can occur include trouble breathing due to a swollen throat, strep
throat (a Group A streptococcus infection) at the same time, and rarely, jaundice
(yellowing of the skin due to liver enlargement), skin rashes, pancreatitis
(inflammation of the pancreas), seizures, and/or encephalitis (inflammation of the
brain). EBV is also associated with (and probably plays a role in) several rare forms
of cancer, including Burkitt’s lymphoma and nasopharyngeal carcinoma.
Reactivation of the virus is rarely a health concern unless the patient is significantly
and persistently immune compromised (as may happen in those who have HIV/AIDS
or in those who have received an organ transplant). Primary infections in these
patients can be more severe.
1. How is EBV infection/Mono treated?
Care is largely supportive, rest, treating the symptoms, avoiding any contact sports or
heavy lifting for several weeks (to avoid spleen rupture). There are no anti-viral
medications or vaccines available to speed healing or prevent infection.
2. Do adults get Mono?
They do, but it is rare because most have already been infected at an earlier age.
When they do, they tend to have less lymph node swelling and sore throat and more
liver enlargement and jaundice.
3. Do EBV infection and Mono occur throughout the world?

Yes. In less developed nations, however, Mono is not as common because most of the
population is infected with EBV earlier in life (when symptoms are minimal).
4. Can EBV be prevented?

Not at this time. It is too common in the population and, because the virus will
reactivate intermittently in a previously infected person (usually without causing any
symptoms), almost everyone is infectious at one time or another.
5. If I have had EBV infection, can I still get Mono?

No. Once you have had an EBV infection, you will not get Mono. You could,
however, experience similar symptoms from another viral illness.
6. Why is Mono sometimes called “the kissing disease”?

This is because EBV does not pass through the air; it is present in saliva and is passed
through mouth-to-mouth contact (and, in the case of children, through saliva transfer
to hands and/or toys, etc.).
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Epidermal Growth Factor Receptor
Also known as: EGFR, EGFR [Her-1], erbB-1

Why get tested?
To determine whether a solid tumor, such as of the lung (non small cell), head and
neck, colon, pancreas, or breast, is positive for EGFR, which helps to guide treatment
and determine prognosis
When to get tested?
If you have been diagnosed with certain invasive cancers and your doctor wants to
determine whether EGFR is being over-expressed in the tumor
Sample required?
A sample of tumor tissue obtained during a biopsy.
EGFR is one of a family of receptors that help regulate cell growth, division, and
death. Normal epithelial cells contain two copies of the EGFR gene and produce low
levels of EGFR protein on the surface of their cells. In a variety of cancers, there is an
increased amount of EGFR protein present in the tumor tissue. This can be due to
amplification (too many copies of the gene are produced), over-expression (an
increased amount of the protein is produced), and/or decreased protein destruction.
Tumors that have increased EGFR protein tend to grow more aggressively, are more
likely to metastasize, and are more resistant to standard chemotherapies. Patients with
these tumors tend to have a poorer outcome.
There are two main ways to test tumors for amplified or over-expressed EGFR: one
method measures the amount of EGFR protein present; the other looks at the genetic
level for gene amplification (evaluates the number of copies of the gene present).

A sample of cancer tissue is obtained by doing a biopsy. The biopsy procedure
required depends on the organ(s) affected.
How is it used?
EGFR testing is used as a prognostic marker to help determine how aggressive a
cancer is likely to be. It may be ordered on those diagnosed with cancer, such as non-
small cell lung cancer, glioblastoma (a type of brain cancer), cancer of the head and
neck, colon, breast, or pancreas.
When is it ordered?
EGFR testing may be ordered as part of an initial workup of particular cancers or
performed on those with certain cancers that are not responding to chemotherapy. It
may be done at any time, but it requires a sample of the tumor tissue. If a sample is
available from a previous biopsy, it can be done on that sample.
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EGFR testing is not diagnostic, but it helps the doctor understand more about the
tumor’s characteristics, evaluate a patient’s overall prognosis, and determine
treatment options. If testing using either of the methods is positive, then the patient is
more likely to have a tumor that is aggressive and resistant to chemotherapy.

EGFR blocking agents are routinely being used for treatment of colon cancer. Clinical
trials are ongoing to study their use in the treatment of non small cell lung cancer, and
their use may soon be considered for breast cancer treatment.
EGFR testing is not available in every laboratory. If your doctor sends your sample to
a reference laboratory, the results may take a few weeks to return.
1. Is there a blood test for EGFR?

Not yet. Researchers have been able to detect excess EGFR, produced by a tumor, in
the bloodstream but a clinically useful test is not yet available.
2.What is the difference between EGFR (Her-1) and Her-2/neu?

EGFR and Her-2/neu are both members of the same family of cell membrane
receptors. They are both measured in tumor tissue and evaluated for over-expression
or amplification. When either EGFR or Her-2/neu is significantly increased in a
cancer, it indicates a more aggressive tumor and a poorer patient prognosis. The
primary differences between EGFR and Her-2/neu are that they are ordered to help
evaluate different types of cancer and that the drugs that have been developed to
target them are specific for that particular receptor, EGFR or Her-2/neu.
Electrolytes
Why get tested?
To detect a problem with the body's fluid and electrolyte balance
When to get tested?
As part of routine health screening, when your doctor suspects that you have an
excess or deficit of one of the electrolytes (usually sodium or potassium), or if your
doctor suspects an acid-base imbalance.
Electrolytes are electrically charged minerals that are found in body tissues and blood
in the form of dissolved salts. They help move nutrients into and wastes out of the
body’s cells, maintain a healthy water balance, and help stabilize the body’s pH level.
The electrolyte panel measures the main electrolytes in the body: sodium (Na+),
potassium (K+), chloride (Cl-), and carbon dioxide (total CO2).
Most sodium is found in the plasma, outside of the body’s cells, where it helps to
regulate the amount of water in your body. Potassium is found primarily inside the
body’s cells. A small but vital amount of potassium is found in the plasma, the liquid
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portion of the blood. Monitoring potassium is important. Small changes in the K+
level can affect the heart’s rhythm and ability to contract. Chloride travels in and out
of the cells to help maintain electrical neutrality, and its level usually mirrors that of
sodium. The CO2 portion of the electrolyte panel measures mainly bicarbonate. The
primary role of bicarbonate, which is excreted and reabsorbed by the kidneys, is to
help maintain a stable pH level (acid-base balance) and, secondarily, to help maintain
electrical neutrality.
Your diet provides sodium, potassium, and chloride; your kidneys excrete them. Your
lungs provide oxygen and regulate CO2. The balance of these chemicals is an
indication of the functional well-being of several basic body functions, including
those performed by the kidneys and heart.
The electrolyte panel is composed of the individual tests for sodium, potassium,
chloride, and total carbon dioxide. A related "test" is the anion gap, which is actually
a value calculated using the results of an electrolyte panel. The occurrence of an
abnormal anion gap is non-specific but can suggest certain kinds of metabolic
abnormalities, such as starvation or diabetes, or the presence of a toxic substance,
such as oxalate, glycolate, or aspirin.
How is it used?
The electrolyte panel is frequently ordered as part of a routine physical, either by
itself or as components of a basic metabolic panel or comprehensive metabolic panel.
It is used to screen for an electrolyte or acid-base imbalance and to monitor the effect
of treatment on a known imbalance that is affecting bodily organ function. Since
electrolyte and acid-base imbalances can be present with a wide variety of acute and
chronic illnesses, the electrolyte panel is frequently ordered for hospitalized patients
and those who come to the emergency room.
If a patient has a single electrolyte that is high or low, such as sodium or potassium,
the doctor may order repeat testing of that individual electrolyte, monitoring the
imbalance until it resolves. If a patient has an acid-base imbalance, the doctor may
order blood gas tests, which measure the pH and oxygen and carbon dioxide levels in
an arterial blood sample, to help evaluate the severity of the imbalance and monitor its
response to treatment.
When is it ordered?
It may be ordered as part of a routine screening or as a diagnostic aid when a patient
has symptoms, such as edema, nausea, weakness, confusion, or cardiac arrhythmias. It
is frequently ordered as part of an evaluation when a patient has an acute or chronic
illness and at regular intervals when a patient has a disease or condition or is taking a
medication that can cause an electrolyte imbalance. Electrolytes are commonly used
to monitor treatment of certain problems, including high blood pressure, heart failure,
and liver and kidney disease.
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Electrolyte levels are affected by how much is taken in through your diet, the amount
of water in your body, and the amount of electrolytes excreted by your kidneys. They
are also affected by compounds such as aldosterone, a hormone that conserves sodium
and increases the loss of potassium, and natriuretic peptide, which increase renal
losses of sodium.
In specific disorders, one or more electrolytes may be in an abnormal concentration.

Your doctor will look at the overall balance but is especially concerned with your
sodium and potassium levels. People whose kidneys are not functioning properly, for
example, may retain excess fluid in the body, diluting the sodium and chloride so that
they fall below normal concentrations. Those who experience severe fluid loss may
show an increase in potassium, sodium, and chloride. Some forms of heart disease,
muscle and nerve problems, and diabetes may also have one or more abnormal
electrolytes.
Knowing which electrolytes are out of balance can help your doctor to determine the
cause and treatment to restore proper balance. If left untreated, electrolyte imbalance
can lead to dizziness, cramps, irregular heartbeat, and possibly death.
Depending on which electrolyte(s) is out of balance and the extent of that change,
treatment may involve changing your diet to lower salt intake, increasing fluids to
dilute the electrolyte concentration, taking diuretics, and medicating the imbalance.
Once a treatment has begun, you may be asked to get regular testing to determine how
well the treatment worked and to make sure the imbalance does not reoccur.
1. What is anion gap?
Anion gap (AG) is a value calculated using the results of an electrolyte panel. It is
used to help distinguish between anion-gap and non-anion-gap metabolic acidosis.
Acidosis refers to an excess of acid in the body; this can disturb many cell functions
and should be recognized as quickly as possible, when present. AG is frequently used
in the hospital and/or emergency room setting to help diagnose and monitor acutely ill
patients. If anion-gap metabolic acidosis is identified, the AG may be used to help
monitor the effectiveness of treatment and the underlying condition.
Specifically, the anion gap evaluates the difference between measured and
unmeasured electrical particles (ions or electrolytes) in the fluid portion of the blood.
According to the principle of electrical neutrality, the number of positive ions
(cations) and negative ions (anions) should be equal. However, not all ions are
routinely measured. The calculated AG result represents the unmeasured ions and
primarily consists of anions, hence the name “anion gap.” The most commonly used
formula is:
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Anion Gap (AG) = Sodium - (Chloride + Carbon Dioxide)
However, there are other AG formulas, so reference ranges are not interchangeable.
Each laboratory formula will have an established normal range that should be
referenced.
The anion gap is non-specific. It is increased when the number of unmeasured anions
increases, indicating a state of anion-gap metabolic acidosis, but it does not tell the
doctor what is causing the imbalance. The metabolic acidosis must be treated to
restore the acid/base balance, but the underlying condition must also be identified and
treated. Causes can include uncontrolled diabetes, starvation, kidney damage, and
ingestion of potentially toxic substances such as antifreeze, excessive amounts of
aspirin, or methanol. A low anion gap can also occur; this is most commonly seen
when albumin (an anion as well as a protein) is low, while immunoglobulins (cations
as well as proteins) are increased.
Ethanol
Also known as: Ethyl Alcohol, Alcohol, EtOH

Why get tested?
To determine if a person has consumed ethanol and to measure the amount of ethanol
present
When to get tested?
When a patient has symptoms that suggest ethanol toxicity or when a person is
suspected of violating drinking-related laws or as part of a drug testing panel
Sample required?
Ethanol may be determined from a blood sample, a urine sample, a saliva sample or a
breath sample. Blood, urine, and saliva samples must be sent to a laboratory for
analysis. A breath sample is analyzed immediately on site using a Breathalyzer.
This test measures the amount of ethanol in the blood, urine, breath, or saliva. Ethanol
(also called ethyl alcohol or alcohol) has been consumed by civilizations throughout
the world for thousands of years. Small amounts of ethyl alcohol can cause euphoria,
relaxation, and decreased inhibition. Moderate amounts can cause impaired judgment
and decreased motor skills; large amounts in a relatively short period of time can
cause acute ethanol toxicity with disorientation, depressed breathing, coma, and even
death. Chronic ingestion of large quantities of alcohol can lead to alcoholism and to
permanent liver damage.
When ethanol is consumed, it is absorbed by the gastrointestinal tract, and carried

throughout the body in the bloodstream. Small amounts of ethanol are excreted in the
urine or exhaled from the lungs, but most is metabolized by the liver. The liver
considers ethanol a toxin. With the help of enzymes, it oxidizes the alcohol first to
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acetaldehyde, then to acetate, and then finally to carbon dioxide and water. The liver
can process about one drink an hour – with one drink being defined as the amount of
ethanol in 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of whisky. A person
who drinks more than 1 drink an hour will have a build up of ethanol in their blood
stream.

A blood sample is obtained by inserting a needle into a vein in the arm; a breath
sample is collected by blowing into a tube or balloon. Urine samples are collected in
plastic containers; sometimes a single urine sample is collected and sometimes two
separate samples may be collected with the first discarded and the second collected
after a measured time. Saliva samples are often collected from the mouth using a
swab.
How is it used?
The ethanol/alcohol test is used for both medical and legal purposes. Samples and
results for each use are usually collected and tested separately.
Medical: The goal of medical testing is to identify the presence of alcohol in order to
effectively treat the patient's symptoms. For medical purposes, blood, and sometimes
urine, alcohol tests are used to detect the presence of ethanol and to evaluate its
concentration. One or more of these tests may be ordered when a patient presents to
the Emergency Room with symptoms suggesting ethanol toxicity. Symptoms may
include confusion, staggering, vomiting, lethargy, and unconsciousness. Other tests,
such as a Complete Blood Count (CBC), glucose, and electrolytes are often ordered at
the same time as there are a variety of other conditions that can cause similar
symptoms. Additional drug testing and testing for the presence of other more toxic
alcohols (such as methanol and isopropyl alcohol) may also be performed if the use of
other substances is suspected.
Legal: The goal of legal testing is to identify the presence of alcohol and to evaluate
its presence in the context of a variety of different laws. Legal testing must be done by
specially trained people and must have a strict chain-of-custody (a paper trail that
records sample movement and handling). Testing may be ordered to determine
whether an erratic driver has a blood alcohol concentration that is over the legal limit,
to determine whether an under-age minor has been drinking, whether someone on
parole has abstained from alcohol, and to determine whether alcohol consumption has
contributed to an accident. Post-mortem ethanol testing may be done to determine
whether alcohol contributed to a person’s death. Legal ethanol testing may also be
performed randomly or “with cause” as part of an employer's drug testing program to
determine whether an employee has alcohol in their system. It may also be part of the
testing that is done as part of an application for life insurance. (These uses are
considered legal alcohol tests because they require chain-of-custody documents.)
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Samples tested for legal purposes may include blood, breath, urine, and/or saliva
testing. Breath testing is the most common test performed on drivers. It uses the tail
end sample of breath from deep in the lungs and uses a conversion factor to estimate
the amount of alcohol in the blood. Blood alcohol testing may be ordered to confirm
or refute findings, and/or ordered as an alternative to breath testing. Urine testing may
also be performed as an alternative. Usually, a patient collects and discards a urine
sample and then collects a second sample 20 to 30 minutes later. The amount of
alcohol in the first sample will be variable because it is unknown how long the urine
has been in the bladder. The second sample will reflect a timed sample, and a
different conversion factor can then be used to estimate blood alcohol. A random
urine sample is sometimes ordered to monitor people for the presence of alcohol.
Saliva alcohol testing is not as widely used, but may be used as an alternate screening
test.
When is it ordered?
Medical ethanol testing is ordered when a patient has symptoms that suggest
intoxication and or ethanol toxicity.
Legal ethanol testing may be ordered whenever there is reason to suspect that a person
has not followed a drinking-related law, and whenever there has been an accident
and/or unexpected death – to determine whether alcohol played a role. Employment
alcohol testing may be performed randomly and when the employer suspects that an
employee has alcohol in their system while on the job. Insurance testing is primarily
performed when a person is applying for a policy.

For medical testing, the detection of ethanol in a sample indicates that a person has
likely been drinking, and the concentration present can give an indication of how
severe the degree of ethanol toxicity is. Symptoms and complications may vary
significantly from person to person, however, depending on their general health, age,
and other medications or drugs that they are taking. The ability to clear the alcohol out
of their body also depends on the availability of the necessary enzymes and the
functioning of the patient’s liver. For legal testing, results obtained are compared to
legal allowable limits.

Different ethanol sample results are not interchangeable. Breath and urine samples are
considered to be good estimates of blood alcohol concentrations in most people but
can be affected by a variety of factors. Urine concentrations lag behind blood
concentrations. Urine samples that contain both glucose and microorganisms (such as
may be seen in diabetics) should not be left at room temperature for extended periods
of time as there is the potential for the microorganisms present to ferment the glucose
in the sample and produce ethanol. This can also be seen in post mortem samples.
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Occasionally two serotonin metabolites, 5-HIAA (5-hydroxyindoleacetic acid) and 5-
HTOL (5-hydroxytryptphol), may be tested to evaluate this phenomenon and confirm
ethyl alcohol ingestion. An increased ratio of 5-HTOL/5-HIAA can be indicative of
alcohol consumption.
Breath sample concentrations can be affected by alcohol consumption within the last
few minutes, ketones (released into the breath by some diabetics and dieters), and by
other substances that contain alcohol such as mouthwash and cough syrup.
1. Are medical ethanol results released for legal purposes?

Rules vary from state to state. In most cases, medical and legal results are evaluated
separately.
2. Can I choose which sample will be collected?

In most cases, there is a primary type of sample that is collected, but another
alternative is often available for confirmation and/or to refute findings.
3. Does everyone metabolize alcohol at the same rate?
A general rule of thumb is one drink equivalent an hour, but there is individual
variation due to differences in factors such as race, gender, and body weight.
Protein Electrophoresis
Immunofixation Electrophoresis
Why get tested?

To help diagnose and monitor multiple myeloma and a variety of other conditions that
affect protein absorption, production, and loss as seen in severe organ disease and
altered nutritional states
When to get tested?
If you have an abnormal total protein or albumin level or if your doctor suspects that
you have a condition that affects protein concentrations in the blood and/or causes
protein loss through the urine.

Protein electrophoresis is a method for separating the proteins found in blood (serum)
or urine. During the test, an electric current is used to move the proteins across a thin
layer of gel-like agar. The distances that individual proteins travel depend on their
size, shape, and electrical charge. These separated proteins may be detected by the use
of a dye that binds to (stains) all of the proteins and reveals a characteristic pattern of
bands. Each band indicates the presence of a particular protein, while the size of the
band is a rough indication of the quantity. This pattern of bands is converted into a
visual graph, showing vertical spikes or peaks where there is a lot of a particular
protein and smaller peaks or valleys where there is less. A newer method called
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capillary zone electrophoresis (CZE) separates proteins by passing them through a
long, thin column, producing a graph that is very similar to the one made by running
the protein through an agarose gel.
Specific proteins of interest can be identified by first fixing them into the gel with
antibodies, then washing away all the other proteins prior to staining. This procedure
is called immunofixation electrophoresis (IFE). A slightly different method,
immunoelectrophoresis, was used in the past to identity specific proteins. However,
this technique has been largely superceded by IFE because IFE is easier to perform
and interpret.
Serum proteins are separated into five or six major groupings by protein
electrophoresis. These fractions are called albumin, alpha 1, alpha 2, beta, and gamma
(the beta fraction is sometimes divided into beta 1 and beta 2). Albumin, which is
produced in the liver, forms its own group and accounts for about 60% of the protein
in the blood. “Globulins” is a collective term used to refer to proteins other than
albumin. With the exception of the immunoglobulins and some complement proteins,
most of the globulins are also produced in the liver. These groups are described more
fully in the table, Protein Groups.
The bands seen on protein electrophoresis form characteristic patterns. Alterations to

these patterns are associated with a variety of different diseases and conditions. For
example, in multiple myeloma (a cancer of plasma cells), the uncontrolled growth and
division of a malignant plasma cell leads to the production of large amounts of a
single type of monoclonal immunoglobulin. In contrast to other proteins in serum,
which are typically of a single type, antibodies (immunoglobulins) must differ from
each other to be able to recognize bacteria, viruses, and other “foreign” substances.
Each time the body is exposed to a virus, for example, one plasma cell replicates and
makes a group (or clone) of plasma cells to produce antibody to eliminate it. Since our
total immunoglobulin represents antibody made by many clones, we refer to it as a
polyclonal pattern. When there is a cancer of plasma cells, only one type of antibody
is produced, termed a monoclonal protein. This abnormal protein can be seen as a
characteristic band on the electrophoresis gel.
How is it used?
Electrophoresis is used to identify the presence or absence of aberrant proteins and to
identify when different groups of proteins are increased or decreased in serum or
urine. It is frequently ordered to detect and identify monoclonal proteins (an excessive
production of one specific immunoglobulin). Protein and immunofixation
electrophoresis are ordered to help detect, diagnose, and monitor the course and
treatment of conditions associated with these abnormal proteins, including multiple
myeloma and a few related diseases.
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Protein is usually excreted in the urine in minute amounts. When it is present in
moderate to large amounts, it often indicates a problem with the kidneys. The primary
reason protein and immunofixation electrophoresis are ordered on urine is to look for
monoclonal protein production. This protein may show up in both the serum and
urine, or it may only be seen in the urine. An example of this is Bence Jones protein,
which is the free light chain component of antibodies. (Normally, antibodies are
composed of four parts, two identical heavy chains and two identical light chains.
Sometimes, in multiple myeloma, only one or the other is produced, or it may be
produced in excess.) The small size of Bence Jones protein allows it to pass through
the kidneys and enter the urine.
Urine protein electrophoresis may also be ordered to help diagnose the cause and
estimate the severity of protein excretion due to kidney damage or disease. This
damage or disease may be due to diabetes, chronic inflammation, an autoimmune
condition, or a malignancy. Electrophoresis is not usually necessary to assess the loss
of small to moderate amounts of protein due to temporary conditions, such as a
urinary tract infection or an acute inflammation.
When is it ordered?
Protein electrophoresis may be ordered when a doctor is investigating symptoms that
suggest multiple myeloma, such as bone pain, anemia, fatigue, unexplained fractures,
and recurrent infections. It may also be ordered as a follow-up to other laboratory
tests, such as an abnormal total protein and/or albumin level, elevated urine protein
levels, elevated calcium levels, and low white or red blood cell counts.
Immunofixation electrophoresis is usually ordered when the protein electrophoresis
test shows the presence of an abnormal protein band that may be an immunoglobulin.
Electrophoresis tests are most frequently ordered when a doctor suspects a disease or
condition that causes a monoclonal protein to be produced. Once a disease or
condition has been diagnosed, electrophoresis may be ordered at regular intervals to
monitor the course of the disease and the effectiveness of treatment. As disease
progresses, the amount of protein goes up; with treatment, it does down. Monoclonal
protein production may be due to a malignant disease, such as multiple myeloma, but
it may also be due to a monoclonal gammopathy of undetermined significance
(MGUS). Most patients with MGUS have a benign course, but they must continue to
be monitored regularly as some may develop multiple myeloma after a number of
years.
Serum protein electrophoresis may also be ordered when symptoms suggest an

inflammatory condition, an autoimmune disease, an acute or chronic infection, a
kidney or liver disorder, or a protein-losing condition, even if the total protein and/or
albumin concentrations are apparently normal. Urine protein electrophoresis may be
ordered when there is protein detected in the urine or when the doctor suspects a
monoclonal protein may be present.
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Protein and immunofixation electrophoresis tests give your doctor a rough estimate of
how much of each protein is present. The value of protein electrophoresis lies in the
proportions of proteins and in the patterns they create on the electrophoresis graph.
The value of immunofixation electrophoresis is in the identification of the presence of
a particular type of immunoglobulin.
For example, certain conditions or diseases may be associated with decreases or

increases in various serum proteins, as reflected below:
Albumin Decreased: with malnutrition and malabsorption, pregnancy, kidney disease

(especially nephrotic syndrome), liver disease, inflammatory conditions, and protein-
losing syndromes
Increased: with dehydration
Alpha1 globulin Decreased: in congenital emphysema (a1-antitrypsin deficiency, a

rare genetic disease) or severe liver disease
Increased: in acute or chronic inflammatory diseases
Alpha2 globulin Decreased: with hyperthyroidism or severe liver disease, hemolysis

(red blood cell breakage)
Increased: with kidney disease (nephrotic syndrome), acute or chronic inflammatory
disease
Beta globulin Decreased: with malnutrition, cirrhosis

Increased: with hypercholesterolemia, iron deficiency anemia, some cases of multiple
myeloma or MGUS
Gamma globulin Decreased: variety of genetic immune disorders, and in secondary

immune deficiency
Increased: Polyclonal: chronic inflammatory disease, rheumatoid arthritis, systemic
lupus erythematosus, cirrhosis, chronic liver disease, acute and chronic infection,
recent immunization. Monoclonal: Waldenstrom’s macroglobulinemia, multiple
myeloma, monoclonal gammopathies of undetermined significance (MGUS)

Immunizations within the previous six months can increase immunoglobulins as can
drugs such as phenytoin (Dilantin), procainamide, oral contraceptives, methadone,
and therapeutic gamma globulin.
Aspirin, bicarbonates, chlorpromazine (Thorazine), corticosteroids, and neomycin can
affect protein electrophoresis results.
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1. Why might my doctor do an electrophoresis when my total protein and
albumin are normal?
He may do a serum electrophoresis because you may have an abnormality even
though the total protein and albumin are normal. This is because the body tries to
maintain a constant amount of protein and may increase or decrease its production of
other proteins to compensate for a deficiency or overproduction of others. Your
doctor may order a urine electrophoresis when there is protein in your urine, because
you may lose protein in your urine even if your blood levels are fairly stable.
2. Is electrophoresis used for anything else?

Yes, any time protein separation is desired. DNA electrophoresis, for instance, is used
to help study the genetic makeup of plants, animals, and humans.
Estrogen
Also known as: Estrogen fractions (over 30 different forms of estrogen have been
described; the most common forms tested are estrone [E1], estradiol [estradiol-17
beta, E2], and estriol [E3]) .
Why get tested?
To measure or monitor your estrogen levels if you are a woman who has unexplained
abnormal menstrual cycles, abnormal or heavy bleeding, infertility, symptoms of
menopause, or any other hormonal alterations; also used to test for fetal-placental
status during early stages of pregnancy; the presence of female-like characteristics in
males may require estrogen measurement as well
When to get tested?
When your doctor thinks that you have symptoms of a hormone imbalance, abnormal
vaginal bleeding, unusual and/or early sex organ development (female), or when your
doctor wants to monitor the health of your placenta and fetus during pregnancy
Sample required?
A blood sample drawn from a vein in your arm, a 24-hour urine sample, or (in some
cases) a fresh saliva sample.
Estrogen is a group of hormones primarily responsible for the development of female
sex organs and secondary sex characteristics. While estrogen is one of the major
female sex hormones, small amounts are found in males. In women, follicular
stimulating hormone (FSH; produced by the pituitary gland) stimulates cells
(follicles) surrounding the eggs in the ovaries, causing them to produce estrogen.
When the estrogen levels reach a certain level, the pituitary produces a surge of
luteinizing hormone (LH), which eventually causes the release of the egg, beginning
the preparation for fertilization.
There are three main estrogen fractions: estrone (E1), estradiol (E2), and estriol (E3).
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 Estrone (E1) is the major estrogen after menopause. It is derived from
metabolites from the adrenal gland and is often made in adipose tissue (fat).
 Estradiol (E2) is produced in women mainly in the ovary. In men, the testes
and adrenal glands are the principal source of estradiol. In women, normal
levels of estradiol provide for proper ovulation, conception, and pregnancy, in
addition to promoting healthy bone structure and regulating cholesterol levels.
 Estriol (E3) is the major estrogen in pregnancy, with relatively large amounts
produced in the placenta (from precursors produced by the fetal adrenal glands
and liver). Estriol levels start to rise in the eighth week of pregnancy and
continue to rise until shortly before delivery. Serum estriol circulating in
maternal blood is quickly cleared out of the body. Each measurement of estriol
is a snapshot of what is happening with the placenta and fetus, but there is also
natural daily variation in the estriol level.
How is it used?
Estrone tests may be done to aid in the diagnosis of an ovarian tumor, Turner’s
syndrome, and hypopituitarism. In males, it may help in the diagnosis of the cause of
gynecomastia or in the detection of estrogen-producing tumors.
Estradiol levels are used to help evaluate ovarian function. Estradiol helps diagnose
the cause of precocious puberty in girls and gynecomastia in men. Its main use has
been in the differential diagnosis of amenorrhea (for example, to determine whether
the cause is menopause, pregnancy, or a medical problem). In assisted reproductive
technology (ART), serial measurements are used to monitor follicle development in
the ovary in the days prior to in-vitro fertilization. Estradiol is also sometimes used to
monitor menopausal hormone replacement therapy.
Estriol, along with alpha-fetoprotein (AFP maternal), human chorionic gonadotropin

(hCG), and inhibin-A (an ovarian and placental hormone) tests, are used to assess the
risk of carrying a fetus with certain abnormalities, such as Down syndrome.
When is it ordered?
Your doctor may order an estrone or estradiol (along with other tests) if you have
symptoms such as pelvic heaviness, abnormal vaginal bleeding, abnormal menstrual
cycles, or if your sex organs (women’s) are developing earlier or later than normally
expected. They may also order estrone and/or estradiol if you are having hot flashes,
night sweats, insomnia, and/or amenorrhea, symptoms of menopause. If you are on
hormone replacement therapy, your doctor may use estrone levels to monitor your
treatment.
If you are having fertility problems, your doctor may use estradiol measurements over
the course of your menstrual cycle to monitor follicle development prior to in vitro
fertilization techniques (timed with a surge in your estradiol level).
If you are pregnant, your doctor may order serial (multiple) samples to look for a
trend, a rise or fall in the estriol level over time. Unconjugated estriol (estriol not
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bound to sex hormone binding globulin) is often measured in the 15th to 20th week of
gestation as part of the triple screen.
Increased or decreased levels of estrogen are seen in many metabolic conditions. Care
must be used in the interpretation of estrone, estradiol, and estriol levels because their
levels will vary on a day-to-day basis and throughout the menstrual cycle. If your
doctor is monitoring your hormone levels, s/he often will be looking at trends in your
levels, rising or lowering over time, rather than at single values. Below are conditions
where one might see an increase or decrease of estrogen levels. It must be
remembered that a diagnosis cannot be made solely based on one test result.
Increased levels of estrogen Decreased levels of estrogen

are seen in: are seen in:
Normal pregnancy Turner syndrome
Precocious puberty Hypopituitarism
Tumors of the ovary, testes, or adrenal Hypogonadism
Cirrhosis After menopause (estradiol)
Failing pregnancy (estriol)
Stein-Levanthal syndrome
(polycystic ovary syndrome)
Anorexia nervosa
Extreme endurance exercise

Blood, urine, and saliva results are not interchangeable. Your doctor will choose
which estrogen and sample type to test for based upon what they are looking for.
Beyond daily and cycle variations, illnesses such as hypertension (high blood
pressure), anemia, and impaired liver and kidney function can affect estrogen levels in
the body.
Some drugs, such as glucocorticosteroids, ampicillin, estrogen-containing drugs,
phenothiazines, and tetracyclines can increase estrogen levels, as can glucose in the
urine and urinary tract infections. Drugs that may decrease levels include clomiphene.
1. Do all males have estrogens?
Yes. Although they are present in amounts far less than in women, they are present
and are needed for hormonal balance and the function of other glands.
2. What are estrogen receptors?
Estrogen receptors are proteins, located on cells from certain tissues, that bind with
estrogen. One risk factor for breast cancer is the presence of excess estrogen. This
excess exposure to estrogen seems to stimulate cancer cell growth, especially if the
tumor contains estrogen receptors. Drugs that block the effect of estrogen may slow
the rate of growth of such cancers.
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3. What are phytoestrogens and environmental estrogens?
Phytoestrogens are estrogen-like compounds from plant sources. The two main
classes are isoflavones, found in soy products, and lignans, found in whole grains and
some fruits and vegetables. It has been proposed that these products could be used as
an alternative to hormone replacement therapy (HRT). Initial studies have shown the
relief of some menopausal symptoms, such as hot flashes, but there is more research
yet to be done.
Environmental estrogens are chemicals, either natural (such as plant sources) or man-
made (such as the insecticide DDT), that mimic the effect of estrogen and may cause
disorders such as infertility, overgrowth of the endometrial lining, premature breast
development, and feminization in young males. They tend to stay in the body for long
periods of time and are being studied for their long-term effects.
4. Where can I find more information on estrogen?

Your doctor may have educational information about estrogen. There is also a great
deal of information on the internet. Some of the best and newest information is
provided by government sources and various national organizations. (See the Links
page for a start.)
Factor V Leiden and PT 20210
Also known as: Factor V Leiden: Activated Protein C Resistance (APC) resistance,
Factor V R506Q; PT 20210: PT G20210A.
Why get tested?
To determine whether you have an inherited gene mutation that increases your risk of
developing a venous thromboembolism (VTE – inappropriate blood clot formation
that blocks the flow of blood in a vein).
When to get tested?
When you have had an unexplained thrombotic episode, especially when you are
relatively young (less than 50 years old) and have no other identified risk factors.
Factor V Leiden and prothrombin 20210 are coagulation factors - a series of proteins
that are activated in a step by step process (called the coagulation cascade) when a
blood vessel is injured. The end result of the coagulation cascade is a blood clot that
creates a barrier over the injury site, protecting it until it heals.
Factor V Leiden is a variant form of Factor V that is caused by a genetic point
mutation - a change in one of the nucleotides on the gene that guides the creation of
Factor V protein. This altered protein activates normally to form, but it resists being
degraded by activated Protein C (APC) during the coagulation cascade. The result of
this resistance is an increased level of thrombin in the blood and an increased risk of
recurrent venous thromboembolism (VTE). It is associated with pulmonary embolism
(blood clots in the lungs) and with recurrent miscarriages, especially in the 2nd and 3rd
trimesters.
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Prothrombin (PT) 20210 is a variant form prothrombin, also caused by a genetic point
mutation. PT 20210 is also associated with an increased risk of VTE.
Factor V Leiden and PT 20210 are independent mutations -- testing of each is

intended to identify whether or not the mutation is present and to determine whether
the person is heterozygous or homozygous for that mutation.
How is it used?
Factor V Leiden and Prothrombin 20210 tests are ordered, along with other tests
related to hypercoagulability, to help diagnose the cause of venous thromboembolism
(VTE). They are used to help determine the reason for an initial thrombotic episode,
especially when it occurs in a relatively young person (under 50 years old), is
unprovoked, or is in an unusual place such as the liver (hepatic), the kidneys (renal),
the brain (cerebral), the pelvis, or in the eye veins. They may also be ordered to
investigate multiple miscarriages, especially when they occur in the 2nd or 3rd
trimester. It is thought that blood clots may affect the placental veins.
Activated Protein C (APC) resistance testing is done to screen for Factor V Leiden.
About 95% of the time, those who have APC resistance will have a Factor V Leiden
mutation. If resistance is present, then a test for the Factor V Leiden gene mutation is
done, both to confirm the diagnosis and to determine whether the patient is
heterozygous or homozygous for the mutation.
The PT 20210 mutation must be diagnosed with genetic testing, checking directly for
the gene mutation, and determining whether the patient is heterozygous or
homozygous. Although prothrombin levels are usually moderately elevated with this
mutation and could be measured, they are not clinically useful in finding this
mutation.
At this time, experts do not recommend screening the general population and are
divided on testing family members of those with a Factor V Leiden or PT 20210
mutation. If the mutation is present, then the person is at a higher risk for developing a
blood clot, but there is variability in how the gene is actually expressed. Many of
those who do have the mutation(s) will never have a VTE.
When is it ordered?
PT 20210 and Factor V Leiden tests are ordered when a patient has a first venous
thromboembolism (VTE) at a relatively young age (less than 50 years old), or in an
unusual part of the body. They may be ordered when a patient has a personal or
family history of recurrent VTE, a first VTE related to oral contraceptive use,
pregnancy, or hormone replacement therapy, or when they are experiencing
unexplained miscarriages especially those occurring in the 2nd or 3rd trimester of the
pregnacy.
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They may or may not be ordered when a family member has a Factor V Leiden or PT
20210 gene mutation. If asymptomatic patients know they have one or more of the
mutations, they may be able to address other controllable clotting risk factors such as
oral contraceptive use, smoking, and hyperhomocysteinemia, and be aware of the risk
factor(s) during exposure to triggering events -- such as immobilization and surgery.
On the other hand they may have the mutation and never have a VTE.
Once APC Resistance testing, Factor V Leiden mutation testing, and PT 20210 gene
mutation testing has been done it is usually not repeated unless there is a need for
verification.

Resistance to Activated Protein C is due to Factor V Leiden 95% of the time, but if
resistance is present the Factor V Leiden mutation should be confirmed with genetic
testing.
Factor V Leiden is the most common inherited clotting disorder in the United States.
Its prevalence is increased in those of European descent, being present in about 5% of
the Caucasian population. A patient with Factor V Leiden may be heterozygous (has
one copy of the changed gene and one normal gene) or homozygous (has two copies
of the changed gene, this is more rare). Those that are heterozygous have about a 5-
10% greater risk than normal of developing a venous thromboembolism (VTE), while
those who are homozygous have a much greater risk of thrombosis, about 80%.
If you have a single gene copy with the PT 20210 mutation, then you are
heterozygous, if both copies are changed, then you are homozygous. Someone with a
heterozygous or homozygous PT 20210 mutation will have a mild to moderate
increase in their thrombin production, raising their risk of developing a VTE a small
but significant amount. Although PT 20210 is less common in the U.S. than Factor V
Leiden (about 1-2% of the general population), it is also more prevalent in Caucasians
than in those of other ethnic backgrounds.

The risks that are associated with Factor V Leiden, PT 20210, and other inherited and
acquired factor deficiencies that are thrombophilic (increase the risk of developing
blood clots ? such as protein C and protein S deficiencies) are independent.You can
have more than one of them and their associated risks are cumulative. Added to these
inherited risks and acquired risks are controllable risk factors, such as oral
contraceptive use, that may exacerbate the combined underlying risk factors. For
instance, if you are heterozygous for Factor V Leiden. you may be at about a 10%
greater than normal risk of developing a VTE. If you use oral contraceptives, that risk
can jump to 35%.
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Pseudohomozygous Factor V Leiden is a very rare condition. It is caused by the
heterozygous inheritance of a Factor V Leiden mutation and a heterozygous Factor V
deficiency. Patients with these mutations have decreased normal Factor V levels as
well as mutated Factor V Leiden protein. Their risk levels are similar to that of a
person who is homozygous for Factor V Leiden mutation.
1. Should someone with a Factor V mutation be on long term anticoagulant
therapy?
Factor V Leiden and prothrombin 20210 are coagulation factors - a series of proteins
that are activated in a step by step process (called the coagulation cascade) when a
blood vessel is injured. The end result of the coagulation cascade is a blood clot that
creates a barrier over the injury site, protecting it until it heals.
2. How is a VTE treated?

Regardless of the underlying cause, a VTE is usually treated with a short course of
anticoagulants (often 3-6 months with a combination of heparin, warfarin, and low-
molecular weight heparins). At the end of this time period the patients risk level is
assessed to see if further treatment is necessary.
Fecal Occult Blood Test
Why get tested?
To screen for gastrointestinal bleeding, which may be an indicator of colon cancer
When to get tested?
As part of a routine examination, annually after age 50 (as recommended by the
American Cancer Society and other major organizations), and as directed by your
doctor
Sample required?
One or more stool samples.
The fecal occult blood test (FOBT) checks for blood in your stool. Normally, there
will not be enough blood lost through the gastrointestinal tract to turn an FOBT
positive or for you to notice it visually in the form of bloody or dark, tarry stools. Any
significant amount of blood being passed should be investigated.
A positive FOBT will tell your doctor that you have bleeding occurring somewhere in
your gastrointestinal tract. This blood loss could be due to ulcers, diverticulosis,
bleeding polyps, inflammatory bowel disease, hemorrhoids, from swallowed blood
due to bleeding gums or nosebleeds, or it could be due to benign or cancerous tumors.
Anything that protrudes into the lumen (the empty space in the intestine), like a polyp
or tumor, and is rubbed against by the fecal waste as it passes through has the
potential to eventually bleed intermittently. Often this small amount of blood is the
first, and sometimes the only, symptom of early colon cancer, making the FOBT a
valuable screening tool.

There are several methods for fecal occult blood testing: the guaiac smear method
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(gFOBT), still preferred by doctors, an over-the-counter (OTC) flushable reagent
pad/tissue method, and methods involving immunochemical assay (iFOBT).
If the guaiac smear or OTC pad methods are being used, your doctor will probably
give you some instructions about dietary restrictions that you should follow and
medications that you should avoid before collecting the FOBT samples. For example,
you should not eat red meat within three days before testing. Other substances that
could cause a false positive test result include fish, turnips, horseradish, and drugs
such as colchicines and oxidizing drugs (for example, iodine and boric acid). Be sure
to carefully follow your doctor's instructions.
With gFOBT, your doctor or laboratory will give you one or more test "cards." You
collect a separate sample from three different stools, usually on consecutive days.
Each stool sample should be collected into a clean container and should not be
contaminated with urine or water. The slide is labeled with your name and the date;
then, with an applicator stick, you apply a thin smear of stool onto each filter paper
square/window contained on the card. Allow the filter paper to dry. Once it is dry, it is
stable. Usually you will collect all of the consecutive samples, then return all of them
to your doctor/laboratory at the same time, sometimes by mailing them.
With the OTC flushable reagent pad/tissue method, you buy test pads/tissues, then
place a test pad/tissue in the toilet after a bowel movement and watch for a color
change. These are also usually done on consecutive days.
With iFOBT, the collection method will depend on the test kit you are using. You
may need to use a special brush to swirl in the toilet bowl and collect some of the
water from around the stool. You would then dab the brush onto a special collection
card and wait for it to dry. Then you would return the card to your doctor or
laboratory. Two or three samples may be needed.
How is it used?
The main use for the FOBT is as a screen for early colon cancer. Blood in the stool
may be the only symptom of early cancer. If the cancer is detected before it
metastasizes (spreads to other areas), the chance that it will be curable is increased.
The FOBT is not diagnostic for cancer; other follow-up procedures would need to be
done to find the source of the bleeding because the blood may also indicate other
gastrointestinal problems.
A secondary use of FOBT is to look for a cause of anemia, such as might be caused
by a bleeding ulcer. If you have symptoms of anemia, such as fatigue or a low
hemoglobin and hematocrit, and/or bloody or dark stools, your doctor may look at the
FOBT.
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When is it ordered?
Fecal occult blood tests are done as part of a routine examination and are
recommended annually after age 50 (by the American Cancer Society and other major
organizations) or as directed by your doctor. Most people who have them done are
asymptomatic. They are used primarily as a screening tool for early detection of colon
cancer.
Your doctor may also order an FOBT if s/he suspects that you have an unexplained
anemia or symptoms, such as bloody or dark, tarry stools.
The FOBT test is normally negative. A positive indicates either blood in the stool or
an interfering substance. Multiple samples are done to: 1) catch intermittent bleeding;
and 2) help rule out false positives.
False positives can occur with FOBT. Depending on the method used, you may need
to avoid: 1) substances or conditions that cause bleeding, such as bleeding gums
following a dental procedure or drugs that may cause gastrointestinal bleeding, such
as anticoagulants, aspirin, steroids, and large doses of iron preparations; 2) other
sources of hemoglobin, such as the ingestion of red meat within three days before
testing; and 3) other substances, such as fish, turnips, horseradish, or drugs such as
colchicines and oxidizing drugs (for example, iodine and boric acid). Your doctor
may have you stay off your medications and follow dietary restrictions before
collecting the FOBT samples.
False negatives may be caused by large doses of vitamin C and by not collecting
multiple samples (because cancers and precancerous polyps produce blood
intermittently).
1. Is the OTC at home test just as good?

While the OTC tests that are dropped into the toilet are fairly sensitive, your doctor
may still prefer the guaiac smear test (even though patients often find stool handling
unpleasant). This may be because the guaiac test has a longer history, because the
interpretation is done by professionals (who are used to looking at them and ruling out
false positives and false negatives), or because your doctor will have more of an
opportunity to know about and follow-up on a positive FOBT result.
2. What kind of procedures might follow a positive FOBT?

An FOBT may be preceded or followed by a digital rectal exam. A positive FOBT
may be followed by:
 Sigmoidoscopy: an examination of the rectum and lower colon with a lighted

instrument to look for abnormalities, such as polyps;
 Colonoscopy: a more thorough examination of the rectum and entire colon;
and
 A double contrast barium enema: a series of x-rays of the colon and rectum.
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fFN
Formal name: Fetal fibronectin

Why get tested?
To help evaluate a pregnant woman’s risk of preterm delivery
When to get tested?
When you are 26 to 34 weeks pregnant and are having symptoms of premature labor
Sample required?
A cervical or vaginal fluid sample.
Fetal fibronectin (fFN) is a glycoprotein that can be used to help predict the short term
risk of premature delivery. fFN is produced at the boundary between the amniotic sac
and the lining of the mother’s uterus (the decidua) in an area called the uteroplacental
(or choriodecidual) junction. Fetal fibronectin is largely confined to this junction and
thought to help maintain the integrity of the boundary. fFN is normally detectable in
cervicovaginal fluid during the first 20 to 24 weeks of pregnancy, and then detectable
again after about 36 weeks.
Finding fFN in cervicovaginal fluids after 36 weeks is not unusual as it is often

released by the body as it gets ready for childbirth. The elevated fFN found in vaginal
fluids early in pregnancy may simply reflect the normal growth and establishment of
tissues at the unteroplacental junction with levels falling when this phase is complete.
What is known is that fFN that is detectible between 24 and 36 weeks of pregnancy is
not normal. Elevated levels reflect a disturbance at the uteroplacental junction and
have been associated with an increased risk of pre-term labor and delivery.
A Dacron swab is used to take a sample of cervical or vaginal fluid from the posterior
portion of the vagina or from the area just outside the opening of the cervix.
How is it used?
Many pregnant women experience symptoms that suggest preterm labor. These may
include uterine contractions, changes in vaginal discharge, backaches, pelvic pressure,
cramping, and cervical dilation. Not all symptomatic women will actually have a
preterm delivery, though. Unfortunately, while premature births can have successful
endings, serious complications are possible when a baby leaves the womb early.
Babies that are less than 37 weeks old frequently have difficulty breathing, eating and
regulating their body temperature. Their lungs and organs are immature and do not
function normally and the strain on them can cause persistent health problems.
Knowing whether or not a woman is likely to deliver prematurely helps the doctor to
plan a course of action. The fFN test is a relatively noninvasive tool to help the doctor
to distinguish between those who are likely to deliver shortly and those who are not.
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Fetal fibronectin is used to screen pregnant women who are within 26 weeks and 34
weeks of gestation and are having symptoms of premature labor. The test helps
predict the risk of premature delivery.
The fetal fibronectin test should only be used on those who:
 Have intact amniotic membranes

 Have a cervix that has not dilated more than 3 centimeters
 Do not have more than slight vaginal bleeding
 Do not have cervical cerclage (a cervix that has been sewn shut during
pregnancy to help keep the baby in the uterus – used when someone has a
weak cervix)
 Have not had sexual intercourse or a pelvic examination in the last 24 hours
The fFN test is not recommended for screening asymptomatic patients, even if they
are considered to be at high risk for premature labor and delivery.
When is it ordered?
The fFN is ordered when a woman is 26 weeks to 34 weeks pregnant and has one or
more symptoms of preterm labor. These symptoms may include: uterine contractions,
a change in vaginal discharge, backache, abdominal discomfort, pelvic pressure,
and/or cramping.
The fFN may be repeated several times if the first fFN is negative and labor
symptoms persist beyond the next 7-14 days. Each test result is valid for the following
7 to 14 days.
The fFN should only be ordered when a woman is symptomatic and meets the
qualifying conditions.
When the fFN test is done on a symptomatic woman who meets the qualifying
conditions, a negative test result means that there is a less than 1% chance of having a
premature delivery within the next 7 to 14 days. The doctor will not rely solely on the
fFN results, however. He will also use his clinical findings and expertise to evaluate
each individual situation.
A negative fFN does not totally eliminate the possibility of a preterm delivery but it
does make it highly unlikely during that time period. Since there are risks associated
with treating a woman for premature labor (in anticipation of a premature delivery), a
negative fFN can reduce unnecessary hospitalizations and drug therapies.
A positive fetal fibronectin test is associated with an increased risk for preterm
delivery and with neonatal complications. However, it will not tell your doctor
whether or not a woman will deliver early, but suggests the need to monitor a
symptomatic woman more closely.
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If the risk for preterm delivery is high, extra measures can be taken to delay delivery
for as long as possible and to help prepare the fetus for birth. Tocolytic agents (a
variety of drugs) can be used to help inhibit uterine contractions, and corticosteroids
can be given to the woman to help mature the baby’s lungs; both of these therapies
have associated risks. In addition, the woman can be transferred to a medical
institution that has the expertise and equipment to handle premature births.
The fFN test is not meant to be used on women with more than one fetus (twins,
multiples), or on those with placental abruption (premature detachment of the
placenta), premature rupture of membranes, placenta previa (a placenta attached to the
lower portion of the uterus), or moderate to heavy vaginal bleeding.
Anything that physically disturbs the cervix or uterus has the potential to elevate fFN
levels. Cervicovaginal fluid samples should be collected before any physical
examinations. Lubricants, lotions, soaps and douches, should be avoided as they may
cause interference with the test as may large numbers of red or white blood cells or
bacteria.
Semen may contain enough fFN to create a positive test result. Sexual intercourse
within 24 hours may lead to a positive fFN, but if the test is performed and is
negative, it is a valid result.
fFN binds to cotton swabs and to glass. Collection must be done with a Dacron swab
and put into a plastic container, or false negative fFN may result.
Fetal fibronectin may also bind to Candida, a vaginal yeast. If the patient has a
vaginal yeast infection, the result may be a false negative.
1. What are the risk factors for preterm labor and delivery?
Risk factors include:
 A previous preterm delivery,

 Maternal age of less than 18 or more than 40 years of age
 Race, non-Caucasians are at a higher risk
 Low or excessive pregnancy weight gain
 Previous history of second-trimester fetal loss
 Uterine abnormalities
 Infection
 Smoking
 Illicit drug use
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2. Why not test after 34 weeks?
Because fFN levels normally rise as fullterm delivery nears and because a baby born
after 34 –35 weeks of gestation is less likely to suffer premature complications,
testing this late in pregnancy is not generally recommended.
3. Why not test asymptomatic women who are at risk?

So far, this has not proved to be clinically useful.
Can preterm labor and delivery be prevented? Generally no, but the use of tocolytic
agents, given to inhibit uterine contractions, may delay delivery. In the meantime
corticosteroids can be given to help the fetal lungs mature and prevent neonatal
respiratory distress syndrome and time is gained to transfer the woman to a tertiary
treatment center.
4. What other tests are used to help determine the risk of preterm delivery?
Measurement of cervical dilatation as determined by transvaginal ultrasonography
and testing for bacterial vaginosis.
Fructosamine
Also known as: Glycated Serum Protein (GSP), Glycated Albumin

Why get tested?
To help monitor your diabetes over time, especially when it is not possible to monitor
using the A1C test. To help determine the effectiveness of changes to your diabetic
treatment plan
When to get tested?
If you are diabetic and your doctor wants to measure your average blood glucose level
over the last 2-3 weeks
The fructosamine test is a measurement of glycated protein. When glucose levels in
the blood are elevated over a period of time, glucose molecules permanently combine
with hemoglobin found inside the red blood cells (RBCs) and with albumin and other
serum proteins– a process called glycation. The more glucose that is present, the
greater the amount of glycated hemoglobin and glycated protein formed. These
combined molecules persist for the life of the RBC or the protein and provide a record
of the average amount of glucose that has been present in the blood over that time
period. Since RBCs live for about 120 days, glycated hemoglobin (hemoglobin A1C)
reveals average blood glucose levels over the past 2 to 3 months. Serum proteins have
a shorter lifespan, about 14 to 21 days, so glycated proteins reflect average glucose
levels over a 2 to 3 week time period.
Keeping blood glucose levels as close as possible to normal allows diabetic patients to
avoid many of the complications and progressive damage associated with elevated
glucose levels. Good diabetic control is achieved and maintained by daily (or even
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more frequent) self-monitoring of glucose levels and by occasional monitoring of the
effectiveness of treatment using either a fructosamine or A1C test.
How is it used?
Fructosamine testing has been available since the 1980s. Both fructosamine and A1C
tests are used primarily as monitoring tools to help diabetics control their blood sugar,
but the A1C test is much more popular and more widely accepted. However, the
American Diabetes Association (ADA) recognizes both tests and says that
fructosamine may be useful in situations where the A1C cannot be reliably measured.
Instances where fructosamine may be a better monitoring choice than A1C include:
 Rapid changes in diabetes treatment – fructosamine allows the effectiveness of

diet or medication adjustments to be evaluated after a couple of weeks rather
than months
 Diabetic pregnancy – good control is essential during pregnancy and the needs
of the mother frequently change during gestation; fructosamine measurements
may be ordered along with glucose levels to help monitor and accommodate
shifting glucose and insulin requirements
 RBC loss or abnormalities – an A1C test will not be accurate when a patient
has a condition that affects the average age of red blood cells (RBCs) present,
such as hemolytic anemia or blood loss. The presence of some hemoglobin
variants may affect certain methods for measuring HbA1c. In these cases,
fructosamine can be used to monitor glucose control.
Since the fructosamine concentrations of well-controlled diabetics may overlap with

those of non-diabetics, the fructosamine test is not useful as a screen for diabetes.
When is it ordered?
Although not widely used, the fructosamine test may be ordered whenever the doctor
wants to monitor a patient's average glucose over the past 2 to 3 weeks. It is primarily
ordered when a diabetic treatment plan is being instituted or altered in order to
monitor the effect of the change in diet or medication. Fructosamine levels also may
be ordered when a diabetic patient is pregnant, or when they have an acute or
systemic illness that may change their glucose and insulin requirements for a period
of time. The fructosamine test may be used when monitoring is required and an A1C
test cannot be reliably used.
If a patient’s fructosamine is increased, then the patient’s average glucose over the
last 2 to 3 weeks has been elevated. In general, the higher the fructosamine
concentration the higher the average blood glucose level. Trends may be more
important that absolute values. If there is a trend from a normal to high fructosamine,
it may indicate that a patient’s glucose control is not adequate – that they are getting
too much sugar, too little insulin, or that their insulin treatment has become less
effective.
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Normal fructosamine levels may indicate that a patient is either not diabetic (and
therefore should not be monitored) or that he has good diabetic control. A trend from
high to normal fructosamine levels may indicate that changes to a patient’s treatment
regimen are effective.
Fructosamine results must be evaluated in the context of the patient’s total clinical
findings. Falsely low fructosamine results may be seen with decreased protein levels,
increased protein loss, or a change in the type of protein produced by the body. In this
case, a discrepancy between the results obtained from daily glucose monitoring and
fructosamine testing may be noticed. Also, someone whose glucose concentrations
swing erratically from high to low may have normal or near normal fructosamine and
A1C levels but still have a condition that requires frequent monitoring.
High levels of vitamin C (ascorbic acid), lipemia (high amount of fat in the blood),
hemolysis (breakdown of RBCs), and hyperthyroidism can interfere with test results.
1. Can I test for fructosamine at home?
No. Although a home test was available in the recent past, it was discontinued in 2002
after the manufacturer was bought by another company and amid concerns that the
test strips were producing falsely high results.
2. Do I need to fast for a fructosamine test?

No. Since it measures glycated protein and determines the average glucose over the
past 2-3 weeks, the test is not affected by food that you have eaten during the day. For
the same reason, fructosamine can be measured at any time during the day.
3. Shouldn’t someone with a family history of diabetes have a fructosamine and

an A1C test?
Not usually. These tests are not recommended for screening non-diabetic patients,
even if you have a strong family history. One or more may be ordered, however, if
you have an elevated fasting glucose.
FSH
Why get tested?
To evaluate your pituitary function, especially in terms of fertility issues
When to get tested?
If you are having difficulty getting pregnant or are having irregular menstrual periods;
if your doctor thinks that you have symptoms of a pituitary or hypothalamic disorder
or symptoms of ovarian or testicular disease; if a doctor suspects that a child has
delayed or earlier than expected sexual maturation
Sample required?
A blood sample drawn from a vein in your arm; sometimes a random urine sample or
24-hour urine collection.
Follicle-stimulating hormone (FSH) is made by the pituitary gland in the brain.
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Control of FSH production is a complex system involving hormones produced by the
gonads (ovaries or testes), the pituitary, and the hypothalamus.
In women, FSH stimulates the growth and maturation of ovarian follicles (eggs)
during the follicular phase of the menstrual cycle. This cycle is divided into two
phases, the follicular and the luteal, by a mid-cycle surge of FSH and luteinizing
hormone (LH). Ovulation occurs shortly after this mid-cycle surge of hormones.
During the follicular phase, FSH initiates the production of estradiol by the follicle,
and the two hormones work together in the further development of the egg follicle.
During the luteal phase, FSH stimulates the production of progesterone. Both
estradiol and progesterone help the pituitary control the amount of FSH produced.
FSH also facilitates the ability of the ovary to respond to LH. At the time of
menopause, the ovaries stop functioning and FSH levels rise.
In men, FSH stimulates the testes to produce mature sperm and also promotes the
production of androgen binding proteins. FSH levels are relatively constant in males
after puberty.
In infants and children, FSH levels rise shortly after birth and then fall to very low
levels (by 6 months in boys and 1-2 years in girls). At about 6-8 years, levels again
rise before the beginning of puberty and the development of secondary sexual
characteristics.
A blood sample is drawn by needle from a vein in the arm. Sometimes, a random
urine sample is collected. A 24-hour collection of urine may be requested if your
doctor wants to measure FSH levels produced over a 24-hour period. FSH is released
intermittently throughout the day and a 24-hour urine collection eliminates problems
due to that variation; a random sample might not show the actual activity of the
hormone.
How is it used?
FSH is often used in conjunction with other tests (LH, testosterone, estradiol, and
progesterone) in the workup of infertility in both men and women. FSH levels are
used to help determine the reason a man has a low sperm count. FSH levels are also
useful in the investigation of menstrual irregularities and to aid in the diagnosis of
pituitary disorders or diseases involving the ovaries or testes. In children, FSH and
LH are used to diagnose delayed or precocious (early) puberty.
When is it ordered?
In women and men, FSH and LH are ordered as part of the workup of infertility and
pituitary or gonadal disorders. FSH may be ordered to determine if a woman has
reached menopause. In children, FSH and LH may be ordered when a boy or girl does
not appear to be entering puberty at an appropriate age (either too late or too soon).
Signs of puberty may include:
 breast enlargement in females
 growth of pubic hair
 genitalia growth in males
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 beginning of menstruation in females.
If any or some of these signs appear at a younger than average age or are delayed
beyond the expected age range for puberty, it may be an indication of a more serious
problem involving the hypothalamus, pituitary, gonads (ovaries or testes) or other
systems. The measurement of LH and FSH may differentiate between benign
symptoms and true disease. Once it is established that symptoms are a result of true
disease, further testing can be done to discern the underlying cause.

In women, FSH and LH levels can help to differentiate between primary ovarian
failure (failure of the ovaries themselves) and secondary ovarian failure (failure of the
ovaries due to disorders of either the pituitary or the hypothalamus). Increased levels
of FSH and LH are consistent with primary ovarian failure. Some causes of primary
ovarian failure are listed below.
Developmental defects:
 Ovarian agenesis (failure to develop ovaries)

 Chromosomal abnormality, such as Turner’s syndrome
 Ovarian steroidogenesis defect, such as 17 alpha hydroxylase deficiency
Premature ovarian failure due to:
 Radiation
 Chemotherapy
 Autoimmune disease
Chronic anovulation (failure to ovulate) due to:
 Polycystic ovary syndrome (PCOS)

 Adrenal disease
 Thyroid disease
 Ovarian tumor
When a woman enters menopause and her ovaries stop working, FSH levels will rise.
Low levels of FSH and LH are consistent with secondary ovarian failure due to a
pituitary or hypothalamic problem.
In men, high FSH levels are due to primary testicular failure. This can be due to
developmental defects in testicular growth or to testicular injury, as indicated below.
 Gonadal agenesis
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 Chromosomal abnormality, such as Klinefelters syndrome
Testicular failure:
 Viral infection (mumps)

 Trauma
 Radiation
 Chemotherapy
 Germ cell tumor
Low levels are consistent with pituitary or hypothalamic disorders.

In young children, high levels of FSH and LH and/or development of secondary
sexual characteristics at an unusually young age are an indication of precocious
puberty. This is much more common in girls than in boys. This premature
development can have many different underlying causes that need to be diagnosed
and treated. Some of the causes include:
 Central nervous system lesions

 Hormone-secreting tumors
 Ovarian tumors or cysts
 Testicular tumors
Normal prepubescent levels of LH and FSH in children exhibiting some signs of

pubertal changes may indicate a benign form of precocious puberty with no
underlying or discernable cause or may just be a normal variation of puberty.
In delayed puberty, LH and FSH levels can be normal or below what is expected for a
youth within the age range of puberty. The test for LH response to GnRH may need to
be performed along with other testing to diagnose the reason for the delayed puberty.
Some of the causes for delayed puberty can include:
 Gonadal (ovary or testes) failure (such as PCOS)

 Hormone deficiency
 Turner’s syndrome (chromosomal abnormality in girls)
 Klinefelter’s syndrome (chromosomal abnormality in boys)
 Chronic infections
 Cancer
 Eating disorder (anorexia nervosa)
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FSH results can be increased with use of cimetidine, clomiphene, digitalis, and
levodopa. FSH results can decrease with oral contraceptives, phenothiazines, and
hormone treatments.
If you’ve recently had a nuclear medicine scan, the radioisotopes used in the scan may
interfere with results of the FSH test.
1. I’m having a hard time getting pregnant. What tests do I need?
Basic tests for infertility often include luteinizing hormone (LH), in the form of an
ovulation test kit (using urine). Your doctor may also ask you to keep track of your
body temperature, which rises slightly when ovulation occurs. Other tests for
infertility include FSH and LH blood tests and other hormonal tests as well as a
postcoital (after intercourse) examination. A hysterosalpingogram (image of fallopian
tubes) may be ordered to see whether your fallopian tubes are blocked. Your husband
may be asked to give a specimen of semen for analysis.
2. I am a young woman, but now I am growing facial hair and still have no
regular period. What’s wrong with me?
You may have polycystic ovary syndrome (PCOS), a hormonal problem seen in 7-
10% of women and a major cause of infertility. With this condition, ovaries may
become larger because of cysts that form in them. Women with PCOS also may have
high levels of androgens and do not ovulate normally. You may need to undergo
several laboratory tests, including FSH, LH, and androgens, to make sure that PCOS
is the condition causing your symptoms. A combination of medications and hormone
therapy may help to alleviate your symptoms.
3. Why would a man need a test for female hormones?

Men also produce FSH and LH in their bodies, and these hormone levels are
important for male reproduction too. In men, FSH stimulates the testes to produce
sperm just as in women FSH stimulates the ovaries to produce eggs. In men, LH can
be measured if testosterone levels are low.
4. Is there a home test for FSH?

Yes. There is an FDA-approved self-test that measures the level of FSH in a urine
sample. It is used as an indicator of perimenopause, which is associated with a rise in
FSH levels.
GFR and EGFR
Formal name: Glomerular Filtration Rate and Estimated Glomerular Filtration Rate
Why get tested?
To assess kidney function
When to get tested?
As a screening test to look for evidence of kidney damage (EGFR) or for changes in
kidney function if you already have kidney disease (GFR)
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Sample required?
EGFR is calculated from your age, weight, gender, and serum creatinine (requires a
blood sample from a vein in your arm); in some formulas, race is also used in the
calculation. GFR is calculated from serum and urine creatinine; it requires a blood
sample from a vein in your arm and a 24-hour collection of urine.
Glomerular filtration rate (GFR) is a measure of the function of your kidneys.
Glomeruli are tiny filters in your kidney that allow waste products to be removed
from the blood, while preventing loss of important proteins and blood cells. The rate
refers to the amount of blood that is filtered per minute. Estimated glomerular
filtration rate (EGFR) is an estimate of the actual GFR.
How is it used?
GFR is considered the most accurate way to detect changes in kidney status. While
measurement of serum BUN (urea nitrogen) and creatinine are easier to do, they
cannot pick up early damage to the kidneys. If kidney damage is detected early, it
may be possible to prevent worsening damage to the kidneys with treatment of high
blood pressure, diabetes, or other diseases that can damage the kidney. Because
EGFR can be calculated based on serum creatinine, an easily performed and
commonly used laboratory test, it is possible to get a close estimate of the actual GFR.
Another method of estimating GFR (EGFR) involves the measurement of the serum
level of a molecule called cystatin C. While this use of the test is gaining interest, this
method is not yet widely used.
When is it ordered?
The EGFR calculation can be determined, with no extra testing, at the same time a
sample is sent for creatinine. The National Kidney Foundation has recommended that
it be calculated automatically every time a creatinine test is done. If you have had a
creatinine measurement, you can calculate it yourself by using the calculator on the
National Kidney Foundation website.
GFR is usually measured if you are on an unusual diet or if you have protein or
albumin in your urine.
EGFR can detect most types of kidney disease in their earliest changes. A normal
EGFR means that kidney disease is unlikely. A low EGFR suggests that some kidney
damage has occurred. GFR results are usually evaluated in the same way. Sometimes,
in very early kidney damage (especially when the kidneys are damaged by diabetes),
EGFR and GFR may actually be high, indicating that the kidneys are working harder
than normal.
The American Kidney Foundation has suggested that all persons “know their GFR
number.” They recommend interpreting GFR (usually by EGFR) based on the
following table:
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Kidney Description GFR Other findings
Damage Stage
1 Kidney damage with 90+ Protein or albumin in
normal or high GFR urine are high, cells
or casts seen in urine
2 Mild decrease in GFR 60-89
3 Moderate decrease in 30-59
GFR
4 Severe decrease in 15-29
GFR
5 Kidney failure < 15
GFR and EGFR increase during pregnancy.

1. How can my GFR be determined?
The GFR cannot be measured directly. The best method for estimating the GFR
(EGFR) is a procedure called an “inulin clearance.” It is not routinely used, however,
because it is expensive and awkward. It involves introducing a fluid into your veins
(IV – intravenous infusion) and then collecting timed urines over a period of hours.
Other clearance methods using radioactive markers have similar drawbacks. The
American Kidney Foundation is now recommending several different predictive
equations that are used in combination with serum creatinine levels to calculate the
EGFR. The use of these equations may become widespread as doctors learn how to
use them to monitor their patients.
GGT
Also known as: Gamma-glutamyl transpeptidase, GGTP

Why get tested?
To screen for liver disease and/or alcohol abuse or to differentiate between liver and
bone disease as a cause for elevated alkaline phosphatase (ALP)
When to get tested?
If your doctor thinks that you have symptoms of a liver disorder.
GGT is an enzyme found mainly in the liver; it is very sensitive to changes in liver
function. It is normally present in low levels in the blood. When the liver is injured or
obstructed, the GGT level rises. It is the most sensitive liver enzyme in detecting bile
duct problems. A rise in GGT can occur even when there is no identifiable cause that
is related to liver disease.
How is it used?
The GGT test helps to detect liver and bile duct injury. While some doctors use it in
all people they suspect of having liver disease, others use it only to help explain the
cause of other changes or if they suspect alcohol abuse. For example, both ALP and
GGT are elevated in disease of the bile ducts and in some liver diseases, but only ALP
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will be elevated in bone disease. If the GGT level is normal in a person with a high
ALP, the cause is most likely bone disease. GGT can also be used to screen for
chronic alcohol abuse (it will be elevated in about 75% of chronic drinkers).
When is it ordered?
A doctor usually orders GGT along with other tests to evaluate a person who has
signs or symptoms that suggest liver disease. Some of the symptoms of liver injury
include jaundice, nausea, vomiting, abdominal swelling, abdominal pain, pruritus
(severe itching), and fatigue.
GGT is increased in most diseases that cause acute damage to the liver or bile ducts,
but is usually not helpful in distinguishing between different causes of liver damage.
For this reason, use of GGT is controversial, and guidelines published by the National
Academy of Clinical Biochemistry and the American Association for the Study of
Liver Diseases do not recommend routine use of GGT. These guidelines suggest that
it can be useful in determining the cause of a high ALP. In persons with a history of
alcohol abuse who have completed alcohol treatment, GGT may be used to monitor
compliance with the treatment program.
Doctors are not usually concerned with low or normal levels, but they do indicate that
it is unlikely that a patient has liver disease.
Elevated GGT levels indicate that something is going on with your liver but not
specifically what. In general, the higher the level the greater the “insult” to your liver.
Elevated levels may be due to liver disease, but they may also be due to congestive
heart failure, alcohol consumption, and use of many prescription and non-prescription
drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), lipid-lowering
drugs, antibiotics, histamine blockers (used to treat excess stomach acid production),
antifungal agents, seizure control medications, antidepressants, and hormones such as
testosterone. Oral contraceptives (birth control pills) and clofibrate can decrease GGT
levels.

Even small amounts of alcohol within 24 hours of your GGT test may cause a
temporary increase in the GGT. If this occurs, your doctor may want to repeat the test
to verify that it is normal.
GGT levels fall after meals, so it is best to be tested when you have not eaten for at
least 8 hours.
Smoking can also increase GGT.
Levels of GGT increase with age in women, but not in men, and are always somewhat
higher in men than in women.
GGT is about twice as high in persons of African ancestry as in those of European
ancestry.
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1. Can my GGT be elevated if I don’t have any symptoms?
Yes, GGT is very sensitive and can be increased when you don’t have symptoms.
This elevation may be temporary, perhaps due to medications you are taking or
alcohol ingested within 24 hours of the test. If other liver enzymes are normal, your
doctor may just wait and then repeat the GGT test. If the GGT is very high and/or
your other liver enzymes are elevated, your doctor may want to do more extensive
testing to search for the cause.
2. I am an alcoholic but I have quit drinking. Will my GGT ever go back to

normal?
Over time, your GGT level will fall from whatever level it was at when you stopped
drinking alcohol to a near normal state. It takes at least a month for GGT to return to
normal after you stop drinking. Abstaining from alcohol will decrease your chances of
further damaging your liver and should allow your liver functions to improve.
Gonorrhea
Why get tested?
To screen for Neisseria gonorrhoeae, which causes the sexually transmitted disease
gonorrhea
When to get tested?
If you have symptoms of gonorrhea or are pregnant
Sample required?
A swab of secretion or discharge from the infected area.
The test is looking for evidence of the bacterium Neisseria gonorrhoeae, which
causes the sexually transmitted disease gonorrhea. An estimated 800,000 cases occur
annually in the United States. Gonorrhea is easily treated but can cause severe
reproductive and health problems if left untreated.
A swab is used to get a sample of secretion or discharge from the infected area such
as the cervix, urethra, penis, anus, or throat. A urine sample is used in some tests.
Many doctors will take a sample from more than one body site to increase the
likelihood of finding the bacteria.
How is it used?
The test is used in two ways:
 to diagnose the cause of symptoms, and

 to screen sexually active people.
A definitive diagnosis is important because gonorrhea can resemble chlamydia, and

the two disorders require different treatment.
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When is it ordered?
A doctor may order the test if you have symptoms such as (for women) a yellow or
bloody vaginal discharge, bleeding associated with vaginal intercourse, or
burning/painful urination; or (for men) pus discharging from the penis or a burning
sensation during urination. Pregnant women should be tested at least once during the
pregnancy.
antibiotics.
Many people contract gonorrhea without knowing it, because symptoms are very mild
or even absent. If you test positive for gonorrhea, you should also be screened for
other sexually transmitted diseases and your sexual partner(s) should be tested and
treated as well.
If you are infected, your risk of contracting other sexually transmitted diseases
increases, including HIV, the virus that causes AIDS.
The diagnosis of a sexually transmitted disease should not be ruled out if the test is
negative; patients' clinical symptoms and history should also be considered.
1. What are the symptoms of gonorrhea?
For women, early symptoms (which are often mistaken for a bladder or vaginal
infection) include bleeding brought on by vaginal intercourse, burning/painful
urination, and a yellow or bloody vaginal discharge. For men, early symptoms include
a discharge of pus from the penis, pain in the penis, and a burning sensation when
urinating. Symptoms of rectal infection include discharge, itching, and painful bowel
movements with blood on the feces.
The symptoms usually appear 2 to 10 days after sexual contact with an infected
partner. The early symptoms can be mild, and most women and many men can be
infected without showing any symptoms.
Untreated gonorrhea can lead to severe complications. Women can develop pelvic
inflammatory disease (PID), an infection that spreads from the vagina and cervix to
the uterus and fallopian tubes. PID can cause scaring of the fallopian tubes, which can
lead to ectopic (or tubal) pregnancy or sterility. The symptoms of PID include heavier
periods with more cramps, abnormal mucus discharges, pain in the lower abdomen,
weakness, fever, vomiting, and pain during intercourse. Other long-term
complications include abscesses and infection around the liver. In men, the infection
can lead to an inflammation of the testicles that can results in sterility. The bacteria
can also spread to the bloodstream and infect the joints, heart valves or brain,
resulting in long-term or permanent organ damage.
3. How is gonorrhea transmitted?

It is generally transmitted through sexual contact (oral, vaginal, or anal) with an
infected partner. Because Neisseria gonorrhoeae can survive outside the body for a
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short time, contact with discharge on a towel or other object used by an infected
person may transmit the infection; however, this is very rare. An infected mother can
spread the disease to her baby during childbirth.
4. How is it treated?
Gonorrhea can be treated with a course of antibiotics.
Gram Stain
Why get tested?
To identify the presence of bacteria in a patient’s specimen so that appropriate
treatment can be given
When to get tested?
If your doctor suspects that you have a bacterial infection.
A Gram stain is used to determine if bacteria are present in an area of the body that is
normally sterile, such as spinal fluid. A sample from the infected area is smeared on a
glass slide and allowed to dry. A series of stains and a decolorizer is applied. The
stained slide is then examined under a microscope where bacteria appear either purple
(gram positive) or pink (gram negative). The test is named for Dr. Christian Gram,
who invented the process.
A Gram stain can predict the type of bacteria causing an infection, such as
pneumococcal pneumonia or a staphylococcal abscess. Viruses cannot be seen with a
Gram stain since they lack the cell wall, which takes up the stain.
How is it used?
A Gram stain and culture of the material from an infected site are the most commonly
performed microbiology tests used to identify the cause of an infection. Often,
determining whether an infection is caused by an organism that is Gram positive or
Gram negative will be sufficient to allow a doctor to prescribe treatment with an
appropriate antibiotic while waiting for more specific tests to be completed. Absence
or presence of white blood cells in the Gram stain can determine the adequacy of the
specimen.
When is it ordered?
A Gram stain is done with a bacterial culture when a bacterial infection is suspected.
Determining the Gram status of an organism allows the doctor to select an appropriate
antibiotic before culture results are available. Gram stains cannot confirm the
organism’s identity or susceptibility to antibiotics. Only a culture of the material can
supply this information.
Bacterial infections should not be ignored, even if the symptoms are mild. You should
consult your doctor so treatment, if necessary, can begin promptly, and the spread and
severity of the disease can be limited. If left untreated, bacterial infections can migrate
throughout the body and cause tissue and organ damage.
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1. What are the treatment options for bacterial infections?
Antibiotics are the main treatment of bacterial infections.
2. What does the doctor look for on the slide?

In addition to color, which indicates whether the organism is Gram positive or Gram
negative, the shape of the organism (such as rod-shaped) and the formation of groups
of organisms are informative. For example, staphylococcus (staph) bacteria are found
in grape-like clusters, while streptococcus (strep) bacteria are found in pairs or chains,
like a string of pearls.
3. What happens if my doctor needs more information than the Gram stain
provides?
The Gram stain is usually done in conjunction with a culture. This allows for more
exact identification of the bacteria causing the infection and determination of the most
appropriate antibiotic.
Growth Hormone
Why get tested?
To identify diseases and conditions caused by deficiencies and overproduction of
growth hormone (GH), to evaluate pituitary function, and to monitor the effectiveness
of GH treatment.
When to get tested?
As part of an evaluation of pituitary function. When you have symptoms of gigantism
(in children) or acromegaly (in adults) suggesting excess GH production. When you
have symptoms of slow growth, short stature, and delayed development (in children)
or decreased bone density, reduced muscle strength, and increased lipids (in adults)
suggesting insufficient GH production. During, and for extended periods after,
treatment for GH abnormalities.
Sample required?
Usually several blood samples, drawn at timed intervals from veins in your arm.
Sometimes a single sample of blood, drawn following a fast or after a period of
strenuous exercise.
Growth hormone (GH) is produced by the anterior pituitary gland, a grape sized organ
found at the base of the brain. Essential for a child’s normal growth and development,
GH promotes linear bone growth from birth through puberty. Children with
insufficient GH production grow more slowly than other children; their small size for
their age is often one of the first symptoms of growth hormone deficiency (GHD).
Excess GH is most often due to a GH-secreting pituitary tumor (usually benign). Too
much GH can cause children’s long bones to continue to grow, resulting in gigantism
and heights of 7 or more feet tall. They may also have thickening of facial features,
weakness, delayed puberty, and headaches.
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Although GH is not as active in adults, it does play a role in regulating bone density,
muscle mass, and lipid metabolism. Deficiencies can lead to low bone densities, less
muscle mass, and altered lipids. Excess GH can lead to acromegaly, marked not by
bone lengthening but by bone thickening and widening. Although symptoms such as
skin thickening, sweating, fatigue, headaches, and joint pain can be subtle at first, they
can lead to enlarged hands and feet, enlarged facial bones, carpal tunnel syndrome,
and abnormally enlarged internal organs.
GH stimulation and suppression tests are usually used to diagnose GH abnormalities.
Since growth hormone is released by the pituitary gland in bursts throughout the day,
random measurements of GH levels are not usually clinically useful. The patient is
given a glucose load (solution) to suppress GH or given intravenous insulin or
arginine (or other substances) to stimulate GH production, then blood samples are
drawn at timed intervals to monitor the effect of the substance given.
Usually GH suppression or stimulation testing is done. After you have fasted for 10 to
12 hours, a blood sample is drawn from a vein in your arm. Then, under medical
supervision, you are given either a standard glucose solution to drink (for a
suppression test), or you are given an intravenous (IV) solution of insulin or arginine
(for a stimulation test) through a vein in your arm. Blood samples are then drawn
from your veins (or from the IV) at timed intervals. GH tests are run on each sample
collected to monitor the change in growth hormone over time.
Sometimes a single sample of blood is drawn following a fast or after a period of
strenuous exercise.
How is it used?
GH testing is usually provocative, using either a GH stimulation test or a GH
suppression test to track GH levels over time. GH testing may be used to screen for
abnormal pituitary function, and to help diagnose the condition causing the
abnormality, its severity, and the complications that have arisen because of it.
Often other blood tests that reflect pituitary function, such as T4, TSH, Cortisol, FSH,
LH, and testosterone (in men), are also ordered. These tests are usually done prior to
GH testing to make sure that they are normal and/or controlled with medication
before GH testing is done. Glucose levels are run on the samples collected during the
GH suppression test (which is an oral glucose tolerance test), both to track glucose
levels, and to make sure that the patient’s system is sufficiently challenged by the
glucose solution given.
IGF-1 (Insulin-like growth factor – 1) is often measured once during GH provocation

testing and often used by itself or with GH as a monitoring tool. Produced in the liver,
IGF-1 mirrors GH excesses and deficiencies but its level is stable throughout the day
– making it a useful indicator of average GH levels.
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GH testing is usually ordered on those with symptoms of growth hormone
abnormalities or as a follow-up to other abnormal test results. It is not recommended
for general screening. GH tests may be ordered to help evaluate pituitary function:
 GH stimulation tests are used to screen for hypopituitarism

 GH suppression tests are used to screen for hyperpituitarism
GH testing may be ordered to evaluate the long-term effects of chemotherapy on

pituitary function in children who undergo such treatment.
Growth hormone tests help identify excess and diminished GH production, give your
doctor information about the severity of your condition, and are part of the diagnostic
workup to find the reason for the abnormal hormone production.
 GH stimulation tests help diagnose growth hormone deficiency (GHD) in

children and adults.
 GH suppression tests help diagnose gigantism in children and acromegaly in
adults. Along with other blood tests and imaging scans, they help identify and
locate pituitary tumors
GH and IGF-1 levels are often monitored for extended periods of time following
treatment for GHD, gigantism, and acromegaly, and are monitored following surgery,
drug treatment, and/or radiation for a pituitary tumor. GH testing may also be done to
test for the use of performance enhancing steroids.
When is it ordered?
GH stimulation testing is ordered when your child has symptoms of GHD, such as
when
 his growth rate slows down in early childhood and he is significantly shorter
than others his age;
 TSH tests show that your child is not hypothyroid (low thyroid levels can also
cause slowed growth);
 X-rays show that his bones are showing delayed development;
 your doctor suspects that your child’s pituitary gland is under active.
Once GHD is diagnosed your doctor may use stimulation testing to confirm the
diagnosis, along with IGF-1 to monitor the effectiveness of GH replacement (if
indicated), and as a child reaches adulthood to see if continued supplementation is
necessary.
Stimulation testing is ordered in adults when patients have symptoms of GHD and/or
hypopituitarism, such as: decreased bone density, fatigue, adverse lipid changes, and
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reduced exercise tolerance. Other hormone testing is done first to rule out other
conditions that may cause similar symptoms.
GH suppression testing is done when children show signs of gigantism, adults show
signs of acromegaly, and/or when their doctor suspects hyperpituitarism. Suppression
testing may be done when a pituitary tumor is suspected, and may be used along with
IGF-1 levels and other hormone levels to monitor the effectiveness of treatment for
these conditions. Monitoring may continue at regular intervals for many years to
watch for recurrence.
Since GH is released by the pituitary in bursts, random GH levels are not very useful.
There is too much overlap between abnormal results and normal daily variation. GH
levels will be higher first thing in the morning, and will increase with exercise and
stress.
If your GH levels are not significantly suppressed during a GH suppression test (they
stay higher than they should) and:
 you have symptoms of gigantism or acromegaly

 other pituitary hormone levels are normal and/or controlled
 your IGF-1 levels are high
then it is likely that you are producing too much GH and it is causing complications.
If you have other pituitary hormones that are abnormal, then you may have a
condition causing hyperpituitarism. If a mass shows up on an X-ray, CT scan, or MRI
then you may have a pituitary tumor (or very rarely a malignancy). If you are being
monitored for a previous tumor, then you may be having a recurrence.
If your GH levels are not significantly stimulated during a GH stimulation test (they
stay lower than they should) and:
 you have symptoms of GHD

 other pituitary hormone levels are normal and/or controlled
 your IGF-1 level is low
then it is likely that you have a deficiency of GH that your doctor may treat. If your
TSH level is low then that should be addressed first as thyroid deficiencies can cause
symptoms similar to GHD. You may also have a more general decrease in pituitary
function.
Pituitary tumors are the most common cause of excess GH production but may also
cause deficiencies. If the tumor produces another of the pituitary hormones (such as
ACTH or prolactin), it may inhibit GH secretion. If the tumor is relatively large it
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may inhibit all pituitary hormone production and cause damage to the surrounding
tissues.
Some other conditions can also cause general hyper- or hypopituitarism. They may be
genetic, due to disease, or to trauma.
Interfering factors include:
 Stress, exercise, and low blood glucose levels

 Drugs that can increase GH include: amphetamines, arginine, dopamine,
estrogens, glucagon, histamine, insulin, levodopa, methyldopa, and nicotinic
acid.
 Drugs that can decrease levels: corticosteroids and phenothiazines.
 Radioactive scan within week of test (with some laboratory methods)
Abnormal GH levels can usually be modified once they are identified. Synthetic GH
is available to alleviate deficiencies in children (treatment of adults with GHD is more
controversial). Combinations of surgery, medication, and radiation can be used to
treat pituitary tumors that are causing excess GH production. The important thing is to
identify GH abnormalities as soon as possible for good outcomes. The bone growth
changes associated with gigantism and acromegaly are permanent, and if left
untreated, the GH deficient child’s short stature will remain.
There can be long term complications from GH abnormalities. Acromegaly, for

instance, can cause colon polyps (increasing a patient’s risk of developing colon
cancer), diabetes, high blood pressure, and visual abnormalities. If a pituitary tumor
permanently damages pituitary cells then multiple hormone replacement may be
necessary. Increased bone growth may also lead to trapped nerves (carpal tunnel),
arthritis, and weak bones.
1. What conditions are treated with GH therapy?
Besides GHD, children may be treated with growth hormone replacement if they
have:
 Chronic renal insufficiency

 Prader Willi syndrome
 Turner’s syndrome
Treating children with GH replacement who are short but do not have GHD is
controversial. This is also true of adults, whether or not they have documented GHD.
The medicine has associated risks and side effects, is expensive, and there is not
enough data to support its benefits.
GH replacement is sometimes given to those with HIV/AIDS-related wasting (loss of
lean muscle mass) to help maintain body weight.
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2. What other tests might be ordered to evaluate my GH production?
Although they are not widely used, other tests, such as insulin-like growth factor,
binding protein-3 (IGFBP-3), and growth hormone releasing hormone (GHRH) are
sometimes ordered to help evaluate GH production.
HCG
Why get tested?
To confirm and monitor pregnancy or to diagnose trophoblastic disease or germ cell
tumors
When to get tested?
As early as 10 days after a missed menstrual period (some methods can detect hCG
even earlier, at one week after conception) or if a doctor thinks that your symptoms
suggest ectopic pregnancy, a failing pregnancy, trophoblastic disease, or germ cell
tumors.
hCG is a protein produced in the placenta of a pregnant woman. A pregnancy test is a
specific blood or urine test that can detect hCG and confirm pregnancy. This hormone
is able to be detected 10 days after a missed menstrual period, the time period when
the fertilized egg is implanted in the woman’s uterus. With some methods, hCG can
be detected even earlier, at one week after conception.
During the early weeks of pregnancy, hCG is important in maintaining function of the
corpus luteum (the mass of cells that forms from a mature egg). Production of hCG
increases steadily during the first trimester (8–10 weeks), peaking around the 10th
week after the last menstrual cycle. Levels then fall slowly during the remainder of
the pregnancy. hCG is no longer detectable within a few weeks after delivery. hCG is
also produced by some germ cell tumors and increased levels are seen in trophoblastic
disease.
How is it used?
Qualitative (reported as positive or negative) hCG testing is routinely used to confirm
pregnancy. Quantitative (reported as a specific number) hCG testing (also frequently
called beta hCG), measures the actual amount of hCG present in the blood. It may be
ordered to help diagnose an ectopic pregnancy, to help diagnose and monitor a
pregnancy that may be failing, and or to monitor a woman after a miscarriage. In
addition, a quantitativen hCG test may be ordered to diagnose trophoblastic disease or
germ cell tumors of the testes or ovary. It may be ordered at regular intervals to
monitor the effectiveness of treatment for these conditions and to detect tumor
recurrence.
When is it ordered?
A qualitative urine or blood hCG test is ordered as early as 10 days after a missed
menstrual period if a woman wishes to confirm whether or not she is pregnant (some
methods can detect hCG even earlier, at one week after conception). In certain
patients, several quantitative blood hCG tests over several days may be ordered to rule
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out an ectopic pregnancy or to monitor a woman after a miscarriage. A doctor will
also order a quantitative hCG test when s/he suspects trophoblastic disease or the
presence of germ cell tumors.
In non-pregnant women, hCG levels are normally undetectable. During early
pregnancy, the hCG level in the blood doubles every two to three days. Ectopic
pregnancies usually have a longer doubling time. Those with failing pregnancies will
also frequently have a longer doubling time or may even show falling hCG
concentrations. hCG concentrations will drop rapidly following a miscarriage. If hCG
does not fall to undetectable levels, it may indicate remaining hCG-producing tissue
that will need to be removed.
hCG is also used to monitor treatment in patients with trophoblastic disease and to
detect recurrent disease after treatment is complete. During therapy, a falling hCG
level generally indicates that the cancer is responding to treatment, while rising levels
may indicate that the cancer is not responding to therapy. Increased hCG levels after
treatment may indicate a recurrence of disease.

Tests performed too early in the pregnancy, before there is a significant hCG level,
may give false-negative results, while blood or protein in the urine may cause false-
positive results. Urine hCG tests may give a false negative result in very dilute urine.
Patients should not drink large amounts of fluid before collecting a urine sample for a
pregnancy test.
Certain drugs such as diuretics and promethazine (an antihistamine) may also cause
false-negative urine results. Other drugs such as anti-convulsants, anti-parkinson
drugs, hypnotics, and tranquilizers may cause false-positive results.
There are reports of false positive serum hCG results due to several different
compounds (not drugs) that may interfere with the test. These include certain types of
antibodies that may be present in some individuals and fragments of the hCG
molecule. Generally, if results are questionable, they may be confirmed by testing
with a different method.
. How does the test that I do at home myself compare with the results of a test
done in a lab?
Home pregnancy testing is very similar to qualitative urine hCG testing in the
laboratory, but there are factors surrounding its use that are important to note.
 First, home tests come with very specific directions that must be followed
explicitly. If you are using a home test, follow the directions extremely
carefully.
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 Second, home tests are sometimes done too soon after the missed menstrual
cycle to result in a positive test—it takes 10 days after conception before the
presence of hCG can be detected by the urine test. That is why a home test is
sometimes negative when the test done by your doctor is positive—the
doctor’s test is often done several days later when hCG levels have become
detectable.
 All urine qualititative hCG tests should be done on a first morning urine
sample, if possible. Urine becomes more dilute after ingestion of liquids
(coffee, juice, water, etc) and urine hCG concentrations may become to low to
register as positive.
Generally, when used correctly, the home test should produce the same result as the
urine hCG test done by your doctor. Qualitative blood testing for hCG may be more
sensitive than urine hCG testing, so sometimes a blood test will indicate pregnancy
when the urine test is negative. Quantitative hCG testing requires a blood sample and
must be done in the laboratory.
2. What is an ectopic pregnancy?
An ectopic pregnancy is the condition when the fertilized ovum (blastocyst) implants
somewhere other than in the uterus. This is a serious condition needing immediate
treatment. Patients with ectopic pregnancies often have abdominal pain and uterine
bleeding. Usually, abnormal levels of hCG are produced in ectopic pregnancies with
slower-than-normal rates of increase.
3. When is a blood hCG test ordered instead of a urine hCG?

The blood hCG test actually measures the amount of hCG in the blood; the urine hCG
is used to detect the presence of hCG. Since hCG is not normally detected in the urine
of a non-pregnant woman, the urine hCG is enough to confirm a pregnancy.
Sometimes, it is important to know how much hCG is present: to evaluate a suspected
ectopic pregnancy or to monitor a woman following a miscarriage. In these
circumstances, your doctor will run a blood hCG.
4. How many days after a miscarriage would it take for a urine pregnancy test to
show a negative result?
Urine hCG disappears at about the same rate as serum hCG, which can take anywhere
from 9 to 35 days, with a median of 19 days. However, the timeframe for when an
hCG result will be negative is dependent on what the hCG level was at the time of the
miscarriage. Frequently miscarriages are monitored with quantitative blood hCG
testing. If the levels of hCG do not fall to undetectable levels, some hCG-producing
tissue may remain and have to be removed.
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Hepatitis A
Also known as: HAV-Ab/IgM, HAV-Ab/total

Why get tested?
To diagnose an infection with hepatitis A or to evaluate the need for or response to the
hepatitis A vaccine
When to get tested?
If you have symptoms of an infection with and/or have been exposed to the hepatitis
A virus (HAV); if you have chronic liver disease; or if you have received the HAV
vaccine.
Hepatitis A antibody is produced in response to an infection with the hepatitis A virus
or to the hepatitis A vaccine. The test detects the presence of this antibody.
How is it used?
There are two versions of the test, and these detect antibodies. Antibodies are
produced by the body to protect itself from antigens (foreign proteins). IgM
(immunoglobulin M) is the first antibody produced by the body when it is exposed to
a virus and is used for early detection of infection. IgM antibodies to HAV are used in
a patient with evidence of acute hepatitis, such as jaundice, dark urine, pale colored
stools, fever, and loss of appetite. IgG (immunoglobulin G) antibodies develop later
and remain present for many years, protecting the person against further infection by
the same virus. A total antibody test (which detects both IgM and IgG antibodies)
detects both current and previous infection with HAV and also will be positive after
receiving the hepatitis A vaccine.
When is it ordered?
Testing for the presence of IgM antibodies to hepatitis A is done if you have the
symptoms and/or are likely to have been exposed to the virus. If you have being
considered for the HAV vaccine, a total antibody test may be ordered before you are
given the vaccine to see if you need it (if the antibodies are already present, the
vaccine won’t help you). Once you have completed the two doses of the vaccine, the
total HAV antibody test can also be used to see if you have responded to the vaccine.
If the test result is positive (or reactive) and you have not gotten the HAV vaccine,
you have had a hepatitis A infection – even if you were not aware of it. About 30% of
adults over age 40 have antibodies to HAV. If you have been given the vaccine, a
positive result means you are immune to HAV and cannot be infected by it.
It is presumed that one infection with hepatitis A produces lasting immunity against
further infections.
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1. How could I have gotten the virus without knowing it?
The virus is found in contaminated water and feces. You may have eaten raw fruit or
vegetables handled by an infected person who did not wash their hands properly or
you may have eaten raw or improperly cooked seafood that had fed in contaminated
waters. Children are often infected by HAV and either do not become sick or have
very mild symptoms such as fever and diarrhea, and are often thought to have “flu.”
2. Is there any way to prevent the disease?
Yes. There is a vaccine available. It is recommended for people traveling to

underdeveloped countries, for children who live in parts of the United States where
HAV is common, and for those who have damage to their liver from some other
cause.
Hepatitis B
Why get tested?
To diagnose and follow the course of an infection with hepatitis B or to determine if
the vaccine against hepatitis B has produced the desired level of immunity
When to get tested?
If you have symptoms of a hepatitis B infection or are likely to have been exposed to
the hepatitis B virus (HBV); if you have chronic liver disease due to some other
cause; or if you have received the hepatitis B vaccine.
Hepatitis B antibodies are produced in response to exposure to the hepatitis B virus
(HBV). The tests detect the presence of these antibodies or parts (antigens) of the
virus itself.
How is it used?
There are several tests used to detect the presence of hepatitis B antibodies.
Antibodies are produced by the body to offer protection from antigens (foreign
proteins). There are also several tests that detect the presence of viral antigens.
The hepatitis B surface antibody (anti-HBs) is the most common test. Its presence
indicates previous exposure to HBV, but the virus is no longer present and the person
cannot pass on the virus to others. The antibody also protects the body from future
HBV infection. In addition to exposure to HBV, the antibodies can also be acquired
from successful vaccination. This test is done to determine the need for vaccination (if
anti-HBs is absent), or following the completion of vaccination against the disease, or
following an active infection.
Hepatitis B surface antigen (HBsAg) is a protein antigen produced by HBV. This

antigen is the earliest indicator of acute hepatitis B and frequently identifies infected
people before symptoms appear. HBsAg disappears from the blood during the
recovery period. In some people (particularly those infected as children or those with
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a weak immune system, such as those with AIDS), chronic infection with HBV may
occur and HBsAg remains positive.
Sometimes, HBV goes into “hiding” in the liver and other cells and does not produce
new viruses that can infect others, or produces them in such low amounts that they
cannot be found in the blood. People who have this form are said to be carriers. In
other cases, the body continues to make viruses that can further infect the liver and
can be spread to other people. In both these cases, HBsAg will be positive. The next
test is helpful for distinguishing these two states.
Hepatitis B e-antigen (HBeAg) is a viral protein associated with HBV infections.

Unlike the surface antigen, the e-antigen is found in the blood only when there are
viruses also present. When the virus goes into “hiding,” the e-antigen will no longer
be present in the blood. HBeAg is often used as a marker of ability to spread the virus
to other people (infectivity). Measurement of e-antigen may also be used to monitor
the effectiveness of HBV treatment; successful treatment will usually eliminate
HBeAg from the blood and lead to development of antibodies against e-antigen (anti-
HBe). There are some types (strains) of HBV that do not make e-antigen; these are
especially common in the Middle East and Asia. In areas where these strains of HBV
are common, testing for HBeAg is not very useful.
Anti-HBe is an antibody produced in response to the Hepatitis B e antigen. In those

who have recovered from acute hepatitis B infection, anti-HBe will be present along
with anti-HBc and anti-HBs. In those with chronic hepatitis B, usually anti-HBe
becomes positive when the virus goes into hiding or is eliminated from the body. In
strains that do not make HBe antigen, anti-HBe is also positive.
Anti-hepatitis B core antigen (anti-HBc) is an antibody to the hepatitis B core antigen.

The core antigen is found on virus particles but disappears early in the course of
infection. This antibody is produced during and after an acute HBV infection and is
usually found in chronic HBV carriers as well as those who have cleared the virus,
and usually persists for life. Anti-HBc testing is either specific for the IgM antibody,
anti-HBc, IgM, which indicates acute infection, or measures total antibody, anti-HBC,
which indicates past infection, either acute or chronic.
HBV DNA is a more sensitive test than HBeAg for detecting viruses in the blood
stream. It is usually used in conjunction with – rather than instead of – the regular
serologic tests. It may be used to monitor antiviral therapy in patients with chronic
HBV infections.
When is it ordered?
These tests are used to determine whether the vaccine has produced the desired level
of immunity as well as to diagnose and follow the course of an infection.
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In a patient with acute hepatitis, anti-HBc IgM and HBsAg are usually ordered
together to detect recent infection by HBV. In persons with chronic hepatitis, or with
elevated ALT or AST, HBsAg and anti-HBc are usually done to see if the liver
damage is due to HBV. If so, HBsAg and HBeAg are usually measured on a regular
basis (every 6 months to a year), since in some people HBeAg (and, less commonly,
HBsAg) will go away on their own. Recent evidence suggests that many of those who
have anti-HBc but no HBsAg may have very low levels of HBV DNA in their blood
and/or in their liver. The significance of this is still being debated. In those who are
being treated for chronic HBV, HBeAg and HBV DNA can be used to determine
whether the treatment is successful (in which case, both will become undetectable). If
a person is given the HBV vaccine, anti-HBs is used to see if it successful; if levels of
the antibody are over 10 IU/mL, the person is probably protected for life from
infection by HBV, unless they have or develop problems with their immune system
(such as HIV infection, renal failure, or treatment with drugs that suppress the
immune system).
All donated blood is tested for the presence of the HBsAg before being distributed.
 Hepatitis B surface antibody (anti-HBs): a positive result indicates immunity

to hepatitis B from the vaccination or recovery from an infection.
 Hepatitis B surface antigen (HBsAg): A negative result indicates that a person
has never been exposed to the virus or has recovered from acute hepatitis and
has rid themselves of the virus (or has, at most, an occult infection). A positive
(or reactive) result indicates an active infection but does not indicate whether
the virus can be passed to others.
 Hepatitis B e-antigen (HBeAg): A positive (or reactive) result indicates the
presence of virus that can be passed to others. A negative result usually means
the virus cannot be spread to others, except in parts of the world where
infection with strains that cannot make this protein are common.
 Anti-hepatitis B core antigen (anti-HBc): If it is present with a positive anti-
HBs, it usually indicates recovery from an infection and the person is not a
carrier or chronically infected. In acute infection, the first type of antibody to
HBc to appear is an IgM antibody. Testing for this type of antibody can prove
whether a person has recently been infected by HBV (where anti-HBc, IgM
would be positive) or for some time (where anti-HBc, IgM would be
negative).
 HBV DNA: A positive (or reactive) result indicates the presence of virus that
can be passed to others. A negative result usually means the virus cannot be
spread to others, especially if tests that can pick up as few as 200 viruses
(copies) in one mL of blood are used.
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While the tests described above are specific for HBV, other liver function tests such
as AST, ALT, and gamma-glutamyl transferase (GGT) may be used to monitor the
progress of the disease. In some cases, a liver biopsy may be performed for
confirmation.
1. If it is possible that I have an HBV infection, will I need to have all of these
tests done?
No. Your doctor will determine which test(s) will be appropriate for your symptoms
and history.
2. Should I get the HBV vaccine?

Yes. Unless there is something in your medical history to the contrary, it is prudent to
get the series of vaccinations. Babies are routinely given the series of shots, and it is
usually wise to be tested to see if you have developed immunity. The Centers for
Disease Control and Prevention (CDC) does not recommend periodic measurement of
anti-HBs in persons who have developed immunity to HBV; even if their antibody
titer falls below 10 IU/mL, the person still appears protected if they are exposed to the
virus (unless they have a problem with their immune system). CDC does not
recommend booster shots to maintain high levels of antibody.
Hepatitis C
Why get tested?
To determine if you have contracted the hepatitis C virus (HCV) and to monitor
treatment of the infection
When to get tested?
If you may have been exposed to the hepatitis C virus, such as through contact with
infected blood, or have risk factors for hepatitis C infection.
Hepatitis C is a virus that can infect and damage the liver. Hepatitis C antibody is
produced in the body in response to exposure to the hepatitis C virus (HCV). The
most common test for HCV looks for these antibodies in your blood. Other tests
detect the presence of viral RNA, the amount of viral RNA present, or determine the
specific subtype of virus.
How is it used?
Each of the five most common tests has a slightly different purpose:
 Anti-HCV tests detect the presence of antibodies to the virus, indicating

exposure to HCV. These tests cannot tell if you still have an active viral
infection, only that you were exposed to the virus in the past. Usually, the test
is reported as “positive” or “negative.” There is some evidence that, if your
test is “weakly positive,” it may not mean that you have been exposed to the
HCV virus. The Centers for Disease Control and Prevention (CDC) revised its
guidelines in 2003 and suggests that weakly positive tests be confirmed with
the next test before being reported.
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 HCV RIBA test is an additional test to confirm the presence of antibodies to
the virus. In most cases, it can tell if the positive anti-HCV test was due to
exposure to HCV (positive RIBA) or represents a false signal (negative
RIBA). In a few cases, the results cannot answer this question (indeterminate
RIBA). Like the anti-HCV test, the RIBA test cannot tell if you are currently
infected, only that you have been exposed to the virus.
 HCV-RNA test identifies whether the virus is in your blood, indicating that
you have an active infection with HCV. In the past, it was usually performed
by a test called a qualitative HCV. Qualitative HCV RNA is reported as a
“positive” or “detected” if any HCV viral RNA is found; otherwise, the report
will be “negative” or “not detected”. The test may also be used after treatment
to see if the virus has been eliminated from the body.
 Viral Load or Quantitative HCV tests measure the number of viral RNA
particles in your blood. Viral load tests are often used before and during
treatment to help determine response to treatment by comparing the amount of
virus before and after treatment (usually after 3 months); successful treatment
causes a decrease of 99% or more (2 logs) in viral load soon after starting
treatment (as early as 4-12 weeks), and usually leads to viral load being not
detected. Some newer viral load tests can detect very low amounts of viral
RNA, and some laboratories no longer do qualitative HCV RNA tests if they
use one of these versions of viral load testing.
 Viral genotyping is used to determine the kind, or genotype, of the virus
present. There are 6 major types of HCV; the most common (genotype 1) is
less likely to respond to treatment than genotypes 2 or 3 and usually requires
longer therapy (48 weeks, versus 24 weeks for genotype 2 or 3). Genotyping is
often ordered before treatment is started to give an idea of the likelihood of
success and how long treatment may be needed.
When is it ordered?
Hepatitis C infection is the most common cause of chronic liver disease in North
America; about 2% of all adults in the United States have been exposed to the virus,
and 75-85% of those are chronically infected. The CDC recommends HCV testing in
the following cases:
 If you have ever injected illegal drugs

 If you received a blood transfusion or organ transplant before July 1992*
 If you have received clotting factor concentrates produced before 1987
 If you were ever on long-term dialysis
 For children born to HCV-positive women
 For health care, emergency medicine, and public safety workers after
needlesticks, sharps, or mucosal exposure to HCV-positive blood
 For people with evidence of chronic liver disease
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* The blood supply has been monitored in the U.S. since 1990, and any units of blood
that test positive for HCV are rejected for use in another person. The current risk of
HCV infection from transfused blood is about 1 case per two million transfused units.
A positive anti-HCV test may be confirmed with an HCV RIBA test, especially if the
test is “weakly positive.” Qualitative HCV-RNA is often used when the antibody test
is positive to see if the infection is still present. HCV viral load and genotyping may
be done to plan treatment; viral load and qualitative HCV RNA are also used to
monitor response to treatment.

If the antibody test result is positive, you have probably been infected with hepatitis
C, even if it was so mild you did not realize you had it.
A positive RIBA confirms that you had been exposed to the virus, while a negative
RIBA indicates that your first test was probably a false positive and you have never
been infected by HCV.
A positive (or detectable) HCV RNA means that you are currently infected by HCV.
HCV antibodies usually do not appear until several months into an infection but will
always be present in the later stages of the disease.
1. If the disease is very mild, why should I be tested?
Hepatitis C often leads to chronic hepatitis, which can progress to cirrhosis and liver
cancer (hepatocellular carcinoma). Early detection of the virus can alert your doctor to
follow your liver function more closely than usual and to consider treating you if you
are chronically infected.
2. Are there other tests used to follow the disease?

Yes. Liver tests, such as ALT and AST, are used to indicate ongoing liver injury.
Persons who are still infected with HCV but always have normal AST and ALT
probably have very mild liver disease and may not need treatment. Other liver tests,
such as albumin, prothrombin time, and bilirubin can also be used; they are typically
normal unless the person has developed cirrhosis. Sometimes a liver biopsy may be
performed to determine how severe the liver damage is.
3. Can I be vaccinated against HCV?

No. Currently, there is no vaccine available. Developing one has been
difficult because the virus has several different molecular configurations, which are
constantly changing.
4. Is there treatment for HCV?

Yes, there are currently a few drugs that can be used to treat HCV infection. Most
commonly, a combination of two drugs (pegylated interferon and ribavirin) is used.
New drugs to treat HCV are being tested currently. Depending on your age, gender,
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the type and viral load of HCV you have and how much damage has occurred to your
liver, your likelihood of cure from HCV may range from very low to as high as 80%.
5. Can I test myself for the virus at home?

There is an FDA-approved test kit available for collecting samples to send to a
laboratory for testing. Confidential test results are provided over the telephone. You
cannot actually perform the test yourself at home.
6. How can I tell if I can spread the infection to others?

If a person has detectable HCV RNA in their blood, they have the potential to spread
the disease to other people. Hepatitis C is spread by exposure to contaminated blood.
Some mechanisms of exposure include the sharing of needles or other 'works' used in
consuming drugs such as cocaine or heroin; use of contaminated equipment for
activities such as body piercing and tattooing; occupational exposure of healthcare
workers to used needles or other sharp objects; through sexual activity that results in
tissue tears; from mother to baby during childbirth; or from cuts sustained during
athletic or other activity.
Her-2/neu
Also known as: HER-2/neu, c-erbB-2
Formal name: Human epidermal growth factor receptor
Why get tested?
To determine whether a breast cancer tumor is positive for Her-2/neu, which helps to
guide treatment and determine prognosis
When to get tested?

If you have been diagnosed with invasive breast cancer and your doctor wants to
determine whether the Her-2/neu gene is being over-expressed in the tumor
Sample required?
A sample of breast cancer tissue obtained during a biopsy; sometimes a blood sample,
drawn from a vein in your arm, is also required.
Her-2/neu is an oncogene. It codes for a receptor for a particular growth factor that
causes cells to grow. Normal epithelial cells contain two copies of the Her-2/neu gene
and produce low levels of the Her-2 protein on the surface of their cells. In about 20-
30% of invasive breast cancers (and some other cancers, such as ovarian and bladder
cancer), the Her-2/neu gene is amplified (far too many copies are produced) and its
protein is over-expressed (an abnormally large amount of the protein is produced).
Tumors that have this over-expression tend to grow more aggressively and resist
hormonal therapy and some chemotherapies, and patients generally have a poorer
prognosis.
There are two main ways to test Her-2/neu status: immunohistochemistry (IHC) and
fluorescent in situ hybridization (FISH). IHC measures the amount of Her-2/neu
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protein present. FISH looks at the genetic level for actual gene amplification – the
number of copies of the gene present. IHC is currently the most widely used initial
testing method; however, if it is indeterminate or negative, then the FISH method is
often done as a follow-up test.
A sample of breast cancer tissue is obtained by doing a fine needle aspiration, needle
biopsy, or surgical biopsy. Her-2/neu protein sometimes is measured in a blood
sample, drawn from a vein in the arm. The amount of Her-2/neu protein present in
serum is loosely associated with the amount of cancer present; however it will not be
positive until the tumor is fairly big and is not widely used for determining Her-2/neu
status.
How is it used?
Her-2/neu testing is used as a prognostic marker to help determine how aggressive a
breast cancer tumor is likely to be.
It is also used as a predictor of response to therapy, such as hormone therapy and
chemotherapy.
The serum Her2/neu test is sometimes used to monitor cancer therapy. If the level is
initially elevated then falls, it is likely that treatment is working; if it stays elevated,
treatment is not working; and if the level falls then rises, the cancer may be recurring.
When is it ordered?
Her-2/neu testing is recommended as part of an initial workup of invasive breast
cancer and is sometimes done with recurrent breast cancer. It is not diagnostic but
helps the doctor determine treatment options and understand more about the tumor’s
characteristics.
Serum Her-2/neu is sometimes ordered initially to establish a baseline and then, if
elevated, used to monitor cancer treatment. However, this method is not widely used
because levels are only elevated when a large amount of cancer is present so early
cancers are likely to be negative for serum Her-2/neu.
If an IHC Her-2/neu test is positive, it means that the Her-2/neu gene is over-
expressing (producing more than a normal amount of) the Her-2/neu protein. If a
FISH test is done, then amplification (production of too many copies) of the Her-
2/neu gene can be detected. If either of these is positive, then the patient is likely to
have a tumor that is aggressive, that will respond poorly to hormone treatment, and
that will be resistant to chemotherapy. These patients may be considered candidates
for Herceptin therapy. [See "Is there anything else I should know?"]
If the IHC is negative but the FISH is positive, the patient still may benefit from
Herceptin, but if both are negative the treatment will not be useful.
Her-2/neu-positive tumors are susceptible to Herceptin (tratuzumab), a drug therapy
that was created to target Her-2/neu protein. Herceptin attaches itself to the excess
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protein molecules and inhibits the growth of the cancer. The development of this
specialized therapy has increased the use of Her-2/neu testing. Herceptin may be used
alone or with some chemotherapy agents but is only useful in those who have Her-
2/neu amplification and protein over-expression.
Her-2/neu testing is not available in every laboratory. Both IHC and FISH require
experience and special training to perform and interpret. Your doctor will probably
send your sample to a reference laboratory and the results may take several weeks to
return.
It takes a small amount of cancer tissue to perform the Her-2/neu test. If a sufficient
sample is not available, your doctor may try running a serum Her-2/neu test and/or
make an assumption that you are Her-2/neu-positive in order to broaden your
treatment options.
1. Besides Her-2/neu, what other laboratory tests may my doctor be ordering on
my breast cancer tissue?
During an initial workup of invasive breast cancer, your doctor will likely do a tissue
test for hormone receptor status. A patient with a positive estrogen and/or
progesterone receptor status may find their response to endocrine/hormone therapy
diminished if they are also Her-2/neu-positive, limiting that treatment option.
2. Does Herceptin work for everyone who is Her-2/neu positive?

Unfortunately, no. Only about one-third of patients who are positive for Her-2/neu
will respond to Herceptin therapy. There are other cellular factors involved that are
not well understood yet. Herceptin is sometimes combined with other chemotherapy
agents to make it more effective.
Herpes
Also known as: Genital Herpes, Oral Herpes, Cold Sores
Formal name: Herpes Simplex Virus, Type1 and Type 2 (HSV-1 and HSV-2)
Why get tested?
To screen for or diagnose infection with the herpes simplex virus
When to get tested?
If you have symptoms of an infection with the herpes simplex virus, such as blisters
or sores around your mouth or in the genital area
Sample required?
A swab or scraping from a blister or sore in the infected area or a blood sample drawn
from a vein in your arm; for meningitis (inflammation of the spinal cord) or
encephalitis (inflammation of the brain), a sample of cerebrospinal fluid (CSF).
Herpes simplex testing is performed to identify an acute herpes infection or to detect
herpes antibodies, an indication of a previous exposure to herpes. One of the most
common viral infections, herpes simplex virus (HSV) exists in two types, HSV-1 and
HSV-2. Both types are contagious and periodically cause small fever blisters
(vesicles) that break to form open lesions. HSV-1 primarily causes blisters or “cold
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sores” around the oral cavity and mouth, while HSV-2 usually causes lesions around
the genital area.
The herpes simplex virus can be passed from person to person through skin contact
while the sores are open and healing, and sometimes asymptomatically when there are
no visible sores. HSV-2 is frequently a sexually transmitted disease but HSV-1 also
may be acquired during oral sex and found in the genital area. According to the
American Social Health Association and their National Herpes Resource Center,
about 50% to 80% of adults in the U.S. have HSV-1 and about 20% have HSV-2.
Because symptoms may be mild, 90% of those who have HSV-2 may be unaware that
they have been infected.
Once someone is infected and the initial infection resolves, they will harbor the HSV
in a latent form. During periods of stress or illness, the virus may reactivate. In most
cases, HSV outbreaks are a painful annoyance rather than a health threat, but the virus
can also cause neonatal herpes (an infant is infected by the mother during birth) and
encephalitis (inflammation of the brain). These illnesses can be fatal and can cause
serious permanent neurological problems in those who survive. Patients with
conditions that cause their immune system to be suppressed, such as those with
HIV/AIDS or those who have had an organ transplant, may have more frequent and
serious outbreaks of HSV.
HSV testing detects either the virus itself, its viral DNA or antibodies to the virus.
During an acute primary infection or reactivation, the virus may be detected by:
 Herpes culture. A sample of fluid is collected from an open sore (the most
common sample). It is incubated in a nutrient environment to grow and isolate the
virus. This test is sensitive and specific, but it takes 2 or more days to complete. Fresh
lesions are the best for this test. Viral shedding decreases over time and can lead to a
false negative result. Once the virus is grown in culture, it is possible to determine if it
is HSV-1 or HSV-2.
 HSV DNA testing. Can be done to detect HSV genetic material in a patient
sample. This method can type and quantitate the virus and is good in circumstances
where the virus is present in low numbers (such as viral encephalitis) or the lesion is
several days old.
 HSV antibody testing. Antibodies to HSV are specific proteins that the body
creates and releases into the bloodstream to fight the infection. HSV IgM antibody
production begins several days after a primary (initial) HSV infection and may be
detectable in the blood for several weeks. HSV IgG antibody production begins after
HSV IgM production. Concentrations rise for several weeks, fall, and then stabilize in
the blood. Once someone has been infected with HSV, they will continue to produce
small quantities of HSV IgG. HSV antibody testing can detect both viral types (HSV-
1 and HSV-2) and tests are available that can detect the early IgM antibodies as well
as the IgG antibodies that remain forever in those who have been exposed.
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Your doctor will take a swab or scraping from a blister or sore in the mouth or genital
area. Occasionally, a sample of cerebrospinal fluid (CSF) may be collected from the
spinal column. For antibody testing, a blood sample is obtained by inserting a needle
into a vein in the arm.
How is it used?
HSV testing is used to detect the presence of the herpes simplex virus in those who
have genital sores, encephalitis, and in newborns suspected of having neonatal herpes
(a rare but serious condition where herpes is contracted during birth). A pregnant
woman who has been diagnosed with herpes may be monitored regularly prior to
delivery to identify a reactivation of her infection (which would indicate the necessity
for a caesarean section to avoid infecting the baby). The primary methods of testing
for the virus are the herpes culture and HSV DNA testing.
Although it is not as sensitive, HSV antibody testing can be used to help diagnose an
acute HSV infection if acute and convalescent blood samples are collected. The
convalescent blood sample is collected several weeks after the acute sample, and HSV
IgG antibody levels are compared to see if they have risen significantly (indicating a
current infection). Antibody testing may also be used to screen certain populations,
such as sexually active people, potential organ transplant recipients, and those with
HIV/AIDS, for a previously contracted HSV infection.
When is it ordered?
A herpes culture or HSV DNA testing may be ordered when a patient has a blister or
vesicle on their genitals or mouth. They may be ordered when a patient has
encephalitis that the doctor suspects may be caused by a virus. HSV testing may be
ordered regularly when a pregnant woman has herpes. A mother and newborn may be
tested for HSV when a baby shows signs of HSV infection (such as meningitis or skin
lesions).
HSV antibody testing is ordered primarily when a patient is being screened for a
previous exposure to HSV. Occasionally, acute and convalescent HSV antibody
testing may be ordered when a current infection is suspected.
A positive herpes simplex culture or HSV DNA test from a vesicle scraping indicates
an active HSV-1 or HSV-2 infection. A negative test result indicates that the herpes
simplex virus was not isolated but does not definitely rule out the presence of virus.
This is because if the specimen taken does not contain actively replicating virus or if
the sample was not transported under optimum conditions, no viable virus may be
detectable, resulting in a false negative result. For example, viruses can be readily
inactivated and if the sample was taken from an older lesion, not a fresh blister, or if
transport of the sample was delayed, there may not be sufficient virus to detect even
though the patient is infected.
The presence of HSV-1 or HSV-2 IgM antibodies indicates an active or recent

infection. HSV-1 or HSV-2 IgG antibodies indicate a previous infection. A significant
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increase in HSV IgG antibodies, measured by comparing acute and convalescent
samples, indicates an active or recent infection. Negative HSV antibody results mean
that it is unlikely that the patient has been exposed to HSV, or that the body has not
had time to begin HSV antibody production.

The most serious, or life-threatening, HSV infections can occur in newborns after
perinatal infection and in immunocompromised individuals. The lesions tend to be
more extensive and persist longer than in immunocompetent individuals. Infection
with HSV can increase HIV viral load. HSV-2 infection is a significant opportunistic
infection in HIV-infected individuals; up to 90% of HIV-infected individuals are co-
infected with HSV-2.
HSV, in combination with human papilloma virus (HPV) infection, has been
associated with a higher risk of developing cervical cancer.
1. How is herpes transmitted?

HSVs are transmitted through direct contact, which can include kissing; vaginal, oral,
or anal sex; or other skin-to-skin contact. Genital herpes is most easily contracted by
having sex with someone who has a vesicle, but it can be transmitted even if there are
no sores or other symptoms. People often catch it by having sex with someone who
doesn’t know s/he is infected.
2. What are the symptoms of herpes?

Many people who have herpes don’t know it because they never have symptoms or
don’t recognize the symptoms they do have. When you are first infected, you may
have obvious and painful lesions at the site of infection. These lesions appear within
two weeks after the virus is transmitted and usually heal within two to four weeks.
The vesicles can appear in the vaginal area, on the penis, around the anus, or on the
buttocks or thighs. This primary episode can include a second outbreak of lesions and
even flu-like symptoms of fever and swollen glands. However, you may not have any
lesions or have symptoms that are so mild that you don’t notice them or mistake them
for something else, such as insect bites or a rash.
After the primary episode, the virus goes into an inactive (latent) state within your
body. It may cause outbreaks from time to time. The outbreaks, which last about a
week, can be blisters or open sores that crust over and then disappear. Sometimes, the
virus can become active and infectious with no noticeable sores. The virus never goes
away, and the frequency and severity of these recurrent episodes vary greatly among
individuals.
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There is no cure for herpes. Some prescription medications can reduce the frequency
and shorten the length of outbreaks.
4. How can herpes be prevented?
Oral herpes (mouth sores, skin lesions in non-genital sites) can’t be prevented.
Exposure occurs during everyday life. However, genital herpes can be prevented by
avoiding sexual contact with someone who has an active herpes infection and through
the use of condoms. For more information, visit the National Herpes Resource Center.
HIV Antibody
Why get tested?

To determine if you are infected with Human immunodeficiency virus (HIV)
When to get tested?
One month to three months after you think you may have been exposed to the virus;
the average time for the antibody to be detected is two weeks
Sample required?
A blood sample collected from a vein in your arm; there are also tests available that
can be performed on urine and/or oral fluid.
HIV, human immunodeficiency virus, is the virus that causes AIDS (acquired
immunodeficiency syndrome), which destroys the immune system and leaves the
body vulnerable to debilitating infections. This test detects HIV antibodies in the
blood. Antibodies to HIV are produced by the body and can be detected in the blood
about 2–4 weeks after exposure to the virus.
How is it used?
HIV antibody testing is used to determine whether or not a person is infected with
HIV. Early treatment of HIV infection and immune system monitoring can greatly
improve long-term health. Also, knowing your HIV status may help you change
behaviors that would put you and others at risk.
Antibodies to the HIV virus can be detected by a screening test called an ELISA. The
ELISA test is repeated if positive. The ELISA method is very sensitive but requires
another test, a Western Blot, to confirm the results because false positives can occur.
These tests can be done on a blood sample in a doctor’s office or a local clinic. There
are also currently approved home test kits available for HIV antibody testing. These
allow you to take a sample of your blood from a finger at home and mail it to a testing
center. You would then hear your results later over the phone, along with appropriate
counseling. There are, however, no available tests that can be performed at home.
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When is it ordered?
Antibody testing for HIV should be ordered if you think you may have been exposed
to HIV. Testing is recommended if:
 You are sexually active (three or more sexual partners in the last 12 months).
 You received a blood transfusion prior to1985, or a sexual partner received a
transfusion and later tested positive for HIV. For more information, go to:
http://www.cdc.gov/hiv/pubs/faq/faq15.htm
 You are uncertain about your sexual partner’s risk behaviors.
 You are a male who has had sex with another male.
 You have used street drugs by injection, especially when sharing needles
and/or other equipment.
 You have a sexually transmitted disease (STD).
 You are a health care worker with direct exposure to blood on the job.
 You are pregnant. (There are now treatments that can greatly reduce the risk
that a pregnant woman who has HIV will give the virus to her baby.)
 You are a woman who wants to make sure you are not infected with HIV
before getting pregnant.

A healthy individual has no antibodies to HIV. If you test positive for HIV
antibodies on both the ELISA and the Western Blot tests, you are considered to be
infected with HIV.

Antibody testing will not detect HIV immediately after exposure, during the window
before the development of antibodies. If you are tested too soon, your result may be
negative despite the fact that you are infected (false negative). Because of this, repeat
testing is important. You should have another HIV antibody test in 3–6 months from
the time of a possible exposure to the virus.
1. What are the symptoms of HIV infection?
The only reliable way to tell if you are infected with HIV is to get tested. This is
because many people with HIV do not experience symptoms for years since the time
of infection, or the symptoms may be very similar to symptoms of other illnesses.
Click here for more information on symptoms of HIV infection.
2. What are the symptoms of AIDS?

The symptoms of AIDS are similar to symptoms of other illnesses. Click here for
more information.
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3. What are the treatments for HIV/AIDS?
Currently, there is no cure for HIV or AIDS. However, there are therapies that can
help. The CDC’s booklet, Living with HIV/AIDS, is available online. The FDA also
offers an online list of FDA-approved therapies. Early treatment is recommended.
4. Should I tell anyone else of my test results?

Yes. If you test positive for HIV, it is important that you tell your healthcare providers
as well as all current and future sex partners and/or anyone with whom you share
needles. Counseling services are available that will help you to inform the people who
need to know. For more information, visit the CDC’s Division of HIV/AIDS
Prevention website for their HIV Counseling, Testing, and Referral Guidelines and
Partner Counseling and Referral Services Guidance.
5. Can you use the HIV antibody test to detect HIV in newborns?
No. Because maternal antibodies are transferred from mother to baby and stay in the
newborn’s system for 6–12 months, a different test must be used. This test is called
the HIV DNA test.
6. Are there HIV testing methods other than a blood test?

Yes. Methods that test either oral fluid or urine are available in some locations. The
Centers for Disease Control and Prevention (CDC) have more information on the
different types of HIV screening tests available in the U.S.
HIV Genotypic Resistance Testing
Why get tested?
If you have been diagnosed with HIV and will be receiving anti-viral therapy or you
are receiving anti-viral therapy that is not working effectively
When to get tested?
When your doctor wants to put you on anti-viral therapy and if your HIV viral load
values rise steadily even though you are receiving anti-viral therapy
In genotypic resistance testing, the genetic code of the particular strain of HIV you
have been infected with is checked to see if there are any genetic mutations or
changes that are known to cause drug resistance. HIV is resistant to an antiviral
medication if it keeps multiplying while a person is taking the drug. Changes
(mutations) in the virus cause resistance. HIV mutates almost every time a new copy
is made, but not every mutations causes resistance. Antiviral drugs control most types
of HIV. However, a mutation that is resistant to a drug will multiply and become the
most common form of the virus in the body. This is called “selective pressure”
because the drug “selects” versions of the virus that are resistant to it. For certain
drugs, single mutations of the gene increase resistance to high levels. For other drugs,
there are several mutations that are associated with resistance.
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How is it used?
Genotypic resistance testing helps doctors make better treatment decisions for their
patients when existing anti-viral therapies are not working effectively. If drug
resistance is found, a new treatment regimen may be chosen.
When is it ordered?
Genotypic resistance testing is ordered when viral load values (a measure of how
much HIV is in your body) rise steadily during therapy, indicating treatment failure
and the possibility of resistance. The test may also be ordered before the start of
therapy for an acute infection if a drug- resistant virus is suspected, so that immediate,
appropriate therapy is possible.
The test result identifies the viral mutations. These are described by a combination of
letters and numbers, for example K103N. Based on the test result, your doctor will
identify whether a given mutation is one known to cause drug resistance. Not all
mutations cause drug resistance. Some mutations are very common, and resistance is
known to certain drugs and/or drug combinations. This is important information for
physicians to help them predict which treatment regimen will work best for each
patient.
Genotypic resistance testing, although relatively new, is available in large laboratories
and reference centers.
The test is not good at detecting “minority” mutations, which affect less than 20% of
the virus population.
Genotypic resistance testing works best on blood samples with a viral load of at least
1,000 copies per milliliter of blood. If your viral load is very low, the test probably
won’t work. It may not detect resistance to all drugs.
1. Are there other viral conditions besides HIV for which genotypic resistance
testing is being used in order to make treatment decisions?
Yes. Determination of hepatitis C virus (HCV) genotype may be useful to predict the
patient's short and long term response to therapy. Prior to initiating treatment for
HCV, molecular characterization of the genotype of HCV may be done to select the
most efficacious therapy and duration of therapy. There are 6 major genotypes of
HCV, and data have shown that patients with genotypes 2 or 3 have a better response
to therapy than those with genotype 1. There are multiple genotypes of hepatitis A
and B that vary by geographical distribution. The impact of the genotype on the
severity and outcome of treatment for these has not been established. Therefore,
routine testing for genotype of hepatitis A and B is not performed.
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HIV Viral Load
Why get tested?
To monitor the status of HIV disease, in conjunction with other lab tests and physical
disease progression, and to guide therapy
When to get tested?
When first diagnosed with HIV, every 2 - 8 weeks at the start of therapy or therapy
changes, and every 3 - 4 months during long-term therapy, or as your doctor
recommends; if therapy is effective, the viral load should decrease within 4 - 6
months.
This test measures the amount of HIV in your blood, lymph nodes, spleen, and other
parts of your body. “Viral load” means the number of HIV particles or copies of the
virus present in the blood.
How is it used?
The viral load test provides important information that is used in conjunction with the
CD4 cell count:
 to monitor the status of HIV disease,

 to guide recommendations for therapy, and
 to predict the future course of HIV.
Evidence shows that keeping the viral load levels as low as possible for as long as
possible decreases the complications of HIV disease and prolongs life.
Public health guidelines state that treatment should be considered for asymptomatic
HIV-infected people who have viral loads higher than 30,000 copies per milliliter of
blood using a test known as a branched DNA test, or more than 55,000 copies using
an RT-PCR test.
There are several methods for testing viral load; results are not interchangeable so it is
important that the same method be used each time.
When is it ordered?
A viral load test is ordered when a patient is first diagnosed with HIV. The test result
functions as a baseline measurement that shows how actively the virus is reproducing
and whether treatment is immediately necessary.
If and when therapy is started, your doctor should order a viral load test and a CD4
count about two to eight weeks after you start a treatment to evaluate whether therapy
is being effective. To monitor long-term therapy, your doctor will order viral load
tests and CD4 counts about every three to six months.
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Viral load tests are reported as the number of HIV copies in a milliliter of blood. If the
viral load measurement is high, it indicates that HIV is reproducing and that the
disease will likely progress faster than if the viral load is low. A high viral load can be
anywhere from 5,000 to 10,000 copies and can range as high as one million or more.
A low viral load is usually between 200 to 500 copies, depending on the type of test
used. This result indicates that HIV is not actively reproducing and that the risk of
disease progression is low.
A viral load result that reads “undetectable” does not mean that you are cured. It may
mean that the level of HIV virus in your blood is below the threshold needed for
detection by this test. Other tests that are ultra-sensitive and that can measure as few
as 20 to 40 copies in a milliliter of blood can be performed to make sure.
If you are not taking your medication as your physician has directed, your viral load
will not drop as significantly as if you take your medication on time.
Change in viral load is also a very important measurement. A rising count indicates an
infection that is getting worse, while a falling count indicates improvement and
suppression of the HIV infection.
A non-infected person should have no circulating HIV virus in his or her blood and,
therefore, a negative or undetectable viral load.

Viral load testing should not be used for diagnosing HIV; the HIV antibody test is still
the preferred method of choice for this.
Viral load testing done by the PCR method is incredibly sensitive, which can give rise
to false-positive results.
1. Will exercise, nutrition, and other lifestyle modifications help decrease my

viral load levels?
There is no direct link between viral load levels and exercise, nutrition, or other
lifestyle factors. However, the CDC does suggest that if you eat healthy foods, you
will stay strong and keep up your energy. This and more information is contained in
the CDC brochure Living with HIV.
HLA-B27
Why get tested?
To determine whether you have human leukocyte antigen B27 (HLA-B27) on the
surface of your cells. This test is sometimes ordered to help assess the likelihood that
you have an autoimmune disorder that is associated with the presence of HLA-B27.
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When to get tested?
When you have symptoms of chronic inflammation, pain, and stiffness in certain
areas of your body, such as your back, neck, and chest, especially if you are male and
the symptoms began in your early 30s.
Human leukocyte antigens (HLA) are a group of proteins that help the body’s
immune system to identify its own cells and to distinguish between “self” and
“nonself.” Everyone has an inherited combination of HLA antigens (a mixture of
types A, B, C, and D) present on the surface of his white blood cells (leukocytes) and
other nucleated cells. While not as unique as a fingerprint, the presence or absence of
each antigen creates a distinctive HLA combination for each person. (This is
important when someone needs a bone marrow or organ transplant, as the donor’s
HLA antigens must be matched up with the recipient’s.)
Human leukocyte antigen B27 (HLA-B27) is found in about 5-10% of the U.S.
population. Its presence has been associated with several autoimmune disorders. The
most common of these disorders is ankylosing spondylitis (AS). Approximately 90%
of patients with AS carry HLA-B27. Other autoimmune disorders that have an
association with the presence of B-27 are juvenile rheumatoid arthritis (80% of
patients) and Reiter’s syndrome (reactive arthritis; 50-80% of patients). HLA-B27 is
also present in 50% of patients with inflammatory bowel disease with spondylitis and
psoriasis vulgaris with spondylitis. While HLA-B27 has not been established as a
cause of these conditions, there is a higher prevalence of this antigen in those affected.
How is it used?
The HLA-B27 test is not a definitive test that can be used to diagnose or rule out a
disorder. It is used as one piece of evidence in the constellation of signs, symptoms,
and lab tests to support or rule out diagnosis of certain autoimmune disorders, such as
AS and Reiter’s syndrome. Both AS and Reiter’s syndrome are chronic progressive
conditions that occur more frequently in men than women, and the first symptoms
usually occur when a patient is in his early 30’s. AS involves pain, inflammation, and
a gradual stiffening of the spine, neck and chest. Reiter’s syndrome is a group of
symptoms that includes inflammation of the joints, urethra, eyes, and skin lesions.
Often the initial symptoms of these autoimmune disorders are subtle and may take
several years before characteristic degenerative changes to bones and joints are visible
on X-rays.
The HLA-B27 test may be ordered as part of a group of tests used to diagnose and
evaluate conditions causing arthritis-like chronic joint pain, stiffness, and
inflammation. This group of tests may include an RF (rheumatoid factor), an ESR
(erythrocyte sedimentation rate), and a CRP (C-Reactive protein).
When is it ordered?
An HLA-B27 test may be ordered when a patient has acute or chronic pain and
inflammation in his spine, neck, chest, eyes, and/or joints, and the doctor suspects an
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autoimmune disorder that is associated with the presence of HLA-B27. Sometimes
doctors must rely on their clinical findings and the HLA-B27 test result when
diagnosing ankylosing spondylitis (and other HLA-B27 related disorders) because the
characteristic changes to the bones may not be detectible for several years. Under
these circumstances HLA-B27 is not diagnostic but adds additional information,
increasing or decreasing the likelihood that the patient has ankylosing spondylitis.
HLA-B27 will be present or absent. If it is present, then the HLA-B27 antigen
(protein structure) exists on the surface of the body’s white blood cells and nucleated
cells. If a patient has HLA-B27 and has symptoms such as: chronic pain,
inflammation, and/ or degenerative changes to his bones (as seen on X-ray), then it
supports a diagnosis of AS, Reiter’s syndrome, or another autoimmune disorder that is
associated with the presence of HLA-B27. This is especially true if the patient is
young, male, and if he experienced his first symptoms before the age of 40.
The presence of HLA-B27 may also seen with other autoimmune conditions such as:
 Isolated acute anterior uveitis

 Undifferentiated spondyloarthropathies
 Enteropathic synovitis
If HLA-B27 is not present, then it is less likely that the symptoms are due to an HLA-
B27 associated autoimmune disorder. (There are exceptions to this, however, about
10% of those with AS and 40-50% of those with Reiter’s syndrome will be negative
for HLA-B27.)
At this time, identifying the presence of HLA-B27 does not predict the likelihood of
developing an autoimmune disease. If a patient does have an associated disorder, the
presence of HLA-B27 cannot be used to tell which disease is present, how quickly it
will progress, its severity, prognosis, or the degree of organ involvement.

Whether or not HLA antigens will be present is genetically determined. Their
production is controlled by genes that are passed from parents to children. If one of
your family members has a HLA-B27 related spondyloarthropathy (AS or other
related condition), and you have the HLA-B27 antigen, then you have a higher risk of
developing a spondyloarthropathy.
With new genetic testing methods it is now possible to separate HLA-B27 into
subtypes. So far about fifteen different subtypes have been identified. The most
common in the U.S. are HLA-B27.05 and HLA-B27.02. How the presence of these
specific subtypes affects the likelihood of developing an autoimmune disease is not
yet known.
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1. What causes the autoimmune disorders?
In most cases the cause is not known. However, in some cases of Reiter’s syndrome,
there is an association between a previous infection by a microorganism such as:
Chlamydia, Campylobacter, Salmonella, Ureaplasma, or Yersinia and the onset of the
disease. It is thought that similarities between the HLA-B27 antigen and the antigens
found on the surface of the microorganisms trigger the immune system to fight both
the microorganism and the patients own tissues – launching the autoimmune disorder
after the resolution of the infection.
Homocysteine
Why get tested?
To determine if you are at increased risk of a heart attack or stroke; to determine if
you are folate-deficient or B12-deficient; to help diagnose a rare inherited disorder
called homocystinurina
When to get tested?
If you have had a heart attack or stroke, or as part of a cardiac risk assessment; when a
doctor suspects a vitamin B12 or folate deficiency or suspects that an infant or young
person may have homocystinuria
Sample required?
A blood sample taken by needle from a vein in the arm; sometimes a urine sample in
addition to the blood sample.
This test determines the level of homocysteine in the blood or urine. Homocysteine is
a sulfur-containing amino acid that is normally present in very small amounts in all
cells of the body. Homocysteine is a product of methionine metabolism. Methionine is
one of the eleven “essential” amino acids - amino acids that must be derived from the
diet since the body cannot produce them. In healthy cells, homocysteine is quickly
converted to other products.
Vitamins B6, B12, and folate are necessary to metabolize homocysteine. Patients who
are deficient in these vitamins may have increased levels of homocysteine.
Recent studies have suggested that people who have elevated homocysteine levels
have a much greater risk of heart attack or stroke than those with average levels.
Increased concentrations of homocysteine have been associated with an increased
tendency to form inappropriate blood clots. When this happens it can lead to heart
attack, strokes, and blood vessel blockages in any part of the body.
Homocysteine can be greatly increased in the blood and urine of patients with a rare
inherited condition called homocystinuria. This disorder is caused by an alteration in
one of several different genes. The affected person has a dysfunctional enzyme that
does not allow the normal breakdown of methionine. Because of this, homocysteine
and methionine begin to build up in the person’s body. A baby with this condition will
appear normal at birth but within a few years will begin to develop signs such as a
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dislocated lens in the eye, a long slender build, long thin fingers, skeletal
abnormalities, osteoporosis, and a greatly increased risk of thromboembolism
(inappropriate clotting in their arteries and veins), and of atherosclerosis (fatty
plaques) that can lead to premature cardiovascular disease. The buildup may also
cause progressive mental retardation, behavioral disorders, and seizures.

A blood sample is taken by needle from a vein in the arm; sometimes a urine sample
is also collected. Your doctor may want you to fast for 10 to 12 hours (no food,
nothing but water) prior to this test.
How is it used?
Homocysteine is commonly used as a screen for people at high risk for heart attack or
stroke. It may be useful in patients who have a family history of coronary artery
disease but no other known risk factors. However, its utility for this purpose continues
to be questioned because the role, if any, that homocysteine plays in the progression
of cardiovascular disease (CVD) has not been established. Routine screening, such as
that done for total cholesterol, is not yet recommended.
A physician may also order a homocysteine test to determine if a patient has B12 or
folate deficiency. The homocysteine concentration may be elevated in patients before
B12 and folate tests are abnormal. Some doctors may recommend homocysteine
testing in malnourished patients, such as the elderly (who often absorb less vitamin
B12 from their diets), and those with drug or alcohol addictions.
A doctor may order both a urine and blood homocysteine to help diagnose
homocystinuria if they suspect that an infant may have this inherited disorder. In some
states, babies are tested for excess methionine as part of their newborn screening. If a
baby’s test is positive, then urine and blood homocysteine tests are often performed to
confirm the findings.
Urine and/or blood homocysteine concentrations may be ordered at intervals to

monitor the effectiveness of treatment in patients who are being treated for elevated
homocysteine.
When is it ordered?
Homocysteine may be ordered as part of a cardiac risk assessment, depending on the
patient’s age and other risk factors. It may also be ordered following a heart attack or
stroke to help guide treatment. It may also be ordered when a doctor suspects that a
patient may have a B12 and/or folate deficiency or when a baby has signs or
symptoms that suggest that they may have homocystinuria.
Recent studies have suggested that people who have elevated homocysteine levels
have a much greater risk of heart attack or stroke than those with average levels. At
present, however, the American Heart Association has not established a direct
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correlation between homocysteine levels and heart attacks but does acknowledge
strong evidence of a relationship between homocysteine levels and heart attack/stroke
survival rates. Blockage of a coronary artery, a precursor to a heart attack, occurs with
more than double the average frequency in people with homocysteine levels in the
highest 25% as compared to those in the lowest 25%.
Since measuring homocysteine levels to determine cardiac risk is a relatively new use
for the test, a standardized interpretation of the measured value has yet to be
determined. In many people, homocysteine levels can be decreased by taking extra
levels of folic acid, vitamin B12, and vitamin B6 - three B-complex vitamins that
drive homocysteine metabolism. The elderly are especially vulnerable and may need
these supplements to keep their homocysteine levels low.
Greatly increased concentrations of homocysteine in the urine and blood mean that it
is likely that an infant has homocystinuria and indicate the need for further testing to
confirm the cause of the increase.
When test results suggest homocystinuria, liver or skin biopsy samples are sometimes
tested to determine whether the enzyme cystathionine beta synthase (CBS) is present.
The absence of this enzyme is the most common cause of homocystinuria. Genetic
tests may be ordered to test for one or more of the most common gene mutations. If
the patient has a strong family history of early atherosclerosis or a family member has
been diagnosed with homocystinuria, then the patient should be tested for the gene
mutation that was found in the family member.
Homocysteine levels can increase with age, when a patient smokes, and with the use
of drugs such as carbamazepine, methotrexate, and phenytoin.
1. What are some good sources of folic acid and vitamins B6 and B12?
Cereal grains are the main source of folic acid. In addition, the Food and Drug
Administration requires the addition of folic acid to grain products in this country.
Fruits and vegetables have significant amounts of vitamin B6, and vitamin B12 can be
found in red meats, poultry, fish, and other seafood. People with high homocysteine
levels also may benefit from taking multivitamins to supplement this amount.
2. Is there a difference in risk between men and women?

Homocysteine levels in women increase after menopause, possibly due to decreased
estrogen production. Even so, the risk for women does not appear to increase with
moderately elevated levels.
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3. Could any medications I may be taking have an effect on my homocysteine
level?
Yes. There are numerous drugs that may either increase or decrease the amount of
homocysteine in your body. You should always keep your doctor and pharmacist
aware of any medications, traditional or herbal, you are taking, since they may
interfere with the test results.
Hormone Receptor Status
Also known as: Estrogen receptors, Progesterone receptors

Formal name: Estrogen and Progesterone receptor status
Why get tested?
To determine whether a breast cancer tumor is positive for estrogen and/or
progesterone receptors, which helps to guide treatment and determine prognosis
When to get tested?
If you have been diagnosed with breast cancer and your doctor wants to determine
whether the tumor’s growth is influenced by the hormones estrogen and/or
progesterone
Sample required?
A sample of breast cancer tissue obtained during a biopsy or a tumor removed
surgically during a lumpectomy or mastectomy.
Estrogen receptors (ER) and progesterone receptors (PR) are specialized proteins
found within certain cells throughout the body. These receptors bind to estrogen and
progesterone, female hormones that circulate in the blood, and promote new cell
growth and division.
Many breast cancer tumors have receptors for estrogen and/or progesterone, often in
large numbers. These tumors are said to be hormone-dependent, and estrogen and/or
progesterone feed their growth. Breast cancer tissue can be tested to see if it is
positive for these receptors.
A sample of breast cancer tissue is obtained (such as by doing a fine needle aspiration,
needle biopsy, or surgical biopsy) or a tumor removed surgically during a
lumpectomy or mastectomy is tested.
How is it used?
Hormone receptor status is used as a prognostic marker. Those with ER-positive and
PR-positive tumors tend to have a better prognosis than those with ER-negative or
PR-negative tumors.
The hormone receptor status test is also used to help determine treatment options,
including endocrine therapy (anti-hormone treatments, such as tamoxifen), when
aprimary tumor has been removed or to help guide treatment decisions when a tumor
recurs.
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When is it ordered?
Hormone receptor status testing is recommended as part of an initial workup of
invasive breast cancer. It is not diagnostic but helps the doctor to determine treatment
options and to understand more about the tumor’s characteristics.
In general, if a patient’s cancer is ER-positive and PR-positive, the patient will have a
better-than-average prognosis, and their cancer is likely to respond to endocrine
therapy (anti-hormone treatments). The more receptors present and the more intense
their reaction, the more likely the response. However, an individual’s response
depends on a variety of factors.
If a patient’s cancer is ER-negative but PR-positive, the patient may still benefit from
endocrine therapy but may have a diminished response.
If the cancer is both ER-negative and PR-negative, then the patient will probably not
benefit from endocrine therapy.
Her-2/neu testing may be done at the same time as hormone receptor status testing. A
patient with a positive estrogen and/or progesterone receptor status may find their
response to endocrine therapy diminished if they are also Her-2/neu-positive.
Hormone receptor status testing is not available in every laboratory. It requires
experience and special training to perform and interpret. Your doctor will probably
send your sample to a reference laboratory and it may take several weeks before your
results are available.
It takes a small amount of cancer tissue to perform the hormone receptor status
testing. If a sufficient sample is not available, your doctor may make an assumption
that your cancer is ER-positive and PR-positive in order to broaden your treatment
options.
1. Is there a blood test that can be done to check my hormone receptor status?
No. The cancer cells do not “shed” the receptors, so they are not detectable in the
blood. They must be evaluated in the cancer tissue itself.
HPV
Why get tested?
To screen for infection with HPV, some types of which are associated with cervical
cancer
When to get tested?
If you are sexually active, have symptoms of HPV infection (genital warts), are age
30 or older, or have an irregular Pap smear
Sample required?
A sampling of cells from the cervical area.
The HPV test is looking for evidence of infection by high-risk types of human
papillomavirus (HPV). HPV is a group of about 100 related viruses that cause skin
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warts and genital warts (also called condylomata). Common in young men and
women, most HPV infections are short-lived and relatively benign. A few types of
HPV (such as HPV-16, HPV-18, HPV-31, and HPV-45), however, are considered
high-risk. They do not usually cause visible warts, but they are persistent and have
been linked to cervical, penile, and other forms of genital cancer. Traditionally, HPV
infection has been detected as abnormal cell changes on a Pap smear, a test used
primarily to detect cancer of the cervix (the lower part of the uterus or womb) or
conditions that may lead to cancer. During a Pap smear, the “normalness” of cervical
cells is evaluated under a microscope. “Low-grade” changes to the cells on a Pap
smear may indicate an HPV infection, but there is no clear distinction between high-
and low-risk types.
A recently developed DNA test for HPV is gaining widespread acceptance as an
additional cervical cancer screening tool and as a follow-up test to abnormal changes
on a Pap smear. It uses the same cervical sample as the Pap smear to detect and
confirm the presence of high-risk types of HPV; it tests for the 13 most common types
of high-risk HPV but does not distinguish between them. If there is a need, further
DNA testing can be done by another method to determine exactly which type(s) of
HPV are present, although this is not frequently done.
A sampling of cells is taken from the cervical area during a pelvic examination using
a type of wooden "spatula," swab, or brush and, if HPV DNA testing is to be
performed, placed into a special liquid preservative.
How is it used?
For women younger than 30 years of age, the Pap smear and pelvic exam are the
primary cervical cancer screening tools. If results indicate abnormal changes that may
be due to a high-risk type of HPV, then DNA HPV testing may be ordered as a
follow-up test. It is not routinely used as a screening tool in this age group because
HPV is very common and rarely causes cancer in those under 30.
The American College of Obstetricians and Gynecologists (ACOG) released
guidelines in August 2003 recommending that women 30 years or older be offered the
HPV DNA test in addition to their Pap smear and pelvic exam. If the HPV DNA test
and Pap smear are negative and the woman does not have an underlying health
condition, such as HIV or immunosuppression, then the guidelines suggest that she
may wait three years before having another Pap smear and HPV DNA test.
The HPV DNA test and Pap smear may be ordered on a more frequent basis to
monitor positive HPV tests, abnormal Pap smear changes, and those patients who
have underlying medical conditions, such as HIV or immunosuppression.
During a pelvic exam, a doctor can detect warts and other lesions through visual
inspection that may warrant further investigation. Some otherwise invisible warts in
the genital tissue may be identified by applying acetic acid to areas of suspected
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infection. This process makes the infected areas whiten when they are examined by a
procedure called colposcopy.
A doctor might also take a small piece of tissue (called a biopsy) from the cervix and
examine it under a microscope. When either the Pap smear or the biopsy indicates a
condition that could lead to cancer in some women (called intraepithelial neoplasia),
the DNA HPV test can determine if the patient is infected with a high-risk strain of
HPV that increases the chance that cancer might develop if not treated.
When is it ordered?
Women who are sexually active with more than one partner—or whose partner has
more than one sex partner—should have regular exams for sexually transmitted
diseases, including HPV. The American Cancer Society recommends that women
over the age of 18 and all sexually active women have a Pap smear yearly to screen
for cancer or situations that may develop into cancer. When results indicate abnormal
changes that may be due to a high-risk type of HPV, then DNA HPV testing may be
ordered as a follow-up test.
Doctors may order the HPV DNA test as a cervical cancer screening test, along with
the Pap smear test, when a woman is 30 years old or older and at intervals of 3 years
if initial testing is negative. Patients who are positive for high-risk HPV, have
abnormal cell changes on their Pap smear, or have underlying medical conditions
should be screened more frequently, with the frequency to be determined by the
patient and their doctor on an individual basis.
See Screening: Cervical Cancer (ages 18-29), (ages 30-49), (ages 50 and up)

On a Pap smear, “low-grade” changes indicate the likely presence of HPV and the
need for further testing. A positive HPV DNA test indicates the presence of a high-
risk type of HPV, but the test does not specify which type is present. If both are
negative, it is unlikely that there is a high-risk HPV infection. If the Pap smear is
abnormal but the HPV DNA test is negative, then follow-up testing and further
monitoring are indicated.
Typing of the HPV is not usually necessary. However, if it is done, then common
findings may include:
 HPV types 6 and 11 typically cause venereal warts, and (along with types 42, 43,
and 44) have a low risk of progressing to cancer.
 HPV types 16, 18, 31, 33, and 36 have a higher risk of progressing to cancer.
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HPV is one of the most commonly transmitted STDs in the world. In 90% of women
who have cervical HPV infection, the infection becomes undetectable within two
years. A few women have persistent infection, which is a key risk factor for cervical
cancer. Regular Pap smears and HPV screening can monitor this risk and provide an
early warning that you might need treatment.
1. How is HPV transmitted?
Genital HPV infection is spread through sexual contact—primarily vaginal, anal, and
oral intercourse. It is possible, though less likely, for the virus to be transmitted by
sexual contact without intercourse. Rarely, a pregnant woman will pass HPV to her
baby during vaginal delivery, resulting in laryngeal papillomatosis (warts on the voice
box).
2. What are the symptoms of HPV infection?

Certain types of HPV cause genital warts and other lesions, but the virus usually
causes no symptoms. Most people with a genital HPV infection do not know they are
infected. That is why regular exams and Pap smears are so important.
3. How is HPV infection treated?

Genital warts can be removed in a number of ways:
 With chemicals,
 By freezing,
 By electrically being burned off, or
 Via surgery or lasers.
For most people, this treatment will clear the warts. If your warts return repeatedly,
the doctor may try injecting them with the drug interferon. Although treatment clears
the symptoms, the virus remains in your body.
Abnormal Pap smears can be treated in a variety of ways, from monitoring over a
period of months to see if they return to normal, to cryosurgery that freezes and
destroys infected cells, to procedures that excise problem tissue.
Untreated genital warts can disappear, stay the same, or grow in size and number and
cluster in large masses. Some types of the virus can lead to cervical or penile cancer.
5. How can HPV be prevented?

For information on prevention, visit the National HPV & Cervical Cancer Prevention
Resource Center.
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6. How common is HPV infection?
It is one of the most common sexually transmitted diseases in the world, with
probably more cases of genital HPV infection than of any other STD in the United
States. About 50% to 75% of sexually active men and women contract genital HPV
infection at some point in their lives. About 5.5 million Americans get a new HPV
infection each year, making HPV the most commonly acquired STD. For more
information, visit the CDC's Division of Sexually Transmitted Diseases.
7. Are men screened for HPV infection?

No, men are not routinely screened for HPV infection. The current commercially
available tests – the Pap smear and DNA HPV tests – are not suitable for testing
males. If the need arose, male samples could be tested for HPV using alternate DNA
HPV testing.
hs-CRP
Why get tested?
May be helpful in assessing risk of developing heart disease
When to get tested?
No current consensus exists on when to get tested; the test is most often done in
conjuction with other tests that are ordered to assess risk of heart disease, such as lipid
profiles.
C-reactive protein (CRP) is a substance made by the liver and secreted into the
bloodstream, increasing when inflammation is present. CRP has been used for many
years as an indicator of bacterial or viral infection and as a monitor of changes in
inflammation associated with many inflammatory and autoimmune diseases.
Some studies have shown that CRP also can be an indicator of risk of cardiovascular
disease in apparently healthy people. However, the level of CRP in the blood is
normally so low that an especially sensitive test is needed to measure it. This test is
called high-sensitivity CRP or hs-CRP.
How is it used?
hs-CRP is most often used to help predict a healthy person's risk of cardiovascular
disease.
People who have hs-CRP results in the high end of the normal range have 1.5 to 4
times the risk of having a heart attack as those with CRP values at the low end of the
normal range.
The CRP molecule itself is not a harmful molecule in the body. The higher level of
CRP is simply a reflection of higher than normal inflammation. The measurement of
CRP does not reflect where the inflammation is. It may come from cells in the fatty
deposits in arterial walls that reflect the process of atherosclerosis. It may come from
other tissues.
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When is it ordered?
Unfortunately, there is no agreement about exactly when the test should be ordered
and on whom the test should be done. There is not yet a consensus about its value, but
the test is being promoted by some as a test to help determine risk for cardiovascular
disease, heart attacks, and strokes.
hs-CRP usually is ordered as one of several tests in a cardiovascular risk profile, often
along with tests for cholesterol and triglycerides. Some experts say that the best way
to predict risk is to combine a good marker for inflammation, like CRP, along with
the ratio of total cholesterol to HDL cholesterol.
To help clarify when CRP testing may be most useful, in January 2003 the American
Heart Association and Centers for Disease Control and Prevention (AHA/CDC)
examined current evidence and then published their recommendations for its use:
 No: not for widespread screening of the general adult population; continue to focus
on major risk factors, such as high blood pressure, high cholesterol, smoking and
diabetes
 Yes: useful as an independent marker of risk and as a “discretionary tool” in the
evaluation of those with moderate risk of cardiovascular disease to help determine
treatment course
 No: not for tracking treatment efficacy due to lack of evidence that reducing hs-
CRP levels improves outcomes, such as survival
The results are generally interpreted on a relative scale. People with the highest values
have the highest risk of cardiovascular disease and those with the lowest values have
the lowest risk. This is often expressed in terms of percentiles. These may be quintiles
(five divisions), quartiles (four divisions), or tertiles (three divisions). For example,
one large study showed that those people in the top quintile of CRP (the 20% of
people with the highest CRP values) have about twice the risk of heart disease as
those people in the bottom quintile (the 20% of people with the lowest CRP values).
The AHA/CDC defined risk groups as follows:
 Low risk: less than 1.0 mg/L

 Average risk: 1.0 to 3.0 mg/L
 High risk: above 3.0 mg/L

Taking nonsteroidal anti-inflammatory drugs (like aspirin, Advil, Motrin, and
Naproxin) or statins (a class of cholesterol-lowering drugs) may reduce CRP levels in
blood. Both anti-inflammatory drugs and statins may help to reduce the inflammation,
thus reducing CRP.
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Because hs-CRP tests are measuring a marker of inflammation, it is important that
any person having the test be healthy in order for the test to be of any value in
predicting the risk of coronary disease or heart attack. Any recent illness, tissue
injury, infection, or general inflammation will raise the amount of CRP and give a
falsely elevated estimate of risk.
Since the hs-CRP and CRP tests measure the same molecule, people with chronic
inflammation, such as those with arthritis, should not have hs-CRP levels measured.
Their CRP levels will be very high due to the arthritis—often too high to be measured
using the hs-CRP test.
1. Is hs-CRP specific for predicting heart disease?
Since CRP is a marker of inflammation, its elevation may reflect a low level of
inflammation that may manifest in the future in different ways. Most studies to date
have focused on heart disease, but new research shows that having CRP in the high
normal range may also be associated with other diseases such as colon cancer,
complications of diabetes, and obesity.
2. I have had cholesterol tests, but never an hs-CRP test. Why?

The hs-CRP test is fairly new, and experts still don't agree on when and how often this
test should be ordered.
3. What is the difference between regular CRP and hs-CRP tests?

Both tests measure the same molecule in the blood. The hs-CRP is for seemingly
healthy people to determine their risk of cardiovascular disease. It measures CRP in
the range from 0.5 to 10 mg/L. The CRP test is ordered for patients at risk for
bacterial or viral infection (such as following surgery) or patients with chronic
inflammatory diseases (such as rheumatoid arthritis). It measures CRP in the range
from 10 to 1000 mg/L.
IGF-1
Also known as: Somatomedin C
Formal name: Insulin-like Growth Factor – 1
Why get tested?
To identify diseases and conditions caused by deficiencies and overproduction of
growth hormone (GH), to evaluate pituitary function, and to monitor the effectiveness
of GH treatment
When to get tested?
As part of an evaluation of pituitary function; if you have symptoms of slow growth,
short stature, and delayed development (in children) or decreased bone density,
reduced muscle strength, and increased lipids (in adults) that suggest insufficient GH
and IGF-1 production; if you have symptoms of gigantism (in children) or acromegaly
(in adults) that suggest excess GH and IGF-1 production; during and after treatment
for GH abnormalities
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The insulin-like growth factor - 1 (IGF-1) test is an indirect measure of the average
amount of growth hormone (GH) being produced by the body. IGF-1 and GH are
peptide hormones, small proteins that are vital for normal bone and tissue growth and
development. GH is produced by the pituitary (a grape-sized gland located at the base
of the brain behind the bridge of your nose) and secreted into the bloodstream in
pulses throughout the day and night with peaks that occur mostly during the night.
IGF-1 is produced, primarily in response to GH stimulation, by the liver and some is
also produced by skeletal muscles. It mediates many of the actions of GH and so
stimulates the growth of bones and other tissues and promotes the production of lean
muscle mass. IGF-1 mirrors GH excesses and deficiencies, but its level is stable
throughout the day, making it a useful indicator of average GH levels.
Like GH, IGF-1 levels normally are low in early childhood, increase gradually during
childhood, peak during puberty, and then decline in adult life. Deficiencies in GH and
IGF-1 may be caused by conditions such as hypopituitarism (hypothalamic-pituitary
disease; resulting in a general lack of GH production by the pituitary) or the presence
of a non-GH-producing pituitary tumor that damages hormone-producing cells.
Deficiencies in IGF-1 also occur where there is a lack of responsiveness to GH (GH
Insensitivity; GHI). GHI may be primary (genetic) or secondary to conditions such as
malnutrition and chronic diseases.
Deficiencies early in life can inhibit bone growth and overall development and can
result in a child with a shorter than normal stature. While levels of GH and IGF-1 are
not as high in adults as in children, they do play a continuing role in regulating bone
density, muscle mass, and lipid metabolism. Therefore, decreased production can lead
to low bone densities, less muscle mass, and altered lipids.
Excess GH and IGF-1 can cause abnormal growth of the skeleton and other signs and
symptoms characteristic of gigantism and acromegaly. With gigantism, which occurs
in the young, bones grow longer, resulting in a very tall person with large feet and
hands. Acromegaly, which occurs in adults, causes bones to thicken and soft tissues,
such as the nose, to swell. Both conditions can lead to enlarged organs, such as the
heart, and a decreased life span. The most common reason for the pituitary to secrete
excessive amounts of GH is a GH-producing pituitary tumor (usually benign).
Frequently, the tumor can be surgically removed and/or treated with drugs or
radiation. In most cases, this will cause GH and IGF-1 levels to return to normal or
near normal levels.
How is it used?
IGF-1 is measured to help diagnose the cause of growth abnormalities and to evaluate
pituitary function. IGF-1 levels reflect integrated GH status and, along with GH
provocation tests, are used to help diagnose GH deficiency. These tests, while
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generally ordered in children suspected of GH abnormalities, may also be used in
adults with GH deficiency. IGF-1 levels and the measurement of GH also provide
information related to GH Insensitivity (GHI).
IGF-1 also may be ordered with other pituitary hormone tests, such as ACTH
(Adrenocorticotropic hormone), to help diagnose hypopituitarism. It also may be used
to monitor the effectiveness of treatment for growth hormone deficiencies and GHI.
IGF-1 testing and a GH suppression test can be used to detect a GH-producing

pituitary tumor. Its presence is then confirmed with imaging scans that help identify
and locate the tumor. If surgery is necessary, GH and IGF-1 levels are measured after
the tumor’s removal to determine whether or not all of it was successfully removed.
Drug and/or radiation therapy may be used in addition to (or sometimes instead of)
surgery to try to decrease GH production and return IGF-1 to normal or near normal
concentrations. IGF-1 may be used to monitor the effectiveness of this therapy at
regular intervals for years afterward to monitor GH production and to detect tumor
recurrence.
When is it ordered?
IGF-1 testing may be ordered, along with a GH stimulation test, when a child has
symptoms of GH deficiency, such as a slowed growth rate and short stature. They also
may be ordered in adults with suspected GH deficiency. An IGF-1 also may be
ordered when a doctor suspects that a person has an underactive pituitary gland. In
addition, IGF-1 levels are ordered to monitor patients on GH therapy.
IGF-1 testing may be ordered, along with a GH suppression test, when a child has
symptoms of gigantism, an adult shows signs of acromegaly, and/or when a doctor
suspects that a patient has hyperpituitarism.
When a GH-producing pituitary tumor is found, GH and IGF-1 are ordered after the
tumor is surgically removed to determine whether all of the tumor has been extracted.
IGF-1 also is ordered at regular intervals when a patient is undergoing the drug and/or
radiation therapy that frequently follow tumor surgery.
IGF-1 levels may be ordered at regular intervals for many years to monitor a patient’s
GH production and to watch for pituitary tumor recurrence.

If IGF-1 concentrations are decreased, then it is likely that there is a deficiency of GH
(GH Deficiency; GHD) or an insensitivity to GH (GH Insensitivity; GHI). If this is in
a child, the GH deficiency may have already caused short stature and delayed
development and may be treated with GH supplementation. While it is normal for
adult levels to be lower than those in children because of an age-related decrease in
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production, adults also may have low IGF-1 due to GHD or GHI and will need to be
treated.
If a decrease in IGF-1 is due to a more general decrease in pituitary function

(hypopituitarism), then several of the patient’s pituitary hormones will need to be
evaluated and may be supplemented to bring them up to normal levels. Reduced
pituitary function may be due to inherited defects or can rise as a result of pituitary
damage following conditions such as trauma, infections, and inflammation.
Decreased levels of IGF-1 also may be seen with nutritional deficiencies (including
anorexia nervosa), chronic kidney or liver disease, inactive/ineffective forms of GH,
and with high doses of estrogen.
Elevated levels of IGF-1 usually indicate an increased production of GH. Since GH

levels vary throughout the day, IGF-1 concentrations are a reflection of average GH
production, not of the actual amount of GH in the blood. This is accurate up to the
point at which the liver’s capacity to create IGF-1 is reached. With severely increased
GH production, IGF-1 levels will stabilize at an elevated maximum concentration.
Increased concentrations of GH and IGF-1 are normal during puberty and pregnancy
but otherwise are most frequently due to pituitary tumors (usually benign). If other
pituitary hormones are also abnormal, then the patient may have a condition causing
general hyperpituitarism.
If IGF-1 is still elevated after the surgical removal of a pituitary tumor, then the
surgery may not have been fully effective. Decreasing IGF-1 concentrations during
subsequent drug and/or radiation therapies indicate that the treatment is lowering GH
production. If levels of IGF-1 become “normalized,” then the patient is no longer
producing excess amounts of GH. When a patient is undergoing long term
monitoring, an increase in IGF-1 levels may indicate a recurrence of the pituitary
tumor.

Patients should fast overnight for their IGF-1 test.
IGF-1 testing is being evaluated as part of a sports-related drug abuse screen for GH-
related performance-enhancing substances. GH and IGF-1 enhancers (supplements
taken by some athletes during the training season to increase muscle mass and
strength) have been banned by U.S. and international sports federations. It is difficult
to detect increases in IGF-1 related to the use of supplements as opposed to those
increases due to rigorous training. Approaches using a combination of GH, IGF-1,
IGF-binding proteins, and other biological markers seem promising and could lead to
the development of anti-doping tests.
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1. What signs and symptoms are seen with deficient GH and IGF-1?
In children the following may indicate GH and/or IGF-1 deficiency:
 slowed growth rate in early childhood relative to group norms
 shorter stature than others of the same chronological age
 delayed puberty
 x-rays showing delayed bone development.
In adults, abnormally low levels of GH and/or IGF-1 may cause subtle, nonspecific
symptoms such as:
 Decreased bone density
 Fatigue
 Adverse lipid changes
 Reduced exercise tolerance.
2. What signs and symptoms are seen with excess GH and IGF-1 production?
In a child, it is unusual tallness that is often first noticed. With an adult, it may be
more subtle: a larger nose, thicker lips, a more prominent jaw, or rings and shoes that
no longer fit. Other signs and symptoms may include:
 Deepened, husky voice
 Enlarged organs - liver, heart, kidneys, and spleen
 Enlarged tongue
 Erectile dysfunction
 Fatigue
 Headaches and visual disturbances
 Joint pain and swelling
 Menstrual cycle irregularities
 Muscle weakness
 Snoring
 Sweating and body odor
 Thickening of the skin, skin tags
 Trapped nerves (Carpal tunnel syndrome)
3.How long do I have to be monitored?

As long as you are considered to have abnormal (low or high) GH production or are
receiving GH replacement therapy, your IGF-1 will need to be monitored.
IMA
Formal name: Ischemia-Modified Albumin
Why get tested?
To help rule out myocardial ischemia (decreased blood flow to the heart)
When to get tested?
When you have had chest pain for a few minutes to a few hours and your doctor
wants to better determine if you have had or are having a myocardial infarction (heart
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attack)
This test measures the amount of ischemia-modified albumin present in the blood.
Albumin is a protein produced by the liver. It normally makes up about 60% of the
protein found in the bloodstream. Albumin is important in helping to regulate the
amount of fluid in the blood vessels and in transporting other compounds throughout
the body. When myocardial ischemia (a decrease in the supply of oxygen to the heart)
occurs, it changes some albumin molecules. Within a few minutes, and persisting for
several hours, ischemia decreases albumin’s ability to bind to metals such as cobalt.
The discovery of this property led to the development of a test that measures the
amount of ischemia-modified albumin by measuring the reduction in metal binding.
Myocardial ischemia may be caused by the partial or complete blockage of a blood

vessel or a narrowed or constricted blood vessel. A blockage can decrease or prevent
blood flow to the heart. It can cause a heart attack (myocardial infarction, MI) and
permanently damage or kill heart muscle cells.
Temporary myocardial ischemia may be seen with angina, an episodic condition

associated with the gradual narrowing of one or more blood vessels and with arterial
spasms. Angina is triggered when the body cannot respond adequately to increased
oxygen demands, and it usually resolves with rest. In some cases, angina can become
unstable (occurring at rest or becoming more severe) and escalate to cause a heart
attack. Both unstable angina and MI are collectively known as acute coronary
syndrome (ACS). Symptoms vary but may include chest pain and pressure that occur
at rest or persist despite rest, shoulder pain, neck pain, nausea, and shortness of
breath.
Patients with these symptoms are typically evaluated in the emergency room. There,
the doctor must try to rapidly differentiate ACS from other conditions with similar
presentations and try to distinguish between the various causes of ACS. To do this, he
may order cardiac biomarkers, tests such as troponin and myoglobin, to detect damage
to the heart, and an electrocardiogram (ECG) to look for heart damage. If these tests
are clearly abnormal, then the patient is started on treatment for MI.
If the tests are not definitive, then determining whether the patient is experiencing
temporary angina, is at a significant risk of having a heart attack in the near future, or
if they can be safely sent home can be a challenge. Researchers are looking for tests
that can help guide the doctor’s decision-making in this situation. The ischemia-
modified albumin test is a potential candidate for this role.
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How is it used?
Ischemia-modified albumin is a fairly new test that has been FDA approved to help
rule out ischemia in patients with chest pain whose diagnosis is not clear. It is a
cardiac biomarker that is meant to be ordered along with or following a troponin test
and an ECG.
If the troponin (which may take several hours to start to increase after an MI) is
negative and the ECG is not definitive, then the ischemia-modified albumin test may
add valuable information about whether myocardial ischemia is occurring. IMA may
be ordered along with a myoglobin test in the first few hours of chest pain to try to
stratify the patient’s risk of having a heart attack in the near future.
When is it ordered?
IMA may be ordered along with or following a troponin, ECG, and sometimes a
myoglobin test when a patient has chest pains that began within the last few hours and
the doctor wants more information about whether the symptoms may be ischemia-
related.
Ischemia-modified albumin is a marker of decreased oxygen availability. Studies have
shown IMA to be sensitive for ischemia but not very specific (it can be elevated with
ischemia in other areas of the body). Its primary value is in its negative predictive
value.
When IMA is not present in a patient who has been having chest pain for a few
minutes to a few hours, then it is unlikely that ischemia has occurred. When IMA and
myoglobin are negative, an ECG is normal, and a troponin is negative (at initial and
repeat testing), then it is unlikely that the patient’s chest pain has or will result in a
heart attack in the near future.
If the patient has been experiencing chest pains for several hours, then the IMA test
may not be as valuable because it may have already risen and fallen back to normal or
near normal levels by the time the blood sample is collected.

Research and current studies are evaluating whether a significantly elevated IMA may
be useful as a positive indicator that myocardial ischemia is occurring. Increases in
IMA have also been seen with ischemia that is occurring in other parts of the body,
such as the skeletal muscles and gastrointestinal tract.
The IMA test is not widely used at present. Although it is regarded as a promising
cardiac biomarker, its ultimate clinical utility has yet to be determined. Many
physicians are adopting a wait-and-see attitude. They want to see more data
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accumulated on its use and on the factors, such as underlying diseases and decreased
albumin levels, that may affect or interfere with its interpretation.
1. Can an IMA test be done in a doctor’s office?

No, the test must be run with specialized equipment. In most cases, the IMA test is
ordered when a person is being evaluated for chest pain in the Emergency Room.
2. If a person has not had a heart attack, why are they still considered at risk?
Often, the situation that is causing the chest pain, such as a partial blockage of an
artery, can worsen, becoming fully blocked and causing an MI. Even a patient with
stable angina (a history of angina episodes) can have his condition escalate (become
unstable), such as when a narrowed artery finally closes.
Indirect Antiglobulin Test

Why get tested?
To detect antibodies directed against red blood cell antigens, in preparation for a
blood transfusion, or during pregnancy and at delivery
When to get tested?
When preparing for a blood transfusion or during pregnancy or at delivery, especially
if you are Rh negative.
The indirect antiglobulin test (IAT) looks for circulating antibodies directed against
red blood cells (RBCs). RBCs normally have structures on their surface called
antigens. You have your own individual set of antigens on your RBCs, determined by
inheritance from your parents. If you have a blood transfusion, your body will
recognize antigens that you do not have as foreign. Your plasma cells then may
produce antibodies to attack these foreign antigens. People who have many
transfusions are more likely to make antibodies to RBCs because they are exposed to
more foreign RBC antigens. When a baby inherits antigens from its father that are not
on its mother’s RBCs, the mother can produce antibodies against the foreign antigens
on her baby’s RBCs inside the womb. This can cause hemolytic disease of the
newborn, usually not affecting the first baby but subsequent children.
The IAT detects the presence of these circulating RBC antibodies in the plasma (fluid
portion of the blood). The first time a person is exposed to a foreign antigen, by
transfusion or pregnancy, their cells may recognize the need to produce an antibody
directed against the foreign RBCs but does not usually have the time to make enough
antibody to actually destroy the foreign cells. When the next transfusion or pregnancy
occurs, the antibody may be strong enough to attach to the transfused RBCs or, if a
woman is pregnant, to her baby’s RBCs, causing the red cells to have a shortened
survival.
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How is it used?
During pregnancy, the IAT is used to screen for antibodies that might cross the
placenta and attack the baby’s red cells, causing hemolytic disease of the newborn.
The most serious cause is antibody in a blood group system called the Rh system. An
Rh negative mother will have an IAT performed early in her pregnancy, at 28 weeks,
and again at the time of delivery. If there are no Rh antibodies present at 28 weeks,
then the woman is given an injection of Rh immune globulin (RhIg) to clear any Rh
positive fetal RBC from the bloodstream to prevent the creation of Rh antibodies by
the mother.
At birth, the baby’s Rh status is determined. If the baby is Rh negative, then the
mother does not require another RhIg injection; if the baby is Rh positive, then
another IAT test will be performed on the mother. If it is negative, an additional test
(Kleihauer-Betke test) determines the number of fetal RBCs present in the mother’s
blood and is used to determine how much RhIg is needed to prevent antibody
production.
Immune-related hemolytic anemia also may be caused when a person produces

antibodies against their own antigens. This can happen with some autoimmune
disorders (such as systemic lupus erythematosus), with diseases such as chronic
lymphocytic leukemia, and with infections such as mycoplasma pneumonia and
mononucleosis. It can also occur in some people with the use of certain medications,
such as penicillin, and in rare cases can be triggered by exposure to cold. If a person is
experiencing symptoms suggesting hemolytic anemia, such as fatigue, dark urine,
back pain, jaundice, paleness, or an enlarged spleen, then a doctor may order both a
DAT and an IAT to help determine whether an RBC antibody is present.
An IAT test is performed as part of a “type and screen” whenever a blood transfusion
is anticipated. If an antibody is detected, then an antibody identification test must be
done to determine which antibodies are present. During a crossmatch, a variation of
the IAT is performed. The donor’s RBCs and the patient’s plasma are mixed and
processed to see if there is any agglutination (clumping of RBCs) in the test tube that
might indicate an incompatibility that would affect the patient if the blood was
transfused to them. In the case of blood transfusions, RBC antibodies must be taken
into account and donor blood must be found that does not contain the antigen(s) that
the body has become sensitized (produced antibodies) to.
Each blood transfusion that a person has exposes them to the combination of antigens
on the donor’s RBCs. Whenever the transfused RBCs contain antigens foreign to the
recipient’s RBCs, there is the potential to create an antibody. If someone has many
blood transfusions over a period of time, they may produce antibodies against many
different antigens. This can make finding compatible blood increasingly difficult.
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If someone has an immediate or delayed reaction to a blood transfusion, the doctor
will order both an IAT and DAT to help investigate the cause of the reaction. Another
IAT may be run after the acute situation has resolved to see if the patient has
developed any new antibodies.
When is it ordered?
An IAT is performed prior to any anticipated blood transfusion and as a follow-up to
a transfusion reaction.
An IAT is performed as part of every woman’s pregnancy workup. In Rh-negative
women, it is also done at 28 weeks, prior to giving an RhIg injection, and after
delivery if the baby is found to be Rh positive. In Rh-negative pregnant women with
known Rh antibodies, the IAT is sometimes ordered as a monitoring tool to roughly
track the amount of antibody present.
If an IAT is positive, then one or more antibodies are present. Some of these
antibodies will be more significant than others. Part of the IAT test is conducted at
room temperature and part at body temperature (37 degrees Celsius). The strength of
the reaction and where it occurs in the testing process can give clues to the
laboratorian about what antibodies may be present and their probable significance. A
positive IAT indicates the need for an antibody identification test to see which
antibodies are present.
If an Rh-negative mom has a negative IAT, then it is safe for a short window of time
(72 hours) to give an RhIg injection to prevent antibody production. If she has a
positive IAT, then the antibody or antibodies present must be identified. If there is an
Rh antibody present, then the RhIg injection is not useful. If she has a different
antibody, then the RhIg injection can still be given to prevent the Rh antibody.
A circulating RBC antibody, once present, will never truly go away. If it has been
many years since antigen exposure, circulating antibody levels may drop to
undetectable levels. If the patient is exposed to the antigen again, however, production
will kick quickly into gear and attack the RBCs.
1. What happened before the RhIg (RhImmune Globulin) injection was

developed?
Prior to development of the injection, Rh-negative mothers would often become
sensitized from the blood of their first Rh positive baby and begin developing anti-Rh
antibodies. Any subsequent Rh-positive babies would have some degree of Rh
disease, due to the mother’s anti-Rh antibodies attacking the baby’s RBCs.
Miscarriages and stillborn babies were relatively common, and those babies who were
born often needed immediate blood transfusions to survive. The injection has largely
prevented these complications, although a small percent of women do still develop Rh
antibodies.
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2. Why would a blood typing be necessary on an Rh-negative woman’s husband?
If the woman’s husband is Rh negative, then all of their babies will be Rh negative
and there will not be an Rh incompatibility. If the father is positive, then each baby
may be either Rh positive or negative.
3. Can I get antibodies from donating blood?

No, you will not be exposed to anyone else’s blood while donating.
4. If I give my own blood prior to surgery (autologous donation) and receive my

own blood back, do I need to worry about antibodies?
No, since you will not be exposed to foreign RBC antigens, your body will not
be stimulated to produce RBC antibodies.
5. Do I need to tell a new doctor about an old, uneventful transfusion?

Yes. It is important for your doctor to have that information because there is a chance
that you became sensitized to one or more antigens due to that transfusion. While this
will not negatively affect your health, it will tell you doctor to be especially vigilant
with any subsequent transfusions.
Influenza Tests
Also known as: Flu test, Rapid flu test, Influenza antigen test
Why get tested?
To determine whether or not you have the influenza A or B; to help your doctor make
rapid treatment decisions; and to help determine whether or not the flu has come to
your community
When to get tested?
When it is flu season and your doctor wants to determine whether your flu-like
symptoms are due to influenza A or B, or to other causes; within 48 hours of the onset
of your symptoms, to help determine treatment options
Sample required?
Depends on testing method being used; usually a nasopharyngeal (NP) swab, a nasal
aspirate or nasal wash; under approved circumstances, a throat swab.
Influenza (the flu) is a viral respiratory infection that tends to be seasonal, beginning
in late November and disappearing in early spring. It is a common respiratory illness
that affects 30 to 50 million Americans each season, bringing headaches, fever, chills,
muscle pains, exhaustion, a stuffy nose, sore throat, and a cough. Symptoms of
influenza tend to be more severe and longer lasting than the flu-like symptoms caused
by the common cold. Influenza and its complications cause more than 100,000
hospitalizations and 20,000 deaths a year in the United States, especially in the very
young, elderly, and in those with compromised immune systems or pre-existing lung
disease.
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There are two types of influenza, A and B, that infect humans and each virus can
mutate to create different antigenic strains. Usually a single strain of influenza virus A
will predominate during a particular flu season, although there may be a mixture of A
and B causing outbreaks in the community at the same time.
Flu testing relies on detecting virus that is being shed in the respiratory secretions of
the person infected. Detectable virus is usually only shed for the first few days that a
person is ill, so most testing must be done during this time period. Anti-viral
medications have been developed to treat either influenza A alone, or both A and B.
These medications, if given within 48 hours of the onset of symptoms, can reduce the
severity of symptoms and reduce the time that a patient is sick by about a day. (They
will not help if given later and they will not work against other viruses or against
bacterial infections.)
Influenza testing can be used to help diagnose the flu and determine treatment options
for an individual patient, and it can be used to help rule out the flu when looking for
other illnesses. A rapid influenza antigen test to detect the virus in nasal secretions is
one of the most common methods to diagnose this infection. Depending on the
method, it may be completed in the doctor's office in less than 30 minutes or be sent
to a laboratory, with the results available the same day. Depending on the particular
type of test used, it can identify the presence of an influenza virus or differentiate
which influenza virus is present (A or B). The main disadvantage of the rapid
influenza antigen test is that it will miss up to 30% of influenza cases and it will
occasionally be positive when the patient does not actually have the flu.
Other methods to detect influenza are more sensitive and specific. Nasal secretions
can be sent to a laboratory where they are stained with fluorescent antibody to
visualize the presence of the respiratory virus. Influenza A can be distinguished from
influenza B within several hours after the specimen is collected, and the appropriate
antiviral therapy can be initiated. This method does require a special microscope and
skilled laboratory personnel to read and interpret the test. It is not usually performed
in a doctor’s office.
Sometimes your doctor will order a viral culture. In this test, the influenza virus is
actually grown and identified in the laboratory. It has the advantage of identifying
which viruses (A, B, or another respiratory virus) and which strains of virus are
present. A rapid culture method, known as shell vial culture, takes only 24 hours of
incubation time to be read; however, a traditional viral culture performed in a large
test tube may require several days before the virus can be detected. Growing the virus
in culture is useful for documenting which strains of influenza are circulating in the
community. Identifying these outbreaks can assist healthcare workers in the
prevention and treatment of the flu throughout a community.
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Sample collection technique is critical in influenza testing. The best sample is usually
a nasal aspirate, but the most frequently used samples are the nasopharyngeal (NP)
swab or nasal wash. The person collecting the sample will use a syringe to push a
small amount of sterile saline into your nose, then either apply gentle suction (for the
aspirate) or use gravity to collect the resulting fluid (saline and mucous) into a cup. To
preserve the organisms in the sample, the sample should be put in a special container,
referred to as "viral transport media" or VTM, for delivery to the laboratory.
The NP swab is collected by having you tip your head back, then a Dacron swab (like
a long Q-tip ) is gently inserted into one of your nostrils until resistance is met (about
1 to 2 inches in), then rotated several times and withdrawn. This is not painful, but it
may tickle a bit and cause your eyes to tear. Doctors usually use NP swabs on adults
but may choose to do a nasal wash or aspirate on a child. In some circumstances, a
doctor may use a throat swab, but this contains less virus than an NP aspirate and so
may not be approved for use in rapid testing.
How is it used?
If it is the flu season, and:
 The flu has reached your community,

 You have clinical symptoms that are essentially the same as the symptoms of
other patients with known cases of the flu,
 You have no evidence of secondary complications,
then your doctor may diagnose you as having the flu without actually testing for
influenza. If you are outside the 48-hour window of anti-viral treatment, they may just
send you home to rest, drink fluids, and use over the counter remedies to soothe your
symptoms. (This is what doctors did before flu testing and treatment were available.)
So why order the flu test at all? Because the flu can be deadly, because knowing it is
in the community can help your doctor minimize its spread and because there is
treatment available that can lessen its severity if it is diagnosed early. (Of course the
best treatment is prevention - getting a flu shot.) The flu test is used to help diagnose
influenza A and B, and to differentiate them from other viral and bacterial infections
which may be serious and must be treated differently.
Rapid (same day) flu tests are best used within the first 48 hours of symptoms to help
diagnose influenza and determine whether or not anti-viral medications should be
used, or they are ordered within the first week to help identify outbreaks. Viral
cultures are usually used to track flu outbreaks and to identify the particular strain that
is causing them (sometimes the influenza will mutate enough to make the flu vaccine
less effective and sometimes an unexpected flu strain will predominate). Viral
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cultures are also be used to identify other viral infections that cause clinical symptoms
similar to the flu. Currently, the rapid influenza antigen test and the fluorescent
antibody detection of influenza cannot distinguish seasonal influenza from avian
influenza (“bird flu”). Influenza virus grown in culture could be sent to a public health
laboratory to determine if the strain of influenza A is the antigenic type (H5N1) found
in birds and chickens.
When is it ordered?
Flu tests are ordered almost exclusively during flu season (late October through
March) when a patient presents with a respiratory infection and symptoms such as:
headaches, fever, chills, muscle pains, exhaustion, a stuffy nose, sore throat, and a
cough. If influenza has already been identified in the community the doctor may order
a flu test to confirm the diagnosis and validate possible anti-viral treatment.
When influenza has not yet been documented in the community, the doctor may order
a rapid flu test both to document the presence of influenza in the area and to help
diagnose their patient's current illness. He may also order an influenza test along with
other viral studies, such as RSV antigen test (respiratory syncytial virus - a virus that
often infects young children and the elderly), or with bacterial tests, such as a strep
test (to check for group A streptococcus, the bacteria that cause strep throat) if the
cause of the infection is unclear.
In rare instances, someone will contract influenza outside of the regular flu season.
(This may happen when someone travels outside of the continental U.S. to a part of
the world where the flu is currently infecting that area's residents.) In this case, the
doctor may order a respiratory viral culture in order to have a more definitive
diagnosis.
If your flu test is positive, it means that you most likely have influenza A (or B), but it
does not tell your doctor how severe your symptoms are likely to be or reveal whether
or not you may experience any secondary complications.
Negative influenza antigen tests may mean that you have something other than
influenza, or that there is not sufficient virus in the specimen to allow it to be
detected. This may be due to either a poor specimen collection or because you have
had the flu for several days (in the later stages of influenza less virus is shed). Your
doctor will use your negative result along with other clinical findings to recommend
the treatment best for you.
Treated or untreated, most influenza infections will go away within 1 or 2 weeks,

although fatigue and a cough may last awhile longer. A few people, however, may
develop serious secondary complications. These complications often arise just as
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influenza symptoms are fading. Anyone is susceptible to complications from the flu,
but the very young, the elderly, and patient who are immune compromised or who
have pre-existing lung disease are most affected. Complications such as pneumonia,
sepsis (widespread infections that can be detected in the blood), and encephalitis (an
inflammation of the brain) can be very serious and may require immediate medical
treatment.
1. What other tests might my doctor order to diagnose my flu-like symptoms?
Your doctor may order a strep test to check for strep throat, blood cultures to check
for bacterial infections in the blood, an RSV antigen test (respiratory syncytial virus -
a virus that often infects young children and the elderly), or a sputum culture to look
for bacterial and/or fungal causes of a respiratory infection. They may also order
blood tests such as a CMP (Comprehensive Metabolic Panel) or CBC (Complete
blood count) to monitor body organ function.
2. Why is the flu such a big deal?

Because the flu can be deadly and because every few decades an especially lethal
influenza emerges. The worst on record is the 1918 Spanish flu pandemic (large scale
epidemic), which killed more than 20 million people worldwide, 500,000 in the
United States alone. In 1957 and 1968 hundreds of thousands died in the U.S. from
Asian and Hong Kong flu variants. The new strain of influenza A, named for its
unique viral antigens (H5N1), is circulating in birds and chickens in Asia. It has
infected humans who have had close contact with the infected birds and has a high
morality rate. There is concern of a world-wide pandemic if this virus is able to
mutate to allow human-to-human transmission of the virus.
3. Can I still get the flu if I've had the vaccination?
Yes. Influenza circles around the globe and moves through communities. As it travels,
it undergoes spontaneous changes (called "antigenic drift") that allow it to evade the
protections of last year's flu shot and re-infect you. The amount of the antigen drift
varies from year to year. Bigger drifts often result in more severe illnesses. Doctors
and researchers carefully track the influenza virus as it moves through the world and
try to anticipate the strain(s) that will eventually appear in the United States the next
season. Each year the flu vaccine is produced based on their observations and
experience, targeted to protect us against the expected strain. It contains inactivated
virus to protect us against both influenza A and B.
In most cases, the flu vaccine will prevent the flu, but it requires a few weeks before it
provides protection and it is not 100% effective. In addition, sometimes the flu will
"breakthrough" -- there will have been enough antigenic drift during the season that
the virus will appear slightly different to the body's immune system, decreasing the
effectiveness of the vaccine's protection. Or, the flu that predominates may end up
being an unexpected strain, not the ones that the vaccine was developed to protect
against. Usually in these cases the vaccination will at least lessen the severity of the
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infection. In individual high risk patients (those with heart, kidney, and lung ailments
for instance), doctors may bolster the protection by prescribing anti-viral treatments as
prophylactics -- they can provide short term protection while influenza moves through
the community (although this comes at a price in terms of cost and medication side
effects).
Lactate
Also known as: Lactic Acid
Why get tested?
To help detect hypoxia (oxygen deficiency) and other conditions that cause excess
production or insufficient clearing of lactate from the blood
When to get tested?
If you have symptoms such as rapid breathing, nausea, and sweating that suggest a
lack of oxygen or an acid/base imbalance; if your doctor suspects that you may have
an inherited metabolic or mitochondrial disorder
Sample required?
A blood sample drawn from a vein in your arm; sometimes a blood sample collected
from an artery and, rarely, a sample of cerebrospinal fluid collected from the spine.
This test measures the amount of lactate in the blood or, more rarely, in the
cerebrospinal fluid. Lactate is the ionic (electrically charged) form of lactic acid. It is
produced by muscle cells, red blood cells, brain, and other tissues during anaerobic
energy production and is usually present in low levels in the blood. Aerobic energy
production is the body’s preferred process, but it requires an adequate supply of
oxygen. Aerobic energy production occurs in the mitochondria, tiny power stations
inside each cell of the body that use glucose and oxygen to produce ATP (adenosine
triphosphate), the body’s primary source of energy.
When cellular oxygen levels are decreased, however, and/or the mitochondria are not
functioning properly, the body must turn to less efficient anaerobic energy production
to metabolize glucose and produce ATP. In this process, the primary byproduct is
lactic acid, which can build up faster than the liver can break it down. When lactic
acid levels increase significantly in the blood, the affected person is said to have first
hyperlactatemia and then lactic acidosis (LA). The body can often compensate for the
effects of hyperlactatemia, but LA can be severe enough to disrupt a person’s
acid/base (pH) balance and cause symptoms such as muscular weakness, rapid
breathing, nausea, vomiting, sweating, and even coma.
Lactic acidosis is separated into two types: A and B. Type A may be due to
inadequate oxygen uptake in the lungs and/or to decreased blood flow
(hypoperfusion) resulting in decreased transport of oxygen to the tissues. The most
common reason for this is shock from a variety of causes including trauma and blood
loss, but LA may also be due to conditions such as heart attack, congestive heart
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failure, and pulmonary edema (fluid in the lungs). Type B is caused by conditions that
increase the amount of lactate/lactic acid in the blood but are not related to a
decreased availability of oxygen. This includes liver and kidney disease, diabetes,
leukemia, AIDS, glycogen storage diseases (such as glucose-6-phosphatase
deficiency), drugs and toxins, severe infections (both systemic sepsis and meningitis),
and a variety of inherited metabolic and mitochondrial diseases (forms of muscular
dystrophy that affect normal ATP production). Strenuous exercise can also result in
increased blood levels of lactate.

A blood sample is obtained by inserting a needle into a vein in the arm. Sometimes,
an arterial sample is collected by inserting a needle into an artery. Occasionally, a
sample of cerebrospinal fluid is collected from the spinal column during a procedure
called a spinal tap. When this test is not done under emergency circumstances, the
patient should be fasting for 8 to 10 hours and should not have exercised for several
hours before the blood collection.
How is it used?
The lactate test is primarily ordered to help detect and evaluate the severity of hypoxia
and lactic acidosis. It may be ordered along with blood gases (to evaluate the body’s
acid/base balance and oxygenation), along with pyruvate (another ion involved in
energy production), and/or along with groups of tests, such as the Comprehensive
Metabolic Panel, Basic Metabolic Panel and Complete Blood Count, in a patient with
evidence of acidosis. In patients being treated for an acute condition (such as shock or
heart attack) or a chronic condition (such as severe congestive heart failure), lactate
levels may be ordered at intervals to help monitor hypoxia and response to treatment.
Lactate measurements are primarily taken from venous blood, but arterial blood
lactate tests may also be ordered, especially when the lactate test is ordered along with
arterial blood gases. A cerebrospinal fluid lactate test may be ordered, along with a
blood lactate test, to help distinguish between viral and bacterial meningitis.
When is it ordered?
Venous or arterial lactate concentrations may be ordered when a patient has
symptoms of hypoxia such as shortness of breath, rapid breathing, paleness, sweating,
nausea, muscle weakness, abdominal pain, or coma. The test may be ordered when a
patient presents with what the doctor suspects is shock, heart attack, severe congestive
heart failure, renal failure, or uncontrolled diabetes. The lactate test will be initially
ordered with other tests to help evaluate the patient’s condition and then, if
significantly elevated, at intervals to monitor the condition.
CSF and blood lactate levels may be ordered when a patient has symptoms of
meningitis such as severe headaches, fever, delirium, and loss of consciousness.
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Lactate concentrations can be increased in any condition that decreases the amount of
oxygen available to the body, increases lactate production, and/or decreases lactate
clearance. This can be anything from localized increases of lactate in muscle due to
strenuous exercise up to life-threatening systemic shock. Excess lactate may be
present in a range of diseases, infections, and inherited metabolic and mitochondrial
disorders. It may also be caused by certain medications, such as metformin
(Glucophage, taken by diabetics) and isoniazid (tuberculosis treatment).
In general, the greater the increase in lactate, the greater the severity of the condition.
The presence of excess lactate is not diagnostic – it does not pinpoint the cause of the
increase – but it does help the doctor to confirm or rule out possible reasons for the
symptoms a patient is experiencing. For instance, when a patient has meningitis,
significantly increased cerebrospinal fluid lactate levels suggest bacterial meningitis
while normal or slightly elevated levels are more likely to be due to viral meningitis.
When a patient is being treated for lactic acidosis, decreasing concentrations over
time reflect a response to treatment.

When the patient is not in acute distress, such as when investigating a metabolic
disorder, lactate concentrations are usually measured when the patient has fasted for 8
to 10 hours and has not exercised. Repeated hand clenching and the extended use of a
tourniquet are avoided as these can temporarily increase lactate levels.
Increased lactate levels may be seen with thiamine (vitamin B1) deficiency.
1. Is there anything I can do to decrease my lactate levels?
Generally, no. However, if your elevated lactate levels are due to an underlying
condition that can be addressed, such as uncontrolled diabetes or a substance that can
be avoided, such as ethanol, then you may be able to lower them. If you have been
diagnosed with a condition, such as a metabolic disorder, following your prescribed
treatment regimen should control your lactate levels. If the increase is due to a
temporary condition, such as shock or infection, then they will usually return to
normal after the condition has been resolved.
2. Why would my doctor choose to measure arterial lactate rather than venous
lactate?
Lactate measurements from arterial blood are thought to be more accurate and,
because a tourniquet is not used, they are not generally affected by the collection
process. Your doctor may order an arterial lactate for these reasons or because arterial
blood gases are also being collected (and the same sample can be used). When other
arterial blood tests are not being ordered, the doctor may order a venous lactate
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because it gives him an adequate evaluation of your lactate concentrations and
because the collection process is not as uncomfortable.
LDH
Why get tested?
To help identify the cause and location of tissue damage in the body, and to monitor
its progress; historically, has been used to help diagnose and monitor a heart attack,
but troponin has largely replaced LDH in this role.
When to get tested?
Along with other tests, when your doctor suspects that you have an acute or chronic
condition that is causing tissue or cellular destruction and he wants to identify and
monitor the problem.
Lactate dehydrogenase (LDH, or LD) is an enzyme that is found in almost all body
tissues but only a small amount of it is usually detectable in the blood. It usually stays
contained within the tissues’ cells. When cells are damaged or destroyed, however,
they release LDH into the bloodstream, causing blood levels to rise. For this reason,
LDH is used as a general marker of injury to cells; it is not useful for determining
which specific cells are damaged.
Elevations of LDH may be measured either as a total LDH or as LDH isoenzymes. A
total LDH level is an overall measurement of five different LDH isoenzymes (slightly
different molecular versions of the LDH enzyme). A total LDH level will reflect the
tissue damage done but it is not specific. By itself, it cannot be used to identify the
underlying cause or its location.
Although there is some overlap, each of the five LDH isoenzymes tends to be
concentrated in specific body tissues. Because of this, measurements of the individual
LDH isoenzyme levels can be used, along with other tests, to help determine the
disease or condition causing cellular damage and to help identify the organs and
tissues involved. In general, the isoenzyme locations tend to be:
 LDH-1, heart, red cells, renal cortex, germ cells

 LDH-2, heart, red blood cells, renal cortex (lesser amounts than LDH-1)
 LDH-3, lungs and other tissues
 LDH-4, white blood cells, lymph nodes; muscle, liver (lesser amounts than
LDH-5)
 LDH-5, liver, muscle
While all of the isoenzymes are represented in the total LDH, LDH-2 usually makes
up the greatest percentage.
How is it used?
Currently, the main use for LDH is as a general indicator of the existence and severity
of acute or chronic tissue damage and, sometimes, as a monitor of progressive
conditions. LDH isoenzymes may also be used in differential diagnosis to help
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determine which organs are likely to be involved.
The overall use of LDH and LDH isoenzymes has decreased. Traditionally, they were
most frequently used, along with other tests such as CK and CK-MB, to help diagnose
and monitor myocardial infarctions (MI, heart attacks). The characteristic rise, peak,
and fall of LDH levels in the blood and the rise of LDH-1 to become higher than
LDH-2 (referred to as the “flipped ratio”) allowed doctors to track the progress and
treatment of a heart attack, and to differentiate it from chest pain caused by other
conditions such as angina. This use of LDH, however, has been almost entirely
replaced by troponin measurements in recent years because troponin is more specific
and sensitive to heart tissue injury than LDH.
When is it ordered?
A total LDH level may be ordered, along with other tests, as a screening test when
your doctor suspects some kind of cellular or tissue damage. If the total LDH is
elevated, then he may order LDH isoenzymes, or more commonly other tests such as
ALT, AST or ALP to help diagnose the condition and to help determine which organs
are involved. Once the acute or chronic problem is diagnosed, total LDH levels may
be used at regular intervals to monitor its progress and/or resolution.
LDH levels may also occasionally be ordered to monitor damage caused by muscle
trauma or injury and to help identify hemolytic anemia (anemia caused by the
breakage of red blood cells – either because they are unusually fragile or because
something is mechanically breaking them (like an artificial heart valve)).
LDH and LDH isoenzymes may still be occasionally ordered along with CK and CK-
MB when a patient has symptoms of a heart attack, but this is increasingly rare. In
most cases today, the doctor will order troponin levels with the CK and CK-MB
instead of LDH.
Elevated levels of LDH and changes in the ratio of the LDH isoenzymes usually
indicate some type of tissue damage. Usually LDH levels will rise as the cellular
destruction begins, peak after some time period, and then begin to fall. For instance,
when someone has a heart attack, blood levels of total LDH will rise within 24 to 48
hours, peak in 2 to 3 days, and return to normal in 10 to 14 days.
Elevated levels of LDH may be seen with:
 Cerebrovascular accident (CVA, stroke)

 Drugs: anesthetics, aspirin, narcotics, procainamides, alcohol
 Hemolytic anemia
 Pernicious anemias (megaloblastic anemais)
 Infectious mononucleosis (Mono)
 Intestinal and pulmonary infarction (tissue death)
 Kidney disease
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 Liver disease
 Muscular dystrophy
 Pancreatitis
 Some cancers
With some chronic and progressive conditions, and some drugs, moderately elevated
LDH levels may persist.
Low and normal levels of LDH do not usually indicate a problem. Low levels are
sometimes seen when a patient ingests large amounts of ascorbic acid (vitamin C).

Many things can affect LDH results that are not necessarily a cause for concern. For
example:
 Strenuous exercise can cause temporary elevations in LDH;

 Hemolysis of blood can cause false positives (“Hemolysis of blood” refers to
breakage of red blood cells in the blood sample which may be due to rough
handling, temperature extremes, or trouble collecting the blood sample (a
“difficult draw”)); and
 If your platelet count is increased, serum LDH will be artificially high and not
reflective of the LDH actually present.
1. Why would more than one LDH isoenzyme be elevated?
Several of the LDH isoenzymes may rise at the same time if more than one organ is
involved as, for example, in the case of a patient who has pneumonia, and then
suddenly has a heart attack. In another example, more than one LDH isoenzyme
might rise if a patient has a progressive disease such as metastatic cancer that is
affecting multiple organs. Also, although the different LDH isoenzymes are
concentrated in specific tissues, there is some overlap in where they are found. A
single cause may elevate several of them to some degree. For instance, vigorous
exercise may temporarily elevate LDH-1, LDH-2, and LDH-5.
Lead
Also known as: Blood lead test, Blood lead level, BLL
Why get tested?
To screen for lead exposure indicated by elevated levels of lead in your blood
When to get tested?
At 1 and 2 years of age as part of a child lead screening program; children considered
to be at risk may need additional testing from 18 months to 6 years of age – check
with your pediatrician and local health department; if your child lives in a house built
prior to 1978; if your occupation or hobby may expose you to lead; if you have
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symptoms suggesting lead poisoning
This test measures the current lead level in your blood. Lead is a soft metal present in
the environment. When it is inhaled or ingested, lead can cause damage to the brain,
organs, and nervous system. Even at low levels, it can cause irreversible damage
without causing symptoms. In an infant, lead can cause permanent cognitive
impairment, behavioral disorders, and developmental delays. Lead exposure can cause
weakness, anemia, nausea, weight loss, fatigue, headaches, stomach pain, and kidney,
nervous system, and reproductive dysfunction. Lead can be passed from mothers to
their unborn children and can cause miscarriages and premature births.
In the past, lead was used in paints, gasoline, water pipes, and other household
products such as the solder used in canned food. Although these uses have been
limited in the U.S., lead is still used in many products and industrial processes both in
the U.S. and around the world. Housing built prior to 1978 is likely to contain lead-
based paint and lead-contaminated household dust, especially if the house was built
prior to 1950. Soil surrounding these houses may also be contaminated with lead.
Lead-based pigments are available in the U.S. in the form of artistic paints and glazes.
Children less than 6 years of age are the most likely to be exposed to lead because of
their increased hand-to-mouth behavior and high absorption rates. The lead gets into
their bodies by their ingesting lead dust or paint chips, inhaling dust, mouthing or
chewing items that contain lead or have been contaminated by lead, and/or by eating
contaminated food or water. Adult lead exposure is usually related to occupational or
recreational (hobby) exposure. Both may be affected by lead exposure. Children of
those who work with lead may also become exposed when lead contamination is
brought home on the work clothes of their parents.
How is it used?
The lead test is used to evaluate the concentration of lead in your blood. Blood lead
represents the amount of lead in the blood at that point in time. It is used to screen for
exposure to harmful levels of lead. It may also be ordered to monitor the effectiveness
of treatment and to confirm that lead levels are decreasing over time.
Lead concentrations are monitored at the local level following State and National
standards. The Centers for Disease Control and Prevention (CDC), the American
Academy of Pediatricians (AAP), and a variety of other organizations make
recommendations regarding screening children for lead exposure. Testing
recommendations and the definition of what is an abnormal blood lead level have
changed significantly over the past 45 years. In 1991, the CDC concluded that
previous levels were not low enough, and in 1997 the blood lead level of concern for
children was decreased from 25 micrograms per deciliter to 10 micrograms per
deciliter.
In recent years, elimination of leaded paint, leaded gasoline, and other common
sources of lead exposure and the monitoring and control of lead in the workplace and
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hobby use have decreased the amount of lead in the environment and decreased the
number of children with elevated blood levels. Many states now target their screening
efforts at those children who are at an increased risk for lead exposure, and the CDC
and AAP have come out with guidelines to help manage those children who do have
elevated blood lead levels.
Blood lead is monitored in workers whose environment contains lead. It is used to

evaluate chronic lead exposure and recent lead exposure. Sometimes, a zinc
protoporphyrin (ZPP) test is also ordered. The ZPP is increased when lead begins to
affect red blood cell production. It is not sensitive enough to use as a screening tool
for children, but it may help evaluate average lead exposure in adults over the last
several weeks.
When is it ordered?
For screening children:
The CDC released guidelines for testing children for lead in 1997 and guidelines for
managing children found to have elevated blood lead levels in 2002. They
recommend that each state develop a plan to detect children who may have been
exposed to lead. The CDC and the AAP recommend that, at a minimum, screening be
offered to:
 every Medicaid-eligible child and those children whose families are part of an
assistance program. These children should be screened at age 1 and again at 2 years of
age.
 at risk children 3-6 years of age who have not been previously tested.
 children who live in or regularly visit a house or apartment built before 1950, or
before 1978 if the dwelling has been/or is undergoing renovation or remodeling.
 children with a playmate or sibling who has or did have lead poisoning.
Check with your local health department regarding lead screening guidelines specific
to the risks in your area.
The CDC and AAP recommend that children of parents who work with lead be
considered for screening, and that immigrant, refugee, and other foreign-born children
be tested when they enter the United States.
Managing children with elevated blood levels:

Since fingerstick samples can be contaminated during collection of the specimen, an
initial elevated result obtained by a fingerstick sample should be repeated with a
venous test for confirmation, usually within a week to a month after the first test.
Follow-up testing is then used to monitor the persistence of an elevated blood lead test
and is recommended whenever a child’s blood lead level is higher than 10
micrograms per deciliter. Those with persistent lead levels above 15-19 micrograms
per deciliter (remain elevated for 3 months or more) and those with initial tests greater
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than 20 micrograms per deciliter should have their home surroundings evaluated to
determine the source of the lead exposure.
For screening adults:

Blood lead tests may be ordered to screen people in the workplace if lead
contamination is a possibility. Family members also may be screened because lead
can be carried home on clothing. This testing conforms to federal and state laws for
occupational exposure.
There is not yet a national guideline for blood lead screening in adults as there is for
children. The clinical cut-off values for elevated blood lead currently vary from state
to state. According to the CDC’s Adult Blood Lead Surveillance program (ABLES), a
national health objective is to reduce all blood levels in adults to less than or equal to
25 micrograms per deciliter.
Adults who work in industries known for lead exposure, such as smelter facilities,
lead plating, auto repair, and construction, should be screened for lead exposure.
Adults who have hobbies that involve lead-based paints, ceramics, or gasoline also
should be tested. For a list of hobbies that may expose you to potentially high levels
of lead, go to Lead Poisoning.
The Occupational Safety and Health Administration (OSHA) has developed rules for
monitoring for lead in the workplace. OSHA requires that employee blood monitoring
programs be triggered by the results found in an initial air monitoring program. If a
worker has an initial blood lead test result of more than 40 micrograms per deciliter,
for example, testing should be done every two months until two consecutives lead
tests show a blood lead level below micrograms per deciliter. Higher levels call for
closer monitoring.
For diagnosis:
For both children and adults, lead testing may be ordered when a patient’s symptoms
suggest potential lead poisoning. These symptoms are non-specific and may include
fatigue, changes in mood, nausea, prolonged stomach distress, headache, tremors,
weight loss, peripheral neuropathy, anemia, reproductive failure, encephalopathy,
memory loss, seizures, and coma. Many children have no symptoms at the time of the
exposure, but potentially permanent damage can still be occurring. Testing for lead
exposure should be considered in children presenting with growth failure, anemia,
sleep problems, hearing loss, or speech, language or attention deficits.

The higher the test result, the more lead is in your blood. However, the amount of lead
in the blood does not necessarily reflect the total amount of lead in your body. This is
because lead travels from the lungs and intestinal tract to the blood and organs, and
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then is gradually removed from the blood and organs and stored in tissues such as
bones and teeth. Blood lead concentrations represent recent exposure or chronic
exposure. The danger that a particular lead level represents depends on the age and
health of the person, the amount of lead they are exposed to, and the amount of time
that they are exposed to elevated lead levels.
Exposure to lead is not healthy for anyone, but children are more vulnerable to its
effects. The national health goal is to have every child’s blood lead level below 10
micrograms per deciliter by the year 2010. Any test results above this level trigger
management and monitoring. Recent studies suggest that there may not be any safe
lead level for children, that even below 10 micrograms per deciliter, some children
will have cognitive impairment. If further studies support this, then the recommended
lead levels may be lowered again in the future.
For non-pregnant adults, a level below 25 micrograms per deciliter is generally

considered to be acceptable. If a worker has levels above 45 micrograms per deciliter,
he must be removed from lead exposure until his blood lead level drops below 40
micrograms per deciliter. Removal may also be recommended if he is symptomatic at
any level below 70 micrograms per deciliter. Because lead will pass through the blood
to an unborn child, pregnant women need to limit their exposure to lead to maintain a
blood level below 10 micrograms per deciliter and as close to zero as possible to
protect the developing fetus.
Most experts agree that a child with a lead level greater than 45 micrograms per
deciliter should be treated with succimer in the hospital unless the patient is
encephalopathic. Any lead level greather than 70 micrograms per deciliter, whether in
a child or an adult, should be considered a medical emergency.
Any child who has an elevated blood lead level needs to have their home or other
environment evaluated. Other people at the residence should be tested as well.
Without the elimination or reduction of the source of the exposure – a lead hazard in
the environment - the elevated lead level will likely recur.

Poisoning with lead is more harmful for children, whose brains and other organs are
still developing. Adults tend to recover from lead ingestion better than children. If you
think your children may be at risk, have them screened as soon as possible.
Lead interferes with absorption of iron. Children with raised blood lead
concentrations should have testing for iron deficiency.
Each person eliminates lead differently. Thus, laboratory tests are just one part of the
picture in lead poisoning cases. Careful monitoring with medical examinations is
needed.
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Physicians should be aware that cultural practices and folk remedies, including soil
ingestion, can increase a person’s risk of lead exposure. Folk remedies prepared by
newly immigrated populations from Southeast Asia are particularly known as possible
sources of lead. Other potential lead sources include imported foods, candy,
cosmetics, costume jewelry, brass keys, and toys or household items containing or
painted with lead.
1. What products in the U.S. still contain lead, besides paint and ceramics?
Some products that still contain lead include car batteries, solder, some pipes,
ammunition, roofing, industrial paints, some PVC, vinyl and plastics, brass objects
including keys, costume jewelry, and X-ray shield materials.
2. How do people get exposed? Is touching these products enough to raise my

blood level?
Just holding a lead object in your hands won’t poison you. Most lead is present as an
inorganic compound and does not move well through the skin. Breathing in or
swallowing lead-laden dust may poison you, however. Some examples of lead
poisoning situations would be:
 touching surfaces covered with lead dust and then transferring the dust to your
mouth with fingers, food, or toys
 a toddler touching the windowsills in a pre-1978 house with their mouth or fingers
and then swallowing lead dust or lead chips
 inhaling dust during a home renovation project on a house built before 1978,
especially when using power sanders or other work practices that generate lead-
contaminated dust
 ingesting lead through gardening in contaminated soil around the foundation of an
older house or garage, or in soil contaminated with leaded gas along older highways,
or abandoned industrial settings
 drinking water through lead pipes – this is more common on the East Coast of the
U.S.
 swallowing lead shot (for a shotgun), a curtain weight, or a lead toy and not passing
it through your system
 inhaling burning lead-painted wood or battery casings in home fireplaces
3. What occupations might result in lead exposure?

Some occupations that put people and their families at risk for lead exposure include:
 lead smelting
 construction
 steel welding
 bridge reconstruction
 firing range instruction and cleaners
 remodeling and refinishing older homes
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 foundry work
 scrap metal recycling
 stained glass making
 using lead glazes in ceramics
 painting metal
 auto repair work
 electrician work
 cable splicing
4. Are there ways to protect myself and my family from getting lead exposure?
Yes. If your home was built before 1978:
 assume that you may have lead or get the house and soil checked by a professional
 damp mop smooth floors and surfaces frequently to control dust
 vacuum carpets and upholstery to remove dust – use a HEPA vacuum filter if
possible
 do a monthly check to look for chipping, peeling, or other damaged surfaces,
especially in window areas and porches; repair any chipping, peeling, or damaged
paint or surface as soon as it is observed, then thoroughly clean the area to remove
lead dust
 learn how to do renovation and repair projects using lead-safe work practices to
avoid creating more lead dust or contamination
For your child:
 frequently wash your child’s hands and toys to reduce lead dust contamination
 avoid using home remedies that contain lead

 keep your children (and pregnant women) away from lead hazards and out of the
area during renovation or repair projects
 don’t let children put objects in their mouths that were not made to be used as a
child’s toy, including keys, jewelry, or dirt
 get your child tested for lead at least at 1 and 2 years of age - contact your local
health department to learn more about screening recommendations for your area
5. Are there ways to protect myself and my family from getting lead exposure if I
work in a dangerous area?
Yes. If you are working in a potentially harmful environment with exposure to lead
dust or fumes:
 wash your hands before you eat, drink, or smoke
 eat, drink, and smoke in areas that are free from lead dust and fumes
 wear a properly fitted respirator with a HEPA filter (N-100 rating); shave your face
to get the best fit
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 keep your street clothes in a clean place; change into different clothes and shoes
before you work with lead
 shower immediately after working with lead, before you go home
 launder your work clothes at the work place or separately from other family
members’ clothes
6. How can I find out if my workplace is dangerous?

For more information about lead poisoning and workplace safety, visit the National
Center for Environmental Health online at http://www.cdc.gov/nceh. You can call 1-
888-422-8737 for information on NCEH programs and publications. For state and
local health department assistance, you can contact CDC Emergency Response (24-hr.
assistance during emergencies only) at 770-488-7100.
LH
Why get tested?
To evaluate your pituitary function, especially in terms of fertility issues
When to get tested?
If you are having difficulty getting pregnant or are having irregular menstrual periods;
if your doctor thinks that you have symptoms of a pituitary or hypothalamic disorder
or symptoms of ovarian or testicular disease; when a doctor suspects that a child has
delayed or earlier than expected sexual maturation
Sample required?
A blood sample drawn from a vein in your arm; sometimes a random urine sample or
24-hour urine collection.
Luteinizing hormone (LH) is produced by the pituitary gland in the brain. Control of
LH production is a complex system involving hormones produced by the gonads
(ovaries or testes), the pituitary, and the hypothalamus.
Women’s menstrual cycles are divided into 2 phases, the follicular and luteal, by a
mid-cycle surge of follicle-stimulating hormone (FSH) and LH. The high level of LH
(and FSH) at mid-cycle triggers ovulation. LH also stimulates the ovaries to produce
steroids, primarily estradiol. Estradiol and other steroids help the pituitary to regulate
the production of LH. At the time of menopause, the ovaries stop functioning and LH
levels rise.
In men, LH stimulates the Leydig cells in the testes to produce testosterone. LH levels
are relatively constant in men after puberty. Testosterone provides negative feedback
to the pituitary and the hypothalamus, helping to regulate the amount of LH secreted.
In infants and children, LH levels rise shortly after birth and then fall to very low
levels (by 6 months in boys and 1-2 years in girls). At about 6-8 years, levels again
rise before the beginning of puberty and the development of secondary sexual
characteristics.
A blood sample is taken by needle from a vein in the arm. Sometimes, a random urine
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sample is used. A 24-hour collection of urine may be requested if your doctor wants
to measure LH levels produced over a 24-hour period. LH is released intermittently
throughout the day and a 24-hour urine collection eliminates problems due to that
variation. A random sample might not show the actual activity of the hormone.
How is it used?
LH is often used in conjunction with other tests (FSH, testosterone, estradiol and
progesterone) in the workup of infertility in both men and women. LH levels are also
useful in the investigation of menstrual irregularities and to aid in the diagnosis of
pituitary disorders or diseases involving the ovaries or testes.
A urine test may be used to detect the surge in LH that indicates that ovulation will
occur in the next 1-2 days.
In children, FSH and LH are used to diagnose delayed and precocious (early) puberty.
LH is sometimes measured in relation to gonadotropin releasing hormone (GnRH) to
distinguish between primary or secondary disorder of the hypothalamic-pituitary axis.
GnRH is the hormone produced by the hypothalamus that stimulates the pituitary to
release LH and FSH. For this test, a baseline blood sample is drawn and then the
patient is given an injection of GnRH. Subsequent blood samples are drawn at
specified times, and the level of LH is measured. This test can help differentiate
between disease of the ovaries or testes (primary) and a disorder of the pituitary or
hypothalamus (secondary). It is also often helpful in the evaluation of precocious or
delayed puberty.
When is it ordered?
In women and men, LH (along with FSH) is ordered as part of the workup of
infertility and pituitary or gonadal disorders.
The test may be ordered along with an FSH test if a women is having irregular
menstrual periods to help determine if she has reached menopause. LH and FSH may
be ordered when a boy or girl does not appear to be entering puberty at an appropriate
age (either too late or too soon). Signs of puberty may include:
 breast enlargement in females
 growth of pubic hair
 genitalia growth in males
 beginning of menstruation in females
If any or some of these signs appear at a younger than average age or are delayed
beyond the expected age range for puberty, it may be an indication of a more serious
problem involving the hypothalamus, pituitary, gonads (ovaries or testes), or other
systems. The measurement of LH and FSH may differentiate between benign
symptoms and true disease. Once it is established that symptoms are a result of true
disease, further testing can be done to discern the underlying cause.
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In women, LH and FSH levels can help to differentiate between primary ovarian
failure (failure of the ovaries themselves or lack of ovarian development) and
secondary ovarian failure (failure of the ovaries due to disorders of either the pituitary
or the hypothalamus). Increased levels of LH and FSH are seen in primary ovarian
failure. Some causes of primary ovarian failure are listed below.
 Ovarian agenesis (failure to develop ovaries)

 Chromosomal abnormality, such as Turner’s syndrome
 Ovarian steroidogenesis defect such as 17 alpha hydroxylase deficiency
Premature ovarian failure due to:
 Radiation
 Chemotherapy
Chronic anovulation (failure to ovulate) due to:
 Polycystic ovary syndrome (PCOS)

 Adrenal disease
 Thyroid disease
 Ovarian tumor
When a woman enters menopause and her ovaries stop working, LH levels will rise.
Low levels of LH and FSH are seen in secondary ovarian failure and indicate a
problem with the pituitary or hypothalamus.
In men, high LH levels indicate primary testicular failure. This can be due to
developmental defects in testicular growth or to testicular injury, as described below.
 Gonadal agenesis
 Chromosomal abnormality, such as Klinefelters syndrome
Testicular failure:
 Viral infection (mumps)

 Trauma
 Radiation
 Chemotherapy
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 Germ cell tumor
Low levels are consistent with pituitary or hypothalamic disorders.
The results for the test for LH response to GnRH can help differentiate between
primary dysfunction (failure of the ovaries or testes) and secondary disorder (a
problem involving the pituitary or hypothalamus). Once the baseline level of LH has
been measured, a dose of GnRH is given by injection. A subsequent increase in the
level of LH indicates that the pituitary responded to the GnRH and points to a
disorder involving the ovaries or testes. A reduced level of LH shows that the
pituitary did not respond to the GnRH and suggests a disease involving the pituitary
or hypothalamus.
In young children, high levels of LH and FSH and/or development of secondary

sexual characteristics at an unusually young age are an indication of precocious
puberty. This is much more common in girls than in boys. This premature
development can have many different underlying causes that need to be diagnosed
and treated. Some of the causes include:
 Central nervous system lesions

 Hormone-secreting tumors
 Ovarian tumors or cysts
 Testicular tumors
Normal prepubescent levels of LH and FSH in children exhibiting some signs of

pubertal changes may indicate a benign form of precocious puberty with no
underlying or discernable cause or may just be a normal variation of puberty.
In delayed puberty, LH and FSH levels can be normal or below what is expected for a
youth within the age range of puberty. The test for LH response to GnRH may need to
be performed along with other testing to diagnose the reason for the delayed puberty.
Some of the causes for delayed puberty can include:
 Gonadal (ovary or testes) failure (such as PCOS)

 Hormone deficiency
 Turner’s syndrome (chromosomal abnormality in girls)
 Klinefelter’s syndrome (chromosomal abnormality in boys)
 Chronic infections
 Cancer
 Eating disorder (anorexia nervosa)
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Some drugs can cause LH to increase, such as anticonvulsants, clomiphene, and
naloxone, while others cause LH to decrease, such as digoxin, oral contraceptives, and
hormone treatments.
If you’ve recently had a nuclear medicine scan, the radioisotopes used in the scan may
interfere with results of the LH test.
1. I’m having a hard time getting pregnant. What tests do I need?
Basic tests for infertility often include LH, in the form of an ovulation test kit (using
urine). Your doctor may also ask you to keep track of your body temperature, which
rises slightly when ovulation occurs. Other tests for infertility include FSH and LH
blood tests and other hormonal tests as well as a postcoital (after intercourse)
examination. A hysterosalpingogram (image of fallopian tubes) may be ordered to see
whether your fallopian tubes are blocked. Your husband may be asked to give a
specimen of semen for analysis.
2. I am a young woman, but now I am growing facial hair and still have no
regular period. What’s wrong with me?
You may have polycystic ovary syndrome (PCOS), a hormonal problem seen in 7-
10% of women and a major cause of infertility. With this condition, ovaries may
become larger because of cysts that form in them. Women with PCOS also may have
high levels of androgens and do not ovulate normally. You may need to undergo
several laboratory tests, including LH, FSH, and androgens, to make sure that PCOS
is the condition causing your symptoms. A combination of medications and hormone
therapy may help to alleviate your symptoms.
3. Why would a man need a test for female hormones?

Men also produce FSH and LH in their bodies, and these hormone levels are
important for male reproduction too. In men, FSH stimulates the testes to produce
sperm just as in women FSH stimulates the ovaries to produce eggs. In men, LH can
be measured if testosterone levels are low.
4. Is there a home test for LH?

Yes, there is a home test that uses a urine sample to help predict ovulation. For more
information, visit the FDA’s web site at http://www.fda.gov/cdrh/oivd/homeuse-
ovulation-urine.html
Lipase
Why get tested?
To diagnose pancreatitis or other pancreatic disease
When to get tested?
If you have symptoms of a pancreatic disorder, such as severe abdominal pain, fever,
loss of appetite, or nausea.
Lipase is an enzyme manufactured primarily by the pancreas. It is released into the
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digestive tract to help digest fatty foods. It is also important in maintaining cell
permeability, that is, allowing the cell wall to let nutrients easily flow in, and to let
waste easily flow out.
How is it used?
The blood test for lipase is used to help diagnose pancreatitis (swelling of the
pancreas) and other pancreatic disease. It is also used to a lesser extent in the
diagnosis and follow-up of cystic fibrosis, celiac disease, and Crohn's disease.
When is it ordered?
A lipase test may be ordered if you show symptoms of a pancreatic disorder, such as
severe abdominal pain, fever, loss of appetite, or nausea.
Normal values for lipase depend on the test used to measure it. In acute pancreatitis,
lipase levels are very high, often 2 to 5 times the normal amount. Slightly high lipase
values may occur in other conditions such as kidney disease, salivary gland
inflammation, or peptic ulcer disease. Occasionally lipase is high due to a tumor
(cancer). The rapid and sharp rise of lipase in the blood within hours after the
beginning of an attack, and the decline after about 4 days, usually indicates acute
pancreatitis.

In acute pancreatitis, elevated lipase levels usually parallel levels of another enzyme
called amylase, and remains elevated longer (for 5 to 7 days).
Both lipase and amylase are usually ordered together to diagnose acute pancreatitis.
Both may also be used to monitor chronic pancreatitis. Both may be moderately
elevated in chronic pancreatic disease and/or levels may fall if the cells that produce
amylase and lipase in the pancreas become damaged or destroyed.
Low lipase levels are often associated with diabetes. (If your body is unable to digest
fat, this condition interferes with insulin metabolism and with insulin's transport of
glucose into the cells.)
Lipase-deficient people may also have high cholesterol and/or high blood
triglycerides, high blood pressure, difficulty losing weight, and varicose veins. Drugs
that may interfere with maintaining proper lipase levels include codeine,
indomethacin, morphine, and drugs with a hydrochloric acid base.
1. What are the treatment options for pancreatitis?
Treatment depends upon the symptoms. If they are absent or mild, there may be no
treatment. If they are more severe, your doctor may suggest "resting the pancreas" by
a spectrum of options ranging from not eating solid foods to fasting combined with IV
(intravenous) fluid replacement for several days to a few weeks (usually requiring
hospitalization). Medication and possible surgery may also be considered for patients
with severe symptoms. Sometimes pain management medications are required.
Nutritional support, such as low-fat diets and frequent small meals, may help relieve
symptoms. Oral pancreatic enzyme replacement is another possible choice.
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2. What are the long-term consequences of pancreatitis?
With acute pancreatitis there is usually no long term damage, and often no further
problems develop. Chronic pancreatitis, which may present as a series of acute attacks
or as an ongoing upset can cause permanent damage. As the pancreas becomes more
scarred, some people develop diabetes and/or the inability to digest foods, especially
fats. The lack of normal pancreatic enzymes may lead to adverse effects on food
digestion and waste production, causing abdominal pain, greasy stools, and formation
of stones in the pancreas. Even if the disease is controlled, the damage done is often
irreversible. If the disease progresses, it could lead to death.
3. Do elevated lipase levels always mean I have a pancreatic condition?

In pancreatitis, the lipase rises quickly, but begins to drop in about 4 days. In other
conditions, the rise is usually not as great, and the level is maintained for a longer
period. Your doctor is the best one to determine if you have a pancreatic disorder. She
will make a diagnosis based on your symptoms, medical history, and test results.
Lipoprotein Subfraction Testing
Also known as: LDL Subclasses, LDL Subfractions, HDL Subclasses, HDL
Subfractions
Formal name: Lipoprotein Subfraction Profile
Why get tested?
To help evaluate your risk of developing coronary artery disease (CAD)
When to get tested?
If you have a personal and/or family history of CAD or peripheral vascular disease at
an early age; if your doctor is trying to assess your risk of developing heart disease;
sometimes to help monitor the effectiveness of lipid-lowering treatment and/or
lifestyle changes.
Lipoprotein subfraction tests separate two of the commonly measured lipoprotein
fractions – HDL (the carrier of good cholesterol) and LDL (the carrier of bad
cholesterol) – into subfractions based on their size, density, and/or electrical charge.
Lipoproteins are heterogeneous particles – containing molecules of proteins,

cholesterol, triglycerides, and phospholipids. As they circulate in the body, various
molecules are removed and others are added to create particles of differing
compositions. This results in a spectrum of lipoprotein particles that vary from large
and fluffy (those with a high proportion of triglycerides) to small and dense (those
with a high proportion of protein). Studies have shown that small dense LDL particles
are more atherogenic (more likely to cause atherosclerosis) than light fluffy LDL
particles. Researchers think that the presence of small dense LDL could be one of the
reasons that some people have heart attacks even though their total and LDL
cholesterol are not particularly high. Although less is known about HDL subclasses,
some initial studies have shown that large fluffy HDL particles may provide more
protection than small dense HDL particles.
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The number of small dense LDL and HDL particles a person has is partially
genetically determined, partially due to gender (males tend to have more small LDL
and HDL than females), and partially due to lifestyle and a person’s general state of
health. Certain diseases and conditions, such as diabetes and hypertension, are
associated with increased levels of small dense LDL.
A variety of methods are used to determine lipoprotein subfractions. These include

ultracentrifugation (separation by density), electrophoresis (separation by charge and
size), and NMR (nuclear magnetic resonance) spectroscopy (which counts the number
of particles in each subfraction). Until recently, these methods were too expensive and
technically demanding to be used on a commercial basis, but lipoprotein subfraction
testing has begun to be offered in some larger laboratories and reference laboratories.
How is it used?
Lipoprotein subfraction testing is not routinely ordered but its use is growing. It may
offer useful information in assessing risk in patients who have a personal or family
history of early heart disease, especially if their total and LDL cholesterol values are
not significantly elevated. LDL subfraction testing is more common than HDL
subfraction testing since LDL has been identified as the primary risk factor for heart
disease and more research and development has focused on LDL measurement.
Subfraction testing is typically done along with a lipid profile. The subfractions are
usually expressed as relative proportions or percents of the LDL and/or HDL.
Since subfractions may be affected by lipid treatment and/or lifestyle changes, LDL
subfraction testing may also be occasionally ordered to monitor the effectiveness of
treatment in decreasing the number of small dense LDL particles.
When is it ordered?
Lipoprotein subfraction testing may be ordered as part of an overall evaluation of
cardiac risk when someone has a personal or family history of early CAD, especially
when they don’t have typical cardiac risk factors, such as high cholesterol, high LDL,
high triglyceride, low HDL, smoking, obesity, inactivity, diabetes, and/or
hypertension.
When a patient with a large proportion of small dense LDL particles has undergone
lipid lowering treatment or lifestyle changes, his doctor may order LDL lipoprotein
subfraction testing, along with other lipid tests, to monitor the effectiveness of
treatment.
Although it is not generally recommended as a screening test, a few doctors are

ordering lipoproteins subfraction testing along with a battery of other cardiac risk tests
when they are attempting to determine a patient’s overall risk of developing CAD.
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In general, the result is interpreted within the framework of a lipid profile and its
associated risk. If the patient has primarily small dense LDL, this finding will add to
the risk of developing CAD above and beyond the risk associated with the total LDL.
On the other hand, the presence of exclusively large fluffy LDL will add no additional
risk. The picture is more complex with HDL subfractions and there is no consensus
on how to include the findings in risk assessment, but in general the presence of large
fluffy HDL is thought to offer more protection than small dense HDL.

It is important to remember that lipoprotein subfraction testing (and other lipid and
cardiac risk factor testing) is not diagnostic. It attempts to evaluate a patient’s
statistical risk of developing CAD but it cannot predict the development or severity of
CAD in a particular patient.
Results of lipoprotein subfraction testing reflect the method and reporting format used
as well as the patient’s total LDL-cholesterol and/or HDL-cholesterol. Since different
methods separate the subclasses based on different physical properties (size, density,
and/or electrical charge), results may not be directly comparable method to method or
laboratory to laboratory.
1. How can I change my lipoprotein subfractions?
Although there is a genetic component, lipoprotein subfractions can be altered by
adopting a diet low in saturated fats, losing excess weight, and exercising regularly.
The use of lipid-lowering drugs may also affect the subfraction distribution.
Lithium
Why get tested?
To determine lithium concentration in the blood in order to maintain a therapeutic
level or to detect lithium toxicity
When to get tested?
At regular intervals to monitor lithium levels; as needed to detect low or toxic
concentrations
This test measures the amount of lithium in the blood. Lithium is a drug that is used to
treat bipolar disorder. Bipolar disorder is a mental condition that is characterized by
cycles of depression and mania. These cycles may be as short as a few days or weeks
or may be months or years long. During a depressive episode, those affected may feel
sad, hopeless, worthless, and lose interest in daily activities. They may be fatigued but
have trouble sleeping, experience weight loss or gain, have difficulty concentrating,
and have thoughts of suicide. During a manic episode, those affected may be
euphoric, irritable, have high energy and grandiose ideas, use poor judgment, and
participate in risky behaviors. Sometimes affected patients will have mixed episodes
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with aspects of both mania and depression. Bipolar disorder can affect both adults and
children.
Lithium is prescribed to even out the moods of the person with bipolar disorder and is
sometimes prescribed for patients with depression who are not responding well to
other medications. It may take several weeks to months for lithium to affect a
person’s mood. Dosages of the drug are adjusted until a steady concentration in the
blood is reached. The actual amount of drug that it will take to reach this steady state
will vary from person to person and may be affected by a person’s age, general state
of health, and other medications that they are taking. Lithium levels must be
maintained within a narrow therapeutic range. Too little and the medication will not
be effective; too much and patients will experience symptoms associated with lithium
toxicity, such as nausea, vomiting, diarrhea, confusion, and tremors. Extremely high
levels can lead to stupor, seizures, and can be fatal.
How is it used?
The lithium test is ordered to measure and monitor the amount of lithium in the blood
in order to determine whether drug concentrations are in the therapeutic range. It may
be ordered every few days when a patient first begins taking lithium to help adjust the
dose to the desired blood level. The test may be ordered at regular intervals or as
needed to monitor blood concentrations. One or more lithium tests may be ordered if
a patient starts taking additional medications (to judge their effect, if any, on lithium
levels) and may be ordered if the doctor suspects toxicity.
When is it ordered?
Lithium is ordered frequently when a patient is starting lithium treatment or returning
to it after an absence. Once stable blood concentrations in the therapeutic range have
been achieved, then lithium may be monitored at regular intervals to ensure that it
remains in this range.
The test may be ordered when a patient’s condition does not appear to be responding
to lithium to determine whether concentrations are too low, the medication is
ineffective, and/or to determine if the patient is complying with therapy (taking the
lithium regularly). It may also be ordered when a patient experiences a troublesome
level of side effects and/or exhibits symptoms that the doctor suspects may be due to
toxicity.
Patients should talk to their doctor about the timing of the sample collection. Lithium
blood levels are generally performed 12-18 hours after the last dose. Since dosage
timing varies and some formulations are time released, collection specifics may vary.

The therapeutic range for lithium has been established at 0.6 – 1.2 (mmol/L). Within
this range, most people will respond to the drug without symptoms of toxicity.
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Response and side effects will be individual, however. Some people’s bipolar
condition will not be adequately treated at the low end of the therapeutic range and
some people will experience excessive side effects at the upper end. Patients should
work closely with their doctor to find the dosage and concentration that works the best
for them.
In general, when lithium results are in the therapeutic range, the doctor and patient are
satisfied that the patient’s bipolar disorder is being appropriately managed and the
patient is not experiencing significant side effects, then the dosage of lithium a patient
is receiving is adequate. If the patient is below the therapeutic range, it is likely that
they are not receiving adequate medication. If they are above the therapeutic range
and/or are experiencing significant side effects at their current dose, then it is likely
that they are taking too much medication. Patients should not decrease or stop taking
their medication without consulting with their doctor, however, as it can worsen their
bipolar symptoms. Dosage determinations and adjustments must be evaluated on a
case-by-case basis.
Lithium is excreted primarily by the kidneys. Long-term use of lithium carries a risk
of decreased kidney function. Patients with kidney disease may have increased
lithium levels because of decreased elimination. Doctors will monitor kidney function
over time with tests such as a BUN and creatinine.
Patients who take lithium may develop hypothyroidism (decreased thyroid function).
Doctors will often regularly monitor a patient’s thyroid function with a TSH and/or a
T4 test.
Women who use lithium during pregnancy are at an increased risk of having their
fetus develop a rare heart valve defect. Women who want to become pregnant should
talk to their doctors about this subject.
A variety of prescribed drugs, over-the-counter medications, and supplements can

increase, decrease, or interfere with the concentrations of lithium in the blood. Drugs
that can increase lithium in the body include anti-inflammatories such as ibuprofen
and naproxen and diuretics such as hydrochlorothiazide and furosemide. Drugs that
can increase the side effects of lithium include antipsychotics such as clozapine and
olanzapine, blood pressure medications such as calcium channel blockers and
angiotensin converting enzyme inhibitors, and antiseizure medications such as
carbamazepine. Drugs that can decrease lithium include theophylline and prescription
levels of caffeine.
Lithium levels and side effects can increase with the loss of salt and water from the
body, such as may occur with a salt-free diet, excessive sweating, or with an illness
that causes vomiting and diarrhea.
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1. How long will I need to be on lithium?
Lithium is usually taken every day for a patient’s lifetime. Bipolar disorder can be
managed but not cured.
2. Who orders lithium tests?

They may be monitored by your primary doctor but may also be ordered and
monitored by a mental health professional.
3. Can I test my lithium level at home?
No, it requires specialized equipment. Most blood samples are collected from a vein
in the arm and tested in the laboratory. However, the FDA has recently approved a
test that can be performed in the doctor’s office (it requires blood from a fingerstick).
This test is not currently in widespread use but may be an option in the near future.
Liver Panel
A liver panel, also known as liver (hepatic) function tests or LFT, is used to detect,
evaluate, and monitor liver disease or damage. It usually consists of seven tests that
are run at the same time on a blood sample. These include:
 Alanine aminotransferase (ALT) – an enzyme mainly found in the liver; the

best test for detecting hepatitis
 Alkaline phosphatase (ALP) – an enzyme related to the bile ducts; often
increased when they are blocked
 Aspartate aminotransferase (AST) – an enzyme found in the liver and a few
other places, particularly the heart and other muscles in the body
 Bilirubin – two different tests of bilirubin often used together (especially if a
person has jaundice): total bilirubin measures all the bilirubin in the blood;
direct bilirubin measures a form that is conjugated (combined with another
compound) in the liver
 Albumin – measures the main protein made by the liver and tells whether or
not the liver is making an adequate amount of this protein
 Total Protein - measures albumin and all other proteins in blood, including
antibodies made to help fight off infections
Other tests that could be requested along with the liver panel are gamma-glutamyl
transferase (GGT), lactic acid dehydrogenase (LDH), and prothrombin time (PT).
When are these tests ordered?

One or more of these tests may be ordered when symptoms suspicious of a liver
condition are noticed. These include: jaundice, dark urine, or light-colored bowel
movements; nausea, vomiting and/or diarrhea; loss of appetite; vomiting of blood;
bloody or black bowel movements; swelling or pain in the belly; unusual weight
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change; or fatigue or loss of stamina. One or more of these tests may also be ordered
when a person has been or may have been exposed to a hepatitis virus; has a family
history of liver disease; has excessive alcohol intake; or is taking a drug that can cause
liver damage.
Many patients with early or mild to moderate liver disease may have few if any
symptoms. Liver disease may be first detected through routine blood testing that is
performed as part of a physical. This testing usually includes a group of 14 tests called
the Comprehensive Metabolic Panel (CMP). Most of the tests found in the liver panel
(all but the direct bilirubin) are included in the CMP. When liver disease is detected
with a CMP blood test, it may be monitored over time with follow-up liver panels.
Lp(a)
Also known as: Lipoprotein little a

Why get tested?
To give your doctor additional information about your risk of developing heart
disease. As part of a targeted screen for coronary artery disease (CAD) and
cerebrovascular disease (CVD).
When to get tested?
When you have a family history of elevated Lp(a) levels and/or a family history of
premature CAD. When you have heart disease but your lipid profile is normal or
shows only mildly elevated levels of cholesterol and/or low-density lipoprotein
(LDL).
Lp(a) is an independent risk factor for heart disease. It is a lipoprotein, an LDL
molecule with another protein (Apolipoprotein (a)) attached to it. In the body,
Apolipoprotein (a) can interfere with the function of plasminogen (resulting in blood
clot formation), and can help bind LDL molecules to artery walls (speeding up plaque
formation and the narrowing and hardening of the arteries).
The Lp(a) molecule consists of a lipid-rich core, surrounded by an Apolipoprotein B-

100 (Apo B-100) molecule and an Apolipoprotein (a) molecule. The size of the Lp(a)
molecule is consistent for one person but it varies across the human population. Lp(a)
size varies because its Apolipoprotein (a) has a genetically varying number of units
(called kringles) in it. As the number of kringles rises, so does the size of the Lp(a)
molecule.
Lp(a) levels will remain fairly constant in an individual over a lifetime but they will
be slightly lower in men, and they will rise a bit higher in post menopausal women.
Lp(a) levels also vary by ethnicity: those patients of African American descent tend to
have levels 3 to 4 times higher than Caucasians but, for reasons that are not well
understood yet, they do not have a higher risk for CAD. This may be because the size
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of the molecule doesn’t correlate with levels in African Americans. In people of
European ancestry, larger forms of Lp(a) are associated with lower blood levels, while
smaller forms are associated with higher levels.
How is it used?
Lp(a) is ordered, along with other lipid tests, to selectively screen for risk factors for
coronary artery disease and cerebral vascular disease. Some doctors have started to
order Lp(a) and several other emerging cardiac risk markers (such as Apo B, hs-CRP,
Apo A, and Homocysteine levels) on patients who have a strong family history of
premature coronary artery disease.
Some doctors may also order these tests on those who already have heart or vascular
disease, but who have normal or only mildly elevated lipids. Since about 50% of the
people who have heart attacks have normal cholesterol levels, doctors are starting to
look at other factors that may have an influence on heart disease. It is thought that
elevated Lp(a) levels can exacerbate other heart and vascular disease processes.
When is it ordered?
Lp(a) may be ordered, along with other lipid tests, when you have a family history of
premature coronary artery disease, and when your doctor suspects a familial
hypercholesterolemia. He may also order an Lp(a) level when you have had a stroke
or heart attack, but have normal or only mildly elevated lipids.
In rare cases, an Lp(a) level may be ordered on a post menopausal woman to see if
elevations in Lp(a) (tied to decreasing estrogen levels) have significantly increased
her risk of developing CAD.
Lp(a) levels are genetically determined and remain relatively constant over an
individual’s lifetime. They are not affected by lifestyle changes or by most drugs.
High Lp(a) levels increase a person’s risk for developing coronary artery disease and
cerebral vascular disease, and can occur in patients with a normal lipid profile.
Elevated levels of Lp(a) are thought to work independently, to add to any underlying
heart or vascular disease processes. Elevated levels of Lp(a) are seen in:
 Chronic renal failure

 Estrogen depletion
 Familial hypercholesterolemia
 Myocardial infarction (heart attack)
 Premature coronary artery disease
 Severe hypothyroidism
 Stenosis of cerebral arteries
 Stroke
Low levels of Lp(a) do not appear to cause problems. They may be seen with:
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 Alcoholism
 Chronic liver disease
 Malnutrition

Although some cardiologists and other doctors are beginning to order Lp(a) levels, it
is not a routinely ordered test. A recent National Institutes of Health (NIH) guideline,
the “Adult Treatment Panel III” (pg. II-21, available in PDF) acknowledged the
possible usefulness of Lp(a) and other emerging cardiac risk tests like Lp(a), but it did
not recommend them for widespread screening.
This is partially due to the fact that Lp(a) levels are genetically determined, and
difficult to change. Niacin and estrogen (for postmenopausal women) have been
shown to lower Lp(a) levels a small amount but their effect appears to be short term
and it is not known if lowering Lp(a) levels actually lowers risk. Experts are currently
not recommending drug treatments for elevated Lp(a) levels, but some are suggesting
that patients with elevated Lp(a) levels should be especially vigilant about lowering
their low-density lipoprotein (LDL – the “bad” cholesterol) levels, which may help
lower their overall risk.
In general, lipids should not be measured during a fever or major infection, within 4
weeks of an acute myocardial infarction (heart attack), a stroke, or major surgery,
right after excessive alcohol intake, when you have severely uncontrolled diabetes,
when you are pregnant, or during rapid weight loss.
1. Why would my doctor want to order an Lp(a) more than once?
Typically, Lp(a) levels are usually only tested once because they are usually fairly
constant. Occasionally your doctor may order a second Lp(a) to confirm the initial
level, or to see if your risk has increased significantly after menopause, or to monitor
the effects of treatment.
Lyme Disease
Formal name: Anti-borrelia burgdorferi IgM/IgG
Why get tested?
To see if you have been exposed to the bacterium that causes Lyme disease
When to get tested?
If you show symptoms of Lyme disease, especially if you have recently been in an
area with a large population of deer and/or suspect you have been bitten by a tick.
Your blood is being tested for antibodies to the Lyme disease bacterium. When you
have these antibodies in your blood, it means that you may have come in contact with
the Lyme disease bacterium known as Borrelia burgdorferi, which is transmitted by a
bite from an infected deer tick.
This test also measures antibodies to other bacteria, so that if the test is positive, an
additional test, called a Western Blot, is used to help your doctor confirm a diagnosis
of Lyme disease.
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How is it used?
The test is used to determine if your blood has made antibodies to the bacterium that
causes Lyme disease. The infection affects many body systems, and in many patients
starts with a “bulls-eye” rash at the site of the bite, and flu-like symptoms. The
disease can progress and eventually cause a variety of chronic symptoms, including
inflammation of the heart, arthritis, and central nervous system disease, including
meningitis.
But because the symptoms of Lyme disease vary from person to person, and because
antibodies to the bacterium do not appear until 3-6 weeks after the tick bite (although
the skin lesion may appear within 3 to 30 days), the infection is difficult to diagnose.
At this point, a blood test can be used to detect levels of antibodies, immunoglobulin
M (IgM) and immunoglobulin G (IgG), that develop against the Borrelia burgdorferi
bacterium.
This test, however, can also detect antibodies to other bacteria. Therefore, if the test is
positive, an additional test, called a Western Blot, is often required to confirm the
presence of specific antibodies to the bacterium that causes Lyme disease. Lastly, A
DNA-based test based on the polymerase chain reaction (PCR) may also be done and
is even more sensitive; it is used to detect the genetic material of the infecting
bacteria. Taken together, these tests will help your doctor confirm a diagnosis. Once
the diagnosis is made, your doctor will recommend appropriate treatment.
When is it ordered?
If you show the tell-tale sign of the tick bite and have recently been in an area with a
large deer population, your doctor will probably diagnose you using these clinical
findings. If you don’t have these clear signs but do have vague, confusing symptoms
ranging from “flu,” numbness, and muscle and joint ache to arthritis, fatigue, and
unexplained nerve or heart problems, your doctor may order these blood tests to see if
you have Lyme disease.
A healthy adult has no antibodies to the Borrelia burgdorferi bacterium. If you test
positive, you have been exposed to the bacterium and most likely have Lyme Disease.
If you test negative, you could still have the disease, but your antibody level is too
low to detect. In that case, your doctor will treat you according to your history and
symptoms.
Antibodies to the bacteria can stay in the blood for a long time; therefore if you have
ever been infected with Borrelia burgdorferi previously, your blood test might still be
positive, even though you may no longer have Lyme disease.
Borrelia burgdorferi belongs to a class of bacteria called spirochetes. Other spirochete
diseases (syphilis, leptospirosis) can cause false-positive results. Antibiotics can
interfere with the test results, so if you are being treated with antibiotics before being
tested for Lyme disease, make sure your doctor knows.
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1. What is the proper treatment for Lyme disease?
Most patients with Lyme disease are treated with antibiotics.
2. Can I do anything to protect myself from becoming infected?

Yes. If you are in the woods or garden in tick-infested areas, avoid contact with the
soil, leaves, and vegetation. Wear closed shoes, light-colored clothing, and use insect
repellant containing DEET. Check your clothing and exposed skin frequently and
remove ticks promptly. Animals such as dogs, cats, horses, and cows can also carry
the deer tick. Check your pet often, particularly the head, neck, ears, and between the
toes. Use a tick repellent prescribed by your veterinarian.
3. How can I recognize the signs if I don’t show the rash?

The rash appears in only about 50% of those infected. This rash may be the classic
“bull’s eye,” but may also be blotchy or red and may be confused with poison ivy,
spider bites, or ringworm. It may appear between a few days and a few weeks after
being bitten and can disappear quickly. If possible, take a picture of the rash to show
your doctor, since the rash may be gone before you can get an appointment with
him/her.
Other symptoms of Lyme disease include fatigue, chills and fever, headache, muscle
and joint pain, and swollen lymph nodes. Check with your doctor if you have any of
these symptoms and cannot explain how you got them.
4. Are deer ticks the only way to get Lyme disease?

No. On the Pacific coast and in southeastern states, the black-legged tick also
transmits Lyme disease.
Magnesium
Why get tested?
To evaluate the level of magnesium in your blood and to help determine the cause of
abnormal calcium and/or potassium levels
When to get tested?
If you have symptoms (such as weakness, irritability, cardiac arrhythmia, nausea,
and/or diarrhea) that may be due to too much or too little magnesium or if you have
abnormal calcium or potassium levels.
This test measures the amount of magnesium in your blood. Normally, only a very
small amount (about 1%) of magnesium is present in the blood.
Magnesium is a mineral that is found in every cell of your body. It is vital to energy
production, muscle contraction, nerve function, and maintenance of strong bones.
About half of the body’s magnesium is combined with calcium and phosphorus to
form bone.
A wide variety of foods contain small amounts of magnesium, especially green
vegetables such as spinach, and most magnesium in the body comes from dietary
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sources. The body maintains magnesium levels in its blood, cells, and bone by
regulating how much it absorbs from the intestines and by how much it excretes or
conserves in the kidneys.
How is it used?
Abnormal levels of magnesium are most frequently seen in conditions or diseases that
cause impaired or excessive excretion of magnesium by the kidneys or that cause
impaired absorption in the intestines. Magnesium levels may be checked as part of an
evaluation of the severity of kidney problems and/or of uncontrolled diabetes and may
help in the diagnosis of gastrointestinal disorders.
Since a low magnesium level can, over time, cause persistently low calcium and
potassium levels, it may be checked to help diagnose problems with calcium,
potassium, phosphorus, and/or parathyroid hormone (involved with calcium
regulation).
Magnesium levels may be measured frequently to monitor the response to oral or
intravenous (IV) magnesium supplements and may be used, along with calcium and
phosphorus testing, to monitor calcium supplementation.
When is it ordered?
Magnesium testing may be ordered as a follow-up to chronically low levels of
calcium and potassium. It also may be ordered if you have symptoms of an
abnormally low magnesium level such as muscle weakness, twitching, cramping,
confusion, cardiac arrhythmias, and seizures.
Although dietary deficiencies of magnesium are rare, your doctor may order a
magnesium level to check for a deficiency as part of an evaluation of malabsorption,
malnutrition, diarrhea, or alcoholism. If you are taking certain medications that can
cause the kidneys to excrete magnesium, testing may be performed as well. If
magnesium and/or calcium supplementation is necessary, then the magnesium blood
level most likely will be checked at intervals to monitor the effectiveness of treatment.
If you have a kidney disorder or uncontrolled diabetes, your doctor may order
magnesium levels to help monitor kidney function and to make sure that you are not
excreting or retaining excessive amounts of magnesium.
Low levels of magnesium (hypomagnesemia) in your blood may mean that you are:
1) not getting enough magnesium in your diet; 2) your intestines are not absorbing
enough magnesium; or 3) your kidneys are excreting too much magnesium.
Deficiencies may be due to:
 Low dietary intake (seen in the elderly, malnourished, and with alcoholism)
 Gastrointestinal disorders (such as Crohn’s disease)
 Hypoparathyroidism (underactive parathyroid gland)
 Long-term diuretic use
 Prolonged diarrhea
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 Post surgery
 Severe burns
 Toxemia of pregnancy
Increased levels of magnesium are rarely due to dietary sources but are usually the
result of an excretion problem or excessive supplementation. Increased levels are seen
in:
 Kidney failure
 Hyperparathyroidism (overactive parathyroid gland)
 Hypothyroidism
 Dehydration
 Diabetic acidosis (when first seen)
 Addison’s disease
 Use of magnesium-containing antacids or laxatives

Since magnesium is an electrolyte, it may be ordered along with other electrolytes
such as sodium, potassium, chloride, CO2, calcium, and phosphorus to evaluate a
patient’s electrolyte balance. If magnesium is low, it is not unusual for potassium also
to be low.
Magnesium blood levels may be low normally in the second and third trimesters of
pregnancy.
1. Why is my doctor checking my calcium and phosphorus along with my

magnesium level?
Low magnesium levels can affect calcium level regulation. Parathyroid hormone and
Vitamin D ordinarily work together along with phosphorus to regulate calcium levels.
Low magnesium levels can make low calcium levels more resistant to change.
Mercury
Also known as: Hg
Formal name: Mercury, Urine and Blood
Why get tested?
To detect excessive exposure to mercury
When to get tested?
If you have symptoms of mercury poisoning, to evaluate a known exposure to
mercury, or to monitor occupational exposure to mercury
Sample required?
A blood sample drawn from a vein in your arm and/or a urine collection.
This test measures the amount of mercury present in blood, urine, or (rarely) hair to
detect acute or chronic excessive exposure. Mercury is an element that exists in three
forms: as a free metal (liquid or vapor), an inorganic compound (mercury salt), and as
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a variety of organic compounds (the most common of which is methyl mercury).
Released by the breakdown of minerals in rocks and soils and through human
activities, such as fossil fuel combustion and waste incineration, mercury is found in
small amounts throughout the environment. It is inhaled with the air that we breathe,
absorbed through the skin, and ingested with food. For the vast majority of people, the
tiny amounts that they are exposed to do not cause any health problems. Some people,
however, are exposed acutely to dangerous concentrations of mercury (such as might
be found at a hazardous waste site) or are exposed chronically to excessive levels
(such as those who work with “heavy metals” in their occupation). The amount of
mercury absorbed by an individual and its effect on their health depends on the type
of mercury, its concentration, and the exposure time. For instance, according to the
ATSDR (Agency for Toxic Substances and Disease Registry), very little metallic
mercury (less than 0.01%) is absorbed by the body, even if it is swallowed. However,
if the same mercury is inhaled as a vapor, about 80% is absorbed into the bloodstream
and about 95% of methyl mercury (the type found in fish and other seafood) is
absorbed by the gastrointestinal tract. This is why it is so dangerous to eat fish caught
in contaminated waters.
Once mercury is absorbed, it finds its way into a variety of body organs, including the
kidney and brain. The body will slowly rid itself of mercury through the urine and
stool, but if excessive amounts are present, they can damage the kidneys, nervous
system, and brain. Pregnant women with elevated levels of mercury can pass it on to
their fetus, affecting development as well as the fetus’s brain, kidneys, and nerves.
After birth, they can expose their nursing infant to mercury through their breast milk.
How is it used?
Mercury testing is done to detect the presence of an excessive amount of mercury. It
may be ordered to determine whether someone has been acutely or chronically
exposed to increased levels of mercury. It may also be ordered to monitor those who
are exposed to mercury in the workplace.
More than one type of sample may be collected and tested.
 Blood is primarily tested to detect the presence of methyl mercury. Other forms of
mercury can also be detected in the blood, but according to ATSDR, the amount
present will decrease by half about every 3 days as the mercury moves into other
organs.
 Urine is used to test for metallic mercury and inorganic forms of mercury, but it
cannot be used to determine exposure to methyl mercury.
 Hair testing may be useful to detect methyl mercury exposures that occurred
several months previously, but hair testing is relatively complex and is not used
frequently.
 Although not routinely used as samples, mercury has been shown to be present in
nails, breast milk, stool, and breath.
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When is it ordered?
Mercury testing may be ordered when a patient has symptoms suggesting excessive
exposure to mercury. Acute symptoms may include: burning in the mouth and lungs,
decreased urine output, nausea, vomiting, diarrhea, and an increased heart rate. Those
who are chronically exposed may have nonspecific symptoms that involve the lungs,
kidneys, and nervous system.
Testing may also be ordered when a patient is known to have been exposed to
mercury to help evaluate the extent of the exposure. Mercury measurements may be
ordered regularly as a monitoring tool for those patients who work in industries that
utilize mercury and may be ordered, along with lead and/or other heavy metals, for
individuals who work with a variety of potentially hazardous materials.

Elevated levels of mercury may indicate excessive exposure to mercury, although this
does not tell you the form or quantity of mercury to which a person was exposed.
Increased blood levels suggest a relatively recent exposure to mercury, while a 24
hour urine sample gives more of an average past history of exposure to metallic or
inorganic mercury.
Normal levels of mercury in blood and urine indicate that it is likely that the patient
has not been exposed to excessive levels of mercury, at least not in the window of
time that the test is measuring.
Increased levels of mercury in hair testing may indicate exposure to increased levels
of methyl mercury but hair samples are rarely used because of issues involving testing
standardization and the fact that hair is subject to many pre-analytical variables (hair
exposure to dyes, bleach, shampoo, etc.).
Measures have been taken in recent years to reduce and control the public’s exposure
to mercury. Stricter regulations and recommendations have lowered the amounts
allowable in the air, water, soil, and food, and in the workplace.
1. What is thimerosal?
Thimerosal is an organic mercury compound that is used in small amounts as a
preservative in some vaccines. Although it is generally regarded as safe, the
thimerosal is now being phased out.
2. Do silver teeth filling contain mercury?
Yes. Dental amalgams (teeth fillings) are about 50% metallic mercury. Some feel that
the tiny amount of mercury vapor released when a person chews may affect their
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health, but internationally most major health organizations feel that the amalgams are
safe at this time. A few countries have begun to restrict their use as a precaution.
Methylmalonic Acid
Also known as: MMA
Why get tested?
To help detect early and/or mild vitamin B12 deficiency, especially at the tissue level;
to help diagnose methylmalonic acidemia, a rare inherited metabolic disorder
When to get tested?
If you have a vitamin B12 concentration in the low end of the normal range and/or
have symptoms of neuropathy, such as numbness and tingling in the hands and feet
Sample required?
A blood sample drawn from a vein in your arm or a random or 24-hour urine sample.

The methylmalonic acid (MMA) test is a sensitive and early indicator of vitamin B12
deficiency at the tissue level. MMA is a compound that is usually produced in very
small amounts during amino acid (protein) metabolism. Normally, B12 acts as a
cofactor in the conversion of methylmalonyl CoA to succinyl CoA. If there is not
enough B12 to act as a cofactor, then methylmalonyl CoA concentrations begin to rise
and the body converts the methylmalonyl CoA to MMA instead. This causes MMA
levels to rise in both the blood and the urine when B12 levels are low.
Increased concentrations of MMA are often detectible before the occurrence of the
hematologic changes (for example, anemia and large red blood cells) seen with B12
deficiency. Some patients with MMA elevations may not have any symptoms at all
while others may have neuropathy (numbness and tingling in the hands and feet) or
mental or behavioral changes (confusion, irritability, depression), symptoms that are
often seen with classic B12 deficiency.
The relationship between MMA and B12 has been known for about 40 years, but the
use of MMA testing is not widespread nor is there agreement on its clinical utility.
Some in the medical community think that MMA may be a better measure of
bioavailable B12 than the usual vitamin B12 test because a relatively large amount of
the B12 found in the blood is bound to proteins and not as freely available to act in
chemical processes. Although some health professionals are convinced that MMA and
homocysteine (which may be elevated when either B12 or folate are deficient) are
valuable in detecting early and mild cases of B12 deficiency, others argue that many
of the mild deficiencies detected do not progress to more severe deficiencies and do
not necessarily need to be identified or treated.
How is it used?
MMA primarily is ordered, sometimes along with homocysteine, to help diagnose an
early or mild B12 deficiency. It may be ordered as a follow-up to a vitamin B12 test
for which the result is in the lower end of the normal range.
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Some researchers have suggested using MMA as a screening tool, especially among
the elderly, who frequently have B12 deficiencies and may have few recognizable
symptoms. However, this use is still controversial in the medical community and only
a few doctors are using MMA for this purpose. MMA testing may not be suitable for
monitoring because it is subject to variation and results do not reliably trend up or
down in response to B12 treatment.
Occasionally, MMA may be ordered along with other tests to help diagnose
methylmalonic acidemia, a rare inherited metabolic disorder that occurs in about 1 in
25,000 to 48,000 people. Babies with this disease are unable to convert
methylmalonyl CoA to succinyl CoA. They appear normal at birth but as they ingest
protein, they begin to show symptoms such as seizures, failure to thrive, mental
retardation, strokes, and severe metabolic acidosis.
When is it ordered?
Methylmalonic acid is not ordered frequently. Until there is more data supporting its
use and consensus on its clinical utility and long-term benefits, it will probably not be
routinely used by doctors.
However, MMA may be ordered, sometimes along with a homocysteine test, when a
vitamin B12 test result is in the lower portion of the normal range, especially if the
patient has symptoms associated with B12 deficiency. An MMA test also may be
ordered as a follow-up to an elevated homocysteine level if the two tests are not
ordered together.
Occasionally, MMA may be ordered when a doctor suspects that an acutely ill infant
may have inherited methylmalonic acidemia.
If MMA and homocysteine levels are increased and B12 concentrations are mildly
decreased, then an early or mild B12 deficiency may be present. This may indicate a
decrease in available B12 at the tissue level. (If only homocysteine levels are
elevated, then folate concentrations should be checked). If MMA and homocysteine
levels are normal, it is unlikely that there is a B12 deficiency.
Blood MMA levels also can be increased with kidney disease, which results in
decreased MMA excretion in the urine so MMA accumulates in the blood.
Moderately to severely elevated levels of MMA may be seen in infants with the rare
inherited disease methylmalonic acidemia.

An elevated MMA test may indicate a B12 deficiency, but the amount of MMA
measured does not necessarily reflect the severity of the deficiency, its likelihood of
progressing, or the presence or severity of any symptoms.
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Some studies have found a high variation in MMA levels when they are measured
over time.
1. If I have an elevated MMA, why might my doctor hesitate to diagnose me with
vitamin B12 deficiency?
If your B12 test result is in the lower end of the normal range and you do not have
significant symptoms, your doctor may feel that you have adequate B12 and will rely
on these findings rather than on the elevated MMA. This may be especially true if
your homocysteine level is normal. Your doctor may be reluctant to start you on
lifelong treatment with B12 injections and/or oral supplementation unless he feels it is
truly necessary.
2. Can either blood or urine be used for the MMA test?

In most cases, it is okay to use blood or urine for this test. Sometimes, your doctor
may want to test both your blood and urine in order to compare the MMA results.
Since homocysteine is a blood test, it may be more efficient to draw blood for both
the MMA and homocysteine tests when they are ordered together.
Mono
Also known as: Mononucleosis spot test, Mononuclear heterophile test, Heterophile
antibody test, Monospot
Formal name: Heterophile antibody titer
Why get tested?
To get screened for mononucleosis
When to get tested?
If you have symptoms of mononucleosis, including fever, sore throat, swollen glands,
and fatigue
The mono test detects heterophile antibodies, which are made by the body in response
to an infection by Epstein-Barr virus (EBV). EBV is very common. According to the
National Center for Infectious Diseases (NCID), as many as 95% of people in the
United States will have been infected by EBV by the time they are 40 years old. It is
spread from person to person through the saliva during close contact. Most of the
time, the infection occurs in childhood and causes few or no symptoms, but when it
first occurs in adolescence, it can cause infectious mononucleosis (mono) in about
half of those infected. Although anyone can have mono, most cases of it are found in
adolescence and its prevalence is highest in populations of young people, such as are
found at high schools, colleges, or in the military.
Mononucleosis is usually a self-limiting condition. It is characterized by the presence
of atypical white blood cells (usually reported as reactive lymphocytes), heterophile
antibodies, and EBV antibodies in an infected person. Patients who have mono
typically have a fever, sore throat, swollen glands, and fatigue. Many will also have
an enlarged spleen and a few may have an enlarged liver. Symptoms of the infection
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usually arise about one month after infection and may last for several weeks. The
associated fatigue may last for several months.
About 70%–80% of patients with mono produce heterophile antibodies. These
proteins are not specific for EBV but, when found in adolescents in conjunction with
mono symptoms, are a good screen for EBV infection.
How is it used?
The mono test is used to help determine whether a patient has infectious
mononucleosis. It is frequently ordered along with a CBC (complete blood count).
The CBC is used to determine whether the number of white blood cells (WBCs) is
elevated and whether a significant number of reactive lymphocytes (a type of WBC)
is present. A strep test may be ordered with the mono test to determine whether a
person’s sore throat is due to a streptococcal infection instead of or in addition to
mononucleosis.
If the mono test is initially negative but the doctor still suspects mono, he may order a
repeat test in a week or so to see if heterophile antibodies have developed and/or order
EBV antibodies to help confirm or rule out the presence of a current EBV infection.
When is it ordered?
The mono test is primarily ordered when an adolescent patient has symptoms such as
fever, headache, swollen glands, and fatigue that the doctor suspects are due to
infectious mononucleosis. The test may be repeated when it is initially negative but
suspicion of mono remains high.
If a patient has a positive mono test, an increased number of white blood cells,
reactive lymphocytes, and symptoms of mononucleosis, then they will be diagnosed
with infectious mononucleosis. If symptoms and reactive lymphocytes are present but
the mono test is negative, then it may be too early to detect the heterophile antibodies
or the affected patient may be in the small number of people who do not make
heterophile antibodies. Other EBV antibodies and/or a repeat mono test may be
performed to help confirm or rule out the mononucleosis diagnosis.
Most infants and young children will not make heterophile antibodies, so they will
have negative mono tests even when infected with EBV. This population is rarely
tested, however, because they do not usually have symptoms of infectious
mononucleosis.
Patients with negative mono tests and few or no reactive lymphocytes may be infected
by another microorganism that is causing mono-like symptoms (such as a
cytomegalovirus (CMV) or toxoplasmosis). If the infection occurs during pregnancy,
it can be important to determine the cause, as some of the mono-like infections (but
not EBV infection) have been associated with pregnancy complications and damage
to the fetus. It is also important to identify strep throat, whenever present, because it
should be treated promptly with antibiotics.
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The mono test is rapid and easy to perform, but it is specific for heterophile
antibodies, not EBV. It can also be positive in patients with lymphoma, systemic
lupus erythematosus (lupus), and some gastrointestinal cancers (although it is not used
as a diagnostic or screening tool in these patients).
When the mono test is negative and/or the doctor wants to obtain more information
about the presence and status of an EBV infection, he may order one or more of a
combination of EBV antibodies. These tests can indicate whether a person is
susceptible to EBV, has had a recent infection, has had EBV infection in the past, or
has a reactivated EBV infection.
Heterophile antibodies decline after the fourth week of illness, and the mono test will
become negative as the infection resolves.
1. How serious is a case of infectious mononucleosis?
The symptoms of the disease usually resolve without treatment in one to four months.
Sometimes, your spleen or liver may enlarge, and you may have to limit your activity
until these organs return to normal size. Heart problems or involvement of the central
nervous system occur only rarely. Infectious mononucleosis may cause severe liver
failure in males with a special XLP gene. In this rare case, mononucleosis can be
fatal.
2. Is mononucleosis really a “kissing disease”?

The spread of EBV requires intimate contact with the saliva (found in the mouth) of
an infected person. Kissing does not have to occur for infection to arise, however.
Saliva on water bottles, toothbrushes, drinking glasses, etc. or hands also can transmit
the virus. Transmission of this virus through the air or blood does not normally occur.
The incubation period, or the time from infection to appearance of symptoms, ranges
from 4 to 6 weeks.
People who have infectious mononucleosis may be able to spread the infection to
others for a period of weeks. Many healthy people can carry and spread the virus
intermittently for life, and testing them for the virus is not practical. For this reason, it
is almost impossible to prevent spreading the virus.
3. Does the Epstein-Barr virus cause chronic fatigue syndrome?
There is no laboratory evidence indicating that EBV infection causes chronic fatigue
syndrome. For more information, visit the Centers for Disease Control and
Prevention's website.
4. Can I get infectious mononucleosis more than once?
Although the symptoms of infectious mononucleosis usually go away in 1 or 2

months, EBV remains inactive in a few cells in the body for the rest of the person's
life. Periodically, the virus can reactivate, and it is commonly found in the saliva of
infected persons. This reactivation usually occurs without symptoms of illness.
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5. Can EBV cause other serious illnesses?
EBV has been linked to certain cancers, such as Burkitt’s lymphoma, Hodgkin’s
disease, nasopharyngeal carcinoma, and AIDS-related lymphoma, and continues to be
studied for possible linkages to other cancers. The incidence of these diseases is rare,
and cases of Burkitt’s lymphoma and nasopharyngeal carcinoma occur predominantly
outside of the United States.
Myoglobin
Why get tested?
To determine whether muscle, particularly heart muscle, has been injured
When to get tested?
Every 2-3 hours for the first several hours after experiencing chest pain that is
suspected to be a heart attack; rarely ordered alone these days as a cardiac biomarker
but ordered with troponin instead to help rule out a heart attack
Blood is being tested for the presence of myoglobin, which is a small protein found in
heart and other muscles. While hemoglobin brings oxygen to most of the body,
myoglobin traps oxygen in muscle to allow muscle cells to work properly. When heart
or other skeletal muscle is injured, myoglobin is released into the blood. It is one of
the first cardiac biomarkers to rise in the blood after a heart attack.
How is it used?
As a cardiac biomarker, myoglobin is used in conjunction with troponin and other
tests to help rule out a heart attack. Myoglobin levels start to rise within 2-3 hours of a
heart attack or other muscle injury, reach their highest levels by about 8-12 hours, and
generally fall back to normal by about one day after injury occurred. Consequently,
myoglobin testing is used to help rule out a heart attack in emergency room situations.
When is it ordered?
Because of the high confidence in the troponin test, many physicians do not order
myoglobin. When it is ordered, it is ordered with troponin to assess persons with chest
pain who are suspected of having a heart attack. Myoglobin levels are often used
every 2-3 hours for the first several hours after a patient who has chest pain comes to
the emergency room.
When myoglobin rises, this means that there has been very recent injury to the heart
or other muscle tissue. If myoglobin does not increase after about 5 hours, a heart
attack is very unlikely, unless the chest pain started more than a day before.
Because myoglobin is also found in other muscles, high levels usually require using
other tests (such as CK–MB or troponin) to tell whether the damage was to heart or to
other skeletal muscle. High levels can occur in accidents, seizures, surgery, or any
muscle disease, such as muscular dystrophy.
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Increased myoglobin levels can occur after muscle injections or strenuous exercise.
Because the kidneys remove myoglobin from the blood, myoglobin levels may be
high in persons whose kidneys are failing. Rarely, heavy alcohol abuse and certain
drugs can cause muscle injury and increase myoglobin.
this is myocardial infarction. Most commonly, a heart attack starts with a kind of
sweat.
arteries of the heart (coronary artery disease or CAD).
Chest pain that occurs during exercise, hard work, or at times of stress, lasts for a few
minutes and goes away with rest is called angina. If the pain lasts longer than just a
few minutes, especially if it occurs when you are resting, seek immediate medical
attention.

having a heart attack. Troponin can pick up damage to heart muscles even when there
is no other evidence of a heart attack. Myoglobin and creatine kinase, two other
proteins found in the heart and in other muscles, do not usually rise in persons with
heart injury unless a heart attack has occurred. Some doctors use the term “mild heart
attack” if troponin is high but one or both of the other muscle proteins are not.

the pain, seek immediate medical attention. Many people who have had a heart attack
die without ever having tried to call an ambulance or get to an emergency room.
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5. Is myoglobin useful to evaluate a stroke, too?
A stroke, sometimes called a “brain attack,” occurs when part of the brain dies. Like a
heart attack, it usually is due to a blockage of one of the blood vessels that brings
blood to the brain. Myoglobin is only found in muscle cells, not in the brain, so it is
not helpful in evaluating a person who may have had a stroke.
O&P
Formal name: Ova and Parasite Exam
Why get tested?
To determine whether you have a parasite infecting your gastrointestinal tract
When to get tested?
When you have diarrhea that lasts more than a few days and/or have blood or mucous
in your loose stools, especially if you have drunk stream or lake water while camping
or have traveled outside of the United States.
Sample required?
A fresh or preserved stool sample, sometimes multiple samples collected on different
days.
An ova and parasite (O&P) exam is a microscopic evaluation of a stool sample. It is
used to look for parasites that have infected the gastrointestinal tract. These parasites
and their ova (eggs, cyst form) are shed - passed out of the body through the feces.
When thin smears of stool are put onto glass slides and put through a staining process,
the parasites and ova can be detected and identified under the microscope. Different
ova and parasites have different shapes, sizes, and internal structures that are
characteristic of their species.
There are a wide variety of parasites that can infect humans. Each type of parasite has
a particular life cycle (maturation process) and a place that it is adapted to live in.
Some spend time in an intermediate host (such as a sheep, cow, or snail) before
infecting humans, some infect humans “by accident”, and some are not picky about
who or what they infect. Most parasites have an adult form and a cyst/egg/ova form.
Some also mature through a larval phase. Those parasites that infect the
gastrointestinal tract are passed out of the body through the feces. The parasite ova are
hardy, they can exist in the environment for some time without a host.
Most people who are infected by parasites become infected by drinking water or
eating food that has been contaminated with the ova. This contamination cannot be
seen - the food and water will look, smell, and taste completely normal. Since an
infected person’s stool is also infectious, without careful sanitation (handwashing and
care with food preparation) they may pass the infection on to others. This is especially
a concern with infants at day care centers and the elderly in nursing homes. Not only
is a parasitic infection easily passed in these populations, but also the immune systems
of those infected may be less effective at getting rid of the infection.
The most common parasites in the United States are three single cell parasites:
Giardia lamblia, Entamoeba histolytica (E. histolytica), and Cryptosporidium parvum.
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They are found in mountain streams and lakes throughout the world and may infect
swimming pools, hot tubs, and occasionally community water supplies.
Cryptosporidium (called crypto), resists chlorine and can live for several days in
swimming pools. They can be removed from the water supply, however, with
adequate filtration. Most parasitic infections in the U.S. are due to these parasites, but
other more worm like parasites such as a roundworms or tapeworms do occasionally
cause infections.
Those that travel outside the U.S., especially to developing nations, may be exposed
to a much wider variety of parasites. In warm climates and places where water and
sewage treatment are less effective, parasites are often much more prevalent. Besides
giardia, crypto, and E. histolytica, there are also a wide range of flat worms,
roundworms, hookworms, and flukes. Visitors usually become infected by eating or
drinking something that has been contaminated with the parasites’ ova (even
something as simple as ice cubes in a drink, or a fresh salad) but some of the parasites
can also penetrate the skin.
The most common symptoms of a parasitic infection are prolonged diarrhea, bloody
diarrhea, mucous in stool, abdominal pain, and nausea. Patients may also have
headaches and fever, and will sometimes have few, or no noticeable symptoms.
How is it used?
The O&P test is used to help diagnose prolonged diarrhea. It is ordered to determine
whether there are parasites present in the gastrointestinal tract and if so, to identify
them. Since there are many other causes of diarrhea, the O&P is often ordered along
with other tests, such as a stool culture (which identifies the presence of pathogenic
bacteria in the stool). Classically, O&P tests were ordered in multiples, such as 3
samples from 3 different bowel movements, often on separate days. This was
considered to be the best way to detect what might be small amounts of ova in the
stool (better chance of not missing an infection). Many physicians now order a single
O&P, following it with additional tests if they feel it is necessary. Your doctor may
also order a giardia, cryptosporidium, or E. histolytica antigen test if they suspect that
one of these parasites may be causing your diarrhea. These tests detect protein
structures on the parasites and can identify an infection, even if no actual parasites or
ova are seen in the stool. They are not replacements for the O&P, however, as they
only test for a particular parasite. The O&P will allow the identification of whatever
parasite may be present.
O&P tests may also be ordered to monitor the effectiveness of treatment for a
parasitic infection.
When is it ordered?
When you have prolonged diarrhea, abdominal pain, and/or blood and mucous in your
stool. When you have symptoms, and have recently traveled outside the U.S., drunk
stream or lake water while camping, or been exposed to someone who has a parasitic
infection (like a family member).
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O&P tests may also be ordered when you have had a parasitic infection, to monitor
the effectiveness of treatment.
If there are no ova or parasites seen, your diarrhea may be due to another cause. There
may also be too few parasites to detect. Your doctor may want to order additional
O&P tests and/or may order other tests to search for the cause of your symptoms.
If a parasite is identified, then you do have a parasitic infection. The type and duration
of treatment will depend on what kinds of parasite(s) are found and on your general
state of health. The number of parasites seen may give your doctor general
information about how heavy or extensive your infection is.

If diarrhea lasts more than a few days it may lead to dehydration and electrolyte
imbalance, dangerous conditions in children and the elderly. They cannot afford to
lose large amounts of fluid.
Drug therapies are usually used to treat giardia and E. histolytica infections. They
may resolve themselves after several weeks but they may also cycle, with symptoms
subsiding, then worsening again. There is no effective treatment for cryptosporidium.
In those with competent immune systems, crypto generally goes away after a few
weeks. In those with compromised immune systems (such as those with HIV/AIDS,
organ transplant, cancer, etc.), however, crypto may be dangerous, becoming chronic
and causing wasting and malnutrition.
Parasitic infections are monitored on a community level. Other than travel related
cases, health officials want to try to determine where your infection came from so that
they can address any potential public health concerns. For instance, if crypto or
giardia is due to contaminated swimming pool water or community water supply,
steps will need to be taken to prevent the spread of the infection.
1. How can I prevent a parasitic infection?

The best way is to avoid food and water that is suspected of being contaminated. This
is especially true if you travel to developing nations, where ice in a drink or a dinner
salad may expose you to parasites. But the clearest mountain stream should also be
suspect, it could be contaminated with giardia. You cannot see most parasites, you
won’t be able to smell them or taste them in the water. If someone in your family has
a parasitic infection, careful handwashing after going to the bathroom can help
prevent passing the parasite on to others.
2. Will an O&P detect all parasites?

No, only those that live in the intestines and whose eggs are passed thorough the
feces. There are other tests specific for other parasites, such as those that cause
malaria and pinworms.
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3. Why does it need to be a fresh stool sample?
The eggs and parasites may break down in unpreserved stool, making the condition
harder to detect.
4. Are those parasitic worms I’m seeing in my stool sample?
Usually no. Most of the common parasites are much too small to be seen with the
naked eye. What you are probably noticing are undigested food fibers. The only way
to be sure though is to look at the sample under the microscope. Parasites have a
characteristic structure, including digestive organs, that fibers do not have.
5. Are there other ways to test for parasites?

Yes, antigen tests have been developed for several common parasites including
giardia, cryptosporidium, and E. histolytica. The antigen tests detect protein structures
on the parasite and they can detect the presence of even fragments of the parasite in a
stool sample. This has the advantage of allowing detection of that particular parasite
even if it is not seen in the O&P examination. Blood antibody tests may be ordered to
determine whether or not someone has been exposed to a parasite in the past (this may
indicate a past or a chronic infection but is not used to detect a current infection).
Sometimes a biopsy of the small intestines is taken, a small amount of tissue that is
examined for parasitic infestation.
6. Once I’ve had a parasitic infection, can I be re-infected?

Yes, you do not become immune once you have been infected, and can become re-
infected if exposed again. This may happen if you have a family member who has an
asymptomatic parasitic infection, such as giardiasis. They can continue to re-infect
you until they are treated.
7. Why shouldn’t I take an over the counter anti-diarrhea medicine?

You should only take this on the advice of your doctor. Diarrhea is one of the
methods your body uses to help rid itself of the infection. If you slow down or prevent
this from happening by taking anti-diarrhea medication you can prolong the amount
of time that you are ill and sometimes make your infection worse.
Osmolality
Why get tested?
To help evaluate the body’s water and electrolyte balance and to help investigate
hyponatremia (low sodium) and increased or decreased urine production; to detect the
ingestion of certain toxins (such as methanol); to monitor the effectiveness of
treatment for conditions affecting osmolality; to help determine the cause of chronic
diarrhea
When to get tested?
When a patient has a low sodium level; when a patient is taking mannitol; when a
doctor suspects that a patient may have ingested a toxin such as methanol or ethylene
glycol; when a patient is producing significantly increased or decreased amounts of
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urine; when a patient has chronic diarrhea
Sample required?
A blood sample drawn from a vein in your arm and/or a random urine sample;
sometimes a fresh, liquid stool sample.
The osmolality test is an indirect measurement of the number of particles (solutes) in
a fluid (solvent). It is used to evaluate the water balance in the body and is based on
the principle that changes in the number of solutes result in changes in the physical
properties of the fluid they are in. Water balance in the body is a dynamic process that
is regulated by increasing or decreasing the amount of water coming into the body in
response to “thirst” and by controlling the amount of water excreted in the urine.
Osmotic sensors in the body register and react to increases and decreases in the
amount of water and particles in the bloodstream. When osmolality increases,
indicating either a decrease in the amount of water in the blood or an increase in the
number of particles, the hypothalamus (a tiny gland in the brain) secretes antidiuretic
hormone (ADH), which tells the kidneys to conserve water. This results in a more
concentrated urine (higher urine osmolality) and a more dilute plasma. When
osmolality decreases in the blood, indicating either an increase in the amount of water
in the blood or a decrease in the number of particles, ADH secretion is suppressed and
the kidneys excrete increased amounts of dilute urine (lower urine osmolality). As the
amount of water in the body decreases, plasma osmolality returns to normal.
Serum osmolality primarily measures sodium and urine osmolality primarily
measures the waste products urea and creatinine. Sodium is the major electrolyte in
the blood, urine, and stool. It works with potassium (which is found primarily inside
cells), chloride, and CO2 (in the form of bicarbonate) to maintain electrical neutrality
in the body and acid-base balance. Sodium comes into the body in the diet and is
normally conserved or excreted by the kidneys in the urine to maintain its
concentration in the blood within a narrow range. Urea and creatinine are produced
and removed by the body at a relatively constant rate.
Glucose and urea are not electrolytes, but as particles (molecules) they do contribute
to osmolality. Normally their contributions are small, but when a patient has a high
blood sugar (hyperglycemia, as found in diabetes) or a high blood urea (seen in
diseases such as renal failure), their influence can be significant. Glucose is
osmotically active. It can draw water out of the body’s cells, increasing the amount of
fluid in circulation, which in turn increases the amount of dilute urine produced.
Mannitol, a drug used to treat cerebral edema (excess fluid in the brain), also has this
property. Urea, however, can move into cells; it does not draw water out of them.
Toxins such as methanol, isopropyl alcohol, ethylene glycol, propylene glycol, and
acetone, and drugs such as acetylsalicylic acid (aspirin) can also affect osmolality
when ingested. Osmolality can be measured or calculated from the major solutes
expected to be in the blood. The difference between measured and calculated results is
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called the “osmotic gap.” Toxins, acetylsalicylic acid, and mannitol can be detected as
an increase in the osmotic gap.
How is it used?
The osmolality test is a snapshot of the number of solutes present in the plasma, urine,
or stool. It is ordered to help evaluate the body’s water balance, its ability to produce
and concentrate urine, to help investigate hyponatremia (low sodium level), to detect
the presence of toxins such as methanol and ethylene glycol, and to monitor
osmotically active drug therapies such as mannitol. It is also ordered to help monitor
the effectiveness of treatment for any conditions found.
Plasma osmolality is primarily ordered to investigate hyponatremia. Hyponatremia

may be due to sodium loss through the urine or due to increased fluid in the
bloodstream. Increased fluid may be due to drinking excessive amounts of water,
water retention, decreased ability of the kidneys to produce urine, or the presence of
osmotically active agents such as glucose, mannitol, and glycine (a chemical used in
surgical irrigation fluids). Marathon runners can experience acute hyponatremia by
drinking large quantities of water in a short period of time. In a few cases, this has led
to the death of the runner. People who chronically drink excessive amounts of water,
by choice or due to a psychological condition, may have chronic hyponatremia.
Patients may also appear to have low sodium levels when the percentage of water in
their blood decreases due to the presence of increased proteins or lipids.
Mannitol, glycine, and the ingestion of toxins such as methanol and propylene glycol
can be detected, evaluated, and monitored by ordering an osmotic gap (also called
osmolal gap). This calculation compares measured osmolality with measurements of
the major solutes. The osmotic gap is the difference between them and represents the
presence of an osmotically active substance in the blood. In order to calculate the
osmotic gap, tests for blood sodium, blood urea nitrogen (BUN), and glucose must be
performed. Some versions of the osmotic gap calculation also include the
measurement of ethanol. An example calculation is:
Plasma Osmotic Gap (Ethanol not always included)
2 x (Na+) + (Glucose/18) + (BUN/2.8) + (Ethanol/3.8)
Note: Glucose, BUN, and Ethanol may be reported in mg/dL (milligrams per
deciliter) or mmol/L (millimole per liter). The numbers shown in the equation above
are used to convert from mg/dL to mmol/L.
Urine osmolality is frequently ordered along with plasma osmolality. It is used to

help evaluate the body’s water balance and to investigate increased and decreased
urine output. Increased urine output may be due to increased fluid intake, lack of
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appropriate amounts of ADH, or diabetes mellitus (increased glucose levels leading to
increased urine output). Decreased urine output may be due to a variety of causes
including decreased blood flow to the kidneys, an appropriate response to
dehydration, or damage to tubular cells in the kidneys. Urine sodium and creatinine
are often ordered along with urine osmolality. Sometimes a urine osmotic gap is
calculated and used to help evaluate the kidney’s ability to excrete acid and reabsorb
bicarbonate, to detect the presence of osmotically active molecules, and to compare
with the plasma osmotic gap.
Stool osmolality may sometimes be ordered to help evaluate chronic diarrhea that
does not appear to be due to a bacterial or parasitic infection or to another identifiable
cause such as intestinal inflammation or damage. Patients with watery chronic
diarrhea may have an osmotically active substance (such as a commercial laxative)
that is inhibiting the reabsorption of water by the intestines. Sometimes a stool
osmotic gap is calculated.
When is it ordered?
A plasma osmolality test and osmotic gap may be ordered when a patient has
symptoms such as thirst, confusion, nausea, headache, lethargy, seizures, or coma that
the doctor suspects may be due to hyponatremia or the ingestion of a toxin such as
methanol or ethylene glycol. A urine osmolality test may be ordered along with
plasma testing when the doctor wants to compare urine results with the plasma
osmolality and/or when the patient is producing increased or decreased quantities of
urine. Both may be ordered when a doctor suspects that the patient may have diabetes
insipidus (a condition characterized by the inability to concentrate urine due to a lack
of ADH). Osmolality testing may be ordered on asymptomatic patients with
unexplained hyponatremia when a low sodium is discovered during testing for other
reasons. Plasma and urine osmolality testing may be ordered frequently to monitor the
effectiveness of treatment for these conditions and at regular intervals to monitor
patients taking mannitol.
Stool osmolality may be ordered when the doctor suspects that a patient’s chronic
diarrhea may be due to an osmotically active substance.
Osmolality is dynamic and will fluctuate as the body responds to and corrects
temporary water imbalances. Plasma and urine osmolality tests must be evaluated in
the context of the patient’s clinical presentation and along with the findings of other
tests, such as sodium, glucose, and BUN. Osmolality results are not diagnostic; they
suggest that a patient has an imbalance but they do not pinpoint the cause.
In general, if a patient has an increased plasma osmolality, it is due to either decreased

water in the blood or increased solutes. If they have decreased plasma osmolality, it is
due to increased fluid levels. When a patient has an increased osmotic gap and is
suspected of ingesting a toxin such as methanol, then it is likely that they have, with
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the size of the gap related to the amount of toxin. During monitoring, if osmolality,
the osmotic gap, and findings such as a low sodium level return to normal, then
treatment has been effective. With mannitol therapy, the monitoring goal is the
maintenance of a stable “therapeutic” osmotic gap and the relief of cerebral edema.
Plasma osmolality may be increased with:
 dehydration
 diabetes insipidus
 hyperglycemia (high glucose)
 hypernatremia (high sodium)
 ingestion of ethanol, methanol, or ethylene glycol
 kidney damage
 mannitol therapy
 shock
Plasma osmolality may be decreased with:
 excess hydration
 hyponatremia
 inappropriate ADH secretion
When a patient has increased urine output and a low osmolality, then they are either
ridding their body of excess fluids or unable to concentrate urine appropriately (which
may be due to diabetes insipidus, a lack of ADH). If they have increased urine output
and a high osmolality, then it may be due to diabetes mellitus. If a patient has
decreased urine output and high osmolality, they may be dehydrated; if they have low
or normal osmolality, they may have kidney damage.
Urine osmolality may be increased with:
 congestive heart failure

 hypernatremia
 inappropriate ADH secretion
 liver damage
 shock
Urine osmolality may be decreased with:
 diabetes insipidus
 excess fluid intake
 hypercalcemia (high calcium)
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 hypokalemia (low potassium)
 kidney tubular damage
If a patient has an increased stool osmolality gap, then it is likely that an osmotically
active substance is causing their chronic liquid diarrhea. This can be seen with
malabsorption and laxative abuse.

Stool samples for osmolality testing must be liquid, fresh (refrigerated or frozen
within about 30 minutes of collection), and uncontaminated with urine. Bacteria in the
stool can change the results of the test within a short period of time.
A calculation is sometimes ordered for “free water clearance” to help evaluate the
ability of the kidney tubules to appropriately concentrate and dilute urine. When urine
osmolality is about the same as plasma osmolality, then free water clearance is zero.
When blood volume decreases and urine is concentrated, then free water clearance
will be negative. When fluid levels are increased and urine is dilute, then free water
clearance will be positive.
p24 Antigen
Why get tested?
To check for infection with HIV after a recent exposure or to monitor your body’s
response to anti-HIV therapy
When to get tested?
If you have been recently exposed to HIV
The p24 test identifies actual HIV viral particles in blood (p24 is a protein found in
HIV). However, the p24 test is generally only positive from about one week to 3 - 4
weeks after infection with HIV. The p24 protein cannot be detected until about a
week after infection with HIV because it generally takes that long for the virus to
become established and multiply to sufficient numbers that they can be detected. The
p24 proteins then become undetectable again after sufficient antibodies to HIV have
been produced because they bind to the p24 protein and eliminate it from the blood.
Once antibodies are produced, the p24 test will register negative even in people who
are infected with HIV. At that point, the regular HIV antibody test will then be
positive. Later in the course of HIV, p24 protein levels again become detectable.
How is it used?
p24 testing may be used to detect early HIV infection and to screen donated blood for
HIV. Since p24 levels rise and fall with HIV levels, the test may also be used to
monitor anti-HIV therapy and to evaluate disease progression. The advantages of the
p24 test are that it can detect HIV infection days earlier, before antibodies develop,
and that it is a quantitative test that tells the intensity of HIV expression in the body,
which is a measure of how fast the disease is progressing.
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When is it ordered?
A p24 test may be ordered if you have been recently exposed to HIV and wish to
know your HIV status. It may also be ordered if you are donating blood or if you
already have HIV and your doctor wants to monitor your response to therapy or to
determine if HIV is progressing into AIDS.
A positive result means that you are infected with HIV: the more p24 protein, the
higher the amount of HIV in your blood.
The p24 test is one of the earlier tests developed to detect HIV infection. Because p24
is only detectable during a short window of time, its utility is limited. However, this
test can still be used when other tests are unavailable.
Pap Smear
Why get tested?
To screen for cervical cancer and certain vaginal or uterine infections
When to get tested?
If you are a woman over the age of 18 and/or sexually active; annually or as advised
by your doctor
Sample required?
Cells from the cervical area.
A Pap smear is a test used to detect abnormal or potentially abnormal cells from the
vagina and uterine cervix. Various bacterial, fungal, and viral infections of the uterus
may also be detected using this test.
The conventional method consists of sampling cells from the cervical area. The
sample is obtained using a type of wooden “spatula,” cotton swab, or brush.
Relatively new liquid-based methods are available that are modifications of the
conventional Pap smear. The specimen is collected as noted above, but is not
“smeared” onto a glass slide. Rather, it is put into a special liquid preservative. This
cell suspension is processed onto a glass slide, stained, and examined.
How is it used?
Your doctor or health provider performs a Pap smear to look for cervical and/or
vaginal cells that are cancerous or could be potentially pre-cancerous. The smeared
cells or cell suspension is placed on a glass slide, stained with a special dye (Pap
stain), and viewed under a microscope by a cytotechnologist or pathologist. The Pap
test can also be used to detect vaginal or uterine infections. This allows infections to
be treated promptly, thus avoiding further discomfort or more serious complications.
When a Pap smear is ordered, an HPV DNA test also may be requested for women
over the age of 30.
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When is it ordered?
Different organizations have varying opinions on the appropriate frequency of Pap
testing (see Screening: Cervical Cancer (ages 18-29), (ages 30-49), (ages 50 and up).
For example, the American Cancer Society recommends that women over the age of
18 and/or those sexually active have an annual Pap smear. In other situations, a Pap
smear may be ordered if a woman has frequent sexual partners, is pregnant, or has
abnormal vaginal bleeding, pain, sores, discharge, or itching. After three consecutive
normal Pap smears, it may be performed less frequently or as your doctor deems
appropriate. The American College of Obstetricians and Gynecologists (ACOG)
issued guidelines in August 2003 recommending that women 30 years of age or older
be offered the option of having an HPV DNA test along with the Pap smear. If both
are negative, testing may be performed less frequently.
A "negative" Pap smear means the cells obtained appear normal, or there is no
identifiable infection. In some instances, the conventional Pap smear may be reported
as "unsatisfactory" for evaluation. This may mean that cell collection was inadequate
or that cells could not be clearly identified. A summary of other reported results
follows. [See also the sidebar on the 2001 Bethesda System for classification of Pap
smear results.]
 Unsatisfactory: inadequate sampling or other interfering substance.

 Benign: non-cancerous cells, but smear shows infection, irritation, or normal
cell repair.
 Atypical cells of uncertain significance: Abnormal changes in squamous cells
(ASCUS) or glandular cells (AGCUS) for which the cause is undetermined.
An ASCUS test result is frequently followed-up with DNA testing to identify
the presence of a high-risk infection with Human Papilloma Virus (HPV).
 Low-Grade changes: infection with HPV, which in some instances can be a
risk for cervical cancer. This test result may sometimes be followed-up with
DNA testing to identify the presence of a high-risk HPV infection.
 High-Grade changes: very atypical cells that may result in cancer.
 Squamous cell carcinoma: cancer is evident and requires immediate attention.

The Pap smear is generally used as a screening test. A small percentage of
abnormalities in women may go undetected with a single Pap smear, which is why it
is important to take Pap smears regularly. The most common errors are those made in
collecting the sample. The Pap smear represents a very small sample of cells present
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in the vaginal area. Even for the most experienced physician, sample collection can be
occasionally inadequate and a repeat Pap may be required.
The Pap smear, when performed routinely, has been a great help in the early detection
of cervical cancer, which is treatable if caught at an early stage. The Pap smear is also
used to monitor any abnormalities or unusual findings. In many cases, these findings
are part of a body's repair process and often resolve themselves without any further
treatment. If you douche, tub-bathe, or use vaginal creams 48 - 72 hours prior to the
examination, your test results might be "unsatisfactory." Other factors that may alter
results include bleeding (menstruation), infection, drugs (such as digitalis and
tetracycline), or having sexual relations within 24 hours prior to examination.
In these cases, a repeat Pap smear may be necessary but does not necessarily mean
there is a significant problem. In some instances, the use of the liquid-based
techniques may eliminate some of the obscuring materials (blood and mucous) that
may prevent a clear and uncluttered presentation of cervical cells. A second advantage
is that the same sample may be used to perform additional testing for HPV if
appropriate.
1. What are the risk factors for cervical cancer?

High risk factors include the age at which sexual intercourse begins (the earlier, the
higher the risk), the number of sexual partners (the greater the number, the higher the
risk), infrequent PAP smears, cigarette smoking, medical history of DES exposure,
and the presence of sexually transmitted disease (examples are Human Papilloma
Virus [HPV], herpes, HIV).
2. Does an abnormal Pap smear always mean cancer?

A single “abnormal” Pap smear does not necessarily indicate that cancer is present.
The membranes in the cervix undergo constant changes and repair. While treatment
may not be necessary, the situation should be monitored closely. This may require a
repeat Pap smear every three to six months until the situation is resolved.
3. If I have cervical cancer, what are my treatment options?

Cervical cancer is a slow, progressive disease and may take years to progress beyond
the cervix. It is because of this fact that regular gynecologic examinations offer the
best opportunity to detect this type of cancer early. Treatment includes a minimally
invasive surgery of the cervix (terms your physician may use are LEEP, conization,
cold-knife, or cryotherapy) which removes pre-cancer or very early stage cancer
tissue. In more advanced cervical cancers, a hysterectomy may be performed. If the
cancer spreads to other tissues (metastasizes), radiation therapy may be required and,
in some instances, additional surgery may be needed.
4. What is the difference between a Pap Smear and the DNAwithPap™ test?
DNAwithPap™ is a trademarked name for a test that combines in a single kit the Pap
smear with a DNA test for high-risk strains of HPV that have been associated with a
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higher risk of cervical cancer in women over the age of 30. Both tests use a sampling
of cells from a woman's cervix.
Phosphorus
Why get tested?
To evaluate the level of phosphorus in your blood and to aid in the diagnosis of
conditions known to cause abnormally high or low levels
When to get tested?
As a follow-up to an abnormal calcium level, if you have a kidney disorder or
uncontrolled diabetes, and if you are taking calcium or phosphate supplements.
The serum phosphorus test measures the amount of phosphate in your blood.
Normally, only a very small amount of phosphate (in the form of inorganic
phosphate) is present in the blood.
In the body, phosphorus exists as a mineral; it is combined with oxygen to form a
variety of phosphates (PO4). Phosphates are vital for energy production, muscle and
nerve function, and bone growth. They also play an important role as a buffer, helping
to maintain the body’s acid-base balance. About 70% to 80% of the phosphates are
combined with calcium to help form bones and teeth, about 10% are found in muscle,
and about 1% is in nerve tissue. The rest is found within cells throughout the body,
where it is mainly used to store energy; about 1% of total body phosphorus is found
within plasma (the liquid part of blood).
Most phosphorus in the body comes from dietary sources. A variety of foods, such as
beans, peas and nuts, cereals, dairy products, eggs, beef, chicken, and fish contain
small amounts of phosphorus. The body maintains phosphorus/phosphate levels in the
blood by regulating how much it absorbs from the intestines and how much it excretes
from or conserves in the kidneys.
How is it used?
Phosphorus testing is very important in people who are malnourished or who are
being treated for ketoacidosis. Phosphorus testing is used to help diagnose and
evaluate the severity of conditions and diseases that affect the gastrointestinal tract,
interfering with the absorption of phosphorus, calcium, and magnesium. Testing also
can help to diagnose disorders that affect the kidneys, interfering with mineral
excretion and conservation, and phosphorus levels are carefully monitored in people
with kidney failure.
When a person has a known problem that affects their phosphorus and/or calcium
levels, phosphorus levels may be monitored regularly to determine the effectiveness
of treatment. Usually, it is not a stand-alone test.
While phosphorus levels are most commonly performed on blood samples, timed
urine phosphorus measurements also may be used to monitor phosphorus elimination
by the kidneys.
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When is it ordered?
A phosphorus test is often ordered to help diagnose diseases and conditions that cause
problems with the body’s utilization of calcium. The test may aid in the diagnosis of
problems with hormones, such as parathyroid hormone (PTH), and Vitamin D, which
functions as a hormone, that regulate the body’s calcium level and, to a lesser degree,
phosphorus levels.
Although abnormal phosphorus levels usually cause no symptoms, phosphorus testing
often is performed as a follow-up to an abnormal calcium level and/or related
symptoms, such as fatigue, muscle weakness, and cramping.
Phosphorus testing may be ordered when symptoms suggest kidney and
gastrointestinal disorders.
If conditions causing abnormal phosphorus and/or calcium levels are found, testing
for both may be ordered at regular intervals to monitor treatment effectiveness.
If you have a kidney disorder, kidney stones, or uncontrolled diabetes, your doctor
may monitor phosphorus levels to make sure that you are not excreting or retaining
excessive amounts.
Dietary deficiencies in phosphorus are rare but may be seen with alcoholism and
malnutrition. Low levels of phosphorus (hypophosphatemia) may also be due to or
associated with:
 Hypercalcemia (high levels of calcium)

 Overuse of diuretics (drugs that encourage urination)
 Severe burns
 Diabetic ketoacidosis (after treatment)
 Hypothyroidism
 Hypokalemia (low levels of potassium)
 Chronic antacid use
 Rickets and osteomalacia (due to Vitamin D deficiencies)
Higher than normal levels of phosphorus (hyperphosphatemia) may be due to or

associated with:
 Kidney failure
 Hypoparathyroidism (underactive parathyroid gland)
 Hypocalcemia (abnormally low levels of calcium)
 Diabetic ketoacidosis (when first seen)
 Phosphate supplementation

Abnormally high levels of phosphorus can lead to organ damage due to calcification
(calcium phosphate deposits in organs, such as the kidneys).
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Phosphate levels are normally higher in children than in adults because their bones are
actively growing. Low phosphate levels in children can inhibit bone growth.
Soft drinks and pre-packaged food items are high in phosphorus content, which some
nutritionists believe contributes to over consumption of phosphorus.
Test results may be impacted by the use of enemas and laxatives containing sodium
phosphate, excess Vitamin D supplements, and by intravenous glucose administration.
1. If there are no symptoms, how will I know if I have abnormal phosphorus
levels?
Abnormal phosphorus levels are usually detected because of the relationship with and
effect on calcium. Calcium is routinely tested as part of the Comprehensive Metabolic
Panel and Basic Metabolic Panel (CMP and BMP), tests that are frequently ordered. If
you have abnormal calcium levels, your doctor usually will check your phosphorus
level.
2. Can vegetarians meet their phosphorus needs without resorting to meat or

dairy?
Yes, but only about 50% of the phosphorus in plant sources such as beans, lentils,
grains, peanuts and almonds is available to the body because we lack the enzymes to
process it. An exception to this is yeast breads because yeast provides the necessary
enzyme.
Plasma Free Metanephrine
Why get tested?
To help diagnose or rule out a pheochromocytoma (tumor of the adrenal gland)
When to get tested?
headaches, rapid heart rate, and sweating.
The plasma free metanephrines test measures the amount of metanephrine and
normetanephrine in the blood. These substances are metabolites (breakdown products)
of epinephrine and norepinephrine. Epinephrine and norepinephrine are
catecholamine hormones that help regulate the flow and pressure of blood throughout
the body and play important roles in the body’s response to stress. They are produced
in the medulla (interior) of the adrenal glands. (Each person has two adrenal glands.
They are small, triangular organs located on top of the kidneys.) The catecholamines
that the adrenal glands create, and their catabolites metabolites (metanephrine and
normetanephrine), are normally found in small fluctuating quantities in both the blood
and urine.
A rare tumor called a pheochromocytoma can produce large amounts of
catecholamines, resulting in significantly increased concentrations of metanephrine
and normetanephrine in both the blood and urine. About 90% of pheochromocytomas
form in the adrenal glands and, while a few are cancerous, most are benign – they do
not spread beyond their original location - although most do continue to grow. The
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catecholamines that pheochromocytomas produce can cause persistent hypertension
(high blood pressure) and/or paroxysms (bouts) of severe hypertension. This can
cause symptoms such as headaches, palpitations, sweating, nausea, anxiety, and
tingling in the extremities. Left untreated, the symptoms may worsen as the
pheochromocytoma grows and, over a period of time, the hypertension that the tumor
causes may damage body organs such as the kidneys and heart and raise the risk of an
affected patient having a stroke or heart attack.
Plasma free metanephrines and urine catecholamines can be used to detect the
presence of pheochromocytomas. Although only about 800 cases a year are diagnosed
in the U.S. (according to the National Cancer Institute), it is important to diagnose and
treat these rare tumors because they cause a potentially curable form of hypertension.
In most cases, the tumors can be surgically removed and/or treated to significantly
reduce the amount of catecholamines being produced and to reduce or eliminate their
associated symptoms and complications.
A blood sample is obtained by inserting a needle into a vein in your arm. Pre-sample
preparation is important for accurate plasma free metanephrine results. Talk to your
doctor about your diet and any medications you are taking. You should discontinue
epinephrine and epinephrine-like drugs for at least one week before the test, stop
using acetaminophen 48 hours before, and be fasting (no food or liquids except water
for about 8 to 10 hours prior to collection). It is especially important not to have any
caffeine, coffee (including decaf), tobacco, tea, or alcohol for at least four hours
before specimen collection. Although there is some disagreement over the specifics of
how the sample should be collected, at the collection site, you may be asked to lie
down and rest quietly for 15 – 30 minutes prior to sample collection, and your blood
may be collected while you are lying down. In other circumstances, you may just be
seated upright with little or no rest time before the sample collection.
How is it used?
Plasma free metanephrines is a relatively new test and there is not yet widespread
consensus on exactly how it should be used. Studies have shown that plasma testing is
more sensitive than the more traditional 24-hour urine catecholamines testing.
However, this sensitivity brings with it a certain number of false positive results,
especially when the test is ordered on patients who do not have a high likelihood of
having a pheochromocytoma. For this reason, plasma free metanephrines is not
recommended as a screen for the general public. Its primary use is to screen
symptomatic patients to detect and to help rule out the likely presence of a
pheochromocytoma. Since both blood and urine test results may be affected by stress,
caffeine, alcohol, and certain drugs, a doctor may investigate a positive result by
evaluating a patient’s stresses and intake, alter or minimize these influences, and then
repeat the test to confirm the original findings.
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Occasionally, the test may be ordered on an asymptomatic person if an adrenal tumor
is detected during a scan that is done for another purpose or if the patient has a strong
personal or family history of pheochromocytomas (as they may recur, and there is a
genetic link in some cases).
When is it ordered?
The plasma free metanephrines test is primarily ordered when a doctor either suspects
that a patient has a pheochromocytoma or wants to rule out the possibility. He may
order it when a patient has persistent or recurring symptoms of hypertension, such as
or when a patient has a family history of pheochromocytomas. It may also be used as

Since the plasma free metanephrines test is very sensitive and pheochromocytomas
are rare, a doctor may see more false positives with this test than true positives. The
negative predictive value of the test, however, is very good. This means that if the
concentrations of the free metanephrines are normal in the blood, then it is very
unlikely that a patient has a pheochromocytoma.
If a symptomatic patient has large amounts of free metanephrines in their blood, then
it is likely that they have a pheochromocytoma. The doctor may order imaging tests
(such as an MRI) to help find the tumor(s). If an asymptomatic patient with a tumor
that has been discovered during a scan for another reason has significantly elevated
free metanephrines, then it is likely that the tumor discovered is a pheochromocytoma.
If a symptomatic or asymptomatic patient has only moderately elevated free

metanephrines, then a doctor may re-evaluate the patient’s medications, diet, and
stress level to look for interfering substances. He may then re-test the patient, perhaps
along with 24-hour urine catecholamine testing, to determine whether the free
metanephrines are still elevated. If they are, then he may order imaging scans; if they
are not, then it is unlikely that the patient has a pheochromocytoma.
If levels are elevated in a patient who has had a previous pheochromocytoma, then it
is likely that either treatment was not fully effective or that the tumor is recurring.
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While the plasma free metanephrines test can help detect and diagnose
pheochromocytomas, it cannot tell the doctor where the tumor is (although the
majority are found in the adrenal gland and most of the rest are found within the
abdominal cavity). It also cannot tell the doctor whether or not the tumor is benign
(although most are).
1. Can I have more than one pheochromocytoma at once?
Yes, especially when there is a strong family history of pheochromocytomas. A
patient may have a tumor in each adrenal gland.
2. Does the amount of plasma free metanephrines detected correspond to the size
of the tumor?
No, it has more to do with the characteristics of the tumor. Even a very small tumor
can produce large amounts of catecholamines.
3. Is it really necessary to follow the dietary restrictions and lie down before
testing?
There is some disagreement over the specifics of how the sample should be collected.
However, it is known that the level of catecholamines (and their metabolites) in the
blood is affected by diet and stress levels. For test accuracy, interfering substances
need to be avoided and the patient’s physical and emotional stress levels should be as
low as possible.
Platelet Count
Why get tested?
To diagnose a bleeding disorder or a bone marrow disease
When to get tested?
As part of a regular complete blood count (CBC) or to diagnose/monitor a bone
marrow/blood disease.
Platelets (thrombocytes) are tiny fragments of cells made in the bone marrow (derived
from megakaryocytes) that circulate in the blood. Because they are very sticky, they
are the first components to be activated when there has been an injury to a blood
vessel and begin the formation of a “blood clot.” The platelet count is a test that
determines the number of platelets in your blood.
How is it used?
Bleeding disorders or other bone marrow diseases, such as leukemia, require the
determination of the number of platelets present and/or their ability to function
correctly.
When is it ordered?
A platelet count is often ordered as a standard part of a complete blood count, which
may be done as part of an annual physical examination. It is almost always ordered
when a patient has unexplained bruises or takes what appears to be an unusually long
time to stop bleeding from a small cut or wound.
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In an adult, a normal count is about 150,000 to 450,000 platelets per microliter (x 10–
6
/Liter) of blood.
If platelet levels fall below 20,000 per microliter, spontaneous bleeding may occur
and is considered a life-threatening risk. Patients who have a bone marrow disease,
such as leukemia or other cancer in the bone marrow, often experience excessive
bleeding due to a significantly decreased number of platelets (thrombocytopenia).
Low number of platelets may occur in some patients with long-term bleeding
problems (e.g., chronic bleeding stomach ulcers), thus reducing the supply of
platelets. Individuals with an autoimmune disorder (such as lupus or Idiopathic
Thrombocytopenia Purpura [ITP], where the body’s immune system creates
antibodies that attack its own organs) can cause the destruction of platelets. Certain
drugs, such as heparin, quinidine, sulfa drugs, oral anti-diabetic drugs, and even
alcohol, may cause decreased platelet counts. Patients undergoing chemotherapy may
also have a decreased platelet count. Up to 5% of pregnant women may experience
thrombocytopenia at term.
More commonly (up to 1% of the population), easy bruising or bleeding may be due
to an inherited disease called von Willebrand’s disease. While the platelets may be
normal in number, their ability to stick together is impaired due to a decrease in von
Willebrand’s factor, a protein needed to initiate the clotting process. Many cases go
undiagnosed due to the mild nature of the disease; however, the more severe form can
be devastating.
Increased platelet counts (thrombocytosis) may be seen in individuals who show no

significant medical problems, while others may have a more significant blood
problem called myeloproliferative disorder (abnormal growth of blood cell elements).
Some may have a tendency to bleed due to the lack of stickiness of the platelets, yet in
others, the platelets retain their stickiness but, because they are increased in number,
tend to stick to each other, forming a clump that can get stuck within a blood vessel
and cause damage, including death (thromboembolism).

Living in high altitudes may cause increased platelet levels, as can strenuous exercise.
Decreased levels may be seen in women before menstruation.
Drugs that may cause increased platelet levels include estrogen and oral
contraceptives.
Other inherited disorders caused by defective platelets or decreased/absent proteins

that activate the platelets include Glanzmann’s Throbasthenia, Bernard-Soulier
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disease, Chediak-Higashi syndrome, Wiskott-Aldrich syndrome, May-Hegglin
syndrome, and Down syndrome. The occurrence of these abnormalities, however, is
relatively rare.
1. How are bleeding disorders treated?

The underlying cause of the bleeding must be determined first and treated. Platelet
concentrates may be transfused to increase the number of circulating platelets. In
some the use of steroids may stimulate an increase in platelet production.
2. Are there signs I should pay attention to for symptoms of high or low platelet
levels?
Bruising for no apparent reason, bleeding from the nose, mouth, or rectum also
without obvious injury, or the inability to stop a small wound from bleeding within a
reasonable period of time may indicate a platelet deficiency.
3.Are there risk factors for high or low platelet levels?

Elevated platelet levels can lead to blood clots. The greater danger is bleeding that
will not stop, or continues for an abnormally long time, due to a low platelet count.
Porphyrin Tests
Formal name: Primary tests: Delta-aminolevulinic acid (ALA), porphobilinogen

(PBG), porphyrins
Why get tested?
To help diagnose and sometimes to monitor porphyrias (a group of inherited disorders
involving disturbance in the metabolism of heme, a component of hemoglobin)
When to get tested?
If a patient has symptoms that suggest an acute neurologic/psychiatric porphyria (such
as abdominal pain, tingling in hands or feet, and/or confusion or hallucinations) or a
cutaneous porphyria (such as reddening, blistering, or scarring on sun-exposed skin)
Sample required?
A blood sample drawn from a vein in your arm, a random or 24-hour urine sample,
and/or a stool sample.
Porphyrin tests are assays that are used to help diagnose, and monitor a group of
disorders called porphyrias. Most porphyrin tests detect and measure the by-products
of heme synthesis. Heme is a part of hemoglobin (the protein inside red blood cells
that allows them to transport oxygen) and a number of other proteins. The synthesis of
heme is a step-by-step process that requires the sequential action of eight different
enzymes. If there is a deficiency in one of these enzymes, a bottleneck forms and
precursors build up in the body’s fluids and tissues and are excreted in urine and
feces. Which precursors build up depends on where the bottleneck is.
There are six major porphyrias, and each one is associated with a different enzyme
deficiency. Most porphyrias are inherited in an autosomal dominant fashion, with one
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normal and one affected gene. This results in about a 50% reduction in the activity of
the heme-related enzyme. Enough heme is synthesized to prevent the affected person
from becoming anemic, but a large excess of one or more precursors is produced.
Porphyrias may be classified according to (1) the affected enzyme, (2) the part of the
body where the excess porphyrins are produced (hepatic - associated with the liver or
erythropoietic - associated with red blood cell production), or (3) the signs and
symptoms of the disease (neurological/psychiatric, cutaneous, or both). Those
porphyrias that cause neurological/psychiatric symptoms present with acute attacks
that may last for days or weeks. They are associated with abdominal pain, nausea,
constipation, depression, confusion, hallucinations, and seizures. Attacks may be
triggered by a variety of drugs (such as anticonvulsants, antibiotics, and hormones)
and environmental factors (such as dietary changes, stress, and exposure to toxic
substances). The cutaneous porphyrias are associated with photosensitivity. Sunlight
exposure, even through a glass window, has a toxic effect on the patient’s skin. This
may cause redness, swelling, and a burning sensation in some patients, while in others
it leads to blistering, skin thickening, hyperpigmentation, and in some cases scarring.
Acute attack porphyrias (neurological/psychiatric) include:
 Acute intermittent porphyria (AIP), the most common of the neurological

porphyrias
 Variegate porphyria (VP), which includes both neurological symptoms and
photosensitivity
 Hereditary coproporphyria (HCP), which may present with neurological symptoms,
photosensitivity, or both
Cutaneous porphyrias include:
 Porphyria cutanea tarda (PCT), the most common porphyria; unlike the other
porphyrias, most cases are due to an acquired enzyme deficiency which is triggered
by liver dysfunction.
 Protoporphyria (also called erythropoietic protoporphyria), which typically begins
in childhood or adolescence; sun-exposed skin turns red accompanied by burning and
itching, but scarring is uncommon.
 Congenital erythropoietic porphyria (CEP), a very rare autosomal recessive
disorder; over time, extreme photosensitivity leads to extensive and severe scarring of
light-exposed areas.
In rare cases, a patient may have two different porphyrias, or a homozygous

deficiency of one enzyme that produces a more severe form of porphyria.
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Individual Tests
Clinical laboratories measure porphyrins and their precursors in urine, blood, and
feces. These tests are listed below:
 Delta-aminolevulinic acid (ALA) in urine

 Porphobilinogen (PBG) in urine
 Porphyrins in urine, feces, or blood
 Zinc protoporphyrin (or free erythrocyte protoporphyrin) in red blood cells
Specialized laboratories may offer testing for one or more of the affected enzymes.
The most commonly measured enzyme is porphobilinogen deaminase (PBG-D) in red
blood cells, which tests for patients with acute intermittent porphyria. A few research
laboratories offer genetic testing for specific gene mutations that cause one of the
porphyrias, but this remains primarily a research tool.

The sample collected depends on the porphyrin tests being ordered. It may be one or
more of the following:
 A blood sample obtained by inserting a needle into a vein in the arm

 A random or 24-hour urine collection (urine must be protected from light during
collection)
 A fresh stool sample that is not contaminated with urine or water.
How is it used?
Porphyrin testing is used to help diagnose and sometimes to monitor porphyrias.
Since the symptoms associated with these disorders may also be seen in a variety of
other conditions, testing is also used to help rule out the presence of a porphyria in
someone who presents with neurologic/psychiatric or cutaneous symptoms.
For acute attacks, porphobilinogen (PBG) and urine porphyrins may be ordered on a
random urine sample. If these are abnormal, they are followed by delta-
Aminolevulinic Acid (ALA), PBG, and/or porphyrin testing on a 24-hour urine
sample. Fecal porphyrins may be ordered to help distinguish between VP and HCP.
For cutaneous porphyrias, whole blood and urine porphyrins are the most frequently
ordered tests. They are used to help diagnose a porphyria, and may be used to monitor
a porphyria. Enzyme testing, such as PBG deaminase, may be ordered to help detect
latent porphyrias in family members of a patient with a diagnosed porphyria.
When is it ordered?
Tests for PBG and porphyrins may be ordered on a random urine specimen when a
patient has symptoms that suggest an acute porphyria, such as abdominal pain,
nausea, constipation, peripheral neuropathy (tingling, numbness, or pain in the hands
and feet), muscle weakness, urinary retention, confusion, and hallucinations. When
the initial tests are abnormal, these tests should be repeated on a 24-hour urine
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collection to determine how much PBG, ALA, and porphyrins are being excreted.
Fecal porphyrin testing may be ordered to help distinguish between porphyrias.
Depending upon the patient’s age and symptoms, a test for urine porphyrins and/or
the free erythrocyte protoporphyrin test should be ordered when a patient presents
with blisters, scarring, redness, or other skin lesions in sun-exposed areas. A positive
urine test is followed by analysis of a 24-hour urine collection to determine which
porphyrins are present.
Enzyme testing is most commonly ordered to confirm the diagnosis of acute
intermittent porphyria (porphobilinogen deaminase in red blood cells). This test is
especially helpful in identifying family members of a known patient who have
inherited the disease but have not yet developed signs or symptoms. Some reference
laboratories can measure porphyrins in plasma, bile or other fluids, but this is not
usually necessary to make a diagnosis.
Care must be taken when interpreting porphyrin test results. Some porphyrins or their
precursors may be mildly to moderately elevated in patients with other diseases or
conditions. In addition, levels of ALA, PBG and porphyrins may fall to near normal
levels between acute attacks of a neurologic porphyria. While negative test results
mean that it is unlikely that a patient’s symptoms are caused by a porphyria, positive
initial tests should be confirmed with follow-up testing.
ALA and PBG are significantly increased in most patients with an acute porphyria.
ALA is less specific than PBG, as it may be elevated in other conditions as well.
Specific porphyrins are elevated in each of the porphyrias, and the pattern of elevation
(which porphyrin is elevated in which sample) determines the diagnosis. Urine, blood,
and stool porphyrins may be increased up to several-fold in a variety of other
conditions. Interpretation of the patterns can be difficult, and this should be done by a
physician or laboratory scientist with expertise in the area.
An abnormal enzyme test or the detection of a gene mutation indicates that a family
member has inherited a porphyria. However, enzyme and gene tests cannot determine
whether that individual will develop signs and symptoms of porphyria or, if they do,
how severe it is likely to be. Fortunately, the majority of gene carriers never have an
attack.
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Results seen with specific porphyrias include:
Urine ALA Urine Fecal Red blood cell

and PBG* porphyrins porphyrins porphyrins
Acute intermittent N N
  URO*
porphyria
Variegate N
  COPRO  PROTO,
porphyria
COPRO
Hereditary N
  COPRO  COPRO
coproporphyria
Porphyria curtanea N  N
 URO, 7-
tarda ↑Isocoproporphyri
carboxyl
n
Protoporphyria N N
 PROTO  PROTO
Congenital N
 URO,  COPRO  URO,
erythropoietic
COPRO COPRO
porphyria
N=Normal; up arrow= increased

*May be increased only during acute attack
URO=Uroporphyrins; COPRO-=Coproporphyrins; PROTO=Protoporphyrins
A variety of drugs, alcohol, and other environmental factors such as diets, stress, and
illness, can trigger acute attacks of a neurologic porphyria in those with latent or
inactive disease. By the same token, sun exposure will induce skin lesions in patients
with a cutaneous porphyria. Lifestyle modification to avoid aggravating factors is the
most effective way to minimize the impact of a porphyria.
1. Will latent porphyria affect my health?
In most cases the answer is no, and the porphyria remains dormant. It is important,
however to have your latent porphyria identified if you have a family history so that
your doctor can tailor any medical treatments to avoid drugs and situations that might
trigger your porphyria.
Potassium
Why get tested?
To determine whether your potassium concentration is within normal limits and to
help evaluate an electrolyte imbalance; to monitor chronic or acute hyperkalemia
(high potassium) or hypokalemia (low potassium)
When to get tested?
As part of a routine medical exam, when you have symptoms such as weakness and/or
cardiac arrhythmia, or when an electrolyte imbalance is suspected; at regular intervals
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when you are taking a medication and/or have a disease or condition, such as high
blood pressure or kidney disease, that can affect your potassium level
Potassium is an electrolyte, a positively charged molecule that works with other
electrolytes, such as sodium, chloride, and total carbon dioxide (CO2) to help regulate
the amount of fluid in the body, stimulate muscle contraction, and maintain a stable
acid-base balance. Potassium is present in all body fluids, but most potassium is found
within your cells. Only about two percent is present in fluids outside the cells and in
the liquid part of the blood (called serum or plasma). Because the blood concentration
of potassium is so small, minor changes can have significant consequences. If
potassium levels go too low or too high, your health may be in considerable danger:
you are at risk for developing shock, respiratory failure, or heart rhythm disturbances.
An abnormal concentration can alter the function of neuromuscular tissue; for
example, the heart muscle may lose its ability to contract.
How is it used?
Potassium testing is frequently ordered, along with other electrolytes, as part of a
routine physical. It is used to detect concentrations that are too high (hyperkalemia) or
too low (hypokalemia). The most common cause of hyperkalemia is kidney disease,
but many drugs can decrease potassium excretion from the body and result in this
condition. Hypokalemia can occur if you have diarrhea and vomiting or if you are
sweating excessively. Potassium can be lost through your kidneys in urine; in rare
cases, potassium may be low because you are not getting enough in your diet.
Potassium concentrations may be ordered at regular intervals to monitor drugs that
can cause your kidneys to lose potassium, particularly diuretics (water pills), resulting
in hypokalemia. Monitoring may also be done if you have a condition or disease, such
as acute or chronic kidney failure, that can be associated with abnormal potassium
levels.
When is it ordered?
Serum or plasma tests for potassium levels are routinely performed in most patients
when they are investigated for any type of serious illness. Also, because potassium is
so important to heart function, it is usually ordered (along with other electrolytes)
during all complete routine evaluations, especially in those who take diuretics or heart
medications. Potassium is ordered when a doctor is diagnosing and evaluating high
blood pressure and kidney disease and when monitoring a patient receiving dialysis,
diuretic therapy, or intravenous therapy.
Increased potassium levels indicate hyperkalemia. Increased levels may also indicate
the following health conditions:
 excessive dietary potassium intake (for example, fruits are particularly high in
potassium, so excessive intake of fruits or juices may contribute to high
potassium);
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 excessive intravenous potassium intake;
 acute or chronic kidney failure;
 Addison's disease;
 hypoaldosteronism;
 injury to tissue;
 infection;
 diabetes; and
 dehydration.
Certain drugs can also cause hyperkalemia in a small percent of patients. Among them
are non-steroidal anti-inflammatory drugs (such as Advil, Motrin, and Nuprin); beta-
blockers (such as propanolol and atenolol), angiotensin-converting enzyme inhibitors
(such as captopril, enalapril, and lisinopril), and potassium-sparing diuretics (such as
triamterene, amiloride, and spironolactone).
Decreased levels of potassium indicate hypokalemia. Decreased levels may occur in a

number of conditions, particularly:
 dehydration,
 vomiting,
 diarrhea, and
 deficient potassium intake (rare).
In diabetes, your potassium may fall after you take insulin, particularly if your
diabetes had been out of control for a while. Low potassium is commonly due to
“water pills” (diuretics); if you are taking these, your doctor will check your
potassium level regularly.
The way that your blood is drawn and handled may cause the potassium level in the
sample to be falsely high. If you clench and relax your fist a lot while your blood is
drawn, this will make potassium rise. If blood comes out of your veins too fast or too
slow, the blood cells can break and increase potassium. Sometimes, if more than one
tube of blood is drawn at the same time, some potassium from the tubes with the
purple tops can get into the other tubes and increase the potassium. If the specimen
does not get from your doctor’s office to the laboratory quickly, the potassium can
also increase. If there are any questions as to how your blood was collected, your
doctor may request that the test be repeated before starting any treatment.
1. What are some good dietary sources of potassium?
A number of fruits, vegetables, and meats are good sources of potassium. Visit
Cyberdiet’s Best Sources of Potassium for a reliable list.
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2. Is there an over-the-counter test I can use to check my potassium levels?
No. Electrolyte tests are performed by trained laboratorians using highly sensitive
instruments.
Prealbumin
Also known as: PA, Tryptophan-rich prealbumin, Thyroxine-binding prealbumin,

TBPA
Why get tested?
To diagnose patients with malnutrition and to monitor patients at risk for poor
nutrition
When to get tested?
If your doctor suspects you are malnourished, because of poor diet, HIV, or an eating
disorder, if you are about to be admitted to the hospital for surgery, if are hospitalized
with certain diseases, or if you are having parenteral (for example, intravenous)
nutrition or hemodialysis
The test measures levels of prealbumin, an important protein found in the blood
serum. Prealbumin has a half-life of only two days, which means that it breaks down
quickly in the body and the amount changes quickly. This short half-life helps doctors
to get a more immediate picture of your nutrition.
How is it used?
The prealbumin test is used to help your doctor diagnose problems with your
nutrition. Prealbumin most often is used to help doctors diagnose protein-calorie
malnutrition. In this condition, which can affect more than 30% of hospitalized
patients, the body breaks down muscle, protein, and body fat. This type of
malnutrition can lead to complications and even death if not treated. Children with
malnutrition may fail to thrive or have stunted growth.
The test is also used to make an assessment of nutritional status:
 before a scheduled surgery,

 in patients who are hospitalized with certain conditions, and
 in patients who are chronically ill.
Many patients have a decline in nutrition during their hospital stay, especially after
surgery. Studies have shown that good nutrition prior to surgery helps to avoid
complications, such as pneumonia and infection, after surgery. If the prealbumin test
indicates that you are malnourished or have poor nutrition, your doctor can help
correct your diet so you get stronger before your surgery. Albumin may be tested
instead to determine nutritional status.
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The test also is used to monitor changes in patients who are receiving parenteral
nutrition (nutrition from outside of the gastrointestinal tract, such as nutrients given
through intravenous treatment). The test also is used to monitor changes in nutrition
status for patients who are receiving hemodialysis, a process that removes waste
substances from your circulating blood. Hemodialysis is part of treatment for patients
with kidney disease.
When is it ordered?
A doctor orders a prealbumin test when signs of malnutrition or poor nutrition are
present. Signs of malnutrition include extreme weight loss, stunted growth (in a
child), weakened resistance to infection, or being unable to think clearly. Hair may
become brittle or begin to fall out, the skin may be dry or yellowish, muscles may feel
weak, and fainting spells may occur. In younger women, menstrual periods may stop.
Generally, a prealbumin or albumin test will be ordered prior to surgery or when a
patient is being treated for certain conditions. Doctors may also order the test
regularly to monitor patients who have had low prealbumin results. Monitoring will
be more or less frequent, depending on the test results.

The prealbumin measurement reflects the state of your nutrition. If prealbumin is low,
other proteins and substances in your blood also may be low.
If your test shows that prealbumin is low, your nutrition probably needs to be
corrected. If prealbumin is very low, you may be considered malnourished and need
immediate medical attention. Lower levels of prealbumin may be seen in patients
with:
 severe or chronic illness, such as cancer;

 hyperthyroidism;
 liver disease;
 serious infections; and
 certain digestive disorders.
If a patient has inflammation, however, it is impossible to know exactly what the

prealbumin value means. When inflammation and malnutrition are both present,
prealbumin levels fall very far, very quickly.
Higher levels of prealbumin are common in patients with:
 high-dose corticosteroid therapy;

 hyperactive adrenal glands;
 high-dose nonsteroidal anti-inflammatory medications; and
 Hodgkin’s disease.
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If a patient is in renal failure, prealbumin results may be falsely higher than they
actually are.

Inflammation can interfere with the results of your prealbumin test, causing it to be
lower than it would be. Certain drugs can also lower your prealbumin level, including
amiodarone, estrogens, and oral contraceptives (birth control pills).
Drugs that can cause your prealbumin level to rise in your blood are anabolic steroids,
androgens (male hormones), and prednisolone.
Recent research has shown that the prealbumin test can predict poor outcomes for
hemodialysis patients. A low initial reading (baseline level) of prealbumin predicts
that a patient may have problems, and steadily dropping prealbumin values are
associated with low survival.
1. What conditions could lead to malnutrition?
Various diseases can lead to so-called protein-calorie malnutrition. Common diseases

linked with this form of malnutrition include:
 cancer,
 chronic illness,
 protein loss in the gastrointestinal tract,
 anorexia and other eating disorders,
 liver disease,
 multiple traumas,
 obesity,
 pancreatitis, and
 burns over 30% or more of your body.
2. What is the difference between prealbumin, albumin, and microalbumin tests?

Albumin and microalbumin are the same molecule while prealbumin, despite the
similar-sounding name, is a completely unrelated molecule. The prealbumin test
measures a protein that reflects your nutritional status, particularly before and after
surgery, or if you are hospitalized or taking nutritional supplements. Albumin testing
is more often used to test for liver or kidney disease or to learn if your body is not
absorbing enough amino acids. Albumin can also be used to monitor nutritional
status. However, prealbumin changes more quickly, making it more useful for
detecting changes in short-term nutritional status than albumin. The microalbumin test
measures very small levels of albumin in your urine and may indicate whether you are
at risk for developing kidney disease.
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Progesterone
Why get tested?
To help determine the cause of infertility, track ovulation, help diagnose an ectopic or
failing pregnancy, monitor the health of a pregnancy, and help diagnose the cause of
abnormal uterine bleeding
When to get tested?
At specific times during a woman’s menstrual cycle to determine whether/when she is
ovulating; during early pregnancy if symptoms suggest an ectopic or failing
pregnancy; throughout pregnancy to help determine placenta and fetal health; and in
cases of abnormal uterine bleeding.
This test measures the level of progesterone in the blood. Progesterone is a steroid
hormone whose main role is to help prepare a woman’s body for pregnancy; it works
in conjunction with several other female hormones.
On a monthly basis, the hormone estrogen causes the endometrium (the lining of the
uterus) to grow and replenish itself, while a surge in lutenizing hormone (LH) leads to
the release of an egg from one of two ovaries. A corpus luteum (small yellow cellular
mass) then forms in the ovary at the site where the egg was released and begins to
produce progesterone. This progesterone (supplemented by small amounts produced
by the adrenal glands) stops endometrial growth and readies the uterus for the
possible implantation of a fertilized egg.
If fertilization does not occur, the corpus luteum degenerates, progesterone levels
drop, and menstrual bleeding begins. If a fertilized egg is implanted in the uterus, the
corpus luteum continues to produce progesterone. After several weeks, the placenta
replaces the corpus luteum as the main source of progesterone, creating relatively
large amounts of the hormone throughout the rest of a normal pregnancy.
How is it used?
Since progesterone levels vary predictably throughout the menstrual cycle, multiple
(serial) measurements can be used to help recognize and manage some causes of
infertility. Progesterone can be measured to determine whether or not a woman has
ovulated, to determine when ovulation occurred, and to monitor the success of
induced ovulation.
In early pregnancy, progesterone measurements may be used, along with human
chorionic gonadotropin (hCG) testing, to help diagnose an ectopic or failing
pregnancy (progesterone levels will be lower than expected), although this will not
differentiate between the two conditions. Progesterone levels also may be measured
throughout a high-risk pregnancy to help evaluate placenta and fetal health.
Progesterone levels may be monitored in women who have trouble maintaining a
pregnancy, as low levels of the hormone can lead to miscarriage. If a woman is
receiving progesterone injections to help support her early pregnancy, her
progesterone levels may be monitored on a regular basis to help determine the
effectiveness of that treatment.
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In women who are not pregnant, progesterone levels may be used, along with other
tests, to help determine the cause of abnormal uterine bleeding.
When is it ordered?
Progesterone levels are measured:
 As part of an infertility assessment, when a woman is having trouble getting

pregnant and the doctor wants to verify that she is ovulating normally
 To determine if ovulation has occurred and when following drug therapy to
induce ovulation
 When symptoms, such as abdominal pain and spotting, suggest an ectopic
pregnancy or threatened miscarriage
 To monitor the effectiveness of treatment when a pregnant woman requires
progesterone injections to help maintain her pregnancy
 To monitor placenta and fetal health during a high-risk pregnancy
 When a non-pregnant woman is experiencing abnormal uterine bleeding

Interpretation of progesterone test results requires knowledge of where a woman is in
her menstrual cycle or pregnancy. Progesterone levels usually start to elevate when an
egg is released from the ovary, rise for several days, and then either continue to rise
with early pregnancy or fall to initiate menstruation.
If progesterone levels do not rise and fall on a monthly basis, a woman may not be
ovulating or having menstrual periods. If levels do not rise normally during an early
pregnancy, the pregnancy may be ectopic and/or may be failing. If serial
measurements do not show increasing progesterone levels over time, there may be
problems with the viability of the placenta and fetus.
Levels of progesterone will be naturally higher during pregnancies that involve

multiples (twins, triplets, etc.) than those in which there is only one fetus.
Increased progesterone levels also are seen occasionally with luteal ovarian cysts,
molar pregnancies, and with a rare form of ovarian cancer.
Increased levels are occasionally due to an overproduction of progesterone by the
adrenal glands.
In late pregnancy, low levels of progesterone may be associated with toxemia and pre-
eclampsia.
Taking estrogen and progesterone supplements also can affect results.
1. Are men tested for progesterone?

Not usually, unless specific adrenal diseases are suspected. Progesterone does not
have an established role in males.
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2. Are there other uses for progesterone?
Yes. Progesterone (in the synthetic form progestin) is often used in hormone
replacement therapy (HRT) for menopausal women. However, the use of combined
progestin and estrogen therapy has become controversial recently based on findings
from a National Institutes of Health study. For more information, read New Facts
About: Estrogen/Progestin Hormone Therapy. Progesterone also is used in some
contraceptive pills.
3. If I am menopausal and on hormone replacement therapy (HRT), is there ever

a need to monitor my progesterone level?
Sometimes. If you still have your uterus and are having symptoms, such as
unexplained uterine bleeding, your doctor may order a progesterone test along with
other tests and procedures. If you do not have a uterus (removed during a
hysterectomy), your HRT will not include progesterone and it will not need to be
checked.
Prolactin
Why get tested?
To determine whether or not your prolactin levels are higher (or occasionally lower)
than normal
When to get tested?
When you have symptoms of an elevated prolactin, such as: galactorrhea and/or
visual disturbances and headaches, as part of a workup for female and male infertility,
and for follow up of low testosterone in men.
Prolactin is a hormone produced by the anterior pituitary gland, a grape sized organ
found at the base of the brain. Normally present in low amounts in men and non-
pregnant women, prolactin?s primary role is to promote lactation (breast milk
production).
Prolactin levels are usually high throughout pregnancy and just after childbirth.
During pregnancy prolactin, estrogen, and progesterone stimulate breast development.
Following childbirth, prolactin helps initiate and maintain the breast milk supply. If a
woman does not breastfeed, her prolactin soon drops back to low pre-pregnancy
levels. If she does nurse, suckling by the infant plays an important role in the release
of prolactin. There is a feedback mechanism between the baby's nutritional needs, the
amount of prolactin secreted by the pituitary, and the amount of milk produced.
Prolactin levels will continue to be high while the mother continues to nurse, but will
eventually fall back to pre-pregnancy levels.
Besides pregnancy, the most common cause of elevated prolactin levels is a
prolactinoma, a prolactin-producing tumor of the pituitary gland. Prolactinomas are
the most common type of pituitary tumor and are usually benign. They develop more
frequently in women but are also found in men. Problems from them can arise both
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from the unintended affects of excess prolactin, such as milk production in the non-
pregnant woman (and rarely, man) and from the size and location of the tumor.
If the anterior pituitary gland and/or the tumor enlarge significantly it can put pressure
on the optic nerve, causing headaches and visual disturbances; and it can interfere
with the other hormones that the pituitary gland produces. In women, prolactinomas
can cause infertility and irregularities in menstruation; in men, these tumors can cause
a gradual loss in sexual function and desire. If left untreated, prolactinomas may
eventually damage the tissues around them.
How is it used?
Prolactin levels are used, along with other tests, to help:
 Determine the cause of galactorrhea

 Determine the cause of headaches and visual disturbances
 Diagnose infertility and erectile dysfunction in males
 Diagnose infertility in females
 Diagnose prolactinomas
 Evaluate anterior pituitary function (along with other hormones)
 Monitor treatment of prolactinomas and detect recurrences
When is it ordered?
Prolactin levels may be ordered when a patient has symptoms of a prolactinoma such
as: unexplained headaches, visual impairment, and/or galactorrhea. They may also be
ordered, along with other tests, when a woman is experiencing infertility or irregular
menses; or when a man has symptoms such as: a decreased sex drive, galactorrhea, or
infertility. Prolactin levels are also often ordered in men as a follow-up to a low
testosterone level.
When a patient has a prolactinoma, prolactin levels may be ordered to monitor the
progress of the tumor and its response to treatment. They may also be used at regular
intervals to monitor for prolactinoma recurrence.
Prolactin levels may be ordered, along with other hormone levels such as growth
hormone, when your doctor suspects that you have more general hypopituitarism (low
levels of pituitary function which result in lowered levels of thyroid or adrenal
hormones). And prolactin levels may be monitored when you have a condition or are
taking medications that may affect dopamine (a brain chemical that regulates and
inhibits the production of prolactin).
Men and non-pregnant women will normally have only small amounts of prolactin in
their blood. Prolactin levels do, however, need to be evaluated based on the time of
day that they are collected. The levels will vary over a 24 hour period - rising during
sleep and peaking in the morning. Ideally, your blood sample should usually be drawn
a couple of hours after waking up, preferably after you have been resting quietly for
30 minutes (although your doctor may have his own reasons for doing them at other
times).
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High levels of prolactin (hyperprolactinemia) are normal during pregnancy, and after
childbirth while the mother is nursing. High levels are also seen with:
 Anorexia nervosa
 Drugs: Estrogen, tricyclic antidepressants, and drugs that block the effect of
dopamine (a brain chemical that regulates and inhibits the production of
prolactin) such as: tranquilizers, some hypertension drugs, and some drugs that
are used to treat gastroesophageal reflux
 Hypothalamic diseases
 Hypothyroidism
 Kidney disease
 Nipple stimulation (moderate increase)
 Other pituitary tumors and diseases
 Polycystic ovary syndrome
 Prolactinomas
Levels of prolactin that are below normal are not usually treated but may be indicative
of a more general hypopituitarism (decreased pituitary function and decreased
hormone production). Low levels may also be caused by drugs such as: dopamine,
levodopa, and ergot alkaloid derivatives.
Stresses from illness, trauma, and even the fear of having the blood test done can
cause moderate increases in prolactin.
Prolactinomas are often small. Along with prolactin levels, your doctor may do an
MRI (magnetic resonance imaging), both to try and locate the tumor within the
pituitary gland and to look at both the size of the tumor and the size of the pituitary
(which often enlarges).
1. What other tests may be done to evaluate an elevated prolactin?
Testosterone (levels will usually be low in a male when prolactin is high), FSH, and
LH (to help evaluate ovulation and fertility), an MRI (to show pituitary enlargement
and help locate a tumor), and an eye examination (to evaluate visual disturbances).
2. If I have an elevated prolactin, why is my doctor testing my thyroid?

Increased levels of prolactin are often seen in people with hypothyroidism (although
they do not cause it). If you have hyperprolactinemia, your doctor will most likely test
you for hypothyroidism.
3. How are prolactinomas treated?
Prolactinomas are usually treated with medications that act like dopamine (such as
bromocriptine or cabergoline). Treatment can reduce prolactin levels and symptoms
and restore fertility, but the medications may have to be taken for several months or
years. Surgery is sometimes necessary if the prolactinomas are large or not
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responding to treatment. This surgery is delicate and requires an experienced surgeon.
Sometimes, despite medication and/or surgery, the prolactinoma will return.
Protein C and Protein S
Why get tested?
To help evaluate a thrombotic episode, to determine whether you may have an
inherited or acquired Protein C or Protein S deficiency
When to get tested?
When you have had an unexplained thromboembolism (a blood vessel blocked by a
blood clot), when your newborn has a severe clotting disorder, such as disseminated
intravascular coagulation (DIC) or purpura fulminans; sometimes when a close
relative has an inherited Protein C or Protein S deficiency.
Proteins C and S are normally present in blood and serve as one system in preventing
excessive blood clotting. Protein C, with the help of Protein S, adjusts the rate of
normal blood clot formation such that blood clots are formed only at those sites where
there is an injury. When a blood vessel or tissue is injured, the body initiates the
coagulation cascade - a step by step process involving the activation of up to 20
protein factors - which results in the formation of a stable blood clot. This clot
prevents additional blood loss and protects the injury until it heals. Once it is no
longer needed other factors break the clot down so that it can be removed.
Thrombin is a clotting factor that can accelerate or decelerate blood clot formation by
promoting or inhibiting its own activation. It forms a feedback loop that uses Protein
C and Protein S to slow down the coagulation cascade. Thrombin first combines with
a protein called thrombomodulin, then activates Protein C. This activated Protein C
(APC) then combines with Protein S (a cofactor) and together they work to degrade
coagulation factors VIIIa and Va (these activated factors are required to produce
thrombin). This has the net effect of slowing down the generation of new thrombin
and inhibiting further clotting. If there is not enough Protein C or Protein S, or if
either one is not functioning normally, then thrombin generation goes on largely
unchecked. This can lead to excessive or inappropriate clotting that may block the
flow of blood in the veins (VTE - venous thromboembolism) and, more rarely, in the
arteries.
Problems with Protein C and Protein S can be inherited or acquired. There are two
types of Protein C deficiencies - type 1 is related to quantity and type 2 to abnormal
function. Protein S exists in 2 forms, free and bound, but only the free Protein S is
available to combine with Protein C. There are 3 types of Protein S deficiencies.
Type 1 deficiency is due to an insufficient quantity, type 2 to abnormal function, and
type 3 to a shift from free Protein S to bound Protein S.
Decreased Protein C and Protein S quantity may be related to insufficient production
or to increased use. Since both proteins are produced in the liver and are vitamin K
dependent; liver disease, a shortage of vitamin K, or anticoagulant therapy that
opposes vitamin K, may result in reduced Protein C and/or Protein S levels.
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Conditions such as disseminated intravascular coagulation (DIC) that cause clotting
and bleeding throughout the body use up clotting factors, including Protein C and
Protein S, at an increased rate, and so, decrease their concentrations in the blood.
Although inherited mutations in the genes that produce Protein C and Protein S are
relatively rare, they can result in:
 a decreased level of Protein C or Protein S being produced,

 an abnormal protein that either cannot bind properly to its cofactor (C or S)
 an abnormal protein which when combined, does not degrade factors VIIIa
and Va normally.
When these mutations occur, they are independent of each other and the mutation is
most likely to be in one or the other (Protein C or Protein S). Changes in the gene
may be heterozygous (one mutated copy of the C or S gene) or homozygous (two
changed copies of C or S). A heterozygous change raises the risk of developing a
VTE a moderate amount but a homozygous change in either gene can cause severe
clotting – it may cause life threatening purpura fulminans or DIC in the newborn, and
it requires a lifetime of vigilance against recurrent thrombotic episodes.
How is it used?
Tests for Protein C and Protein S may look at their function (activity) or quantity.
They are usually ordered to help diagnose the cause of a venous thromboembolism
(VTE) – especially if the blood clot is in a relatively young person (less than 50 years
old) or has formed in an unusual location, such as the veins leading to the liver or
kidney or cerebral veins.. While immediate treatment of the VTE does not depend on
the test result, your doctor will want to determine its cause and the likelihood of
recurrent clotting once your condition has stabilized.
Functional tests for Protein C and free Protein S are usually ordered, along with other
tests for hypercoaguability, to screen for sufficient, normal, factor activity. Based on
those results, quantities of Protein C and Protein S are often measured to look for
decreased production due to an acquired or inherited condition, and to classify the
type of deficiency. If the shortage is due to an inherited genetic change, the quantity
of Protein C or Protein S available and its degree of activity can be used to help
determine whether a person is heterozygous or homozygous.
A test that shows decreased activity or quantity of Protein C or Protein S should
usually be repeated on another occasion before a diagnosis is made because there are
a variety of conditions that can cause temporary changes in the level and function of
Proteins C and S. If an acquired deficiency is identified, Protein C or Protein S
concentrations may be monitored occasionally as the underlying condition progresses
– as may happen with liver disease - or, is resolved – as may happen with Vitamin K
deficiency. An inherited change is usually not monitored but your doctor will keep it
in mind when you are exposed to situations that increase your risk of clotting, such as
surgery, chemotherapy for cancer, or oral contraceptive use.
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When is it ordered?
Protein C and Protein S tests are ordered when you have had a thrombotic episode,
especially when you are relatively young (less than 50 years old) and/or do not have
any other obvious reasons for developing a blood clot. Protein C and Protein S tests
should not, however, be ordered for at least 10 days after the episode and they should
not be ordered while you are on anticoagulant therapy. Usually this means that your
doctor will treat your venous thromboembolism (VTE), eliminate the immediate
blood clotting threat and put you on a limited course of anticoagulant therapy (often
about 3 to 6 months). During this time period, your doctor may order other tests to
look for underlying diseases or conditions such as liver disease, vitamin K deficiency,
or cancer, that may causing inappropriate blood clotting.
When your situation is stable, your doctor will often order Protein C and free Protein
S function/activity levels, along with other tests associated with hypercoaguability, to
help determine the cause of the thrombus and to help evaluate your risk of
recurrence. Protein C and Protein S concentrations (quantity) may be measured with,
or after, function/activity levels to determine whether a sufficient amount of each is
being produced, to determine the severity of any deficiencies, and to classify the type
of deficiency. When an acquired condition is identified, Protein C and/or Protein S
levels may be occasionally monitored when your doctor wants to evaluate the
progress or resolution of the condition (to see if the protein levels have decreased
further or returned to near normal levels).
Although Protein C and Protein S tests are not recommended as routine screens, they
may sometimes be ordered on close relatives of someone who has an inherited Protein
C or Protein S deficiency – especially if the person affected has a severe form or had
their first VTE at a young age.
Elevated levels of Protein C and Protein S are not usually associated with medical
problems, although it has been reported that Protein C may be increased when taking
oral contraceptives or during pregnancy. If both the activity and the concentrations of
Protein C and Protein S are normal, it usually indicates adequate clotting regulation.
Low levels of Protein C or Protein S can result in excessive formation of blood clots.
If the protein is dysfunctional (normal levels of protein but they do not work
correctly), the coagulation process will also not be sufficiently regulated. Either
situation can lead to an increased risk of developing a clot that blocks the flow of
blood in the veins (called a venous thromboembolism or VTE), but the severity of the
risk depends on how abnormal and how deficient the protein is.
Decreased concentrations of Protein C and Protein S may be seen with vitamin K

deficiency, liver disease, severe infections (inflammatory conditions), renal disease,
cancers, disseminated intravascular coagulation (DIC), HIV, during pregnancy,
immediately following a thrombotic episode, and with warfarin or heparin
anticoagulant therapy. These conditions reflect the decreased production or increased
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use of Protein C and/or Protein S. They may be mild and temporary (as with
pregnancy) or have variable severity and be acute, chronic, or progressive.
If other factor deficiencies such as decreased Antithrombin, or inherited conditions,

such as Factor V Leiden or Prothrombin 20210 are also present the effects of a
Protein C or Protein S deficiency can be exacerbated. Fresh frozen plasma contains
Protein C and Protein S and it can be used as a short term preventative when a patient
is having a necessary surgical procedure. There is also a concentrate of Protein C
available that can be used to provide temporary protection.
PSA
Why get tested?
To screen asymptomatic and symptomatic men for prostate cancer, to help determine
the necessity for a biopsy of the prostate, to monitor the effectiveness of treatment for
prostate cancer, and to detect recurrence of prostate cancer
When to get tested?
The frequency of PSA testing is an individual decision that should be determined
through discussion with your physician. There is continued debate among experts and
national organizations over when and how often to order the PSA test to screen
asymptomatic men. (For specific details, see prostate cancer screening for adults and
adults 50 and up). PSA testing may be performed when a man has symptoms
suggestive of prostate cancer such as difficult, painful, and/or frequent urination. It
may also be ordered during and at regular intervals after prostate cancer treatment.
This test measures the amount of prostate specific antigen (PSA) in the blood. It was
developed as a tumor marker to screen for and to monitor prostate cancer. It is a good
tool, but not a perfect one. Elevated levels of PSA are associated with prostate cancer,
but they may also be seen with prostatitis (inflammation of the prostate) and benign
prostatic hyperplasia (BPH). Mild to moderately increased concentrations of PSA
may be seen in those of African American heritage, and levels tend to increase in all
men as they age.
PSA is a protein produced primarily by cells in the prostate, a small gland that
encircles the urethra in males and produces a fluid that makes up part of semen. Most
of the PSA that the prostate produces is released into this fluid, but small amounts of
it are also released into the bloodstream. PSA exists in two forms in the blood: free
(not bound) and complexed (bound to a protein). The most frequently measured PSA
test is the total PSA, which measures the sum of the free PSA and the cPSA (PSA
complexed with other plasma proteins). When a doctor orders a “PSA test,” he is
referring to a total PSA.
Free PSA and cPSA tests can also be ordered individually. The tests that measure
them were developed to better differentiate between cancer-related and non-cancer-
related PSA increases. Both of the tests operate on the principle that patients with
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prostate cancer frequently have altered ratios of the two forms of PSA - decreased
amounts of free PSA and increased amounts of cPSA.
PSA is not diagnostic of cancer. The gold standard for identifying prostate cancer is
still the prostate biopsy, collecting small samples of prostate tissue and identifying
abnormal cells under the microscope. The total PSA test and digital rectal exam
(DRE) are used together to help determine the need for a prostate biopsy. The goal of
testing is to minimize unnecessary biopsies and to detect clinically significant prostate
cancer while it is still confined to the prostate. The term clinically significant is
important because while prostate cancer becomes relatively common in men as they
age, many of the cases are very slow-growing. Doctors must try to both detect
prostate cancer and to differentiate between slow-growing cases and prostate cancers
that may grow aggressively and metastasize (spread to other parts of the body). Over-
diagnosing and over-treatment are issues with which doctors are currently grappling.
In some cases, the treatment can be worse than the cancer, with the potential for
causing significant side effects, such as impotence and incontinence. The PSA test
and DRE can detect most cases of prostate cancer, but they cannot, in general, predict
the course of a patient’s disease.
How is it used?
The total PSA test and digital rectal exam (DRE) are ordered to screen both
asymptomatic and symptomatic men for prostate cancer. Since the DRE can cause a
temporary elevation in PSA, the blood is usually collected prior to performing the
DRE. If either the PSA or the DRE are found to be abnormal, then the doctor may
choose to follow this testing with a prostate biopsy and perhaps imaging tests, such as
an ultrasound. If the DRE is normal but the PSA is moderately elevated, the doctor
may order a free PSA test to look at the ratio of free to total PSA. This can help to
distinguish between prostate cancer and other non-cancer causes of elevated PSA.
Since the total PSA test can be elevated temporarily for a variety of reasons, a doctor
may order another PSA a few weeks after the first to determine if the PSA is still
elevated.
The cPSA is a relatively new test that may be ordered, along with the DRE, as an
alternative to the total PSA. There is hope that this test could be more specific than
the total PSA (better at detecting cancer-related PSA), but findings have been mixed
and its ultimate clinical utility has yet to be established. The cPSA is an option that
doctors can discuss with their patients. Its use may expand and/or be better defined as
additional studies are conducted and findings are reported.
If prostate cancer is diagnosed, then the total PSA may be used as a monitoring tool to
help determine the effectiveness of treatment. It may also be ordered at regular
intervals after treatment to detect recurrence of the cancer.
In cases where the cancer appears to be slow-growing and the doctor and patient
decide to monitor its progress rather than pursue immediate treatment (called
“watchful waiting”), total PSA levels are ordered at frequent intervals to monitor the
change in PSA over time.
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When is it ordered?
There is no consensus among the experts currently about when the PSA test should be
ordered to screen asymptomatic males. Over-diagnosing, identifying cases of prostate
cancer that may never cause significant health problems, must be balanced against
missing the detection of aggressive cancers. There are national organizations, such as
the National Cancer Institute and Centers for Disease Control and Prevention, that do
not recommend routine screening at this time. Others, such as the American Cancer
Society (ACS), recommend that doctors offer total PSA tests and DRE annually to all
men, beginning at age 50 and to those at an increased risk of prostate cancer, such as
American men of African descent and men with a family history of the disease,
beginning at age 40 or 45. The ACS recommends that doctors discuss the testing
options, benefits, and potential side effects with their male patients so that they can
make informed choices. (See Prostate Cancer Screening for Adults and Adults 50 and
Up.) The total PSA test and DRE may also be ordered when a patient has symptoms
that could be due to prostate cancer, such as difficult, painful, and/or frequent
urination, back pain, and/or pelvic pain. Since these symptoms are seen with a variety
of other conditions, including infection and prostatitis, the doctor will also frequently
order other tests, such as a urine culture. Some of these conditions can themselves
cause temporary increases in PSA levels. If a total PSA level is elevated, a doctor may
order a repeat test a few weeks later to determine whether the PSA concentrations
have returned to normal.
A free PSA is primarily ordered when a patient has a moderately elevated total PSA
that does not appear to be caused by a non-cancer-related condition. The results give
the doctor additional information about whether a patient is at an increased risk of
having prostate cancer and help with the decision of whether to biopsy the prostate.
The total PSA may be ordered during treatment of patients who have been diagnosed
with prostate cancer to verify the effectiveness of treatment and at regular intervals
after treatment to monitor for cancer recurrence. It is also ordered at regular intervals
when a patient with cancer is participating in “watchful waiting” and not currently
treating their prostate cancer.

The normal value for total PSA has been set at less than 4.0 ng/ml (nanograms per
milliliter of blood). There are some that feel that this level should be lowered to 2.5
ng/ml in order to detect more cases of prostate cancer. Others argue that this would
exacerbate over-diagnosing and over-treating cancers that are not clinically
significant.
There is agreement that patients with a total PSA level greater than 10.0 ng/ml are at
an increased risk for prostate cancer (more than a 67% chance, according to the ACS).
Levels between 4.0 ng/ml and 10.0 ng/ml may indicate prostate cancer (about a 25%
chance, according to the ACS), BPH, or prostatitis. These conditions are more
common in the elderly, as is a general increase in PSA levels. Concentrations of total
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PSA between 4.0 ng/ml and 10.0 ng/ml are often referred to as the “gray zone.” It is
in this range that the free PSA is the most useful. When patients in the gray zone have
decreased levels of free PSA, they have a higher probability of prostate cancer; when
they have elevated levels of free PSA, the risk is diminished. The ratio of free to total
PSA can help the doctor decide whether or not a prostate biopsy should be performed.
When the cPSA test is used as a screening tool, increased levels may indicate an
increased risk of prostate cancer, while lower levels indicate a decreased risk.
In addition to the introduction of the free PSA and cPSA tests, there have been efforts
to increase the usefulness of the total PSA as a screening tool. While none of these
efforts have been widely accepted yet, researchers are studying them and some
doctors are utilizing them. They include:
 PSA velocity. This is the change in PSA concentrations over time. If the PSA
continues to rise significantly over time (such as 3 or more years), then it is more
likely that prostate cancer is present. If it climbs rapidly, then the patient may have a
more aggressive form of cancer.
 PSA doubling time. This is another version of the PSA velocity. It measures how
rapidly the PSA concentration doubles.
 PSA density. This is a comparison of the PSA concentration and the volume of the
prostate (as measured by ultrasound). Patients with larger prostates tend to produce
more PSA, so this factor is an adjustment to compensate for the size.
 Age-specific PSA ranges. Since PSA levels naturally increase as a man ages, it has
been proposed that normal ranges be tailored to a man’s age.
During treatment for prostate cancer, the PSA level should begin to fall. At the end of
treatment, it should be at very low or undetectable levels in the blood. If
concentrations do not fall to very low levels, then the treatment has not been fully
effective. Following treatment, the PSA test is performed at regular intervals to
monitor the patient for recurrence. Since even tiny increases can be significant,
patients may want to have their monitoring PSA tests done by the same laboratory
each time so that testing variation is kept to a minimum.

Prostate manipulation by biopsy or resection of the prostate will significantly elevate
PSA levels. The blood test should be done before surgery or six weeks after
manipulation.
Rigorous physical activity affecting the prostate, such as bicycle riding, may cause a
temporary rise in PSA levels. Excessive doses of some chemotherapeutic drugs, such
as cyclophosphamide and methotrexate, may increase or decrease PSA levels.
In some men, PSA may rise temporarily due to other prostate conditions, especially
infection. A recent study found that in about half of men with a high PSA, values later
return to normal. Some authorities recommend that a high PSA should be repeated
(between 6 weeks and 3 months after the high PSA) before taking any further action.
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Some physicians will prescribe a course of antibiotics if there is evidence that there is
infection of the prostate.
1. If I have prostate cancer, what are my options?
The most common treatments include radiation, hormone therapy, and surgery. For
more information, visit the American Cancer Society's prostate cancer treatment
discussion.
2. Will PSA testing detect all prostate cancers?

No. Sometimes cancer cells do not produce much PSA, and the test will be negative
even when the disease is present.
PSEN1
Also known as: PS1, PS-1, Presenilin 1, S182

Formal name: PS1 or PSEN1 genetic mutation analysis
Why get tested?
To screen for a rare mutation in the PSEN1 gene known to be associated with Early
Onset Familial Alzheimer’s Disease (EOFAD, also called Alzheimer's disease Type 3
or AD3)
When to get tested?
If you are an adult who has symptoms of dementia and a strong family history of early
onset Alzheimer’s Disease (AD that begins before age 60-65) or if you are an
asymptomatic adult with an identified PSEN1 genetic mutation (and AD3) in your
family line.
This test looks for mutations in the PSEN1 gene, which have been associated with
Early Onset Familial Alzheimer’s Disease (EOFAD, also called Alzheimer's Disease
Type 3 or AD3). Although most AD starts after the age of 65 (late onset), about 5-
10% of cases of the disease begin in people under 65 years of age. Much of this early
onset AD is familial - it runs in family lines and is caused by a genetic mutation.
There have been three genes identified so far that are associated with AD3; all are
very rare. Of these, PSEN1 is the most common and is thought to cause about half the
cases of AD3.
Since PSEN1 is a dominant gene, it only takes one mutated copy, inherited from
either your mother or father, to cause AD3. Why PSEN1 is associated with AD3 is
not yet known. The normal role of the PSEN1 gene and the function of presenilin 1,
the protein it produces, are being studied but are still not fully understood; however, it
appears to be an enzyme involved in breaking down the protein found in the
Alzheimer’s disease plaques. PSEN1 is a rare mutation. So far, about 40 mutations of
the PSEN1 gene have been identified but only in about 50 different family lines
worldwide.
The PSEN1 genetic mutation analysis is new and not widely accepted yet. In its
present form, it is only capable of identifying about 30-60% of patients who have
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AD3 caused by a PSEN1 mutation. The analysis is made easier if a patient already has
an identified PSEN1 mutation in their family line.
How is it used?
PSEN1 genetic mutation analysis is used to screen asymptomatic or symptomatic
adults who have a strong family history of early onset Alzheimer’s Disease, especially
when a PSEN1 mutation has been identified in other family members. It may be used
to aid in the differential diagnosis of early onset Alzheimer’s Disease (versus some
other form of early onset dementia) but usually only in those with a family history of
AD3. PSEN1 is also occasionally used prenatally and, where appropriate, with genetic
counseling to assess the risk of having and passing on a PSEN1 mutation.
When is it ordered?
The test is usually ordered for asymptomatic or symptomatic adults with a strong
family history of early onset Alzheimer’s Disease, especially when there are multiple
family members in multiple generations (preferably three generations) who have had
AD3. It is NOT useful as a screen for the general population or for those who have
late onset AD.
If you have one of the PSEN1 mutations, it is highly likely that you will eventually
develop AD3, usually at a similar age to other affected family members. The
penetrance of the gene (symptoms, severity, and rate of progression), however, can
vary from individual to individual. Since it is a dominant gene, if you have a PSEN1
mutation, each of your children will have a 50% chance of having the PSEN1
mutation.
It should be remembered that the PSEN1 genetic mutation analysis, in its current
form, is only capable of picking up 30-60% of PSEN1-caused AD3. If your test is
negative, there is still a chance that you have an unidentified PSEN1 mutation.
PSEN1 genetic mutation is almost exclusively family-related and is not associated
with late onset AD. A few cases of PSEN1 genetic mutation will show up without a
strong family history because of “alternate” paternity, new mutations, or because a
parent died before symptoms developed so this element of the family history was
unknown.
The PSEN1 test is a new, relatively expensive test that has limited use and is still
rarely ordered. It is performed in only a few laboratories in the world, so if your
doctor recommends the test, your blood sample will need to be sent to a reference lab
and results may take longer to return.
1. My father has been diagnosed with early onset AD. Can my doctor tell if my
father has a genetic mutation without a blood test?
No, the symptoms for AD3, sporadic early onset AD, and late onset AD are the same
except for the age of onset. You cannot tell whether someone has a genetic mutation
just by looking at them. If there is a strong family history of early onset AD, and
especially if another family member has been diagnosed with a genetic mutation, your
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doctor may suspect a genetic problem, but a blood test is the only way to confirm this
suspicion.
2. What other genes cause AD3 and is testing available for them?
The other genes that have mutations associated with AD3 are PSEN2 and APP
(amyloid precursor protein). PSEN2 testing is available. APP testing is available in a
couple of places in the world, but it is still essentially a research tool. It should be
noted that PSEN2 and APP mutations are very rare. They have only been identified in
a very small number of specific family lines.
PTH
Why get tested?
To determine whether PTH levels are responding normally to changes in blood
calcium levels; to distinguish the cause of calcium imbalances, and to evaluate
parathyroid function.
When to get tested?
When calcium blood levels are higher or lower than normal, and when your doctor
wants to determine how well your parathyroid gland is functioning.

Parathyroid hormone (PTH) helps the body maintain stable levels of calcium in the
blood. It is part of a 'feedback loop' that includes calcium, PTH, vitamin D, and, to
some extent, phosphate and magnesium. Conditions and diseases that disrupt this
feedback loop can cause inappropriate elevations or decreases in calcium and PTH
levels and lead to symptoms of hypercalcemia (raised blood levels of calcium) or
hypocalcemia (low blood levels of calcium).
PTH is produced by four parathyroid glands that are located in the neck beside the
thyroid gland. Normally, these glands secrete PTH into the bloodstream in response to
low blood calcium levels. Parathyroid hormone then works in three ways to help raise
blood calcium levels back to normal. It takes calcium from the body’s bone,
stimulates the activation of vitamin D in the kidney (which in turn increases the
absorption of calcium from the intestines), and suppresses the excretion of calcium in
the urine (while encouraging excretion of phosphate). As calcium levels begin to
increase in the blood, PTH normally decreases.
How is it used?
PTH is ordered to diagnose the cause of a low or high calcium level.
High blood calcium levels (called ‘hypercalcemia’) may be due to a condition called
hyperparathyroidism, where there is overproduction of PTH by the parathyroid gland.
Hyperparathyroidism is separated into primary, secondary, and tertiary
hyperparathyroidism. Primary hyperparathyroidism is most frequently due to a
parathyroid tumor (usually benign, but vary very rarely cancerous) that secretes PTH
without feedback control. This puts PTH constantly in the “ON” position, where it
can cause hypercalcemia, and can lead to kidney stones, calcium deposits in organs,
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and decalcification of bone. With primary hyperparathyroidism, patients will
generally have high calcium and high PTH levels.
Secondary hyperparathyroidism is usually due to kidney failure. In patients with
kidney disease and/or failure, phosphate may not be excreted efficiently, disrupting its
balance with calcium. Kidney disease may also make the patient unable to produce
the active form of vitamin D, and this in turn means that they are unable to absorb
calcium properly from the diet. As phosphate levels build up and calcium levels fall,
PTH is secreted. –With secondary hyperparathyroidism, patients will generally have
high PTH levels and low or normal calcium levels.
Low blood calcium levels (called ‘hypocalcemia’) can sometimes be due to a

condition called hypoparathyroidism, where there is a failure of the parathyroid gland
to produce PTH;PTH measurement can help to diagnose this condition. PTH levels
can also be used to monitor patients who have conditions or diseases that cause
chronic calcium imbalances, and to monitor those who have had surgery or other
treatment for parathyroid tumors.
Calcium should be monitored at the same time as PTH: It is not just the levels in the
blood that are important, but the balance between, and the response of the parathyroid
to changing levels of calcium. Usually doctors are concerned about either severe
imbalances in calcium metabolism (that may require medical intervention), or in
persistent imbalances (that indicate an underlying problem).
When is it ordered?
PTH may be ordered when a test for calcium is abnormal. PTH may be ordered
when you have hypercalcemia, which may cause symptoms such as fatigue, nausea,
abdominal pain, and thirst. PTH may also be ordered when you have hypocalcemia,
which may cause symptoms such as abdominal pain, muscle cramps and tingling
fingers. Your doctor may order a PTH, along with calcium (and other tests) as a
monitoring tool when you have had treatment for diseases or conditions that affect
calcium regulation, such as the removal of a parathyroid tumor, or when you have
chronic conditions such as kidney disease.

The doctor will look to see if they are in balance as they should be. If both PTH and
calcium levels are normal then it is likely that the body’s calcium regulation system is
functioning properly.
Low levels of PTH may be due to conditions causing hypercalcaemia, or to an

abnormality in PTH production causing hypoparathyroidism. Excess PTH secretion
may be due to hyperparathyroidism, which is most frequently caused by a benign
parathyroid tumor.
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Calcium - PTH Relationship
 If calcium levels are low and PTH levels high, then PTH is responding as it
should. Depending on the degree of hypocalcaemia, your doctor may
investigate the low calcium further by looking at your vitamin D, phosphorus,
and magnesium levels.
 If calcium levels are low and PTH levels are normal or low, then PTH is not
responding and you probably have hypoparathyroidism.
 If calcium levels are high and PTH levels are high, then your parathyroid
gland is producing inappropriate amounts of PTH and your doctor may order
x-rays or other imaging studies to check for the cause and severity of
hyperparathyroidism.
 If calcium levels are high and PTH levels are low, then your calcium
regulation system is working normally but your doctor will do further
investigation to check for non-parathyroid related reasons for your elevated
calcium.

PTH is broken down into several molecular fragments including: an N-terminal, a C-
terminal, and a mid-region fragment. While each of these fragments can give the
doctor information about calcium regulation, intact PTH is measured most frequently
as it is the major biologically active form.
PTH levels will vary during the day, peaking at about 2 am. Specimens are usually
drawn about 8 am.
Drugs that may increase PTH levels include: phosphates, anticonvulsants, steroids,
isoniazid, lithium, and rifampin.
1. Can I have an abnormal PTH level without having symptoms?

Yes, if your calcium level changes slowly you may not have any noticeable
symptoms. In this case the imbalance will most likely be detected by finding an
abnormal calcium during a regular health check, then checking your PTH level.
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2. What does vitamin D have to do with PTH?
If you do not have enough vitamin D, your body will not be able to absorb calcium
properly. Vitamin D regulates the intestinal absorption of calcium, while PTH
regulates the activation of vitamin D. Too much and too little vitamin D can
imbalance calcium metabolism.
Rheumatoid Factor
Why get tested?
To help diagnose rheumatoid arthritis (RA) and Sj?gren’s syndrome
When to get tested?
If your doctor thinks that you have symptoms of RA or Sj?gren’s syndrome.
This test detects evidence of rheumatoid factor (RF), which is a type of autoantibody.
An antibody is a protective protein that forms in the blood, typically in response to a
foreign material, usually another protein known as an antigen. Autoantibodies,
however, are antibodies that are capable of targeting one’s own proteins rather than
those of an outside agent, such as bacterial protein. Rheumatoid factors are
autoantibodies directed against a fragment of the class of immunoglobulins known as
IgG and are members of a class of proteins that become elevated in states of
inflammation. Rheumatoid factor is elevated in almost all patients with inflammation
and is, therefore, a sensitive test for monitoring the level of inflammation associated
with rheumatoid arthritis. It is not a diagnostic test, however, due to its low
specificity. Experts still do not understand exactly how RF is formed or why, but it is
believed that RF probably does not directly cause joint damage but that it helps to
promote the body's inflammation reaction, which contributes to the tissue destruction
seen in rheumatoid arthritis.
How is it used?
The test for rheumatoid factor (RF) is used to help diagnose rheumatoid arthritis
(RA). The test may also be used to help diagnose an arthritis-related condition called
Sj?gren’s syndrome. About 80% to 90% of patients with this syndrome have high
amounts of RF in their blood.
When is it ordered?
The test for RF is ordered when you have signs of RA. Symptoms may include
stiffness in your joints for a long time in the morning, swelling, nodules under your
skin, and evidence on X-rays of swollen joint capsules and loss of cartilage and bone
if the disease has progressed.
If you still have symptoms of RA but your first RF test is negative, the test may need
to be repeated. The levels vary with the degree of symptoms and inflammation and
may be negative in periods of remission or inactive disease.
The RF test also may be ordered to help diagnose Sj?gren’s syndrome. Symptoms
include extremely dry mouth and eyes, dry skin, and joint and muscle pain. Many
connective tissue disorders are autoimmune diseases, and RA and other diseases, such
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as Raynaud’s syndrome, scleroderma, autoimmune thyroid disorders, and systemic
lupus erythematosis, are common among people with Sj?gren's syndrome.
The presence of RF indicates that you may have rheumatoid arthritis (RA). Positive
RF test results are found in the majority of cases of rheumatoid arthritis. In addition,
more than 50% of patients with high levels of RF in their blood have Sj?gren’s
syndrome. Many patients with RA also have Sj?gren’s syndrome. (Women more
often have both of these diseases. About two to three times as many women as men
have RA, and women have 90% of the cases of Sj?gren’s syndrome.)
If you have a positive RF test result but do not have RA or Sj?gren’s syndrome, there
may be another reason, such as endocarditis; systemic lupus erythematosus (lupus);
tuberculosis; syphilis; sarcoidosis; cancer; viral infection; or disease of the liver, lung,
or kidney. You may also test positive if you have received skin or kidney grafts from
a person who does not have your identical genetic profile.
A negative RF test result means that you do not have RA, or it is too early in your
disease progression to detect RF, or possibly you are in a remission phase. If your
symptoms appear to be those of RA or Sj?gren’s syndrome, your doctor may order
the RF test again as your condition progresses.
The RF test has a high false positive rate, and the result must be used along with the
patient’s symptoms and history to make a diagnosis of RA, Sj?gren’s syndrome, or
another condition.
Interfering factors for the RF test generally include having many vaccinations or
lipemia (a large amount of fats in the blood) or specimen handling. Methyldopa, a
blood pressure drug, can increase the amount of RF detected by the test.
1. Does a high amount of RF mean that I have a bad case of arthritis?
Not necessarily. While it is true that high amounts of this autoantibody are found in
people with a severe, active case of rheumatoid arthritis, high RF levels may also
result from Sj?gren’s syndrome or other inflammatory conditions. Increased RF levels
in your blood also can mean that you have endocarditis; systemic lupus erythematosus
(lupus); tuberculosis; syphilis; sarcoidosis; cancer; viral infection; or disease of the
liver, lung, or kidney, among other diseases. You may also test positive if you have
received skin or kidney grafts from a person who does not have your identical genetic
profile.
2. Will my case of rheumatoid arthritis only get worse?

Not necessarily. In some people, RA lasts only a few months or perhaps a year or two
and then goes away without causing any real damage. Other people have mild or
moderate disease, with periods of worsening symptoms, called flares. Still others have
a severe form of the disease that is active most of the time and leads to serious joint
damage.
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RSV
Formal name: Respiratory Syncytial Virus
Why get tested?
To determine whether an infant, an elderly patient, or an immunocompromised patient
has respiratory syncytial virus (RSV) and to help determine whether or not RSV
season has started in your community
When to get tested?
When it is RSV season (late fall through early spring) and your doctor wants to
determine whether your runny nose, congestion, coughing and/or difficulty breathing
are due to RSV or to other causes
Sample required?
Usually a nasal aspirate or nasal wash; occasionally a nasopharyngeal (NP) swab.
RSV testing is used to detect respiratory syncytial virus, a common viral respiratory
infection. RSV tends to be seasonal, causing community epidemics in young children,
older adults, and immunocompromised patients that begin late in the fall (November
or December) and disappear in early spring. In these high-risk groups, RSV can cause
pneumonia and bronchiolitis (inflamed bronchioles, the smaller airway
passages/branches of the lower respiratory tract, often called croup). Affected patients
may have symptoms such as severe coughing, difficulty breathing, and high fevers.
Each year more than 100,000 people are hospitalized with RSV infection and,
according to the Centers for Disease Control and Prevention, about 11,000 people a
year die from its complications, with most deaths occurring in the elderly.
RSV testing detects virus that is being shed in the respiratory/nasal secretions of an
infected person. Since detectable amounts of virus are usually only shed for the first
few days of an infection, most testing must be done during this time period. There are
several methods to test for the virus, but rapid RSV antigen testing is by far the most
popular. Rapid RSV antigen tests are frequently performed on-site, in the doctor’s
office or the emergency room, with most results available within an hour. In some
cases, the sample may be collected and sent to a laboratory for a more sensitive
testing method. Results of these RSV tests are usually available the same day.
Occasionally, a doctor will order a viral culture (to grow the RSV virus) or a test to
detect the virus’s genetic material. These tests have the advantage of identifying not
only the RSV virus but also other respiratory viruses that may be present. The main
disadvantages of these tests are that they are not available in every laboratory and that
the results take longer than the rapid RSV test. This makes them less clinically useful
for evaluating an individual patient, but they can be useful for documenting that RSV
(or another virus, such as influenza) has reached a community and for identifying
outbreaks in particular populations, such as a nursing home, school, or neighborhood.
Sample collection technique is critical in RSV testing. The best and most frequently
used sample is a nasal aspirate or wash. A syringe is used to push a small amount of
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sterile saline into your nose, then gentle suction is applied (for the aspirate) or the
resulting fluid is collected into a cup (for a wash).
Sometimes, a nasopharyngeal (NP) swab is used, although it is not preferred because
of decreased virus quantity in the sample. The NP swab is collected by having you tip
your head back, then a Dacron swab (like a long Q-tip) is gently inserted into one of
your nostrils until resistance is met (about 1 to 2 inches in), then rotated several times
and withdrawn. This is not painful, but it may tickle a bit and cause your eyes to tear.
How is it used?
RSV testing is usually only ordered during the RSV season (late fall to early spring)
on patients who have moderate to severe symptoms and lower respiratory tract
involvement. It is primarily ordered on infants (between the ages of 6 months and 2
years), elderly patients, and those with compromised immune systems (such as those
who have pre-existing lung disease or who have had an organ transplant). Older
children and the rest of the general population are not routinely diagnosed/tested
because most of them will experience only relatively mild upper respiratory infections
with symptoms such as a runny nose, sneezing, coughing, sore throat, and fever.
RSV testing is also ordered to document and track the spread of RSV in the
community. Since most cases of RSV are self-limiting, community health efforts are
focused on containing and preventing the spread of RSV as much as possible to
minimize the chance of spreading the virus to high-risk patients. Treatment of RSV is
primarily supportive (minimizing pain and fever and easing breathing). Those with
mild symptoms may only be tested for RSV if it is necessary to help track its spread.
RSV testing is frequently ordered along with influenza testing if they are both known
to be present in the community. These tests are used to detect the presence of RSV (or
influenza) and to evaluate the likelihood that an individual patient’s symptoms may be
due to another cause (such as a bacterial infection).
Viral cultures (or sometimes genetic respiratory virus testing) may be ordered to help
track RSV outbreaks and to identify other viral infections that may cause clinical
symptoms similar to RSV.
When is it ordered?
RSV tests are ordered almost exclusively during “cold and flu season” – late fall to
early spring. They are ordered when a patient, usually an infant or elderly person,
presents with a lower respiratory infection and symptoms such as wheezing, severe
coughing, rapid breathing (primarily in infants), fevers, headaches, a runny stuffy
nose, and a sore throat.
When RSV has already been identified in the community, the doctor may order a
rapid RSV test to confirm the suspected diagnosis in the symptomatic patient. If
influenza is also in the community, RSV testing may be ordered along with influenza
testing to determine which virus the patient has. He may also order bacterial tests,
such as a strep test (to check for group A streptococcus, the bacteria that cause strep
throat) when the cause of the infection is unclear.
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If a rapid RSV test is positive, then it is likely that the patient has respiratory syncytial
virus. A positive viral culture or genetic viral test can confirm the presence of RSV in
the community. A positive RSV cannot, however, tell a doctor how severe a patient’s
symptoms are likely to be or how long ago they were infected (symptoms usually
appear 4-6 days after infection).
Negative rapid RSV tests may mean that you have something other than RSV or that
there is not sufficient virus in the specimen to allow it to be detected. This may be due
to either a poor specimen collection or because you are not shedding detectible levels
of virus into your respiratory secretions. Adults tend to shed less virus than infants do
and those who have had RSV for several days will shed less than those with a more
recent infection.
Most RSV infections will go away within 1 or 2 weeks. People can be, and usually
are, re-infected with different strains of RSV from year to year, although subsequent
infections tend to be less severe than the first/primary infection. Since most RSV
infections are mild, symptoms from these re-infections are usually attributed to “a
cold.” These cases of RSV are usually not formally diagnosed and are often just
treated by the patient with over-the-counter cold remedies for symptom relief.
1. Is there a blood test for RSV?
There are blood tests for RSV antibodies – the immune system’s response to the virus.
These tests can detect previous exposure to RSV, but they are not usually considered
clinically useful for diagnosing an active case of RSV.
2. Is there a vaccine like the “flu” shot to prevent RSV?

Not currently, although it is considered a high priority by researchers.
3. Are antibiotics useful when I have RSV?

No, RSV is due to a virus – not a bacteria – so antibiotic therapy is not indicated or
helpful. There is a short-term drug therapy that is given to some high-risk patients. It
does not prevent or cure RSV infection, but it minimizes lower respiratory tract
involvement (reducing the need for hospitalization in affected patients). This
immunotherapy is often used in neonates in the intensive care nursery to protect them
during RSV season. Premature infants can be especially vulnerable to RSV as they
often do not get protective antibodies from their mothers.
Rubella
Why get tested?
To determine if you have sufficient rubella antibodies to protect you from the rubella
virus; to verify a past infection or detect a recent infection
When to get tested?
Prior to or at the beginning of a pregnancy to verify immunity; if a pregnant woman
has symptoms of rubella, such as fever and rash; if a newborn shows signs of
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abnormal development or birth defects that may be caused by an in utero infection; if
there is need to verify a recent rubella infection or to verify immunity.
This test measures the presence of rubella antibodies in the blood. Antibodies are
proteins that the body creates in response to an infection or exposure to a
microorganism or other foreign substance. Rubella antibodies are produced in
response to an infection by the rubella virus. There are two types of rubella
antibodies: IgM (short-term) and IgG (long-term). The first type to appear in the
blood after exposure is the IgM rubella antibody. The level of this protein in the
blood rises and peaks within about 7 to 10 days after infection and then tapers off over
the next few weeks, except in an infected newborn where it may be detected for
several months to a year. The IgG rubella antibody takes a bit longer to appear than
the IgM, but once it does, it stays in the bloodstream for life, providing protection
against re-infection. The presence of IgM rubella antibodies in the blood can indicate
a recent infection while the presence of IgG antibodies may indicate a recent or past
rubella infection or that a rubella vaccine (a measles, mumps, rubella vaccine) has
been given and is providing adequate protection.
The rubella virus generally causes a mild infection marked by a fine red rash that
appears on the face and neck and then travels to the trunk and limbs before
disappearing a few days later. The virus is passed through nasal and throat secretions
and can cause symptoms such as fever, enlarged lymph nodes, runny nose, red eyes,
and joint pain. Symptoms may be so minimal, especially in children, that they are
not perceived as being from a viral illness. In most patients, rubella goes away within
a couple of days without any special medical treatment and causes no further health
issues. The primary concern with rubella infection is when a pregnant woman
contracts it for the first time during the first three months of her pregnancy. The
developing fetus is the most vulnerable to the virus at this time and if it is passed on to
the fetus by the mother, it can cause miscarriage, stillbirth, and/or congenital rubella
syndrome (CRS), a group of serious birth defects that will permanently affect the
child. CRS can cause delayed development, mental retardation, deafness, cataracts,
an abnormally small head, liver problems, and heart defects.
Because of the severe consequences for developing fetuses, a national campaign was
started in 1969 to immunize all children in the United States and to work to eradicate
rubella infection, first in the U.S. and then throughout the world. Prior to this time,
rubella infections would emerge as cyclic outbreaks that lasted for several years.
According to the Centers for Disease Control and Prevention, during the 1962-1965
rubella epidemic, 12.5 million cases of rubella occurred in the United States and there
were 20,000 infants that were born with CRS. Due to vaccination efforts, these
numbers have decreased drastically. In 2004, there were only 9 cases of rubella
recorded in the United States and about half of the cases occurred in people who were
born outside the U.S. (in countries without widespread vaccination programs). People
should not become complacent with this reduction, however, and assume that the
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rubella virus has gone away. Anyone who has not received the vaccination as a child
(and a few that have) is still vulnerable to rubella infection.
How is it used?
The rubella test is used to confirm the presence of adequate protection against the
rubella virus and to detect a recent or past infection. It can also be used to identify
those who have never been exposed to the virus and those who have not been
vaccinated. The IgG rubella test (usually just called a rubella test) is ordered on all
pregnant women and those planning to become pregnant to verify that they have a
sufficient amount (titer) of rubella antibodies to protect them from infection.
Both the IgM and IgG antibody tests may be ordered on a person, pregnant or not,
who has symptoms that the doctor suspects are due to a rubella infection. They may
also be ordered on a newborn that is suspected to have become infected during
pregnancy or that presents with congenital birth defects that the doctor suspects may
be due to a rubella infection.
Sometimes an IgG rubella test is ordered to provide proof of protection against the
rubella virus. This may be required of a health care worker or a person starting
college and is still ordered on women in some states as part of the blood testing
required to obtain a marriage license.
When is it ordered?
The IgG rubella test is ordered when you are pregnant, planning on becoming
pregnant, or whenever a check of immunity against rubella is required. IgM and IgG
rubella tests are ordered when a pregnant woman has a fever and rash and/or other
symptoms that may indicate a rubella infection. Since many conditions can cause
similar symptoms, the doctor will need to order the tests in order to confirm the
diagnosis. IgM and IgG tests may be ordered on a newborn when the mother was
diagnosed with a rubella infection during pregnancy and/or when a newborn is born
with birth defects (hearing loss, cardiovascular abnormalities, cataracts, central
nervous system disease) that could be due to CRS. Since IgM and IgG rubella
antibodies take some time to appear after infection, the tests may be repeated in 2 to 3
weeks to see if the antibody levels have become detectible (when initially absent) and
to determine whether the levels are rising or falling over time.
In an adult or child, the absence of IgG rubella antibodies means that the person likely
has not been exposed to the rubella virus or been vaccinated and is not protected
against it. The presence of IgG antibodies but not IgM antibodies indicates a history
of past exposure to the virus or vaccination and indicates that the person tested should
be immune to the rubella virus. The presence of IgG antibodies, but not IgM
antibodies, in a newborn means that the mother’s IgG antibodies have passed to the
baby in utero and these antibodies may protect the infant from rubella infection during
the initial six months of life. The presence of IgM antibodies in a newborn indicates
that the baby was infected during pregnancy (because the mother’s IgM antibodies do
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not pass to the baby through the umbilical cord). The presence of IgM antibodies,
with or without IgG antibodies, in a child or adult indicates a recent infection with the
rubella virus.
Occasionally, a patient will have a false positive test for IgM rubella antibodies
because the test components cross react with other proteins in their body. To confirm
the IgM result, the doctor may order an IgG test to establish a baseline level of
antibody and may repeat the IgG test again in 2-3 weeks to look for a significant
increase in the amount (titer) present, indicating a recent rubella infection.
It is possible to test for the genetic material of the virus and to culture a body fluid
sample, such as a throat swab, for the rubella virus. The rubella virus takes at least a
week or more to be detected in culture, and special molecular assays or specifically
prepared antibodies must be used to determine if the virus is present. This may
occasionally be done to help a doctor diagnose rubella infection in a newborn.
Because this procedure is complex and expensive, most diagnostic laboratories refer
this testing to a reference lab such as the Centers for Disease Control and Prevention
(CDC). The number of cases of rubella and congenital rubella is monitored by the
CDC to track the effectiveness of the rubella vaccine and to detect any outbreaks of
the disease.
1. Should pregnant women be vaccinated for rubella?
The rubella vaccine should not be given to a pregnant woman, and a woman should
avoid getting pregnant for at least one month after taking the vaccine.
2. Does the vaccine have any risks?

The vaccine contains a live virus that has been altered so it promotes an antibody
response but does not cause a rubella infection. Some people may have a rash that
lasts 2–3 weeks after vaccination and pain in their joints, especially their hands and
wrists. Side effects are rarely seen in young children who get the vaccine. Patients
who have suppressed immune systems, such as those with HIV/AIDS and cancer
patients undergoing chemotherapy, should consult with their doctors before getting a
rubella vaccine.
3. How soon after I have been exposed to the virus will I get it?
If you are going to have symptoms, the rash usually begins 15–17 days after coming
in contact with an infectious person, but it may take as long as 3 weeks. A person is
usually infectious about a week before the rash is visible and for 1-2 weeks
afterwards. A newborn who was infected during pregnancy may remain infectious for
several months.
4. What do the letters in the MMR vaccine stand for?

Measles, Mumps, and Rubella. Since all three of these are common viral illnesses,
they are contained within one vaccine. Measles is also known as Rubeola and is
different from Rubella (German Measles).
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Semen Analysis
Why get tested?
To learn about the health of your reproductive organs, particularly if your partner is
having trouble becoming pregnant, or after a vasectomy to determine if the operation
was successful
When to get tested?
When you think you might have a fertility problem or after you have had a
vasectomy.
A semen analysis measures the quantity and quality of both the liquid portion, called
semen, and the microscopic, moving cells, called sperm.
Semen is the turbid, whitish substance that is released from the penis during
ejaculation. Sperm are the cells in semen with a head and a tail that enables them to
travel to the egg. A sperm contains one copy of each chromosome (all of the male’s
genes) and fuses with the female’s egg, resulting in fertilization.
A typical semen analysis measures:
 the volume of semen,

 the semen consistency (thickness),
 sperm concentration,
 total number of sperm,
 sperm motility (percent able to move as well as how vigorously and straight
the sperm move),
 the number of normal and not normal (defective) sperm,
 coagulation and liquefaction,
 fructose (a sugar in semen),
 pH (acidity),
 the number of immature sperm, and
 the number of white blood cells (cells that indicate infection).
Additional tests may be performed if semen is abnormal, such as a test for sperm
antibodies. If assisted reproductive technology is contemplated (for example, in vitro
fertilization), sperm function tests may also be performed. Sometimes a test called
cryosurvival is done to see how well semen will survive for long-term storage, if a
couple would like to store sperm for future pregnancies.
How is it used?
A semen analysis is used to determine whether a man might be infertile—unable to
get a woman pregnant. The semen analysis has many parts and test a lot of aspects of
the semen and sperm. A semen analysis to determine fertility should be performed on
a minimum of two samples at least seven days apart over a period of two to three
months because some conditions can affect sperm levels.
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The semen analysis also can be used to count sperm after a man has a vasectomy. If
there are still a lot of sperm present in the semen, the man and his partner will have to
take precautions so that his partner will not become pregnant. He will have to return
for one or more sperm counts until the sperm are cleared from his sample(s).
When is it ordered?
A semen analysis is recommended following a vasectomy and when a physician

thinks that the patient might have a fertility problem. At least 10%-20% of married
couples experience problems conceiving. Male factors are implicated about 40% of
the time. Male infertility has many causes and some of these, such as varicocele
(enlargement of the veins draining the testes), can be treated successfully. If male
factors are involved, analysis of the semen is necessary to determine the feasibility of
using assisted reproductive technology to facilitate pregnancy.
The typical volume of semen collected is around one-half to one teaspoonful (2-6
milliliters) of fluid. Less semen would indicate fewer sperm, which would affect
fertility. More semen indicates too much fluid, which would dilute the sperm, also
impeding fertility.
Sperm concentration (also called sperm density) is measured in millions of sperm per
milliliter of semen. Normal is greater than or equal to 20 million per milliliter (and
more than 80 million sperm in one ejaculation). The fewer sperm a sample has, the
less chance a man has of getting a woman pregnant. A man who has just had a
vasectomy would want to have no sperm in his sample.
Motility is the percentage of moving sperm in a sample. The more slowly moving or
immobile sperm in a sample, the less likely it is that a man could get a woman
pregnant. The progression of the sperm is rated on a basis from zero (no motion) to 3
or higher for sperm that move in a straight line with good speed. If less than half of
the sperm are motile, a stain is used to identify the percentage of dead sperm. This is
called a sperm viability test.
Morphology analysis is the study of the size, shape, and appearance of the sperm
cells. The analysis evaluates the structure of 200 sperm, and any defects are noted.
The more abnormal sperm that are present, the lower the likelihood of fertility.
To give sperm a chance to replenish, a man should abstain from ejaculating for two to
four days before the sample is collected. Follow the instructions that are provided to
you.
Sperm are very temperature-sensitive. If collection is done at home, the sample should
be kept at room temperature (70°F/21°C) at all times. Never refrigerate the sample or
try to warm it to body temperature.
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Several factors can affect the sperm count and other semen analysis values. A man
may have a lower sperm count if he has physical damage to the testicles, has gone
through radiation treatment of his testicles, or has had exposure to certain drugs (such
as azathioprine or cimetidine). A man with a higher level of estrogens may have lower
sperm counts.
Some of the common causes of male infertility are extremely high fever, failure of the
testicles, obstruction of the tubes that carry semen to the penis, and a less than normal
amount of sperm in the sample (oligospermia).
1. What are the biggest signs of fertility in a semen analysis, out of the all of the
many things that are checked?
Sperm count (number of sperm), motility (percentage of living sperm), and
morphology (normal shape of the sperm) are most closely linked with good fertility
rates.
2. I had good motility on my first sperm sample, but later it was very low. What
could cause that?
If you had a good motility on the first reading, you may have a low sperm motility
later because of a genital infection or because of an inflamed prostate gland.
3. I would like to have my sperm tested, because my wife is having trouble

getting pregnant. For various reasons, I don’t want to have my sperm collected
in the doctor’s office. For religious reasons, I don’t want to wear a condom
during the sex act. What can I do?
Masturbation in the privacy of your home would be the best solution. A small
pinprick in the condom may be an acceptable compromise for you if you must collect
the sample during intercourse.
4. Shouldn’t they check my wife’s fertility first?

When a couple cannot become pregnant, it is much easier, less invasive, and less
expensive for the man to be tested first. A man requires only semen analysis, and the
samples can be collected and ruled out very quickly. If the man’s semen is normal,
then it makes sense to move ahead with the more invasive and expensive tests for
female infertility.
SHBG
Also known as: Testosterone-estrogen Binding Globulin (TeBG)

Formal name: Sex Hormone Binding Globulin
Why get tested?
To help evaluate whether the concentration of SHBG is affecting the amount of
testosterone available to the body’s tissues
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When to get tested?
If your total testosterone results seem inconsistent with clinical signs, suggesting a
testosterone deficiency or excess production.
The Sex Hormone Binding Globulin (SHBG) test measures the concentration of
SHBG in the blood. SHBG is a protein that is produced by the liver. It binds tightly to
testosterone, dihydrotestosterone (DHT), and estradiol (an estrogen) and transports
them in the blood in a metabolically inactive form. The amount of SHBG in
circulation is affected by age and sex, by decreased or increased testosterone or
estrogen production, and can be affected by certain diseases and conditions such as
liver disease, hyperthyroidism or hypothyroidism, and obesity.
Changes in SHBG concentrations can in turn affect the amount of testosterone that is
available to be used by the body’s tissues. Normally, about 40% to 60% of
testosterone is bound to SHBG, and most of the rest is weakly and reversibly bound to
albumin (another protein). Only about 2% is immediately available to the tissues as
free testosterone.
A total testosterone does not distinguish between bound and unbound testosterone; it
determines the overall quantity of testosterone. In many cases, this is sufficient to
evaluate excessive or deficient testosterone production; but, if a patient’s SHBG level
is not normal, then the total testosterone may not be an accurate representation of the
amount of testosterone that is available to a patient’s tissues.
How is it used?
A SHBG test is primarily ordered to help evaluate the status of a patient’s androgens
(male hormones). With men, the issue of concern is testosterone deficiency, while
with women the concern is excess testosterone production. A total testosterone may
be ordered prior to or along with a SHBG test, which can be useful in determining
whether or not a total testosterone measurement is reflecting the amount of
testosterone that is available to the body’s tissues.
SHBG and testosterone levels may be ordered on an adult male to help determine the
cause of infertility, a decreased sex drive, and erectile dysfunction, especially when
total testosterone results are inconsistent with clinical signs.
In women, small amounts of testosterone are produced by the ovaries and adrenal
glands. Even slight increases in testosterone production can disrupt the balance of
hormones and cause symptoms such as amenorrhea, infertility, acne, and hirsutism
(hair growth on the face and chest). These symptoms and others are often seen with
polycystic ovarian syndrome, a condition characterized by an excess production of
androgens. SHBG and testosterone testing may be useful in helping to detect and
evaluate excess testosterone production and/or decreased SHBG concentrations.
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For both sexes, a free testosterone, albumin level, and one or more other hormones,
such as prolactin, estradiol, and LH (lutenizing hormone) may also be performed to
help evaluate a patient’s existing balance of hormones.
Sometimes, a total testosterone and SHBG are ordered to help evaluate free androgens
by calculating the Free Androgen Index (FAI). This equation gives doctors an idea of
the quantity of testosterone that is not bound to SHBG and is calculated as follows:
FAI=Total Testosterone / SHBG.
When is it ordered?
Currently, the SHBG test is not performed frequently or routinely. In many cases,
doctors feel that the total testosterone (and perhaps free testosterone) provides
sufficient information. SHBG is ordered primarily when the total testosterone results
do not seem to be consistent with clinical signs, such as decreased sex drive in men or
hirsutism in women.
When SHBG levels are increased beyond what is expected, there is likely to be less
free testosterone available to the tissues than is indicated by the total testosterone. If
SHBG concentrations are decreased, more of the total testosterone is “bioavailable”
(not bound to SHBG).

SHBG concentrations are normally high in children of both sexes. After puberty,
SHBG levels decrease more rapidly in males than in females. Levels are normally
stable in adults and then begin to increase in the elderly male at the same time that
total testosterone levels begin to decrease. In postmenopausal women, SHBG,
testosterone, and estrogen concentrations decrease as hormone production by the
ovaries tapers off.
Bioavailable testosterone is becoming an increasingly important concept to both
doctors and researchers. It may be measured by removing the SHBG-bound
testosterone from the collected blood sample and then analyzing what’s left. An
estimate can also be calculated using the Free Androgen Index (see above).
Although SHBG is not usually ordered to diagnose or monitor these conditions,
increases in SHBG are seen with liver disease, hyperthyroidism, anorexia, and
estrogen use (replacement and oral contraceptive). Decreases in SHBG are seen with
obesity, hypothyroidism, androgen use, and Cushing’s disease.
1. Are there other uses for the SHBG test?
Not yet, but researchers are evaluating conditions in which there are changes in
testosterone and SHBG levels to see if there may be additional clinical uses for the
test.
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2. Can I change my level of SHBG?
Not directly and there is no reason to do so. The important thing is evaluating a
patient’s hormone balance. In some cases, testosterone and/or estrogen replacement
therapy may be used to correct a deficiency. Researchers are now exploring the
benefits and risks of testosterone replacement in elderly men (men undergoing
“andropause”) and postmenopausal (or surgical menopause) women. It will be some
time before it is established whether (and when) this treatment is safe, effective, and
clinically useful.
Sickle Cell
Why get tested?
To screen for the presence of sickle cell trait or to confirm the presence of sickle cell
disease
When to get tested?
If you are an American of African descent, to determine if you carry one or both
genes for sickle cell disease; prenatal screening also is available.
Blood is tested for the presence of Hemoglobin S (Hgb S), which causes sickle cell
disease. The red blood cell (RBC) is responsible for carrying oxygen from the lungs
to all tissues/organs of the body. Hemoglobin is the main component of the RBC and
exists in various forms and amounts: Hemoglobin A, Hemoglobin A2, and
Hemoglobin F. One genetic abnormality of hemoglobin is known as Hemoglobin S.
In sickle cell disease, one abnormal gene is inherited from each of the parents.
How is it used?
The test is used to screen for, and to confirm and identify, the presence and amount of
Hemoglobin S (Hgb S). In the screening test, a chemical is added to the patient’s
blood, which reduces the amount of oxygen it carries. In those who carry the sickle
cell gene, the reduced amount of oxygen will cause crystals to form. These crystals
alter the shape of the RBC, resulting in the characteristic sickle shape. To confirm and
identify the amount of Hgb S present, a test called hemoglobin electrophoresis is
performed. It involves placing a patient’s blood on a special type of paper and
subjecting it to an electromagnetic field. Different types of hemoglobin will migrate
in patterns forming unique bands that enable a definitive diagnosis.
When is it ordered?
Because sickle cell disease is a genetically inherited disorder, an individual may have
the trait (carry one mutated gene from one parent) or the disease (carries two mutated
genes, one from each parent), thus the screening test is often performed on infants and
children. If you are of African-American ancestry (8–10% of African-Americans
carry at least one gene for this trait), you may wish to be tested prior to starting a
family.
If the screening test is negative, it means that the gene for sickle cell trait is not
present. If the screening test is positive, the hemoglobin electrophoresis test must be
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performed to confirm whether one mutated gene or both are present. When the
hemoglobin electrophoresis test is performed, no Hemoglobin S is present in an
unaffected person. In those who have sickle cell trait, 20% to 40% of the hemoglobin
is Hemoglobin S. In sickle cell disease, as much as 80% to 100% of the hemoglobin
may be Hemoglobin S. In general, individuals who have sickle cell trait do not have
any significant symptoms and live a normal life. Those individuals who carry both
abnormal genes (sickle cell disease) may experience hemolytic anemia (breakdown of
red blood cells), growth impairment, jaundice, organ failure, infections, and death.
Because of this abnormal (sickle-cell) shape of the RBC in this disease, red blood
cells can become stuck in small capillary blood vessels, thereby blocking the blood
supply to various organs. Eight to 10 percent of the African-American population
carry at least one abnormal gene, and less than 1% carry both genes. A sickle cell test
can screen for presence of the abnormal gene.
The test can fail to detect hemoglobin S (sickle cell disease or trait) under the
following circumstances:
 if you have a blood transfusion within three to four months before the sickle
cell test;
 if you have the red blood cell disease polycythemia (increased red blood cell
production);
 if you test an infant less than 3 months old; or
 if you are taking certain drugs, such as phenothiazines.
Because of the severity of the disease, people of African ancestry who are planning to
have children may wish to seek counseling from their physician to ensure that neither
carries the sickle cell trait.
1. What is the treatment for sickle cell disease?

The life span of a patient with sickle cell disease has increased significantly to over 50
years of age. Common causes of death include infections, clots or occlusions of blood
vessels, and kidney failure. There is no cure for sickle cell disease. Treatment is based
on the existing symptoms at the time of crisis. This may include transfusions,
antibiotics, on-going fluid intake through intravenous (IV) solutions and/or drinking
of fluids, and medication to reduce pain. Red blood cell exchange has been used in
sickle cell crisis. More recently, bone marrow transplants have shown to be effective.
2. If I have sickle cell trait, will I still need treatment?

Patients with sickle cell trait generally do not require any long-term treatment. Under
certain circumstances, those individuals with the trait who are exposed to reduced
levels of oxygen (excessive exercise or high altitudes) may experience some crisis-
like symptoms like pain or difficult breathing.
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3. Do people who are not of African ancestry get sickle cell disease?
Sickle cell gene is found primarily among African descendents. The trait form confers
protection against the parasite that causes malaria. The trait may appear in individuals
from the Mediterranean coastal areas and may be seen in those from biracial
backgrounds.
4. Is there pre-natal testing for sickle cell disease?
Prenatal testing is available. Amniotic fluid may be tested at 14–16 weeks to provide
a definitive answer. Genetic counseling is strongly encouraged if a positive sickle
screen from one or both parents is determined.
Sodium
Why get tested?
To determine whether your sodium concentration is within normal limits and to help
evaluate electrolyte balance and kidney function; to monitor chronic or acute hyper-
or hyponatremia (high or low sodium levels)
When to get tested?
If you are experiencing dehydration, edema, problems with blood pressure, or have
non-specific symptoms; often part of routine laboratory evaluations; also to monitor
certain chronic conditions, like high or low blood pressure.
This test measures the level of sodium in the blood. Sodium is a mineral that is vital to
normal body function. It is an electrolyte, a positively charged molecule that works
with other electrolytes, such as potassium, chloride, and total carbon dioxide (CO2),
to help regulate the amount of fluid in the body. Sodium is present in all body fluids
but is found in the highest concentration in the blood and in the fluid outside of the
body’s cells. We get sodium in our diet, from table salt (sodium chloride or NaCl),
and to some degree from most of the foods that we eat. Most people have an adequate
intake of sodium. The body uses what it requires and the kidneys excrete the rest in
the urine to maintain sodium concentration within a very narrow range. It does this
by:
 producing hormones that can increase (natriuretic peptides) or decrease
(aldosterone) sodium losses in urine,
 producing a hormone that prevents water losses (antidiuretic hormone [ADH]), and
 controlling thirst. (Even a 1% increase in blood sodium will make you thirsty and
cause you to drink water, returning your sodium level to normal.)
Abnormal blood sodium is usually due to some problem with one of these systems.
When the level of sodium in the blood changes, the water content in your body also
changes. These changes can be associated with dehydration or excess fluid (edema),
especially in the legs.
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How is it used?
Blood sodium testing is used to detect hyponatremia (low sodium) or hypernatremia
(high sodium) associated with dehydration, edema, and a variety of diseases. Your
doctor may order this test, along with other electrolytes, to screen for an electrolyte
imbalance. It may be ordered to determine if a disease or condition involving the
brain, lungs, liver, heart, kidney, thyroid, or adrenal glands is causing or being
exacerbated by a sodium deficiency or excess. In patients with a known electrolyte
imbalance, a blood sodium test may be ordered at regular intervals to monitor the
effectiveness of treatment. It may also be ordered to monitor patients taking
medications that can affect sodium levels, such as diuretics.
Urine sodium levels are typically tested in patients who have abnormal blood sodium
levels to help determine whether an imbalance is from taking in too much sodium or
losing too much sodium. Urine sodium testing is also used to see if a person with high
blood pressure is eating too much salt. It is often used in persons with abnormal
kidney tests to help the doctor determine the cause of kidney damage, which can help
guide treatment.
When is it ordered?
This test is a part of the routine lab evaluation of most patients. It is one of the blood
electrolytes, which are often ordered as a group. It is also included in the basic
metabolic panel, widely used when someone has non-specific health complaints, and
in monitoring treatment involving IV fluids or when there is a possibility of
developing dehydration. Electrolyte panels and basic metabolic panels are also
commonly used to monitor treatment of certain problems, including high blood
pressure, heart failure, and liver and kidney disease.
A blood sodium test may ordered when a patient has symptoms of hyponatremia, such
as weakness, confusion, and lethargy, or symptoms of hypernatremia such as thirst,
decreased urinary output, muscle twitching, and/or agitation.
A low level of blood sodium means you have hyponatremia, which is usually due to
too much sodium loss, too much water intake or retention, or to fluid accumulation in
the body (edema). If sodium falls quickly, you may feel weak and fatigued; in severe
cases, you may experience confusion or even fall into a coma. When sodium falls
slowly, however, there may be no symptoms. That is why sodium levels are often
checked even if you don’t have any symptoms.
Hyponatremia is rarely due to decreased sodium intake (deficient dietary intake or

deficient sodium in IV fluids). Most commonly, it is due to sodium loss (Addison’s
disease, diarrhea, excessive sweating, diuretic administration, or kidney disease). In
some cases, it is due to increased water (drinking too much water, heart failure,
cirrhosis, kidney diseases that cause protein loss [nephrotic syndrome]). In a number
of diseases (particularly those involving the brain and the lungs, many kinds of
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cancer, and with some drugs), your body makes too much anti-diuretic hormone,
causing you to keep too much water in your body.
A high blood sodium level means you have hypernatremia, almost always due to
excessive loss of water (dehydration) without enough water intake. Symptoms include
dry mucous membranes, thirst, agitation, restlessness, acting irrationally, and coma or
convulsions if levels rise extremely high. In rare cases, hypernatremia may be due to
increased salt intake without enough water, Cushing syndrome, or too little anti-
diuretic hormone (called diabetes insipidus).
Sodium urine concentrations must be evaluated in association with blood levels.

Concentrations may mirror blood levels or be the opposite. The body normally
excretes excess sodium, so the concentration in the urine may be elevated because it is
elevated in the blood. It may also be elevated in the urine when the body is losing too
much sodium. In this case, the blood level would be normal to low. If blood sodium
levels are low due to insufficient intake, then urine concentrations will also be low.
1. How much salt should I eat to maintain normal sodium levels and are the
sodium requirements the same for men and women?
Most sodium comes from table salt and canned and pre-prepared foods. According to
the National Heart, Lung, and Blood Institute, adult Americans average 4–5 grams
(4,000–5,000 mg) of sodium per day. However, you only need about one tenth of that
(500 mg) to meet the needs of the body. Total daily sodium intake should not exceed
2400 mg. Here are the U.S. Recommended Dietary Allowances (RDA) for sodium for
adults (both men and women), children, and infants:
 Adults: 500mg
 Children: 400 mg
 Infants: 120-200 mg
2. Is anyone at particular risk for low or high sodium levels?

Yes. People who have diarrhea, profuse sweating, kidney disease, or congestive heart
failure may have low sodium levels.
Stool Culture
Why get tested?

To determine whether you have pathogenic bacteria in your gastrointestinal tract
When to get tested?
When you have diarrhea that lasts more than a few days and/or have blood or mucous
in your loose stools.

The stool culture is a test that allows the detection and identification of pathogenic
bacteria in the stool. In the laboratory, a small amount of a fresh fecal sample is
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applied to a variety of nutrient media (thin layers of gelatin like material in sterile
covered plastic dishes). These media are selective, each encourages the growth of
some bacteria and discourages the growth of others. Once inoculated, the media are
incubated and checked daily for bacterial growth. Bacteria that are present in the stool
grow as colonies that look like dots on the surface of the gel. The physical
characteristics of the colonies - their shape, color, and some of their chemical
properties are unique to each type of bacteria and allow them to be differentiated.
The bacteria in the stool are representative of the bacteria that are present in the
gastrointestinal tract and it is a far from sterile environment. Bacteria and fungi called
“normal flora” inhabit the gastrointestinal tract. They play an important role in the
digestion of food and they form a protective barrier against the growth of other
pathogenic bacteria. Normal flora are usually in balance but sometimes one, such as
Clostridium difficle, will become pathogenic by overgrowing. This upsets the balance
of the normal flora and may lead to the production of toxins that can irritate and
damage the intestinal tract. Bacterial overgrowth is usually a side effect of the
administration of broad-spectrum antibiotics (which depresses the growth of the other
normal flora) but it may also be seen in patients who are immunosuppressed.
Other pathogenic bacteria are usually brought into the body when someone eats food
or drinks water that has been contaminated. This may include raw or undercooked
eggs, poultry or beef, unpasteurized milk, and contaminated water from lakes,
streams, and (occasionally) from community water supplies. Those that travel outside
the U.S., especially to developing nations, may face a greater risk of being exposed to
a pathogenic bacteria. Some of these bacteria may be “true pathogens” while others
are strains of gastrointestinal bacteria that are normal flora for the locals, but cause
gastrointestinal distress to the tourist. Visitors may become infected by eating or
drinking anything that has been contaminated with the bacteria (things as simple as
tap water, ice cubes in a drink, a fresh salad, or food from a vendor’s stall).
The most common symptoms of a pathogenic bacterial infection are prolonged
diarrhea, bloody diarrhea, mucous in stool, abdominal pain, and nausea. If diarrhea
lasts more than a few days, it may lead to dehydration and electrolyte imbalance -
dangerous conditions in children and the elderly. Dehydration can cause symptoms
such as: thirst, dry skin, fatigue, light-headedness, and fever. Severely affected
patients may require hospitalization to replace lost fluids and replace lost electrolytes.
A serious complication that may occasionally arise is hemolytic uremic syndrome. It
is most frequently seen in children infected with Eschericia coli 0157:H7 and may
lead to the destruction of red blood cells and to kidney failure.
The most common pathogenic bacteria and their most frequently encountered sources
include:
 Salmonella, often found in raw eggs (even intact disinfected eggs), raw
poultry and in reptiles. Pets, such as lizards and turtles, may carry salmonella
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in their intestines without being ill themselves. Some humans may become
carriers of salmonella.
 Shigella, from fecally contaminated food and water, and from infected-person
to person when careful sanitation is not observed. For instance, it can be a
challenge to prevent the spread of shigella within a family, and in a day care or
nursing home setting.
 Campylobacter, from raw or undercooked poultry. It is the most common
cause of bacterial diarrhea in the U.S. It may become especially serious if it
spreads to bloodstream and occasionally causes long-term complications such
as arthritis, and Guillain-Barré syndrome (an autoimmune condition affecting
the nervous system).
 Escherichia coli 0157:H7 (other strains of E. coli are normal flora). Found in
raw or undercooked hamburger / beef or unpasteurized cider. Causes bloody
diarrhea and may lead to hemolytic uremic syndrome.
Others include: Staphylococcus aureus, Clostridium difficile and strains of Yersinia

and Vibrio.
How is it used?
A stool culture is used, often along with other tests such as an O&P (to look for
parasites), to help determine the cause of your prolonged diarrhea.
When is it ordered?
Stool cultures may be ordered when you have had diarrhea for several days and when
you have blood and/or mucous in your loose stools. This is especially true when you
have eaten food or drunk fluids that you or your doctor suspect may have been
contaminated with a pathogenic bacteria, such as undercooked meat or raw eggs, or
the same food that has made others ill. Recent travel outside the United States may
also suggest possible food contamination.
If you have had a previous pathogenic bacterial infection of your gastrointestinal tract
and have been treated for it or gotten better on your own, your doctor may order one
or more stool cultures to verify that the pathogenic bacteria are no longer detectable.
This can be important because in some cases people can become carriers of the
bacteria. For instance, people with Salmonella typhi may become carriers (like
"typhoid Mary") - they are not ill themselves any more but they can infect other
people.
Results are frequently reported out as “isolated” – which means the particular
pathogen was found in your stool sample, or “not isolated” - which means that
bacteria was not found. Negative results usually reflect the fact that the stool culture
was checked for pathogens at several intervals and none were found (not isolated). A
report may say something like: “no Campylobacter isolated in 24 or 48 hours,” “no
Salmonella or Shigella isolated in 24 or 48 hours,” etc. If the culture is negative for
the major pathogens, then it is likely that your diarrhea is due to another cause. It is
also possible that the pathogenic bacteria are present in the gastrointestinal tract but
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were not found in this particular stool sample. If your doctor suspects this is the case
and your symptoms continue, he may occasionally order another stool culture.
If your stool culture is positive for pathogenic bacteria, then that is the most likely
cause of your prolonged diarrhea. The stool culture report may say something like,
“Salmonella isolated, species to follow” (which means the doctor is still trying to
identify the particular type of salmonella), or “Salmonella enteritidis isolated” (which
means that you have an infection caused by this particular pathogenic bacterium).
Usually it will be a single type of bacteria causing your infection, but it is possible to
have more than one present.
Severe pathogenic bacterial infections of the gastrointestinal tract, and those causing
complications, may be treated with antibiotics but many uncomplicated cases are left
to run their course. Those patients with competent immune systems will usually get
better on their own within a week or so. Patients are instructed in how to prevent the
spread of the infection and are treated and monitored for symptoms such as
dehydration.
Pathogenic bacterial infections are monitored on a community level. Other than travel
related cases, health officials want to try to determine where your infection came from
so that they can address any potential public health concerns. For instance if your
salmonella or shigella is due to eating food from a particular restaurant, the health
department will want to investigate whether or not other people have also become ill
from their food, and visit the restaurant to determine the source of the infection,
taking steps to ensure that the spread of the infection is stopped.
1. What can be done to prevent a bacterial infection?
The best way is to not drink water or eat food that may be contaminated and to be
careful with sanitation measures such as hand washing. Food that might be
contaminated, such as raw meats and eggs should be cooked thoroughly. Cooked
foods and foods that are served raw should not touch any surfaces that may have been
contaminated. When you are traveling to developing nations, it is best to only drink
bottled water, carbonated drinks, and hot cooked foods. Avoid fresh fruits and
vegetables, limiting yourself to those that you can peel yourself. Food from food
vendors is generally not considered safe. If someone in your household has an
infection that is causing diarrhea, careful hand washing by all family members is
recommended and it may be best to have the person infected not prepare food or drink
for others until the infection is over.
2. Why must the stool sample be fresh?

Bacteria in the stool will continue to multiply. If the stool is not fresh, or in a nutrient
solution, the proportion of the different kinds of bacteria in the stool can change – no
longer representing the proportions present in the gastrointestinal tract. Overgrowth of
normal bacteria can sometimes prevent the detection of the pathogenic bacteria as can
exposing the stool sample to temperature extremes.
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3. Why shouldn’t I take an over the counter anti-diarrhea medicine when I have
infectious diarrhea?
You should only take this on the advice of your doctor. diarrhea is one of the methods
your body uses to help rid itself of the infection. If you slow down or prevent this
from happening by taking anti-diarrhea medication you can prolong the amount of
time that you are ill and sometimes make your infection worse.
4. Once I’ve had a pathogenic bacterial infection, can I be re-infected?

Generally yes. You may develop an immunity (for awhile) against the particular strain
of pathogenic bacteria that caused your infection but there are many other types and
strains of pathogenic bacteria that can make you ill if you are exposed to them.
5. What else can cause diarrhea?

diarrhea can be due to a viral infection, parasitic infection, food intolerance, due to
certain medications (directly causing diarrhea or indirectly by decreasing normal
flora), to a bowel disease or to a bowel dysfunction. Diarrhea may also be caused or
exacerbated by psychological stresses.
Strep Throat
Why get tested?
To determine if a sore throat (pharyngitis) is caused by a group A streptococcal
bacterial infection (“strep throat”)
When to get tested?
If you have a sore throat that your doctor thinks may be due to a bacterial respiratory
infection
Sample required?
A swab rubbed against your tonsils and the back of your throat.
This test identifies the presence of the bacteria Streptococcus pyogenes, also known as
group A beta-hemolytic streptococcus and group A streptococcus. Group A
streptococci can infect the back of the throat (the pharynx) and cause “strep throat,”
the most common bacterial cause of pharyngitis (sore throat).

A doctor, nurse, or other healthcare professional uses a tongue depressor to hold down
your tongue and then inserts a special swab into your mouth and rubs it against the
back of your throat and tonsils. The swab may be used to do a rapid strep test in a
doctor’s office or clinic or it may be sent to a laboratory, where a rapid strep test
and/or a throat culture is performed.
How is it used?
This test is used to determine whether a patient has pharyngitis that is due to a group
A streptococcal infection.
Most sore throats are caused by a virus and may resolve without therapy within a few
days. The bacteria group A streptococci cause pharyngitis in 5-15% of adults and 15-
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30% of children. It is important that these strep infections be promptly identified and
treated with antibiotics. Strep throat is contagious and can spread to close contacts. If
the infection is not treated, secondary complications may develop, such as rheumatic
fever (which can damage the heart) and glomerulonephritis (which affects the
kidneys). Because streptococcal infections are routinely diagnosed and treated, these
complications have become much more rare in the United States, but they do still
occur.
A rapid strep test and/or a throat culture can be used to diagnose group A streptococci
as the cause of your sore throat and allow your doctor to prescribe the proper
antibiotics for treatment.
If results of the rapid test, which takes 10 - 20 minutes, are positive, further testing is
not needed and your doctor will start you on antibiotic therapy. If the rapid strep test
is negative, a culture to grow the bacteria should be done to confirm the results. A
throat culture is more accurate than the rapid strep test, but it may take several days to
get results.
When is it ordered?
Your doctor will typically order this test if you have a sore throat and a fever that
might be due to an upper respiratory infection. Symptoms vary and may include:
 sore throat
 fever
 headache
 tonsils that appear red with white or yellow spots at the back of the throat
 a swollen, tender neck
 weakness
 loss of appetite

A positive throat culture or rapid strep test indicates the presence of group A
streptococci, the bacteria that cause strep throat. A negative rapid test indicates that
you probably do not have strep throat, but the possibility cannot be ruled out until the
laboratory performs a culture. Note that recent antibiotic therapy or gargling with
some mouthwashes may affect test results.
Strep throat spreads from person-to-person through contact with respiratory secretions
that contain the streptococcal bacteria. During flu season, the early symptoms of
influenza (fever, chills, headache, sore throat, muscle pain) may mimic strep throat.
Rarely, these same symptoms may be due to a more serious acute illness, septicemia
(bacteria growing in the blood). To differentiate between strep and the flu, a rapid
strep test and a rapid influenza test may both be done. If both tests are negative and
the clinical signs warrant it, a complete blood count (CBC) may be ordered to
evaluate the patient’s white blood cells and blood cultures may be drawn to rule out
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sepsis. The treatment for each of these infections differs greatly and making a prompt
diagnosis is imperative to starting the correct therapy.
Most patients with streptococcal pharyngitis will eventually recover without antibiotic
treatment but will be contagious for a longer period of time and are at a greater risk of
developing secondary complications.
Strep throat is most common in 5- to 10- year olds. Up to 20% of school children may
be "carriers," persons who have the bacteria but who have no symptoms. Carriers can
still spread the infection to others.
1. How long does treatment for strep throat usually last?
Ten to 14 days, depending on the antibiotic prescribed.
2. How long should I stay away from other people if I have a positive test result?
You should complete at least 24 hours of antibiotics before close respiratory contact
with others.
3. When can my child go back to school?

Usually after one full day of therapy and absence of significant fever
4. If one child in my family has strep throat, is everyone going to get sick?
Other family members, including adults, can contract an infection from the bacteria.
The doctor will usually test all family members who have sore throats and may in
some instances want to test the whole family for strep throat. Although antibodies
may protect those who have had previous strep infections, there are so many serotypes
of this organism that being immune to all of them is unlikely. Therefore, people can
get strep throat again and again.
5. What is an ASO test and how is it used to detect a strep infection?

Antistreptolysin O (ASO) is a blood test used to help diagnose a current or past
infection with group A strep (Streptococcus pyogenes). It detects antibodies to
streptolysin O, one of the many strep antigens. This test is rarely ordered now
compared to thirty years ago. For an acute strep throat infection, this test is not
performed; the throat culture is used. However, if a doctor is trying to find out if
someone had a recent strep infection that may not have been diagnosed, this test could
be helpful. In addition, it may be used to help diagnose rheumatic fever, which occurs
weeks after a strep throat infection when the throat culture would no longer be
positive.
6. Do other group A streptoccous infections occur?

Group A streptococcus can also cause infections that occur separately from strep
throat, such as impetigo (a relatively common skin infection) and (rarely) more
invasive conditions such as toxic shock syndrome or necrotizing faciitis (the so-called
“flesh-eating bacteria”).
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Susceptibility Testing
Introduction
The world is teeming with microorganisms - bacteria, fungi, parasites, and viruses.
Our immune systems have evolved to fight those that threaten us and to co-exist
peacefully with countless others. Every person has a balance of normal flora, a
mixture of microorganisms that live on the surface of the skin and in the digestive
tract. In general, these tiny life forms are helpful, aiding in the digestion of food and
serving as a barrier against pathogenic (disease-causing) microorganisms. Most cause
no problems unless there is a disruption in the balance, the patient’s immune system is
depressed, or an injury or stressor creates a breach in the immune system’s protection.
If this happens, there may be an opportunistic overgrowth of one type of normal flora,
or one or more pathogenic microorganisms may find their way into the body and
cause an infection.
When a patient’s immune system cannot rid itself of a pathogen, or restore its normal
flora balance, then doctors turn to antimicrobials for assistance. These are drugs
(antibacterial, antiviral, and antifungal) that have been developed to combat the
offending microorganisms. They target different physical characteristics of the “bug”
– such as its ability to multiply, its cell wall, or metabolism. Different antimicrobials
are effective against different kinds of microorganisms. Some are narrowly focused,
meant to eliminate one specific family of bacteria, for instance, without disrupting the
balance of normal flora. Others are broad spectrum, developed to inhibit the growth of
many microorganisms. When used, broad spectrum antimicrobials may affect both
pathogens and normal flora.
Some microorganisms are resistant to certain antimicrobials, however. Susceptibility

testing is often used to determine the likelihood that a particular drug treatment
regimen will be effective in eliminating or inhibiting the growth of the infection. The
remainder of this article explains how susceptibility (also called “sensitivity”) testing
is performed and how drug resistance occurs, focusing exclusively on bacterial
infections. (A companion piece focusing on viral resistance and susceptibility testing
will soon follow.)
Bacterial Susceptibility Testing

When a doctor suspects that a patient has a bacterial infection, he orders a “culture
and susceptibility test” to help determine the cause. (Your doctor may refer to this as a
“culture and sensitivity,” - sensitivity is a more casual term for susceptibility that has
been widely used.) Susceptibility is the likelihood that a particular antimicrobial will
be effective in killing or sufficiently inhibiting the growth of specific pathogen that is
causing an infection. Susceptibility testing measures whether or not the
microorganism can grow when it is exposed to a variety of antimicrobials in a
laboratory test.
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A culture of the infected area must be done to obtain the organism for identification
and to allow susceptibility testing to be performed if warranted. Referred to by the
type of body fluid or cells collected (such as: blood culture, urine culture, sputum
culture, wound culture, etc.), the culture involves incubating a sample at body
temperature in a nutrient- rich environment. This process promotes the growth
(replication) of any microorganisms present in the sample. Samples from the skin,
stool, or sputum will grow normal flora as well as pathogenic bacteria if they are
present. Other body samples, such as blood and urine, are usually sterile; they will
show little or no growth unless a pathogenic microorganism is present.
The pathogenic bacteria are isolated (separated out from any other microorganisms
present) and identified using biochemical and enzymatic tests. Each type of bacteria
that may be clinically significant in the specimen (a pathogen) is tested individually to
determine the ability of antimicrobials to inhibit its growth. Susceptibility testing is
performed by growing the pure bacterial isolate in the presence of varying
concentrations of several antimicrobials and then examining the amount of growth to
determine which antimicrobials at which concentrations inhibit the growth of the
bacteria. Results of the testing are reported as “Susceptible” (likely, but not
guaranteed to inhibit the pathogenic microorganism), “Intermediate” (may be
effective at a higher than normal concentration), and “Resistant” (not effective at
inhibiting the growth of the organism). If there is more than one pathogen, the
laboratory will report results for each one.
Doctors choose an appropriate antimicrobial agent from those on the report that were
categorized as “Susceptible.” If there are no “Susceptible” choices, then the doctor
may select one categorized as “Intermediate.” This may mean a higher dosage of
antimicrobial and may involve a longer duration of therapy and a higher risk for
medication side effects. A pathogen may be “Resistant” to all of the antimicrobials
that are usually used to treat that type of infection. If this is the case, then the doctor
may prescribe a combination of antibiotics that work together to inhibit the bacteria
when neither one alone will be effective. These drug therapies may be more expensive
and have to be given intravenously, sometimes for extended periods of time. Some
infections due to resistant bacteria have proven very difficult to treat.
Bacterial Resistance
Bacterial resistance may be innate (natural) or acquired. Some bacteria have an innate
resistance to the specific target (bacterial multiplication, cell wall, or metabolism) of a
particular type of antimicrobial. This resistance is part of the bacteria’s normal
physical characteristics. Since bacteria multiply very rapidly, they go through many
generations in a short period of time. There is always the potential for antimicrobial
resistance to arise through a genetic change (mutation). If this change gives the
bacteria a survival advantage, it may be passed on to subsequent generations.
An acquired resistance may develop through a selection process. When a patient is

treated with an antimicrobial, the most susceptible bacteria are the ones that are killed
first. If treatment is stopped before all of the pathogenic bacteria are killed, the
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survivors may develop a resistance to that particular antimicrobial. The next time they
are exposed to the same drug, it may be ineffective as the bacteria and their progeny
are likely to retain resistance to that antimicrobial.
Resistance can also develop when bacteria that are resistant share their genetic
material with susceptible bacteria. This may occur more frequently in a healthcare
setting, where many patients are treated with antimicrobials and many have
compromised immune systems. For instance, resistant strains of bacteria, such as
MRSA (methicillin resistant Staphylococcus aureus), have been a problem in
hospitals for decades and are now becoming common in the community.
When a resistance trait arises in bacteria, for whatever reason, the resistant organism
may spread to other people, throughout a community, and potentially across the
world. Once a strain of bacteria has become resistant to one or more drugs, the only
recourse is to try to inhibit its spread and to try to find another drug that will kill it.
The second or third choice drugs that are available are often more expensive and toxic
(associated with more side effects). This challenge is compounded by the fact that
bacteria are becoming resistant faster than new antimicrobials are being developed.
Prevention
Sooner or later, every antimicrobial will have one or more strains of bacteria that are
resistant to it, and eventually its usefulness will diminish. The best that we can do is to
try to push that time further into the future, to use antimicrobials appropriately, and
prolong the time that they are effective. Steps that we can take to do this are listed
below.
Things that you can do:
 Don’t ask your doctor for antibiotics when you don’t need them, such as when you
or your child has a viral illness, such as the common cold or flu. (For a good source of
information for parents on common illnesses in children, what causes them, and
appropriate treatments, visit the following link:
http://www.dobugsneeddrugs.org/parents/index.html.)
 When prescribed, take the full course of antibiotics as instructed.
 Don’t take your own or anyone else’s left over antibiotics.
 Limit the use of antibacterial products.
 For multi-drug resistant tuberculosis, consider taking part in directly observed
treatment (DOT) and commit yourself to the months of treatment prescribed.
Things your community and doctor can do:
 Don’t over prescribe antibiotics.
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 Track outbreaks of resistant bacteria; prompt identification, isolation, and treatment
can minimize their spread.
Things that are being done on a national level:
 Reduction of the use of antibiotics in animal feed, only use what is necessary to
keep animals healthy, not to promote faster growth. Avoid the use of antibiotics that
are also commonly used to treat people. (This is a growing area of concern as resistant
bacterial strains can arise in the treated animals and then share their resistance with
pathogenic bacteria that affect humans).
 Promotion of the wise usage of antibiotics. (There is currently a CDC campaign

underway, Get SMART, http://www.cdc.gov/drugresistance/community, that is
working to reduce inappropriate antibiotic use and to reduce the spread of resistance
to antibiotics).
Common Questions
Would a doctor ever prescribe an antibiotic without or before performing a culture?
Yes. In certain situations, a doctor may choose a therapy while a culture is incubating
and in others, he may prescribe therapy without ever ordering a culture. While it is
impossible to predict which microorganism is causing an infection unless a culture is
performed, some organisms are seen more frequently than others. For instance, most
urinary tract infections (UTIs) are caused by the bacterium Escherichia coli. Knowing
this, a doctor may rely on his experience to deduce which “bug” is most likely to be
causing the infection and to choose a drug that is effective in most cases. In addition,
there are certain life-threatening infections that must be treated immediately, with no
time to wait for the results of a culture. In other instances, a culture would not be
attempted because a specimen may not be obtainable (such as with otitis media – ear
infections) or the pathogen may not be easily isolated from other flora in the specimen
(such as with community-acquired pneumonia). In these cases, the doctor chooses
therapy to cover the most common pathogens that cause these infections.
Sweat Test
Also known as: Sweat electrolytes, Iontophoretic sweat test

Formal name: Sweat chloride
Why get tested?
To diagnose cystic fibrosis (CF)
When to get tested?
When a patient has symptoms that suggest CF; as a follow-up, confirmatory test to
help diagnose CF
Sample required?
A sweat sample collected using a special sweat stimulation procedure.
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The sweat test measures the amount of sodium and chloride in sweat. Sodium and
chloride are part of your body’s electrolyte balance, and combine to form the salt
found in sweat. They help regulate the fluid balance in your tissues. Normally,
chloride travels in and out of the body’s cells, helping to maintain electrical neutrality
and water balance. This movement occurs through a protein, the cystic fibrosis
transmembrane conductance regulator (CFTR) that serves as a channel, letting
chloride out of cells and into the surrounding fluid and also reducing sodium
absorption. Sodium levels thus usually mirror those of chloride.
Except for sperm cells in males and egg cells (oocytes) in females, every cell in the
body has 46 chromosomes, organized in 23 pairs. A gene on chromosome 7 is
responsible for the normal production of CFTR. Patients with CF have a mutated gene
on each chromosome 7. With the mutation, the CFTR protein may be dysfunctional or
totally absent. Since CFTR levels are usually highest in the epithelial cells lining the
internal surfaces of the pancreas, sweat glands, salivary glands, intestine, and
reproductive organs, these are the areas most affected by CF. Dysfunctional or absent
CFTR causes the cells to be impermeable to chloride conductance and results in
increased sodium and chloride concentrations in sweat.
Two methods of sweat analysis are most frequently used: chloride concentration and
conductivity measurement. The sweat chloride analysis is recommended as the
diagnostic test for CF. Sweat conductivity may be used to screen for CF.
A sweat sample is collected using a special sweat stimulation procedure. A tiny
amount of a sweat-stimulating liquid is applied to a small patch of skin on the arm or
leg. An electrode is then placed over the site and a weak electrical current stimulates
the area. This is a painless procedure that may create a tingling or warm sensation.
After several minutes, the area is cleaned and sweat is collected for about thirty
minutes, either into a plastic coil of tubing or onto a piece of gauze or filter paper. The
sweat obtained is then analyzed.
1. If one of my children has CF, should my other children be tested?
Yes. If the genetic mutations causing your child’s CF are known, your doctor may
prefer to test the other siblings for these specific mutations. This will let you know if
your children have CF or are just carriers. Carriers are not ill and do not need
treatment, but they may want to consider genetic counseling before they decide to
have children themselves. Some argue that testing on siblings not be done unless they
are symptomatic; testing and counseling for reproductive choices can be done later.
2. What other tests may my doctor recommend if my child has CF?

Your doctor may do other tests, such as chest X-rays as well as lung function and
pancreas function testing, to find out how severe your child’s CF is. This can guide
them in recommending a treatment plan and/or a referral to a special CF center where
your child can get expert help, advice, and monitoring.
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Syphilis
Also known as: VDRL, RPR, FTA, Darkfield microscopy
Why get tested?
To screen for syphilis infection
When to get tested?
If you have symptoms of a syphilis infection, if you have another STD, or are
pregnant
Sample required?
A scraping from a chancre in the affected area, a blood sample from a vein in your
arm, or a spinal tap, depending on the test being used.
The test is looking for evidence of Treponema pallidum, the bacterium that causes
syphilis. Syphilis is a common sexually transmitted disease. It is easily treated but can
cause severe health problems if left untreated.
There are several different screening methods and tests; therefore, different samples
are needed.
 For new infections, your doctor may take a scraping from a chancre (sore) on
the affected area (the cervix, penis, anus, or throat).
 Your doctor may draw blood from a vein in your arm for an additional test.
 If you have late or latent stages of the disease, your doctor will order a spinal
tap to check for infection of the nervous system.
How is it used?
The test is used to diagnose infection with syphilis in sexually active persons.
Pregnant women also are screened, and many states in the U.S. require a blood test for
syphilis when applying for a marriage license to prevent the spread of infection to
others, especially a newborn baby.
When is it ordered?
A doctor may order the test:
 if you have symptoms, such as a chancre (sore) on the genitals or throat;

 if you are being treated for another sexually transmitted disease, such as
gonorrhea;
 if you are pregnant, because untreated syphilis can infect and even kill a
developing fetus; or
 if you complain of non-specific symptoms that resemble those of syphilis, to
determine the exact cause of your illness.

If a scraping reveals presence of the syphilis bacterium (a positive test), you have an
infection that requires treatment with a course of antibiotics.
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The blood test detects the antibodies that the body produces to combat infection, so a
positive test indicates that you have either a current or past infection. The blood test
might not find antibodies for up to three months after exposure to the bacteria. In
addition, the antibodies remain in the body for years, so if you have had a past
infection with syphilis and were treated, your test results could still be positive.
Therefore, to avoid being retreated, keep a record of the previous treatment and show
it to your doctor.
Some syphilis tests are not highly-specific and may give a falsely positive result.
Positive tests should be retested with a more specific test method.
If you are sexually active, you should consult your doctor about any suspicious rash
or sore in the genital area.
If you are infected, tell your sexual partner(s) to get tested and treated.
If you are infected, your risk of contracting other sexually transmitted diseases
increases, including the risk of being infected with HIV, the virus that causes AIDS.
1. What are the symptoms of syphilis?
The first symptoms of syphilis may not be seen immediately. The primary stage
begins within 10 days to three months of being infected. A sore, called a chancre,
appears, usually on the part of the body exposed to your partner’s ulcer, such as the
penis or vagina. The chancre may be painless and go unnoticed, and it disappears
within a few weeks.

Secondary syphilis begins three to six weeks after the chancre appears. It is marked
by a skin rash that usually heals in several weeks or months. There may be other
symptoms as well, such as fever and sore throat. If untreated, syphilis may continue
into a latent stage, during which you have no symptoms and are no longer contagious.
However, about one-third of all cases will progress into the complications of late, or
tertiary, syphilis. In these cases, the bacteria can damage the heart, eyes, brain,
nervous system, bones, joints, or almost any other part of the body. This stage can last
for years, with the final stage leading to mental illness, blindness, other neurological
problems, heart disease, and death.
3. How is syphilis transmitted?

The bacterium is passed on through direct contact with a syphilis sore. This generally
happens through sexual contact, such as vaginal, anal, or oral sex. An infected mother
can spread the disease to her fetus, with serious and potentially fatal consequences for
the baby.
Syphilis can be treated with the antibiotic penicillin. Newly acquired infections can be
cured easily. A longer treatment may be needed to cure someone who has been
infected for more than a year.
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Tau/A?42
Also known as: Alzheimer biomarkers

Formal name: Amyloid Beta 42 peptide and Tau protein
Why get tested?
In patients with dementia, to help discriminate between Alzheimer’s Disease and
other forms of dementia
When to get tested?
Usually done in a research setting; typically ordered along with cognitive and imaging
tests in cases where dementia may be due to Alzheimer's Disease
Sample required?
A sample of cerebrospinal fluid (CSF) collected using a spinal tap.
Amyloid beta 42 peptide (A?42) and Tau are two proteins associated with the
development of neurofibrillary tangles (twisted protein fragments that clog nerve
cells) and senile plaques (areas of dead nerve cells and protein deposits) that are found
in the brains of patients with Alzheimer’s Disease (AD).
Abnormal forms of Tau, a brain phosphoprotein, make up part of the structure of

neurofibrillary tangles, while A?42, which is formed from beta amyloid precursor
protein, is associated with the creation of senile plaques. While the formation of
neurofibrillary tangles and senile plaques is a normal part of aging, in people with AD
they are present in greater numbers than in people without AD.
The roles of beta amyloid precursor protein (and A?42) and tau protein in the
development of AD are not fully understood; however, this is an active area of
research. The measurement of these two proteins in CSF is being evaluated for
potential roles in diagnosis and monitoring of AD.

Cerebrospinal fluid (CSF) samples are collected using a lumbar puncture (spinal tap)
procedure. This procedure is usually done in a hospital or clinic.
How is it used?
Tests for Tau protein and A?42 may be used as supplemental tests to help establish a
diagnosis of Alzheimer's Disease.
If a patient has symptoms of dementia, such as memory loss, behavioral changes, and
decreased ability to perform daily life functions, the doctor will do a thorough work-
up to try to determine the cause. This work-up may include a variety of cognitive tests
to assess memory and possibly scanning tests of the brain to look for abnormalities.
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Tau protein and A?42 are not currently part of a typical assessment of a patient.
However, abnormal levels of these two proteins in CSF may help distinguish AD
from other forms of dementia.
When is it ordered?
Currently, Tau protein and A?42 tests primarily are performed in research settings, in
conjunction with cognitive tests and brain scans. Some doctors may order them
outside of research settings; however, information on how to interpret the results is
limited.
In a symptomatic patient, low A?42 along with high Tau reflects an increased
likelihood of Alzheimer’s Disease, but it does not mean that the person definitely has
AD. If a patient does not have abnormal levels of these proteins, then the dementia is
more likely due to a cause other than AD.

Assessments of A?42 and Tau protein levels do not establish a diagnosis of
Alzheimer’s Disease; they represent a common finding that may be used in
conjunction with other tests and the patient’s clinical and family history to suggest a
diagnosis of AD.
In AD patients, the findings of low A?42 levels and high Tau protein levels appear to
be unrelated to the cause or the age of onset of Alzheimer’s Disease.
1. My mother has been diagnosed with Alzheimer’s disease. Shouldn’t I be tested
for A?42 and Tau protein levels to see if I am at risk?
A?42 and Tau protein levels are not screening tests. They cannot predict your risk of
having AD.
2. How is Alzheimer’s disease definitively diagnosed?

Alzheimer's Disease is currently diagnosed based on cognitive changes and by ruling
out other causes of these changes. It is definitively confirmed after death, by looking
for microscopic changes in a person’s brain tissue. The microscopic evaluation
involves looking for the number of senile plaques and neurofibrillary tangles found in
the brain. Since plaque and tangle formation is also seen in normal aging, the sample
must be compared to a control sample, normal (non-AD) brain tissue from a person of
the same age. If your doctor diagnoses you with Alzheimer’s, it will be either with
possible Alzheimer’s Disease (meaning it could be due to another cause, such as a
stroke) or probable Alzheimer’s Disease (meaning they have ruled out as many other
causes as possible AND that you have symptoms. Sometimes other indications, such
as characteristic changes on brain scans and/or low A?42 and high Tau protein levels
in CSF may be ordered to help in the diagnosis.)
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TB Skin Test
Also known as: PPD (Purified Protein Derivative), Mantoux, Latent Tuberculosis
Infection test
Formal name: Tuberculin Skin Test
Why get tested?
To help determine whether or not you may have been exposed to and become infected
by the Mycobacterium tuberculosis (TB) bacteria
When to get tested?
When you have diseases or conditions that weaken your immune system and put you
at a greater risk of developing active tuberculosis. When you have had close contact
with someone who has active TB, or work or live in a high risk environment. When
you have lived for a period of time in a foreign country where TB may be more
common. Sometimes as part of an examination prior to starting school or a new job
(such as a teacher, day-care employee, or healthcare worker).
Sample required?
No sample is required. A small amount of purified protein derivative (PPD) solution
is injected just under the first layer of skin of your inner forearm.
Tuberculosis (TB) is an infectious disease caused a bacterial infection. It may affect
many body organs, but primarily targets the lungs. Tuberculosis, caused by
Mycobacterium tuberculosis and once called consumption, has been causing death for
thousands of years.
TB may cause a latent infection or an active, progressive disease. About 90% of the
people who become infected with TB manage to control its growth and confine the
TB to a few cells in the body. The bacteria in these cells are inactive but still alive.
The patient is not sick, they do not have any symptoms, and they are not infectious,
but they do have a "latent TB infection." If the patient's immune status is later
compromised, the latent TB bacteria may begin to grow again, leading to an active
case of tuberculosis disease. This active TB does cause illness in the patient and it can
be passed to others through respiratory secretions such as sputum (spit or phlegm) or
aerosols released by coughing, sneezing, laughing, or breathing.
If it is positive, further testing will be done to look for signs of active tuberculosis.
No sample is required. The test is performed on the patient's skin. A purified protein
derivative (PPD) solution that contains TB antigens, but not live bacteria, is used to
provoke a hypersensitivity skin reaction (a red raised bump) in those who may have
been infected by TB.
A healthcare worker will wipe your inner forearm with alcohol and let the skin dry.
Using a 1cc syringe and a tiny needle, he will inject a small amount of PPD solution
just under the first layer of your skin. When done correctly, the injection forms a
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small bubble of fluid that looks like a blister. The site should be left uncovered and
undisturbed. It will need to be examined by a healthcare worker at 48 and/or 72 hours
to see if a local skin reaction has occurred.
How is it used?
The TB skin test is not a general screen but is used to screen particular populations:
 Those with diseases or conditions that weaken their immune systems, such as
those with HIV or AIDS that make them more vulnerable to a TB infection.
 Those who are in confined living conditions such as nursing homes, schools,
and correctional facilities
 Healthcare workers and others whose occupations bring them in close contact
with those who may have active TB
 Those who have been in close contact with someone who has an active case of
TB
 Those who come from or have lived for a period of time in a foreign country
where TB may be more common.
The TB skin test is also used sometimes in the evaluation of how well a person’s
immune system is working, and as part of a routine examination prior to starting
school or a new job. Since mothers can pass TB to their unborn children, pregnant
women are sometimes screened, but there are some risks involved that should be
discussed with the doctor.
The TB skin test is used to help diagnose latent TB infection before it progresses to
active disease. If your doctor suspects that you have active tuberculosis disease other
tests, such as chest X-rays and AFB cultures, are used to confirm the diagnosis.
The TB skin test is used to monitor high risk patients (usually on an annual basis). If
they have a positive reaction, other tests, such as chest X-rays, are done to check for
signs of active disease.
When is it ordered?
TB skin tests are ordered when the doctor wants to screen their patient for a latent TB
infection. They may be done yearly in those that are part of a high-risk group - either
because they have a disease that weakens their immune system or because they work
or live around others in high risk groups. TB skin tests are not used as a general
population screen (as TB is relatively rare in the U.S.), but are frequently done prior
to a person joining an at risk population, such as: going to college, or becoming a
teacher or healthcare worker.
Since TB is airborne and passed through respiratory secretions, TB skin tests may be
ordered when someone has been in close contact with a patient who has an active case
of TB (although it is usually about 6 weeks after contact and initial infection before a
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positive result would emerge) , or when you have been in a foreign country where TB
may be more common.
TB skin tests should not be done when a person has had a previous positive reaction
as they are more likely to have a severe local reaction.

At 48 or 72 hours, usually, a healthcare worker will interpret your test results by
looking at the injection site on your forearm. A positive result will form a red and
swollen circle at the site of the injection. The size (diameter) of the swollen raised
circle determines whether or not it is significant and likely due to a latent TB
infection. The size that is considered positive varies with the health status and age of
the individual. Even when infected, children, the elderly, and patients who are
severely immune compromised (such as those with AIDS) may have smaller, delayed,
or even negative reactions to the TB skin test.
Negative results may mean that you have not been exposed to TB or that it is too
early, it takes about 6 weeks after infection before a positive test can be determined. If
your doctor wants to confirm a negative result they may repeat the TB skin test.
Positive results may be due to a latent or active TB infection or occasionally due to a
false positive. Positive results may also be seen in those who have received a BCG
(bacillus Calmette-Guerin) vaccination. [This is a vaccine that is not used in the
United States but is often routinely administered in other countries that have a higher
incidence of TB.]
Positive results must be followed up by other tests such as chest X-rays to look for
signs of active TB disease. If active TB disease is suspected, AFB cultures may be
used to confirm the diagnosis.
If you have had a positive TB skin test, usually you should not have another one done.
A positive will remain positive and the skin reaction of any subsequent TB skin tests
will likely become increasingly severe - to the point that they may require medical
attention. Even a negative test may still result in moderate pain, itching, or redness. If
the test is not done according to guidelines, however, it will need to be repeated.
You may not respond to a TB skin test if you have had a recent viral infection or a
"live" vaccine for conditions such as measles, mumps, chickenpox, influenza, or if
you have overwhelming tuberculosis, another bacterial infection, or are taking
immune suppressive drugs such as corticosteroids.
1. What about the multiple puncture prong test for TB?
This is called the “tine” test and is rarely used any more. It involved the use of a
device with multiple prongs/pins that were either dipped into a tuberculin solution and
then pricked the skin, or pricked the skin through a drop of tuberculin that had been
applied to the surface of the skin. The tine test was not considered as accurate because
the amount being delivered could not be controlled. Any positive tine tests had to be
followed up with the regular TB/PPD skin test.
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2. Should I get a TB skin test if I am pregnant?
Only under your doctor’s supervision, if there is a need to do so. There have not been
enough studies done to clearly document the safety of the PPD solution during
pregnancy. On the other hand, since TB can be passed from mother to child through
the amniotic fluid during pregnancy, if you are at an increased risk of contracting TB
your doctor may want you to have a TB skin test done.
3. Are there any other ways to test for latent TB infection?

Yes, the FDA recently approved a blood test called the QFT (QuantiFERON - TB
test). It’s clinical utility has yet to be determined but it may prove useful when used in
conjunction with the TB skin test, helping to confirm or rule out latent TB infection. It
is not routinely available and, since the blood sample is only stable for about 12
hours, its use may be limited for the foreseeable future.
Testosterone
Why get tested?
To determine if your testosterone level is abnormal, which may help to explain
difficulty getting an erection (erectile dysfunction), inability of your partner to get
pregnant (infertility), or premature or delayed puberty if you are male, or the
appearance of masculine physical features if you are female
When to get tested?
If you are male and your doctor thinks that you may be infertile or if you are unable to
get or maintain an erection; if you are a boy with either early or delayed sexual
maturity; if you are a female but have male traits, such as a low voice or excessive
body hair, or are infertile.
Testosterone is a steroid hormone (androgen) made by the testes in males. Its
production is stimulated and controlled by luteinizing hormone (LH), which is
manufactured in the pituitary gland. In males, testosterone stimulates development of
secondary sex characteristics, including enlargement of the penis, growth of body hair
and muscle, and a deepening voice. It is present in large amounts in males during
puberty and in adult males to regulate the sex drive and maintain muscle mass.
Testosterone is also produced by the adrenal glands in both males and females and, in
small amounts, by the ovaries in females. In women, testosterone is converted to
estradiol, the main sex hormone in females.
How is it used?
Testosterone testing is used to diagnose several conditions in men, women, and boys.
These conditions include:
 delayed or precocious (early) puberty (boys);

 decreased sex drive (men);
 erectile dysfunction (men);
 infertility (men and women);
 testicular tumors (men); and
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 excessive body hair, also called hirsutism, and masculinization, also called
virilization (women).
When is it ordered?
In boys, the test is ordered, often along with the FSH and LH tests, if puberty is
delayed or slow in developing. Although there are differences from individual to
individual as to when puberty begins, generally by the age of 10 years, there are
hormonal and physical manifestations of the onset of puberty. A delay can occur if the
testes do not produce enough testosterone or if the pituitary does not produce enough
LH.
The test also can be ordered if a young boy seems to be undergoing a very early
(precocious) puberty with obvious secondary sex characteristics, such as an enlarged
penis, development of muscle mass, and growth of body hair. Causes of precocious
puberty in boys, due to increased testosterone, include various tumors and congenital
adrenal hyperplasia.
In men, the test may be ordered when infertility is suspected or if the patient has a
decreased sex drive or erectile dysfunction, all of which can result from low
testosterone levels.
In women, testosterone testing may be done if a patient has irregular or no menstrual
periods, is having difficulty getting pregnant, or appears to have masculine features,
such as facial and body hair, male pattern baldness, and a low voice. Testosterone
levels can rise because of tumors that develop in either the ovary or adrenal gland or
because of other conditions, such as polycystic ovarian syndrome (PCOS).
There is great variability in testosterone levels between men and a broad range in age-
related values for testosterone. It is normal for testosterone levels to decline as men
age.
However, in males, a decreased testosterone level may indicate hypothalamic or
pituitary disease or damage to the testes. Genetic diseases also can cause decreased
testosterone production in young men (Klinefelter’s, Kallman’s, and Prader-Willi
syndromes) or testicular failure and infertility (as in myotonic dystrophy, a form of
muscular dystrophy). A decreased testosterone level also can indicate impaired
testosterone production because of acquired damage to the testes, such as alcoholism,
physical injury, or viral diseases like mumps.
Increased testosterone levels in males can indicate testicular tumors , adrenal tumors
that are producing testosterone, or use of androgens (also called anabolic steroids).
Increased testosterone in boys is usually the cause of early puberty.
In women, increased testosterone levels can indicate PCOS or an ovarian or adrenal
gland tumor.

Alcoholism and liver disease in males can decrease testosterone levels. Drugs,
including androgens and steroids, can also decrease testosterone levels. Prostate
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cancer responds to androgens, so many men with advanced prostate cancer receive
drugs that lower testosterone levels.
Women taking estrogen therapy may have increased testosterone levels.
Anticonvulsants, barbiturates, and clomiphene can cause testosterone levels to rise.
1. If I have a low testosterone level, will taking supplemental testosterone help?
Maybe. Testosterone supplements, either with patches or injections, can raise
testosterone levels. They may help to relieve some symptoms and to prevent muscle
and bone loss that occurs with aging in men. However, this has not been definitively
proven, and there is concern that testosterone replacement therapy may increase the
risk of developing prostate cancer. This is because cancers grow in response to
androgens, such as testosterone. In addition, although men with erectile dysfunction
may have low testosterone, in many cases testosterone administration does not
improve the symptoms. Therefore, consult your doctor for a medical evaluation and
consultation to determine if this is the right therapy for you.
2. I am a woman, so why do I need a testosterone test?

Women’s bodies also produce testosterone but in small amounts. It is needed for
hormonal balance and to help women’s bodies to function normally. If your body is
producing too much testosterone, however, you may have more body hair than
average, have abnormal or no menstrual periods, or be infertile. A testosterone test
can help your doctor to understand what is causing your symptoms.
3. Is the amount of body hair directly proportional to the amount of testosterone

in my body?
Studies have shown a proportional relationship of testosterone levels to the amount of
body hair. The hair growth response to testosterone differs in different parts of the
body. Hence, in some men, for example, testosterone promotes hair growth in the
abdomen and back while hair growth is suppressed in the scalp, leading to male
pattern baldness. Genetics plays a major role in the expression of the 5 alpha
reductase enzyme, which converts testosterone to the hair-altering compound
dihydrotestosterone, leading to a family tendency towards balding. The drug
finasteride (propecia) inhibits the action of 5 alpha reductase, and can reverse male
pattern baldness in some men.
4. What are free and bioavailable testosterone?

Testosterone is present in the blood as "free" testosterone (2-3%) or bound
testosterone. The latter may be bound to either albumin (a serum protein) or to a
specific binding protein called Sex Steroid Binding Globulin (SSBG) or Sex Hormone
Binding Globulin (SHBG). The binding of testosterone to albumin is not very tight
and is easily reversed; so the term bioavailable testosterone (BAT) refers to the sum
of free testosterone plus albumin-bound testosterone. Alternatively, it is the fraction
of circulating testosterone that is not bound to SSBG. It is suggested that BAT
represents the fraction of circulating testosterone that readily enters cells and better
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reflects the bioactivity of testosterone than does the simple measurement of serum
total testosterone. Also, varying levels of SSBG can result in inaccurate
measurements of BAT. Decreased SSBG levels can be seen in obesity,
hypothyroidism, androgen use, and nephritic syndrome. Increased levels are seen in
cirrhosis, hyperthyroidism, and estrogen use. In these situations, measurement of free
testosterone may be more useful. However, technically, free testosterone is difficult to
measure accurately.
Therapeutic Drug Monitoring
What is therapeutic drug monitoring?
Therapeutic drug monitoring is the measurement of specific drugs at intervals in order
to maintain a relatively constant concentration of the medication in the bloodstream.
Drugs that are monitored tend to have a narrow “therapeutic range” – the quantity
required to be effective is not far removed from the quantity that causes significant
side effects and/or signs of toxicity. Maintaining this steady state is not as simple as
giving a standard dose of medication. Each person will absorb, metabolize, utilize,
and eliminate drugs at a different rate based upon their age, general state of health,
genetic makeup, and the interference of other medications that they are taking. This
rate may change over time and vary from day to day.
Not all medications require therapeutic monitoring. Most drugs have a larger
therapeutic range and can be prescribed based upon pre-established dosing schedules.
The effectiveness of these treatments is evaluated, but it is not usually necessary to
determine the concentration of the drug in the bloodstream. Examples of this include
high blood pressure medications and many of the antibiotics given to treat bacterial
infections. If the infection resolves and the blood pressure is lowered, then the
treatments have been effective.
Why is it important?
Many of the drugs that are monitored therapeutically are taken for a lifetime. They
must be maintained at steady concentrations year after year while the patient ages and
goes through life events such as pregnancies, temporary illnesses, infections,
emotional and physical stresses, accidents, and surgeries. Over time, patients may
acquire other chronic conditions that also require lifetime medication and that may
affect the processing of their monitored drugs. Examples of these conditions include
cardiovascular disease, kidney disease, thyroid disease, liver disease, and HIV/AIDS.
Therapeutic drug monitoring follows these changes and accommodates them. It
identifies patient noncompliance (when the patient does not take the medication
regularly as prescribed), identifies the effect of drug interactions (may cause drug
concentrations that are higher or lower than expected at a given dosage), and helps to
tailor dosages to fit the current needs of the specific patient. Along with tests such as
BUN, creatinine, and liver panel to check kidney and liver function, monitoring can
help identify decreases in the efficiency of and dysfunctions in the body in
metabolizing and eliminating therapeutic drugs.
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What drugs are monitored?
There are several categories of drugs that require monitoring, as summarized in the
table below.
Drug Category Drugs in that Category Treatment Use
Cardiac drugs Digoxin, digitoxin, Congestive heart failure,

quinidine, procainamide, N- angina, arrhythmias
acetyl-procainamide (a
metabolite of procainamide)
Antibiotics Aminoglycosides Infections with bacteria

(gentamicin, tobramycin, that are resistant to less
amikacin)Vancomycin, toxic antibiotics
Chloramphenicol
Antiepileptics Phenobarbital, phenytoin, Epilepsy, prevention of
valproic acid, seizures, sometimes to
carbamazepine, stabilize moods
ethosuximide, sometimes
gabapentin, lamotrigine
Bronchodilators Theophylline, caffeine Asthma, Chronic
obstructive pulmonary
disorder (COPD), neonatal
apnea
Immunosuppressants Cyclosporine, tacrolimus, Prevent rejection of
sirolimus, mycophenolate transplanted organs,
mofetil, azathioprine autoimmune disorders
Anti-cancer drugs Methotrexate Psoriasis, rheumatoid
arthritis, various cancers,
non-hodgkin's
lymphomas, osteosarcoma
Psychiatric drugs Lithium, valproic acid, some Bipolar disorder (manic

antidepressants (imipramine, depression),
amitriptyline, nortriptyline, depression</TR
doxepin, desipramine)
Protease inhibitors Indinavir, ritonavir,

lopinavir, saquinavir,
atazanavir, nelfinavir HIV/AIDS
How does TDM work?

Through years of testing, the optimum therapeutic blood level range for each drug has
been determined. In this range, most people will be effectively treated without
excessive side effects or symptoms of toxicity. The drug dosage to reach this level
must be individually determined. When a patient starts on a monitored drug (or
returns to it after an absence), the doctor adjusts the dose upwards and tests blood
concentrations frequently until the appropriate steady state level is achieved. If a
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patient’s levels are too high, the doctor will adjust them lower. Often, each different
dosage level will take a short period of time to stabilize so these corrections up and
down may take place over a few days or weeks (although if they are causing
symptoms associated with toxicity, they will be decreased relatively rapidly to relieve
these symptoms). It is important that patients work closely with their doctors during
this process and not make their own adjustments or stop taking their medication.
Abrupt changes can sometimes worsen conditions and cause acute symptoms.
Once the patient’s results are in the therapeutic range and their clinical signs indicate
that the treatment is appropriate, then the doctor may monitor the drug at regular
intervals and as needed to accommodate changes in patient status to ensure that the
drug stays in the therapeutic range. The frequency of testing required will depend on
the drug and on the needs of the patient. If treatment does not appear to be fully
effective or if the patient has either excessive side effects or signs of toxicity, then
testing will be done to see if blood concentrations have become too low or high. If
they have, then the dosage will be adjusted; if they have not, then the patient and
doctor may need to re-evaluate the use of that specific medication and consider
switching to another type of drug if it is available.
The timing of blood collection is an important part of therapeutic drug monitoring.
When a person takes a dose of a drug, the amount in the blood rises for a time period,
peaks, and then begins to fall, usually reaching its lowest level (trough) just before the
next dose. To be effective, peak levels should be below toxic concentrations and
trough levels should remain in the therapeutic range. Through experience and studies,
doctors know when to expect peaks and troughs to occur and will request blood
sample collections as either trough levels (usually drawn just before the next dose),
peak levels (timing varies depending on the drug), or sometimes will request a
random level. Consistent and accurate interpretation of the results depends on the
timing of sample collection. If a patient is unable to take their medication and have
their blood drawn at the appropriate time interval, then they should talk to their doctor
before the sample is collected.
Frequently Asked Questions
1. How does the doctor determine how much drug to give me?
There are many factors to consider. Some of them are your weight, body composition,
age, temperature, nutrition, renal, liver, and heart conditions, burns, shock, and
trauma. Your doctor takes these into account when prescribing a dosage quantity and
frequency and then tailors your medication based upon the results of therapeutic
monitoring.
2. What should I do if I forget to take my medication on time?

Do not double your dose the next time. Consult your doctor or pharmacist to find out
what you should do.
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3. Can I monitor myself at home?
No. Blood must be collected at specific times and tests must be performed using
special laboratory equipment.
TORCH
Why get tested?
To screen for several infectious diseases that can cause birth defects in newborns and
illness in adults
When to get tested?
If you become ill while pregnant or if a baby is born with congenital abnormalities
that may be caused by an infection with one of the diseases included in the panel.
TORCH is an acronym for a group of infectious diseases that can cause illness in
pregnant women and may cause birth defects in their newborns. The test is a screen
for the presence of any of the antibodies to these infections. Confirmation of an active
infection may require more specific tests.
The following tests make up the TORCH panel:
 Toxoplasmosis is a parasitic infection that can be passed from mother to baby

through the placenta during pregnancy. An infection with Toxoplasma gondii
can cause eye and central nervous system infections as well as brain and
muscle cysts. If acquired during the pregnancy, it may result in a miscarriage
or cause birth defects, though this depends on the time during the pregnancy in
which the infection was acquired by the mother. Toxoplasmosis is acquired by
ingesting the parasite when handling the excrement of infected cats, drinking
unpasteurized goat’s milk, and, most commonly, by eating contaminated meat.
 Other infections, such as syphilis, hepatitis B, enterovirus, Epstein-Barr virus,
varicella-zoster virus, and human parvovirus
 Rubella is the virus that causes German measles. If contracted early in the
pregnancy, the infant may develop heart disease, retarded growth, hearing
loss, blood disorders, vision problems, or pneumonia. Problems that may
develop during childhood include central nervous system disease, immune
disorders, or thyroid disease.
 Cytomegalovirus (CMV)is another viral infection that the mother may have
acquired. More than half of all American adults have been infected with CMV
at some point in their life and, in most cases, it does not cause severe illness. It
may pass to the fetus during the birth process but can also infect newborns
through breast milk. Infected infants may have severe problems, such as
hearing loss, mental retardation, pneumonia, hepatitis, or blood disorders.
 Herpes simplex virus (HSV)is a common viral infection. The two most
common infections with HSV are “cold sores” affecting the lips and genital
herpes. Both of these infections can recur. HSV is most commonly acquired
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through oral or genital contact. Newborns who contract the virus usually do so
during travel through the birth canal of a woman who has a genital infection
with HSV. The virus may spread throughout the newborn’s body, attacking
vital organs. Treatment with specific antiviral medication should begin as soon
as possible in the infected newborn. Even if treated, surviving babies may
have permanent damage to the central nervous system.
How is it used?
Blood may be tested from either the mother or the newborn infant to determine if the
illness observed in the newborn is caused by infection with one of the pathogens
included in the panel. A blood test can determine if the person has had a recent
infection, a past infection, or has never been exposed to the virus. Patients with recent
infection with one of the TORCH agents will have IgM antibody to the specific agent,
and those with a past infection will have an IgG antibody, which is life-long. If
neither immunoglobulin is detectable, there has been no infection with these
microorganisms.
When is it ordered?
The test is ordered if a pregnant woman is suspected of having any of the TORCH
infections. Rubella infection during the first 16 weeks of pregnancy presents major
risks for the unborn baby. If a pregnant woman has a rash and other symptoms of
rubella, laboratory tests are required to make the diagnosis. A physician cannot tell if
a person has rubella by their clinical appearance since other infections may look the
same. Women infected with toxoplasma or CMV may have flu-like symptoms that are
not easily differentiated from other illnesses. Antibody testing will help the physician
diagnose an infection that may be harmful to the unborn baby.
The test may be ordered on the newborn if the infant shows any signs suggestive of
these infections, such as exceptionally small size relative to the gestational age,
deafness, mental retardation, seizures, heart defects, cataracts, enlarged liver or
spleen, low platelet level, or jaundice.
Results are usually given as positive or negative, indicating the presence or absence of
IgG and IgM antibodies for each of the infectious agents. Presence of IgM antibodies
in the newborn indicates high likelihood of infection with that organism. IgM
antibodies produced in the mother cannot cross the placenta so presence of this type
of antibody strongly suggests an active infection in the infant. Presence of IgG and
absence of IgM antibody in the infant may reflect passive transfer of maternal
antibody to the baby and does not indicate active infection in the baby.
Likewise, the presence of IgM antibody in the pregnant woman suggests a new
infection with the virus or parasite. Further testing must be done to confirm these
results since IgM antibody may be present for other reasons. IgG antibody in the
pregnant woman may be a sign of past infection with one of these infectious agents.
By testing a second blood sample drawn two weeks later, the level of antibody can be
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compared. If the second blood draw shows an increase in IgG antibody, it may
indicate a recent infection with the infectious agent.
Use of the TORCH panel to diagnose these infections is becoming less common since
more specific and sensitive tests to detect infection are available. Relying on the
presence of antibodies may delay the diagnosis since it takes days to weeks for the
antibodies to be produced. Detection of the antigen or growing the microorganism in
culture can be done earlier in the infectious process and are more specific.
1. If I have a positive antibody test, does that mean I am infected?
A positive IgG antibody test does mean you have been infected either in the past or
present with the agent. If the blood sample is drawn close to the onset of illness, a
positive IgG probably means your exposure was more than a month ago and may have
occurred years prior to this current illness. By comparing the amount of antibody
present in two blood samples drawn 2-3 weeks apart, the physician can tell if the IgG
levels are increasing (associated with recent infection) or they are stable (associated
with past infection). Interpreting a positive IgM antibody test is more difficult since
false positive results may occur. Any positive results should be confirmed with
additional specific tests before the diagnosis is considered valid. If your doctor
suspects that you or your newborn may have one of these infections, even though the
results were negative, other tests for the suspected infection should be done.
2. What type of testing is used to confirm infection with these microorganisms?

To make the diagnosis of an active infection with one of the TORCH agents, more
specific confirmatory tests may be required. In a baby, cerebrospinal fluid testing
(requiring a lumbar puncture or “spinal tap”) is often used to confirm toxoplasmosis,
herpes and rubella; urine may be cultured for cytomegalovirus; and skin lesions may
be scraped and cultured for herpes simplex virus. Making the diagnosis of
toxoplasmosis in the pregnant woman or the baby may require additional blood
samples, which are sent to a reference lab that specializes in this testing.
Total Protein and A/G Ratio

Also known as: TP, Albumin/Globulin ratio
Why get tested?
To determine your nutritional status or to screen for certain liver and kidney disorders
as well as other diseases
When to get tested?
If you experience unexpected weight loss or fatigue or if your doctor thinks that you
have symptoms of a liver or kidney disorder.
The total protein test is a rough measure of all of the proteins in the plasma portion of
your blood. Proteins are important building blocks of all cells and tissues; they are
important for body growth and health. Total protein measures the combined amount
of two classes of proteins, albumin and globulin. Albumin is a carrier of many small
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molecules, but its main purpose is to keep fluid from leaking out of blood vessels,
while globulin proteins include enzymes , antibodies , and more than 500 other
proteins. The ratio of albumin to globulin (A/G ratio) is calculated from values
obtained by direct measurement of total protein and albumin. It represents the relative
amounts of albumin and globulins.
How is it used?
Total protein measurements can reflect nutritional status, kidney disease, liver
disease, and many other conditions. If total protein is abnormal, further tests must be
performed to identify which protein fraction is abnormal, so that a specific diagnosis
can be made.
When is it ordered?
Total protein is ordered to provide general information about your nutritional status,
such as when you have undergone a recent weight loss. It is also ordered along with
several other tests to provide information if you have symptoms that suggest a liver or
kidney disorder, or to investigate the cause of abnormal pooling of fluid in tissue
(edema).

Low total protein levels can suggest a liver disorder, a kidney disorder, or a disorder
in which protein is not digested or absorbed properly. Some laboratories also report
the calculated ratio of albumin to globulins, termed the A/G ratio. Normally, there is a
little more albumin than globulins, giving a normal A/G ratio of slightly over 1.
Because disease states affect the relative changes in albumin and globulins in different
ways, this may provide a clue to the physician as to the cause of the change in protein
levels. A low A/G ratio may reflect overproduction of globulins (such as seen in
multiple myeloma or autoimmune diseases) or underproduction of albumin (such as
occurs with cirrhosis) or selective loss of albumin from the circulation (as occurs with
nephrotic syndrome). A high A/G ratio suggests underproduction of immunoglobulins
(as may be seen in some genetic deficiencies and in some leukemias). More specific
tests, such as albumin, liver enzyme tests, and serum protein electrophoresis must be
performed to make an accurate diagnosis.

Prolonged application of a tourniquet during blood collection can result in a blood
sample that has a higher protein concentration than the rest of the circulation. This
will mean that the test result for total protein will be falsely elevated (higher than the
actual concentration in the circulation). Drugs that may decrease protein levels
include estrogens and oral contraceptives.
1. Can I test for protein levels at home?
No, there is no home test available.
2. Will a high protein diet raise my total protein?

No, increasing your intake of protein will not increase your total protein test result.
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3. What type of nutrition is recommended for optimal protein levels?
A well-balanced diet that follows the recommendations of the United States
Department of Agriculture and is summarized by the Food Pyramid.
TPMT
Also known as: Thiopurine s-methyltransferase
Why get tested?
To detect patients who are at risk of developing severe side effects if treated with the
class of thiopurine drugs that includes azathioprine, mercaptopurine, and thioguanine
When to get tested?
Prior to thiopurine drug treatment
Thiopurine drugs suppress the immune system and are used to treat patients after
organ transplants and in the treatment of a wide range of diseases, such as leukemia
(especially pediatric acute lymphoblastic leukemia), inflammatory bowel disease, and
skin disorders like eczema. The most commonly used thiopurine drug is called
azathioprine.
One person in every 300 lacks thiopurine s-methyltransferase (TPMT), which is an
enzyme that helps remove thiopurine drugs, such as azathioprine, from the body when
they are present above therapeutic levels. Individuals with no TPMT enzyme can
become severely ill if treated with normal doses of thiopurine drugs because toxic
levels of the drug accumulate. These patients develop suppression of their bone
marrow (myelosuppression), which leads to a reduction in blood cells, which in turn
can cause infection and abnormal bleeding. Such side effects can be avoided if TPMT
is measured before starting treatment.
How is it used?
TPMT is measured in patients who are about to start treatment with a thiopurine drug,
such as azathioprine, or if the doctor suspects that the patient is experiencing side
effects due to TPMT deficiency. The test identifies individuals at risk of developing
severe side effects, such as lowering of blood cell counts.
When is it ordered?
A doctor may order a blood TPMT test before starting a patient on thiopurine drug
treatment or if the doctor suspects that existing side effects may be due to a deficiency
of this enzyme.
If a patient has no detectable TPMT activity, they are at risk of developing severe side
effects to thiopurine drugs. Usually, the doctor will find an alternative drug treatment.
A low blood TPMT activity also puts the patient at risk of less serious side effects,
such as hair loss, stomach pain, diarrhea, and inflammation of their pancreas. In this
case, the doctor may reduce the dose of thiopurine drug given.
If a patient has normal blood TPMT activity, the doctor can treat the patient with a
standard dose of a thiopurine drug.
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The TPMT enzyme activity is measured in red blood cells, so if you have recently
received a transfusion of blood, the results of this test may be inaccurate.
1. What does TPMT normally do in the body?
No one really knows the answer to this question. The enzyme is found in many cells,
but interest in the enzyme is purely in looking at patients who are on thiopurine drugs.
2. I’ve heard this test can be done genetically. Is that true?

Yes. Whether or not a person has functional TPMT enzyme can be assessed not only
at the protein level but also at the DNA, or genetic, level. Functionally, the same
information is obtained and since the protein test is more established, easier and less
expensive to perform, it remains the test of choice at this time.
Trichomonas
Why get tested?
To diagnose an infection with Trichomonas vaginalis
When to get tested?
If you have symptoms of infection, including vaginal discharge or pain during
urination
Sample required?
A swab of secretions taken from the vagina in women or the urethra in men.
The test is looking for infection by Trichomonas vaginalis, a sexually transmitted,
microscopic parasite that causes vaginal infections in women and urethritis in some
men.
In women, a swab of secretions is collected from the vagina. In men, a swab is
inserted into the urethra.
How is it used?
The secretions collected on the swab are examined under a microscope or cultured to
detect the presence of Trichomonas vaginalis.
When is it ordered?
Your doctor may order the test if you complain of symptoms, such as vaginal
discharge or pain on urination. If you have an infection with another sexually
transmitted disease, your doctor might test for trichomonas as well.
antibiotics.
Trichomonas is one of the most common sexually transmitted diseases. It infects an
estimated 2 million women in the United States each year, mainly those who are 16–
35 years old.
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An infected person is at greater risk of getting other sexually transmitted diseases, so
the doctor may want to test for these other infections also.
Trichomonas infection can affect pregnancy, contributing to premature birth and low
birth weight. You should inform your physician if you may be pregnant. The doctor
may medically manage a woman who is infected and in her first three months of
pregnancy differently.
Trichomonas is one of the most common sexually transmitted diseases. It infects an
estimated 2 million women in the United States each year, mainly those who are 16–
35 years old. An infected person is at greater risk of getting other sexually transmitted
diseases, so the doctor may want to test for these other infections also.
Trichomonas infection can affect pregnancy, contributing to premature birth and low
birth weight. You should inform your physician if you may be pregnant. The doctor
may medically manage a woman who is infected and in her first three months of
pregnancy differently.
1. What are the symptoms of a trichomonas infection?
In women, the most common symptoms include a foul-smelling or frothy green
discharge from the vagina and itching or redness in and around the vagina. Other
symptoms can include pain during sexual intercourse, discomfort or swelling in the
lower abdomen or groin, and the frequent urge to urinate, often with pain and burning.
However, 50% of women with T. vaginalis infections have no symptoms.
Most infected men have no symptoms but when they do, symptoms include discharge
from the urethra, a frequent urge to urinate, and a burning sensation on urination.
2. How is trichomonas transmitted?
The parasite is transmitted through sexual contact.
It is usually treated with an antibiotic called metronidazole. Most antibiotics created
to treat bacterial infections will not be effective against this parasitic infection. All
current sexual partners must be treated at the same time or the patient is likely to
become re-infected.
4. How can it be prevented?

The Centers for Disease Control recommend the following guidelines:
 Abstain from sexual intercourse; or

 Use a latex condom properly, every time you have sexual intercourse, with
every partner.
 Limit your sexual partners. The more sex partners you have, the greater your
risk of encountering someone who has this or other STDs.
 If you are infected, your sexual partner(s) should be treated. This will prevent
you from getting reinfected.
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Triple Screen
Also known as: Triple test, AFP Maternal, msAFP, Quad Screen, 4-marker screen
Why get tested?
To assess the risk of carrying a fetus with abnormalities, such as Down syndrome
When to get tested?
Women in the 15th to 20th week of pregnancy
The msAFP screen involves three or four tests that each measure a difference
substance found in the blood: AFP, hCG, unconjugated estriol, and inhibin A. Inhibin
A is the newest marker to be added to this screen; it increases both the sensitivity and
specificity of the test.
 During development, AFP levels in fetal blood and amniotic fluid rise until
about 12 weeks, and then levels gradually fall until birth. AFP is a protein
produce by fetal tissue. AFP crosses the placenta and appears in the maternal
blood.
 hCG is a hormone produced by the placenta. Levels in maternal blood rise for
the first trimester of pregnancy and then fall to less than 10% by the end of
pregnancy.
 Unconjugated estriol is produced by the fetus through metabolism. This
production process involves the liver, adrenals, and the placenta. Some of the
unconjugated estriol crosses the placenta and can be measured in the mother’s
blood.
 Inhibin A is a hormone produced by the placenta. Inhibin is a dimer (has 2
parts) and is sometimes referred to as DIA or dimeric inhibin A. Levels in
maternal blood decrease slightly from 14 to 17 weeks gestation and then rise
again.
A baby with an open neural tube defect has an opening in its spine, head, or
abdominal wall that allows higher-than-usual amounts of AFP to pass into the
mother’s blood. The other markers are not used in the evaluation of risk for carrying a
fetus with a neural tube defect.
In pregnancies where the fetus is carrying the chromosomal defect that results in
Down syndrome, the levels of AFP and unconjugated estriol tend to be low and hCG
and inhibin A levels high.
How is it used?
msAFP is used as a preliminary screening test in pregnancy. It indicates the risk of
carrying a fetus with certain abnormalities, including Down syndrome and neural tube
defects.
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1. If the AFP result is high, there is a higher risk of the fetus having a neural tube
defect, such as spina bifida or a condition called anencephaly.
2. A mathematical calculation involving the levels of these 3 or 4 substances
(AFP, hCG, unconjugated estriol, and, sometimes, inhibin A) and
considerations of maternal age, weight, race, and diabetic status are used to
calculate a risk for Down Syndrome and a few other chromosomal
abnormalities in the fetus. This risk is compared with a cut-off . If the risk is
higher than the cut-off value, it is considered positive or increased risk.
When is it ordered?
The test is usually ordered between the 15th and 20th weeks of pregnancy.
The interpretation of a test result should be provided by a genetic counselor or
clinician who can explain the meaning of the results and offer choices about follow-
up. If a screen is positive, more definitive tests are needed to confirm a diagnosis.
These include ultrasound and perhaps amniocentesis. These tests are used to help
women and their doctors make decisions about the management of their pregnancies.
These are screening tests. Not all fetal abnormalities will give positive test results. Of
all women who have positive AFP screening results, only a very small number of
them have babies who actually have a neural tube defect or chromosomal
abnormality.
More definitive tests are needed to diagnose these abnormalities in a fetus. Multiple
gestation (for example, twin or triplet) pregnancies will cause high AFP levels. The
test result is also very dependent on accurate determination of the gestational age of
the fetus. If the gestational age of the fetus has not been accurately determined, the
results may be either falsely high or low.
In general, the risk of carrying a fetus with Down syndrome increases with the
mother’s age. About 40% of women over the age of 35 will screen positive primarily
because their age-related risk is so high.
1. What is Down syndrome?
Down syndrome is a chromosomal abnormality, sometimes called Trisomy 21.
Affected people have an extra copy of some or all of chromosome 21. Most affected
children have some retardation of growth and development. The risk of Down
syndrome increases with the mother’s age, especially in women over 40 years old. For
more information, visit the National Down Syndrome Society.
2. What is a neural tube defect?

Neural tube defects are serious birth defects: the brain, spinal cord, or their coverings
do not develop completely. There are 3 kinds of neural tube defects:
 Anencephaly: incomplete development of the brain and the skull.

 Encephalocele: a hole in the skull through which brain tissue protrudes.
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 Spina bifida: the most common neural tube defect, in which the spine does not
close properly during early pregnancy. (For more information on spina bifida,
visit the Spina Bifida Association of America.)
3. What can I do during pregnancy to prevent formation of a neural tube defect?

The U.S. Public Health Department recommends that all women of childbearing age
should take 0.4 mg of folic acid.
Troponin
Why get tested?
To determine if you have had a heart attack or injury to heart muscle
When to get tested?
2-3 times during a 12- to 16-hour period if you are having chest pain or other
symptoms that may be due to a heart attack.
This test measures the concentration of cardiac-specific troponin in your blood.
Troponin is a family of proteins found in skeletal and heart muscle fibers; it helps
muscles contract. There are three forms of troponin: C, I, and T. Cardiac troponin I
and T are different enough from the troponin I and T found in skeletal muscle that
they can be specifically tested for. These types of troponin are normally present in
very small quantities in the blood. When there is damage to heart muscle cells, cardiac
troponin I and T are released into circulation. The more damage there is, the greater
the concentration of troponin I and T.
When a patient has a heart attack, levels of troponin can become elevated in the blood
within 3 or 4 hours after injury and may remain elevated for 10 to 14 days.
How is it used?
Troponin tests are primarily ordered for people who have chest pain to see if they
have had a heart attack or other damage to their heart. Either a troponin I or a troponin
T can be performed; usually a laboratory will offer one test or the other. The troponin
test may be ordered by itself or along with other cardiac biomarkers, tests for
substances such as CK, CK–MB, and myoglobin. Troponin I and troponin T tests
have begun to replace CK and CK-MB tests because they are more specific for heart
injury (versus skeletal muscle injury) and are elevated for a longer period of time, but
many doctors still prefer to have the additional information they get by ordering more
than one cardiac biomarker.
The troponin test will usually be ordered when a patient first comes into the
emergency room and then may be ordered again at 6 and 12 hours. The troponin test
is used to help diagnose a heart attack, to detect and evaluate mild to severe heart
injury, and to separate it from chest pain that may be due to other causes. In patients
who have delayed getting treatment and have been having heart-related chest pain,
discomfort, or other symptoms such as sweating, radiating pain in the arms, shoulders,
jaw, neck, nausea, and/or lightheadedness for more than a day, the troponin test is the
test of choice. This is because it will still be elevated in the blood if the symptoms
were/are due to heart damage.
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When is it ordered?
Troponin tests are usually ordered, often along with other heart tests such as CK, CK–
MB, or myoglobin, when a patient has prolonged chest pain or other symptoms that
could be related to heart injury. Typically, troponin is done 2 or 3 times during a 12-
to 16-hour period. In patients with stable angina (predictable episodes of chest pain
related to an inadequate flow of blood to the heart that resolve with rest and/or
medication), the troponin test may be ordered when the patient’s symptoms escalate,
occur when the patient is at rest, and/or no longer ease with treatment, signs that the
angina is becoming unstable, putting the patient at a much higher risk of having a
heart attack or other serious heart problem in the near future.
Normally, troponin levels are very low; even slight elevations can indicate some
degree of damage to the heart. When the patient has significantly elevated troponin
concentrations and other clinical signs, such as an abnormal ECG (electrocardiogram
– an evaluation of the rhythm of the heart), then it is likely the patient has had a heart
attack. If CK, CK-MB, and myoglobin concentrations are normal but troponin levels
are increased, then it is likely that either a lesser degree of heart injury is present or
that the injury took place more than 24 hours in the past. If the first troponin
performed is normal but subsequent (6 hour and 12 hour samples) troponin tests are
increased, then the heart injury likely occurred within a couple of hours prior to the
first test and had not had time to increase. When a CK test is elevated but a CK-MB
(which is more heart-specific than CK) and troponin test are normal, then it is likely
that whatever symptoms are present are due to another cause, such as skeletal muscle
injury. When a patient with chest pain and/or known stable angina has normal
troponin, CK, and CK-MB concentrations, then it is likely that their heart has not
been injured.
Troponin will remain high for 1–2 weeks after a heart attack. Troponin is not
generally affected by damage to other muscles so that muscle injections, accidents,
strenuous exercise, and drugs that can damage muscle do not affect troponin levels.

Increased troponin concentrations should not be used by themselves to diagnose or
rule out a heart attack. A physical exam, clinical history, and ECG are also important.
Some people who are having a heart attack will have normal troponin concentrations,
and some people with increased troponin concentrations have no apparent heart
injury. Troponin levels may also be elevated with acute or chronic conditions such as
myocarditis (heart inflammation), congestive heart failure, severe infections, kidney
disease, dermatomyositis, and polymyositis.
Heart attack means that some of the muscle tissue in your heart has died. A medical
term for this is myocardial infarction. Most commonly, a heart attack starts with a
kind of heavy pressure or pain in the chest, often extending into the neck or left arm.
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You may have trouble catching your breath, or you may feel weak and break into a
cold sweat.
blockage is usually due to atherosclerosis (often called hardening of the arteries). This
blockage occurs gradually over many years as lipid plaques are deposited along the
walls of the blood vessels. These plaques narrow and stiffen the arteries and can
rupture unexpectedly, totally blocking off the affected artery.
Many other problems can cause chest pain, and it is not possible to tell just from the
type of chest pain whether or not you are having a heart attack. Many people have
chest pain from straining the muscles in their chest, from emotional stress, and with
some lung problems. Chest pain that occurs during exercise, hard work, or at times of
stress, lasts for a few minutes and goes away with rest is often caused by angina. A
relatively rare form of chest pain may be due to temporary heart spasms called variant
angina. These spasms usually occur at night when the patient is resting and can cause
severe but temporary pain.
If chest pain lasts longer than just a few minutes, especially if it occurs when you are
resting, seek immediate medical attention.

having a heart attack. Troponin can pick up damage to heart muscles even when there
is no other evidence of a heart attack. Myoglobin and CK, two other proteins found in
the heart and in other muscles, do not usually rise in persons with temporary chest
pain. CK is not usually elevated when heart injury is slight. In patients who have had
a heart attack, these cardiac biomarkers will rise and then fall again within 12 to 48
hours.

you have been previously diagnosed with angina and the drugs you were prescribed
do not ease the pain, seek immediate medical attention. Many people who have had a
heart attack die without ever having tried to call an ambulance or get to an emergency
room.
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Trypsin
Why get tested?
To screen for cystic fibrosis and pancreatic insufficiency by evaluating pancreas
function
When to get tested?
If you or your newborn or infant have symptoms of pancreatic insufficiency or cystic
fibrosis such as persistent diarrhea, foul-smelling bulky greasy stools, malnutrition,
and vitamin deficiency
Sample required?
A fresh stool sample, uncontaminated with urine.

Trypsin and chymotrypsin are proteolytic enzymes. Their job is to digest protein in
the small intestine. Normally, their precursors (their inactive forms: trypsinogen and
chymotrypsinogen) are produced in the pancreas and transported to the small
intestine. In the small intestine, trypsinogen is activated, turned into trypsin, by an
enzyme in the intestinal mucosa and then trypsin in turn activates chymotrypsinogen
to chymotrypsin. Together, they form powerful chemicals responsible for breaking
down the protein in food into smaller pieces called peptides. Trypsin and
chymotrypsin will be detectable in the small intestine and in the stool if the pancreas
is functioning normally.
In people with cystic fibrosis, mucous plugs can block the pancreatic ducts that lead
into the small intestine, preventing trypsinogen and chymotrypsinogen from reaching
the intestine. These mucous plugs can also block small airway passages in the lungs,
making one susceptible to respiratory infections and chronic pulmonary disease. It is
usually the respiratory complications of cystic fibrosis that eventually prove fatal for
patients with this disease.
In individuals with pancreatic dysfunction (tissue damage or blockage), there may be
either blocked pancreatic ducts or the cells that produce trypsinogen and
chymotrypsinogen may be damaged or destroyed. This is often seen in conditions
such as chronic pancreatitis and pancreatic cancer; such cell damage causes pancreatic
insufficiency, in which not enough of the enzymes reach the small intestine to digest
food properly.
A fresh stool sample is collected, uncontaminated with urine. For an infant, a urine
collection bag with adhesive edges that can be stuck to the baby’s skin and a plastic-
lined diaper are both used to keep urine out of the stool and to keep the stool from
soaking into the diaper.
How is it used?
The test is used to screen symptomatic newborns and infants for cystic fibrosis and to
evaluate both children and adults for pancreatic insufficiency.
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When is it ordered?
The trypsin/chymotrypsin test is easy and noninvasive. It is used as a screen for cystic
fibrosis and pancreatic function. It is done when a newborn or infant has symptoms of
cystic fibrosis such as persistent diarrhea, foul-smelling bulky greasy stools,
malnutrition, and vitamin deficiency. It is also ordered when a child or an adult has
these symptoms, in order to help diagnose pancreatic insufficiency.
A positive result is normal, indicating the presence of trypsin and chymotrypsin in the
stool. A negative result is not diagnostic, but it does indicate that further testing, both
for pancreatic insufficiency and for cystic fibrosis, may be indicated. Other pancreas
dysfunctions, such as acute and chronic pancreatitis, can cause negative results.
If someone's pancreas is not functioning correctly, the individual will need to be
monitored closely by his physician. He may find symptom relief and nutritional
improvement by taking doctor-prescribed oral enzymes and vitamin supplements.
1. What other tests might my doctor do to check for cystic fibrosis?
Your doctor may order newborn immunoreactive trypsin testing (IRT), sweat chloride
testing, and/or CF gene mutation testing.
2. What other laboratory tests may be done if I or my child has a negative

trypsin test?
Your doctor may order a stool test for fecal fat or a blood test for amylase or lipase to
look at other aspects of pancreas and digestive function.
Trypsinogen
Also known as: Trypsin-like immunoreactivity, Serum trypsinogen

Formal name: Immunoreactive trypsin (IRT)
Why get tested?
To screen for cystic fibrosis (CF) and pancreatic insufficiency by evaluating
pancreatic function
When to get tested?
When you or your infant have symptoms of pancreatic insufficiency such as persistent
diarrhea, foul-smelling bulky greasy stools, malnutrition, and vitamin deficiency;
these are also symptoms of cystic fibrosis (CF), so trypsinogen may be ordered as part
of newborn general population screening and/or if a newborn has meconium ileus (no
stools in the first 24 to 48 hours of life)

Trypsinogen is a proenzyme, an inactive precursor to the proteolytic enzyme trypsin.
Normally, trypsinogen is produced in the pancreas and transported to the small
intestine. In the small intestine, it is activated, turned into trypsin by an enzyme in the
intestinal mucosa, forming a powerful chemical responsible for breaking down the
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protein in food into smaller pieces called peptides.
In people with cystic fibrosis, mucous plugs can block the pancreatic ducts that lead
into the small intestine, preventing trypsinogen from reaching the intestine and
preventing the breakdown of food proteins. Infants are screened using a test called
immunoreactive trypsin (IRT). Those newborns with CF may have elevated levels of
IRT in their blood for several months, whereas in normal infants, any temporary false-
positive elevations in trypsinogen will usually fall to normal low levels within a few
weeks.
In other diseases, such as chronic pancreatitis and pancreatic cancer, pancreas tissue
damage may cause blockages that prevent trypsinogen from reaching the small
intestine. The cells that produce trypsinogen can also become damaged or be
destroyed, decreasing the body's supply. Both blockages and cell damage can cause
pancreatic insufficiency.
How is it used?
Immunoreactive trypsin (IRT) is used as part of a newborn screening program to
screen for an increased risk of cystic fibrosis and is used to help diagnose pancreatic
insufficiency in both children and adults.
When is it ordered?
This test is ordered as part of a newborn screen for cystic fibrosis, in cases of
meconium ileus (no stools in the first 24 to 48 hours of life), and as an initial test for
cystic fibrosis in symptomatic young infants who are not creating enough sweat to do
a sweat chloride test. A trypsinogen test is also ordered when children or adults
present with symptoms suggesting cystic fibrosis and pancreatic dysfunction such as
persistent diarrhea, foul-smelling bulky greasy stools, malnutrition, and vitamin
deficiency.
Trypsinogen testing is not diagnostic; there are a fair number of false positives and
problems other than CF and pancreatic dysfunction that can cause a positive IRT. An
elevated level must be followed with other testing. When diagnosing CF, this may
include another IRT in a month, CF gene mutation testing, and/or sweat chloride
testing.
If an IRT level is elevated, an infant may have cystic fibrosis; an infant or adult may
have abnormal pancreatic enzyme production, pancreatitis, or pancreatic cancer; or
the elevated IRT may be a false positive. Elevated levels need to be followed with
further testing. If the IRT level is negative but the infant is symptomatic, other testing
for CF, such as sweat chloride and/or CF gene mutation testing, should be considered.

IRT testing will not identify heterozygous carriers of a CF mutation. Their
trypsinogen production and function will not be affected. In patients who do have CF,
the degree of IRT elevation does not reflect the severity of the disease.
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1. What other tests might my doctor do to check for pancreas function?
Your doctor may order a stool test for fecal fat or trypsin/chymotrypsin or a blood test
for amylase or lipase to look at other aspects of pancreas and digestive function.
Tumor Markers
What are they?

Tumor markers are substances, usually proteins, that are produced by the body in
response to cancer growth or by the cancer tissue itself. Some tumor markers are
specific, while others are seen in several cancer types. Many of the well-known
markers are also seen in non-cancerous conditions. Consequently, these tumor
markers are not diagnostic for cancer.
There are only a handful of well-established tumor markers that are being routinely
used by physicians. Many other potential markers are still being researched. Some
marker tests cause great excitement when they are first discovered but, upon further
investigation, prove to be no more useful than markers already in use.
The goal is to be able to screen for and diagnose cancer early, when it is the most
treatable and before it has had a chance to grow and spread. So far, the only tumor
marker to gain wide acceptance as a general screen is the Prostate Specific Antigen
(PSA) for men. Other markers are either not specific enough (too many false
positives, leading to expensive and unnecessary follow-up testing) or they are not
elevated early enough in the disease process.
Some people are at a higher risk for particular cancers because they have inherited a
genetic mutation. While not considered tumor makers, there are tests that look for
these mutations in order to estimate the risk of developing a particular type of cancer.
BRCA1 and BRCA2 are examples of gene mutations related to an inherited risk of
breast cancer and ovarian cancer. For more information, see our overview on genetic
testing.
Why are they done?
Tumor markers are not diagnostic in themselves. A definitive diagnosis of cancer is
made by looking at biopsy specimens (e.g., of tissue) under a microscope. However,
tumor markers provide information that can be used to:
 Screen. Most markers are not suited for general screening, but some may be
used in those with a strong family history of a particular cancer. In the case of
genetic markers, they may be used to help predict risk in family members.
PSA testing for prostate cancer is an example.
 Help diagnose. In a patient that has symptoms, tumor markers may be used to
help identify the source of the cancer, such as CA-125 for ovarian cancer, and
to help differentiate it from other conditions. Remember that tumor markers
cannot diagnose cancer themselves but aid in this process.
 Stage. If a patient does have cancer, tumor marker elevations can be used to
help determine how far the cancer has spread into other tissues and organs.
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 Determine prognosis. Some tumor markers can be used to help doctors
determine how aggressive a cancer is likely to be.
 Guide Treatment. Some tumor markers, such as Her2/neu, will give doctors
information about what treatments their patients may respond to (for instance,
breast cancer patients who are Her2/neu positive are more likely to respond to
Herceptin treatment).
 Monitor Treatment. Tumor markers can be used to monitor the effectiveness
of treatment, especially in advanced cancers. If the marker level drops, the
treatment is working; if it stays elevated, adjustments are needed. The
information must be used with care, however. CEA, for instance, is used to
monitor colorectal cancer, but not every colorectal cancer patient will have
elevated levels of CEA.
 Determine recurrence. Currently, one of the biggest uses for tumor markers is
to monitor for cancer recurrence. If a tumor marker is elevated before
treatment, low after treatment, and then begins to rise over time, then it is
likely that the cancer is returning. (If it remains elevated after surgery, then
chances are that not all of the cancer was removed.)
Common Tumor Markers Currently in Use

Usual
Tumor Markers Cancers What else? When/How Used
Sample
AFP (Alpha-feto Liver, germ cell Also elevated Help diagnose, monitor Blood
protein) cancer of ovaries or during treatment, and
testes pregnancy determine recurrence
B2M (Beta-2 Multiple myeloma Present in many Determine prognosis Blood
microglobulin) and lymphomas other conditions,
including
Crohn’s disease
and hepatitis;
often used to
determine cause
of renal failure
BTA (Bladder Bladder Gaining Help diagnose and Urine
tumor antigen) acceptance determine recurrence
CA 15-3 Breast and others Also elevated in Stage disease, monitor Blood
(Cancer antigen including lung, benign breast treatment, and
15-3) ovarian conditions; determine recurrence
doctor can use
CA 15-3 or CA
27.29 (two
different assays
for same
marker)
CA 19-9 Pancreatic, Also elevated in Stage disease, monitor Blood
(Cancer antigen sometimes pancreatitis and treatment, and
19-9) colorectal and bile inflammatory determine recurrence
ducts bowel disease
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CA 72-4 Ovarian No evidence Help diagnose Blood
(Cancer antigen that it is better
72-4) than CA-125 but
may be useful
when combined
with it
CA-125 (Cancer Ovarian Also elevated Help diagnose, monitor Blood
antigen 125) with endo- treatment, and
metriosis, some determine recurrence
other diseases
and benign
conditions; not
recommended
as a general
screen
Calcitonin Thyroid medullary Also elevated in Help diagnose, monitor Blood
carcinoma pernicious treatment, and
anemia and determine recurrence
thyroiditis
CEA (Carcino- Colorectal, lung, Elevated in Monitor treatment and Blood
embryonic breast, thyroid, other conditions determine recurrence
antigen) pancreatic, liver, such as
hepatitis, COPD,
cervix, and bladder
colitis,
pancreatitis, and
in cigarette
smokers
EGFR (Her-1) solid tumors, such Not available in Guide treatment and Tissue
as of the lung (non every laboratory determine prognosis
small cell), head
and neck, colon,
pancreas, or breast
Breast Increased in Determine prognosis Tissue
hormone- and guide treatment
Estrogen dependent
receptors cancer
hCG (Human Testicular and Elevated in Help diagnose, monitor Blood, urine
chorionic trophoblastic pregnancy, treatment, and
gonadotropin) testicular failure determine recurrence
Breast Oncogene that Determine prognosis Tissue
is present in and guide treatment
Her-2/neu multiple copies
in 20-30% of
invasive breast
cancer
Monoclonal Multiple myeloma Overproduction Help diagnose, Blood, urine
immunoglobulin and Waldenstrom’s of an monitor treatment, and
s macroglobulinemia immunoglobulin determine recurrence
or antibody,
usually detected
by protein
electrophoresis
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NSE (Neuron- Neuroblastoma, May be better Monitor treatment Blood
specific small cell lung than CEA for
enolase) cancer following this
particular kind of
lung cancer
NMP22 Bladder Not widely used Help diagnose and Urine
determine recurrence
Progesterone Breast Increased in Determine prognosis Tissue
receptors hormone- and guide treatment
dependent
cancer
PSA (Prostate Prostate Elevated in Screen for and help Blood

specific benign prostatic diagnose, monitor
antigen), total hypertrophy, treatment, and
and free prostatitis and determine recurrence
with age
Prostate-specific Prostate Not widely used, Help diagnose Blood
membrane levels increase
antigen (PSMA) normally with
age
Prostatic acid Metastatic prostate Not widely used Help diagnose Blood
phosphatase cancer, myeloma, anymore,
(PAP) lung cancer elevated in
prostatitis and
other conditions
S-100 Metastatic Not widely used Help diagnose Blood
melanoma
TA-90 Metastatic Not widely used, Help diagnose Blood
melanoma being studied
Thyroid Used after Determine recurrence Blood
thyroid is
Thyroglobulin removed to
evaluate
treatment
Uric Acid
Why get tested?

To detect high levels of uric acid, which could be a sign of the condition gout
When to get tested?
When your doctor thinks that you might have gout or when monitoring certain
chemotherapy or radiation therapies for cancer

Uric acid is a product of the metabolism (breakdown) of purines. Purines are
chemicals that come from both the breakdown of foods and nucleic acids (DNA) in
the body. If uric acid levels in the body are low, there are no symptoms. Doctors don't
need to test for low levels of uric acid.
Too much uric acid, however, can gather in the body, and this condition should be
tested for. Because uric acid is a waste product, the body must get rid of it. Two-thirds
of uric acid is disposed of in the urine; the remainder is disposed of in the feces.
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Excess uric acid can cause the condition called gout. This can be a result of
overproduction of uric acid or a decreased ability of the kidneys to secrete uric acid.
Other reasons for high uric acid include leukemia or multiple myeloma (types of
cancer), high blood pressure during pregnancy, alcoholism, Down syndrome, lead
poisoning, poor diet, liver disease, obesity, and psoriasis. Stress or very strenuous
exercise also can raise uric acid levels. Failure of the kidneys, which means the body
is not able to get rid of uric acid fast enough, is another cause of high uric acid levels.
A person undergoing chemotherapy or radiation also can have dangerous levels of
uric acid in the blood due to the breakdown of tumor cells and the release of purines
(and thus uric acid) into the blood. Many drugs also can affect uric acid levels.
How is it used?
The uric acid test is used to learn whether the body might be breaking down cells too
quickly or not getting rid of uric acid quickly enough. The test also is used to monitor
levels of uric acid when a patient has had chemotherapy or radiation treatments.
When is it ordered?
The uric acid test is ordered when a doctor suspects high levels of uric acid. Often
patients with high levels of uric acid will be suffering from pain in their toes or joints.
These patients often have a disease called gout, which is an inherited disorder that
affects purine breakdown. The test may also be ordered if a patient appears to have
failing kidneys.
The test also is ordered as a monitoring test when a patient has undergone
chemotherapy or radiation, to learn whether uric acid levels are getting dangerously
high. Monitoring also can be done when a patient is found to have gout or renal
failure. Patients who have high uric acid levels are generally put on a drug regimen to
help lower uric acid levels.
Higher than normal uric acid levels mean that the body is not handling the breakdown
of purines well. The doctor will have to learn the cause of the over-production of uric
acid, or whether the body is unable to clear away the uric acid, because of kidney
failure.
Higher than normal levels of uric acid must be treated. Uric acid can cause white
crystals of the acid to form in the body joints, which are the cause of the painful signs
of gout. Uric acid can also form kidney stones or otherwise damage the kidneys.
There has been some discussion among doctors about the exact limits of a "normal"
test result for uric acid. The range of normal results is wide. Uric acid levels can vary
every day in the same patient or throughout the year. Sometimes doctors will order
several uric acid tests over a period of time to get a better idea of a patient's level of
uric acid.
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Many drugs can increase or decrease the level of uric acid. In particular, diuretic
drugs like thiazide drugs can cause uric acid levels to go up.
Aspirin (and other salicylates) have varying effects on uric acid. Uric acid is handled
by the kidney in a very complicated pattern. After being filtered through the
glomerulus, the uric acid ia almost all reabsorbed from the urine, then is secreted back
into the urine, with a small amount then being reabsorbed once again. At low aspirin
levels (as may occur in persons taking aspirin only occasionally), aspirin blocks
secretion of uric acid bythe kidneys and can increase blood uric acid. On the other
hand, in high doses (as may be used to treat rheumatoid arthritis), aspirin blocks
reabsorption of uric acid by the kidneys to a greater extent than it blocks secretion,
leading to lower uric acid.
People with high uric acid levels need to drink a lot of fluids, and often are treated
with drugs. Foods that are high in purine content should be avoided, including organ
meats (like liver and kidneys), sardines and anchovies. Alcohol also should be
avoided, because it slows down the removal of uric acid from the body. Fasting, a
starvation diet, or strenuous exercise all raise uric acid levels.
1. If I have high levels of uric acid, can they be lowered easily or will I have to
take drugs for the rest of my life?
Depending on the condition that causes your high levels of uric acid, you may not
need to take drugs for a long time. If you have a sudden attack caused by high uric
acid, as with an attack of gout, your doctor may treat you with the drug colchicine and
a nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen. This treatment
usually is short-term.
However, you may have to stay on a maintenance therapy for a few years, until your
uric acid levels come under control. You may be given drugs that help to rid your
system of uric acid salts, such as probenecid, or you may be given drugs that interfere
with uric acid production, such as allopurinol.
If you have had chemotherapy or radiation, you may have to take uric acid tests more
often and possibly treat the condition over time.
2. What is gout?
Gout is one of the most common forms of arthritis. A gout attack usually happens at
night, and within 12 or so hours there may be severe pain and swelling in the joint.
Gout usually affects only one or two joints at the same time, usually in the feet and
ankles. It often occurs in the big toe, and people can notice it at night when their
bedding rubs on their toe and causes extreme pain. Gout happens when uric acid
crystals become solid in the joints. These crystals cause inflammation.
Without treatment, an early attack of gout usually goes away in a week. It may be
months or years until the next attack. As time goes on, more joints can become
affected and the disease may cause disabilities or eventually cripple the patient,
according to the American College of Rheumatology. That is why it is important to
get treated right away if you think you may have gout. Your doctor will order a uric
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acid test and may have to take fluid from the joint through a needle to look for the
microscopic crystals.
3. I heard women don’t get gout. Is that true?

Gout affects mostly men, and it is very rare in women until after menopause, the time
in life when a woman’s monthly period stops.
Urine Culture
Why get tested?
To diagnose a urinary tract infection (UTI)
When to get tested?
If you experience symptoms of a UTI, such as back pain or frequent and painful
urination.
The urine culture test detects and identifies bacteria and yeast in the urine. Urine is
produced by the kidneys, located on either side of the spine at the base of the ribcage.
The kidneys filter waste out of the blood and produce urine, a yellow fluid, to carry
the wastes out of the body. Urine travels through tubes called ureters from the kidneys
to the bladder, where it is stored temporarily, and then through the urethra as it is
voided. Urine is generally sterile, but sometimes bacteria (or, more rarely, yeast) can
move from the skin outside the urethra and migrate back up the urinary tract to cause
a urinary tract infection (UTI).
With a urine culture, a small sample of urine is placed on one or more agar plates (a
thin layer of a nutrient gel) and incubated at body temperature. Any microorganisms
that are present in the urine sample grow over the next 24 to 48 hours as small circular
colonies. The size, shape, and color of these colonies give clues as to which bacteria
are present, and the number of colonies indicates the quantity of bacteria originally
present in the urine sample. A laboratorian observes the colonies on the agar plate,
counting the total number and determining how many types have grown. Ideally, if a
good clean sample was collected for the test (see below), then the only bacteria
present should be due to an infection. Usually, this will be a single type of bacteria
that will be present in relatively large numbers. Sometimes, more than one type of
bacteria will be present. This may be due to an infection that involves more than one
pathogen (disease-causing microorganism); however, it is more likely to be due to
contamination from the skin picked up during the urine collection.
The laboratorian will take a colony from each type of bacteria present that appears
significant in number or type, smear it on a slide, dry it, and stain it with dyes (called
a gram stain). The laboratorian then examines the microorganisms under the
microscope. Different types of bacteria will have different colors and shapes that can
differentiate different types of bacteria present. For instance, the bacterium Eschericia
coli, which causes the majority of urinary tract infections, will appear as gram-
negative rods (pink rods) under the microscope and Lactobacillus, which is a common
vaginal contaminant in women’s urine samples, will appear as gram-positive bacilli
(thin purple rods). Some of these bacteria, such as Lactobacillus, are easy for an
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experienced laboratorian to identify and are nonpathogenic (do not cause an infection)
and do not require any further investigation. Others, such as gram-negative rods,
represent groups of similar bacteria and will require additional testing to determine
exactly which type of bacteria is present.
Based upon the information obtained, the laboratorian gives the doctor an initial
report of the quantities and types of bacteria (or yeast) present in the urine. Examples
would be: “no growth in 24 hours” (nothing grew on the agar), “less than 10,000
organisms/ml” (a small amount of bacteria was present) or “greater than 100,000
organisms per ml of gram negative rods, ID and susceptibility to follow” (the patient
probably has an infection caused by a gram negative bacteria that needs to be further
identified).
If there is no or little growth on the agar after 24 to 48 hours of incubation, the urine
culture is considered negative for pathogens and the culture is complete. If there is
one or more pathogen present, further testing is performed. Biochemical tests are used
to identify which bacteria are present and susceptibility testing evaluates the ability of
the bacteria to grow in the presence of a specific selection of antimicrobial drugs to
help determine which drug treatments are likely to be effective in resolving the
infection.
When is it ordered?
A urine culture may be ordered when symptoms indicate the possibility of a urinary
tract infection, such as pain and burning when urinating and frequent urge to urinate.
Antibiotic therapy may be prescribed without requiring a urine culture for
symptomatic young women, who have an uncomplicated lower urinary tract infection.
If there is suspicion of a complicated infection, or symptoms do not respond to initial
therapy, then a culture of the urine is recommended. Pregnant women without any
symptoms may be screened for bacteria in their urine, which could affect the health
and development of the fetus.
The presence of a single type of bacteria growing at high colony counts (greater than
10,000 colony forming units (CFU)/ml) is considered a positive urine culture. A
culture that is reported as no growth in 24 or 48 hours or less than 10,000 CFU/ml
usually indicates that there is no infection. If the symptoms persist, however, the
culture may be repeated to look for the presence of bacteria at lower colony counts
(less than 10,000 CFU/ml) or other microorganisms that may cause these symptoms.
The presence of white blood cells and low numbers of microorganisms in a
symptomatic patient is a condition known as acute urethral syndrome.
If a culture shows growth of several different types of bacteria, then it is likely that
the growth is due to contamination. This is especially true if the organisms present
include Lactobacillus and common nonpathogenic vaginal bacteria in women. If the
symptoms persist, the doctor may request a repeat culture on a sample that is more
carefully collected.
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The presence of a significant amount of a single type of bacteria usually indicates an
infection. Susceptibility testing is performed to guide antimicrobial treatment. Any
bacterial infection may be serious and can spread to other areas of the body if not
treated. Since pain is often the first indicator of an infection, prompt treatment,
usually with antibiotics, will help to alleviate the pain.
Females get UTIs more often than males. Even school-age females may have frequent
UTIs. For males with a culture-proven UTI, the doctor may order further tests to rule
out the presence of a kidney stone or structural abnormality that could cause the
infection.
If you have recurrent urinary tract infections, culture and susceptibility testing may be
performed with each episode. For patients who have frequent UTIs, their bacteria may
become resistant to antibiotics over time, making careful selection of antibiotic (and
the full course of treatment) essential. Those with kidney disease and/or with diseases
that affect the kidneys, such as diabetes and those with compromised immune
systems, may be more prone to recurring UTIs.
1. The doctor’s office called back to say they need a new urine sample, the first
was contaminated. What happened?
If the skin and genital area were not cleaned well prior to collecting the sample, the
urine culture may grow three or more different types of bacteria and is assumed to be
contaminated. The culture will be discarded because it cannot be determined if the
bacteria originated inside or outside the urinary tract. A contaminated specimen can
be avoided by following the directions to carefully clean yourself and by collecting a
mid-stream clean catch urine sample.
2. My doctor said I had symptoms of a urinary tract infection and prescribed

antibiotics without performing a urine culture. Why?
The reason is because bacteria known as Eschericia coli (E. coli) cause the majority
of lower urinary tract infections. This organism is usually susceptible to a variety of
antibiotics, such as trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin.
In most patients with uncomplicated disease, the UTI will be resolved after empiric
therapy with one of these antibiotics.
3. What happens if my infection goes untreated?

If your infection is not treated, it can move from the lower urinary tract to the upper
urinary tract and infect the kidney itself, and possibly, enter the bloodstream, causing
septicemia (sepsis). Symptoms of septicemia include fever, chills, elevated white
blood cell count, and fatigue. Your doctor will often use blood cultures to determine if
you have septicemia and will prescribe antibiotics accordingly.
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4. What puts me at risk for recurrent urinary tract infections (UTI)?
There are a wide variety of factors that predispose a person to acquire a UTI. After the
neonatal period, the incidence in females is higher than in males due to the anatomical
differences in the female genitourinary tract. In infants and young children, congenital
abnormalities are associated with UTI. In adults, sexual intercourse, diaphragm use,
diabetes, pregnancy, reflux, neurologic dysfunction, renal stones, and tumors all
predispose to UTI. In a hospital, nursing home, or home care setting, indwelling
catheters and instrumentation of the urinary tract are major contributing factors to
acquiring a UTI.
Urine Metanephrines
Why get tested?
To help diagnose or rule out a pheochromocytoma (tumor of the adrenal gland) or
other neuroendocrine tumor
When to get tested?
headaches, rapid heart rate, and sweating
Sample required (A 24-hour urine sample).
This test measures the amount of metanephrines that are excreted in the urine over a
24-hour period. Metanephrines are the inactive metabolites of the catecholamines
epinephrine (adrenaline) and norepinephrine. Catecholamines are a group of similar
hormones produced in the nervous system and in the medulla (central portion) of the
adrenal glands. The adrenal glands are small, triangular organs located on top of each
kidney. The primary catecholamines are dopamine, epinephrine (adrenaline), and
norepinephrine. These hormones are released into the bloodstream in response to
physical or emotional stress. They help transmit nerve impulses in the brain, increase
glucose and fatty acid release (for energy), dilate bronchioles (small air passages in
the lungs), and dilate the pupils. Norepinephrine also constricts blood vessels
(increasing blood pressure) and epinephrine increases heart rate and metabolism.
After completing their actions, the hormones are metabolized to form inactive
compounds. Dopamine becomes homovanillic acid (HVA), norepinephrine breaks
down into normetanephrine and vanillylmandelic acid (VMA), and epinephrine
becomes metanephrine and VMA. Both the hormones and their metabolites are
excreted in the urine.
Urine metanephrine testing measures the amount of both metanephrine and
normetanephrine. These metabolites are usually present in the urine in small
fluctuating amounts that increase appreciably during and shortly after the body is
exposed to a stressor. Pheochromocytomas (rare adrenal gland tumors) and other
neuroendocrine tumors, however, can produce large amounts of catecholamines,
resulting in greatly increased concentrations of the hormones and their metabolites in
both the blood and urine. The catecholamines that pheochromocytomas produce can
cause persistent hypertension (high blood pressure) and/or bouts or episodes of severe
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hypertension. This can cause symptoms such as headaches, palpitations, sweating,
nausea, anxiety, and tingling in the extremities.
About 90% of pheochromocytomas are located in the adrenal glands. While a few are
cancerous, most are benign – they do not spread beyond their original location -
although most do continue to grow. Left untreated, the symptoms may worsen as the
tumor grows and, over a period of time, the hypertension that the pheochromocytoma
causes may damage body organs, such as the kidneys and heart, and raise the risk of
an affected patient having a stroke or heart attack.
The metanephrine test can be used to help detect the presence of pheochromocytomas.
Although only about 800 cases a year are diagnosed in the U.S. according to the
National Cancer Institute, it is important to diagnose and treat these rare tumors
because they cause a potentially curable form of hypertension. In most cases, the
tumors can be surgically removed and/or treated to significantly reduce the amount of
catecholamine being produced and to reduce or eliminate associated symptoms and
complications.
How is it used?
Urine metanephrine testing is primarily used to help detect and rule out
pheochromocytomas in symptomatic patients. It may also be ordered to help monitor
the effectiveness of treatment when a pheochromocytoma is discovered and removed
and to monitor for recurrence. Urine metanephrine testing may be ordered by itself or
along with a plasma metanephrine test. Plasma and urine catecholamine testing also
may be ordered, either along with urine metanephrines or as follow-up tests. Since
catecholamine secretion tends to fluctuate over time, a 24-hour urine test for
metanephrines or catecholamines may detect excess production that is missed with the
blood test. It is up to the doctor to decide which test or test combinations will give
him the most information. In many cases, urine and plasma metanephrines may be
preferred as they are usually present in greater quantities than catecholamines in the
urine and can persist in the blood even when catecholamine levels have returned to
normal.
Since these tests are affected by drugs, foods, and stresses, there will be a certain
number of false positives. For this reason, metanephrine testing is not recommended
as a screen for the general public. Doctors will frequently investigate a positive result
by evaluating a patient’s stresses and intake, work to alter or minimize these
influences, and then repeat the test to confirm the original findings.
Occasionally, metanephrine testing may be ordered on an asymptomatic person if an
adrenal or neuroendocrine tumor is detected during a scan that is done for another
purpose or if the patient has a strong personal or family history of
pheochromocytomas (as they may recur and there is a genetic link in some cases).
When is it ordered?
Urine metanephrines are ordered when a doctor either suspects that a patient has a
pheochromocytoma or wants to rule out the possibility. He may order it when a
patient has persistent or recurring hypertension along with symptoms such as
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or when a patient has a family history of pheochromocytomas. It also may be used as
Because the metanephrine test is sensitive to many outside influences and
pheochromocytomas are rare, a doctor may see more false positives with this test than
true positives. If a symptomatic patient has large amounts of metanephrines in his
urine, further investigation is indicated. If there are no interfering substances or
stresses identified, then there is a good possibility that he may have a
pheochromocytoma. The doctor may order plasma metanephrine and/or urine or
plasma catecholamine testing to help confirm the findings. If these are also elevated,
then imaging tests (such as an MRI) may be ordered to help find the tumor(s). If an
asymptomatic patient with a tumor that has been discovered during a scan for another
reason has significantly elevated metanephrines, then it is likely that the tumor
discovered is a pheochromocytoma.
Serious illnesses and stresses can cause moderate to large temporary increases in
metanephrine levels. Doctors must evaluate the patient as a whole - his physical
condition, emotional state, medications, and diet. When interfering substances and/or
conditions are found and resolved, the doctor will frequently re-test the patient to
determine whether the metanephrines are still elevated. If they are, then he may order
imaging scans; if they are not, then it is unlikely that the patient has a
pheochromocytoma.
If levels are elevated in a patient who has had a previous pheochromocytoma, it is

likely that either treatment was not fully effective or that the tumor is recurring. The
negative predictive value of the test, however, is relatively good. This means that if
the concentrations of the metanephrines are normal, then it is much less likely that the
patient has a pheochromocytoma.

While metanephrine testing can help detect and diagnose pheochromocytomas, it
cannot tell the doctor how big the tumor is (even small tumors can produce large
amounts of catecholamines), where the tumor is (although the majority are found in
the adrenal gland and most of the rest are found within the abdominal cavity), or how
many tumors are present (although it is usually just one). It also cannot tell the doctor
whether or not the tumor(s) are benign (although most are).
It is very important to talk to your doctor before discontinuing any prescribed
medications. He will work with you to identify interfering substances and drug
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treatments to determine which of them can be safely interrupted and which must be
continued for your well-being. Some of the substances that can interfere with
metanephrine testing include: acetaminophen, aminophylline, amphetamines, appetite
suppressants, coffee, tea, and other forms of caffeine, chloral hydrate, clonidine,
dexamethasone, diuretics, epinephrine, ethanol (alcohol), insulin, imipramine, lithium,
methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors, nicotine,
nitroglycerine, nose drops, propafenone (Rythmol), reserpine, salicylates,
theophylline, tetracycline, tricyclic antidepressants, and vasodilators. The effects of
these drugs on metanephrine testing will be different from patient to patient and are
often not predictable.
1. Can I have tumors in both of my adrenal glands?
Yes. Usually a single adrenal tumor will arise in one gland or the other, but multiple
tumors can form. This is more likely in patients with a strong family history of
pheochromocytomas.
2. If I avoid all of the interfering substances mentioned, could I prevent a

pheochromocytoma?
No. They interfere with accurate test results, but they do not cause or exacerbate the
tumor itself.
3. Why haven’t I heard about pheochromocytomas?

Because they are rare. They are important to diagnose, however, because they are a
potentially curable cause of hypertension (which is usually controllable but not
curable).
4. Will my doctor ever test for HVA or VMA?

Yes, occasionally, but in most cases metanephrine and catecholamine testing give
your doctor the information he needs. HVA and VMA may be more useful in the
diagnosis of other neuroendocrine tumors. Most pheochromocytomas do not produce
dopamine or HVA.
5. Is it really necessary to collect urine for 24 hours?

Yes, for accurate test results it is essential that all of the urine be collected. Because
the catecholamines are released at varying times, the one sample not included might
be the one with the most metanephrines in it.
Urine Protein
Why get tested?
To detect excessive protein escaping into the urine, to help evaluate and monitor
kidney function, and to detect kidney damage
When to get tested?
As part of a routine physical, as a follow-up to a previous positive urine protein test,
or if you have a disorder or disease that frequently affects the kidney
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Sample required?
A random or 24-hour urine sample; occasionally a split 24-hour sample, with the
night collection separated from the day collection.
The urine protein test measures the amount of protein being excreted in the urine.
There are several different kinds of urine protein tests. A semi-quantitative protein
“dipstick” may be performed as part of a urinalysis, generally on a random urine
sample. The quantity of protein in a 24-hour urine sample may be measured and
reported as the amount of protein excreted per 24 hours. Also, the amount of protein
in a random urine sample may be measured and reported as the ratio of protein to
creatinine. Since saving all of the urine for a 24-hour period can be cumbersome for
adults and difficult for infants and children, a random urine protein to creatinine ratio
may sometimes be substituted for a 24-hour urine protein sample. Creatinine, a
byproduct of muscle metabolism, normally is excreted into the urine at a constant
rate. When a creatinine measurement is performed along with a random urine protein
test, the resulting protein/creatinine ratio approaches the accuracy of the 24-hour urine
protein test.
Albumin, a protein produced by the liver, makes up about 60% of the protein in the
blood. The rest is a mixture of globulins, including immunoglobulins. Proteins usually
are not found in the urine. The kidneys (two organs found in the back at the bottom of
the rib cage) filter the blood, removing wastes and excreting them out of the body in
the form of urine. When the kidneys are functioning normally, they retain or reabsorb
filtered protein molecules and return them to the blood. However, if the kidneys are
damaged, they become less effective at filtering, and detectible amounts of protein
begin to find their way into the urine. Often, it is the smaller albumin molecules that
are detected first. If the damage continues, the amount of protein in the urine
increases, and globulins may also begin to be lost.
Proteinuria (protein in the urine) is frequently seen in chronic diseases, such as
diabetes and hypertension, with increasing amounts of protein in the urine reflecting
increasing kidney damage. With early kidney damage, the patient is often
asymptomatic. As damage progresses or if protein loss is severe, the patient may have
symptoms such as edema (swelling and fluid retention), shortness of breath, nausea,
and fatigue. Excess protein production, such as may be seen with multiple myeloma,
can also lead to proteinuria.
The presence of albumin in the urine (albuminuria) has been shown to be a sensitive
indicator of kidney disease in patients with diabetes and with hypertension. Therefore,
in some situations the doctor may test specifically for albumin, as opposed to total
protein, in the urine (see microalbumin).
How is it used?
Urine protein testing is used to detect protein in the urine, to help evaluate and
monitor kidney function, and to help detect and diagnose early kidney damage and
disease. A dipstick urine protein is performed routinely as part of a urinalysis. It is
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used to screen the general population for the presence of protein in the urine. If slight
to moderate amounts of protein are detected, then another urinalysis and dipstick
protein may be performed at a later time to see if there is still protein in the urine or if
it has dropped back to undetectable levels. If there is a large amount of protein in the
first sample and/or the urine persists in the second sample, then the doctor may order
a 24-hour urine protein as a follow-up test. Since the dipstick primarily measures
albumin, the 24-hour urine protein test also may be ordered if a doctor suspects that
proteins other than albumins are being released.
The urine protein test tells the doctor that protein is present in the urine, but it does
not indicate which types are present or the cause of the proteinuria. When a doctor is
investigating the reason, he also may order a serum and urine electrophoresis test to
determine which proteins are being excreted and in what quantities. This is especially
true if he suspects abnormal protein production, such as with multiple myeloma. He
may order a Comprehensive Metabolic Panel (CMP) to look at albumin and total
protein levels in the blood and to help evaluate kidney and liver function. If kidney
disease or damage is suspected, he also may order imaging scans to evaluate the
appearance of the organ.
A protein to creatinine ratio may be ordered on a random urine sample if a child
shows evidence of significant and persistent protein in their urine on a dipstick urine
test. Children (as well as adults) sometimes have some degree of transient proteinuria
without apparent kidney dysfunction and may have a higher excretion of protein into
their urine during the day than at night. The doctor may monitor their urine at
intervals to see if the amount of proteinuria changes over time.
Either a 24-hour urine protein or a random protein to creatinine ratio may be ordered
to monitor a patient with known kidney disease and/or damage. A dipstick urine
protein and/or a protein to creatinine ratio may be used to screen patients on a regular
basis when they are taking a medication that may affect their kidney function.
When is it ordered?
A dipstick urine protein is measured frequently as a screening test whenever a
urinalysis is performed. This may be done as part of a routine physical, a pregnancy
workup, when a urinary tract infection is suspected, as part of a hospital admission, or
whenever the doctor wants to evaluate kidney function. It may also be done when a
previous dipstick has been positive for protein to see if the protein excretion persists.
The 24-hour urine protein test may be ordered as a follow-up test when the dipstick
test shows that there is a large quantity of protein present in the urine and/or when
protein is shown to be persistently present. Since the dipstick primarily measures
albumin, the doctor may order a 24-hour urine protein test even when there is little
protein detected on the dipstick if he suspects that there may be proteins other than
albumin being released.
When a doctor is diagnosing the cause of proteinuria he also may order a urine
electrophoresis test to determine exactly which proteins are being excreted and in
what quantities. A serum electrophoresis also may be ordered to look at the proteins
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in the blood, especially if abnormal protein production is suspected. Other blood tests,
such as a Blood Urea Nitrogen (BUN) and creatinine, may be ordered to evaluate
kidney function and an albumin and/or total protein test may be performed to look at
the proteins in the blood.
A protein to creatinine ratio may be ordered on a random urine sample when a child
shows evidence of significant and persistent protein in their urine on a dipstick urine
test. It may also be ordered when a patient has known kidney disease and/or damage
and the doctor wants to monitor kidney function over time. A dipstick urine protein
and/or a protein to creatinine ratio on a random urine sample may be used as a screen
for kidney involvement when a patient is taking a medication that may potentially
affect kidney function.

Protein in the urine is a warning sign. It may indicate kidney damage or disease or be
a transient elevation due to an infection, medication, vigorous exercise, or emotional
or physical stress. In some people, it may be present during the day and absent at
night when the patient is lying down (orthostatic proteinuria). In pregnant women,
elevated urine protein levels can be associated with pre-eclampsia.
When kidney damage is present, the amount of protein present is generally associated
with the severity of damage, and increasing amounts of protein over time indicate
increasing damage and decreasing kidney function. Proteinuria is associated with
many diseases and conditions, including:
 Amyloidosis
 Bladder cancer
 Congestive heart failure
 Diabetes
 Drug therapies that are potentially toxic to the kidneys
 Glomerulonephritis
 Goodpasture’s syndrome
 Heavy metal poisoning
 Hypertension
 Kidney infection
 Multiple myeloma
 Polycystic kidney disease
 Systemic lupus erythematosus
 Urinary tract infection

The different methods of detecting protein in the urine vary in performance. For
example, a positive dipstick protein may be elevated due to other sources of protein,
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such as blood, semen, or vaginal secretions in the urine. Since it measures primarily
albumin, the dipstick occasionally may be normal when significant quantities of other
proteins are present in the urine. A 24-hour urine sample gives the protein excretion
rate over 24 hours. It will be accurate only if all of the urine is collected. The protein
to creatinine ratio is more of a snapshot of how much protein is in the urine at the time
the sample is collected. If it is elevated, then protein is present; if it is negative, it is
possible that the patient was just not excreting measurable amounts of protein at that
time.
1. Can I test for protein in my urine at home?
Potentially yes. There are dipsticks available that allow patients to monitor the protein
in their urine. This is usually not necessary, though, unless your doctor is monitoring
a known kidney condition.
2. Does kidney damage go away?

In general, it does not. The goal is to detect kidney disease and damage early to
minimize the damage and prolong kidney function. If the proteinuria detected is due
to a kidney infection or urinary tract infection, the kidneys frequently will return to
normal as the infection resolves. If it is due to a medication, then in most cases the
kidneys are likely to return to normal or near normal function when the medication is
stopped.
3. Should I eat more protein to make up for lost protein?

This is something to discuss with your doctor. If you have severe protein shortages,
that will need to be addressed, but ingesting additional protein also puts additional
stress on your kidneys.
Vancomycin
Why get tested?
To measure and monitor the concentration of vancomycin in the blood
When to get tested?
At intervals during vancomycin treatment
Sample required (Blood sample)
This test measures the concentration of vancomycin in the blood. Vancomycin is an
antimicrobial that is used to treat serious infections caused by gram-positive bacteria.
Developed in the 1950s, vancomycin was originally prescribed primarily when
organisms proved resistant to penicillin or when a person was allergic to penicillin. Its
use declined with the introduction of other antimicrobials such as methicillin, but has
risen again with the emergence of methicillin-resistant strains of Staphylococcus, such
as Staphylococcus aureus.
Intravenous vancomycin may be given to treat infections such as septicemia (infection

of the blood), endocarditis (infection of the membrane surrounding the heart),
osteomyelitis (infection of the bone), some pneumonias, and meningitis (infection of
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the spinal cord). It is often the drug of choice for methicillin-resistant Staphylococcus
epidermidisand Staphylococcus aureus infections, especially when they are associated
with implanted prosthetic devices such as heart valves, artificial hips, and indwelling
catheters. Vancomycin may also be given prophylactically (to prevent an infection) to
some people before specific surgeries and dental procedures. Intravenous vancomycin
administration is necessary to get drug into the circulation because the oral
vancomycin is poorly absorbed. Oral vancomycin is prescribed to treat some resistant
Clostridium difficile infections, infections that occur in the gastrointestinal tract where
absorption into the circulation is not needed.
The effectiveness of vancomycin depends on sustaining blood levels at a minimum

concentration for duration of therapy. Excessive concentrations of vancomycin must
be avoided because high levels can result in toxicities - specifically ototoxicity
(damage to hearing) and nephrotoxicity (kidney damage). The amount of vancomycin
given per dose depends on a variety of factors, including kidney function, other
nephrotoxic drugs the patient may be taking, age, and weight.
A patient with decreased kidney function may not be able to clear the drug out of his
system efficiently, resulting in increased concentration in the blood. If a patient is
given too little drug and is unable to maintain a sufficient minimum dose in the blood,
then it is unlikely that treatment will be effective. The vancomycin test can be used to
monitor the amount of drug in the blood to ensure that it is adequate but not
excessive.
How is it used?
When a vancomycin dose is given, its concentration rises in the blood, peaks, and
then falls. The next dose is timed to be given in anticipation of the falling level. The
goal is to overlap the doses enough so that a minimum concentration is always
maintained in the blood. Measurement of blood levels are ordered at times to reflect
the lowest concentration (trough) and the highest concentration (peak) to evaluate the
adequacy of dosing and adequacy of clearance of the drug. Trough levels are collected
just prior to a patient’s next vancomycin dose. Peak levels are collected 1 to 2 hours
after the completion of the intravenous vancomycin dose. The trough and peak values
are used by clinical pharmacists and doctors to calculate rates of absorption and
clearance of the drug. These results are then used to determine the appropriate amount
of drug and the appropriate timing between doses to assure that the blood
concentration remains in the therapeutic range.
When is it ordered?
There is not a widespread consensus on the use of the vancomycin test. Some doctors
will order trough levels every few days throughout vancomycin treatment. Some will
order both trough and peak concentrations at regular intervals. Many do not feel that
general monitoring is necessary and will only order the tests on patients who are at
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increased risk of nephrotoxicity (because of other medications, decreased kidney
function, etc.) and on those who are not responding to treatment as expected.
If trough levels of vancomycin are above the minimum level, then the patient should
be receiving enough of the drug to be effective. If the patient’s infection is not
responding to the treatment, then the doctor may either continue the drug for a longer
period of time or consider other treatment options. If peak concentrations are below
maximum levels, then the patient is at less risk of developing nephrotoxicity and/or
ototoxicity (but may still experience either complication). Peak concentrations may
vary, depending on the consistency of collection timing and on changing drug
clearance rates. If the peak concentration is excessive, the doctor may either alter the
dose or alter the dosing schedule.
An intravenous vancomycin dose must be given slowly. Patients given the dose at a
rapid rate are at an increased risk of developing “red man syndrome,” a histamine
reaction that causes flushing of the face, a rash on the upper body, and a significant
drop in blood pressure.
Kidney function tests such as BUN (Blood Urea Nitrogen) and creatinine and
creatinine clearance may be ordered prior to the start of vancomycin therapy and at
intervals, or as needed, to evaluate changes in kidney status.
1. Why isn’t vancomycin more widely used?

The medical community tries to be conservative in its use of vancomycin, reserving it
for patients with few other treatment options to stave off the emergence of
vancomycin-resistant microorganisms. In recent years, some resistant and
intermediate (decreased sensitivity) strains of Staphylococcus aureus (called VISA
and VRSA for Vancomycin Intermediate/Resistant Staphylococcus aureus) and
strains of Enterococcus have emerged.
2. Will I be tested if I am taking oral vancomycin?

Oral vancomycin therapy is rarely monitored as only tiny amounts of the drug are
absorbed and carried in the blood. Occasionally, a patient with impaired renal
function will be monitored to verify that the drug is not building up in the body.
3. Can I test vancomycin levels at home?

Although a patient may receive intravenous vancomycin therapy at home, usually
administered by a home health professional, blood levels cannot be monitored at
home. The test requires specialized equipment and must be performed in the
laboratory. The home health professional may draw a blood sample prior to
administering the next dose of drug. This sample will be sent to a laboratory for
analysis.
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4. Should all antibiotic therapy be monitored like vancomycin?
No, not all antibiotics require monitoring. Unlike vancomycin, most antibiotics have a
larger therapeutic range in which they are effective but will not cause side effects.
Because of this, they can be prescribed based upon pre-established dosing schedules.
Vitamin D
Formal name: 25-hydroxy-vitamin D (Calcidiol); 1,25 dihydroxy-vitamin D

(Calcitriol)
Why get tested?
To investigate a problem related to bone metabolism or parathyroid function
When to get tested?
If you have an abnormal calcium, phosphorus, and/or parathyroid hormone level or if
you have evidence of bone disease or bone weakness.
These tests measure the concentrations of various forms of vitamin D in your blood.
The term vitamin D actually refers to a number of different but related chemical
compounds (termed sterols), some of which are inactive and some of which are active
forms. The two most common vitamin D tests measure calcidiol (an inactive form)
and calcitriol (the active form). The test for calcidiol (sometimes called 25-hydroxy-
vitamin D) is used to assure that the body has adequate vitamin D supply. The test for
calcitriol (sometimes called 1,25 dihydroxy-vitamin D) is used to assure that the
kidney is converting an appropriate amount of calcidiol to the active hormone
calcitriol.
The main role of the active hormone calcitriol is to help regulate the absorption of
calcium, phosphorus, and (to a lesser extent) magnesium. Vitamin D is vital for the
growth and health of bone; without it, bones will be soft, malformed, and unable to
repair themselves normally, resulting in diseases called rickets in children and
osteomalacia in adults.
Vitamin D comes from two sources. The body is able to form vitamin D by exposure
to sunlight. This is the basis of referring to vitamin D as the sunshine vitamin -- it is
formed from 7-dehydrocholesterol in the skin when the skin is exposed to light.
Vitamin D also can be ingested -- either in foods or in vitamin supplements. The
different compounds of vitamin D are distinguished by the use of subscript numbers.
Vitamin D2 comes from diet and vitamin preparations. Vitamin D3 is endogenous
(produced in the body). Vitamins D2 and D3 are slightly different chemical structures,
but both lead to production of the active hormone calcitriol.
Vitamin D3 as formed in the skin or vitamin D2 as supplied from the diet are inactive
forms that are converted by the liver into yet another inactive form called calcidiol.
Calcidiol is the main form of vitamin D stored in the body and measured in the
circulation. Calcidiol is converted to active form calcitriol by the kidney. About
99.9% of vitamin D in the blood is calcidiol and 0.1% is calcitriol.
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How is it used?
Vitamin D tests are used to determine if bone weakness, bone malformation, or
abnormal metabolism of calcium (reflected by abnormal calcium, phosphorus or PTH
tests) is occurring as a result of a deficiency or excess of vitamin D.
Since vitamin D is a fat-soluble vitamin and is absorbed from the intestine like a fat,
vitamin D tests are sometimes used to monitor individuals with diseases that interfere
with fat absorption, such as cystic fibrosis and Crohn?s disease, to assure that they
have adequate amounts of vitamin D. Vitamin D tests also are used to determine
effectiveness of treatment when vitamin D, calcium, phosphorus, and/or magnesium
supplementation is prescribed.
When is it ordered?
Either calcidiol or calcitriol tests may be ordered when a patient has an abnormal
blood calcium, phosphorus, and/or magnesium level or evidence of bone disorders.
If calcium is low or the patient has symptoms of vitamin D deficiency, such as bone
malformation in children (rickets) and bone weakness, softness, or fracture in adults
(osteomalacia), the calcidiol test usually is ordered to identify a possible deficiency in
vitamin D.
If calcium is high or the patient has a disease that might produce excess amounts of
calcitriol, such as sarcoidosis or some forms of lymphoma, the calcitriol test usually is
ordered.
Vitamin D tests also may be used to help diagnose or monitor problems with
parathyroid gland functioning since parathyroid hormone is essential for vitamin D
activation. When vitamin D, calcium, phosphorus, or magnesium supplementation is
necessary, vitamin D levels are sometimes measured to monitor treatment
effectiveness.
Low blood levels of calcidiol may mean that you are not getting enough exposure to
sunlight or enough dietary vitamin D to meet your body?s demand; that there is a
problem with its absorption from the intestines; or that enough is not being converted
to calcidiol in the liver (which means that it is not making it into the bloodstream).
Occasionally, drugs used to treat seizures, particularly phenytoin (Dilantin), can
interfere with the liver?s production of calcidiol.
High levels of calcidiol usually reflect excess supplementation from vitamin pills or
other nutritional supplements.
Low levels of calcitriol are often seen in kidney disease and are one of the earliest
changes to occur in persons with early kidney failure.
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High levels of calcitriol may occur when there is excess parathryoid hormone or when
there are diseases, such as sarcoidosis or some lymphomas, that can make calcitriol
outside of the kidneys.
High levels of vitamin D and calcium can lead to the calcification and damage of
organs, such as the kidneys, as the body tries to lower blood calcium levels by
depositing calcium phosphate compounds into the organs.
If magnesium levels are low, they can cause a low calcium level that is resistant to
vitamin D and parathyroid hormone regulation. It may be necessary to supplement
both magnesium and calcium to regain normal function.
1. Is fortifying milk and cereals with vitamin D a good practice?
Yes. The amount of vitamin D produced by the body may be insufficient, especially
when there is limited exposure to sunlight (winter, places with overcast and cloudy
weather). Since dietary vitamin D is found naturally only in a few foods, such as cod
liver oil, dietary intake would not be sufficient for most people. However, in the
United States vitamin D is routinely added to milk, fortified cereals, and fruit juices to
ensure adequate dietary availability. Fortification has been a real success story in the
United States, drastically reducing the rate of juvenile rickets and making it a
relatively rare occurrence.
2. Can I get my vitamin D from yogurt and cheese?

Maybe. Although all milk is fortified, many dairy products are not. Since there is no
Recommended Dietary Allowance (RDA) for vitamin D, you will not find it listed on
most food labels.
3. Are there other uses for vitamin D?

Yes, there is a topical form of vitamin D cream that is used to treat psoriasis. Research
is being done in other areas, including the potential use of vitamin D to help control
autoimmune conditions.
4. Is vitamin D a necessary component of calcium supplements?

Since absorption of calcium is dependent on vitamin D, many manufacturers of
calcium supplements add vitamin D to assure optimal calcium uptake. If you have
adequate amounts of vitamin D from other sources the additional vitamin D is not
necessary. The amount of vitamin D in these tablets is not likely to lead to excess
vitamin D or be harmful either.
West Nile Virus
Why get tested?
To determine the cause of viral meningitis (inflammation of the lining of the brain and
spinal cord) or encephalitis (inflammation of the brain) that occurs during the summer
season; to detect the presence of West Nile virus (WNV) and to track its spread in the
community and across the United States
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When to get tested?
If a patient has symptoms suggesting WNV such as headache, fever, stiff neck, and
muscular weakness and a diagnosis of encephalitis and/or meningitis; also used as a
screen for WNV in donated units of blood
Sample required?
Cerebrospinal fluid collected from a spinal tap and/or a blood sample drawn from a
vein in your arm.
West Nile virus (WNV) is an infection that is transmitted to humans primarily by
mosquitoes. It is not usually transmitted person-to-person, but there have been cases
of WNV being passed on to others through blood donations, organ transplants, and
rarely from a mother to child through breast milk. About 80% of people infected with
WNV experience no symptoms. In the other 20%, it causes relatively mild flu-like
symptoms such as headache, fever, and muscular weakness that resolve without
treatment after a few days to a few weeks. Only 1 in 150 people infected with WNV
becomes seriously ill with an infection that affects the central nervous system. These
patients may have encephalitis (inflammation of the brain) and/or meningitis
(inflammation of the lining of the brain and spinal cord) and/or may experience
muscular paralysis. This serious form of WNV is much more common in the elderly
and in the immunocompromised. While the inflammation eventually resolves, some
nerve damage and paralysis may linger and/or be permanent.
How is it used?
West Nile virus (WNV) testing is used to determine whether someone is currently or
has recently been infected with the WNV. Testing of symptomatic and seriously ill
patients can help distinguish WNV from other conditions (such as bacterial
meningitis) causing similar symptoms that may be treated. WNV testing also is used
to screen units of blood for the virus and to track its spread through a community and
across the country. Detecting the presence of WNV in the community can alert health
providers and promote prevention measures.
Testing involves either a measurement of WNV antibodies (specific proteins created
by the body’s immune system in response to a WNV infection) or of WNV nucleic
acid (genetic material from the virus itself).
Antibody Testing
There are two types of WNV antibodies: IgM and IgG. IgM antibodies are the first to
be produced by the body in response to a WNV infection. They are present in most
individuals within 8 days of the initial exposure. Antibody titers continue to rise for a
short time period and then will taper off. Eventually, after several months, the level of
IgM falls below detectible levels.
Until recently, IgM WNV antibody testing was labor-intensive and not well
standardized from lab to lab. This issue has been largely resolved by the introduction
of two commercial IgM WNV antibody-capture assays that can be used as an initial
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test on symptomatic individuals. These tests are standardized and easier to perform
but, like the methods before them, they may be positive both with WNV and with any
related flaviviruses (viruses in the same family, such as St. Louis Encephalitis virus
and Japanese Encephalitis virus). Therefore, positive WNV IgM tests must be
confirmed by another method before a diagnosis is established and reported to the
Centers for Disease Control and Prevention.
If the IgM test is negative, but symptoms and clinical signs still suggest WNV, the
test may be repeated on a new specimen collected a few days later.
IgG WNV antibody testing can be used, along with IgM testing, to help confirm the
presence of a recent or previous WNV infection. If the IgG test is positive, then
another convalescent blood sample may be collected and tested a couple of weeks
later to determine whether the amount of WNV IgG antibody (the titer) is rising,
falling, or stable.
If someone who has received donated blood or an organ transplant within the previous
month becomes ill and tests positive for WNV, the blood or organ is traced back to its
donor, who is then tested for IgM and IgG WNV antibodies to determine whether
they are the source of the recipient’s WNV. If a breastfeeding baby contracts WNV,
the mother will likely be tested to determine whether the infection may have passed to
the baby through the mother’s milk (a rare but documented event).
Since the majority of patients who become infected with WNV have no symptoms
and no associated health problems, antibody testing is not used as a general screening
test on asymptomatic people.
Nucleic Acid Testing

Nucleic acid testing involves amplifying and measuring the West Nile virus’s genetic
material to detect the presence of the virus in blood or tissue. While it can specifically
identify the presence of WNV, there must be a certain amount (number of copies) of
virus present in the sample in order to detect it.
Since humans are incidental hosts of WNV (birds are the primary hosts), virus levels
in humans are usually relatively low and do not persist for very long. Nucleic acid
testing is most useful as a screen for WNV in donated units of blood and for testing
birds and mosquito pools to detect the presence and spread of WNV in the
community. It is possible to determine that WNV has spread to a particular area and is
in the bird and mosquito population before any human cases are identified. This gives
the community health services an opportunity for prevention by alerting people to its
presence and the need for preventative measures, such as the use of bug repellents,
limiting exposure to mosquitoes at dusk and dawn, and community spraying for
mosquitoes.
439
It also may be useful when ordered post mortem on a patient’s blood or tissues to
determine whether WNV may have caused or contributed to the patient’s death.
When is it ordered?
Antibody testing is usually ordered during the WNV season (the peak mosquito
season is generally July to October, but in some regions they may be present year-
round) or if patients have traveled to areas where WNV is currently present. IgM
antibody testing is primarily ordered when a patient has new symptoms suggesting a
current WNV infection.
Two to four weeks after a positive WNV test, IgM and IgG WNV tests may be
ordered on a convalescent basis to determine whether IgG levels are rising or stable
and to determine whether the patient has begun to produce IgG WNV antibodies. If an
initial IgM test is negative but symptoms persist and other conditions are ruled out,
another IgM test may be ordered a few days later to determine whether IgM WNV
antibodies are now present.
Testing is not usually done on asymptomatic people, but when a blood or organ
recipient becomes infected with WNV, both IgM and IgG antibodies may be ordered
on the donor (who is frequently asymptomatic) to help determine whether they were
the source of the infection.
Antibody Testing
If the IgM WNV antibody is positive in blood or cerebrospinal fluid (CSF) and
confirmed by another method, then it is likely that the patient has a current WNV
infection, or that they had one in the recent past. If the IgM antibody is found in the
CSF, it suggests neuroinvasive (related to the central nervous system) WNV.
If the IgG is also positive, then it is likely that the patient contracted the WNV
infection at least 3 weeks prior to the test. If the IgG is positive and the IgM level is
low or not detectible, then it is most likely that the patient was previously exposed to
WNV and is not currently infected.
The presence of WNV antibodies may indicate an infection, but they cannot be used
to predict the severity of an individual patient’s symptoms or their prognosis.
Nucleic Acid Testing

If a nucleic acid test is positive for WNV, then it is likely that the virus is present in
the sample tested (donated blood; a tissue sample from a human, bird, or other animal;
or a mosquito pool sample) and is present in the geographic location where the sample
was collected.
A nucleic acid test may be negative for WNV if there is no virus present in the sample
tested or if it is present in very low (undetectable) numbers. A negative test cannot be
used to definitely rule out the presence of WNV.
440
West Nile virus is moving westward across the United States. In some warm areas, it
is present year-round, but in most regions, it is seasonal – cases occur during the
mosquito season. The amount of WNV present depends in part on the number of
infected birds and the mosquito population. Prevention depends on controlling
individual exposure and on controlling the mosquito population. According to the
Centers for Disease Control and Prevention (as of March 31, 2004), there were 9,858
confirmed human cases of WNV in the U.S. in 2003 and 264 deaths attributed to it as
the cause. Nucleic acid testing and viral culture are used in research settings to
identify the strain of virus causing the infection and to study its attributes. Different
strains of WNV have been isolated and associated with different epidemics around the
world.
1. Is there a vaccine for West Nile virus?
Not for humans yet, but there should be one or more vaccines available in the next
few years. A vaccine has been developed by mixing West Nile virus with a vaccine
for yellow fever, altering the proteins coating the established vaccine. This new
vaccine has been successfully tested for safety and effectiveness in animals and now
testing is being started in humans.
Another potential West Nile virus vaccine that uses an inactive protein (instead of a
live virus) also has been developed and undergone some initial testing. It would have
the advantage of being able to be given to anyone, even those who were pregnant or
immunosuppressed.
2. Will West Nile virus ever be eradicated now that it is in the U.S?
Probably not. Like the flu and other viruses, it has become a seasonal issue in many
parts of the world.
3. Is it safe to donate and receive blood?
Yes. There is no risk for the donor, and WNV nucleic acid testing has been added to
the list of extensive testing that is done to make the U.S. blood supply as safe as it can
possibly be for the recipients. As an additional tool in reducing WNV in the blood
supply, blood collection centers have recently started asking potential donors during
WNV season if they have had a recent fever or headache (symptoms of an infection
with WNV or other virus).
White Blood Cell Count
Why get tested?
If your doctor thinks that you might have an infection or a disease that affects the
production of white blood cells, and to monitor treatment
When to get tested?
As part of a complete blood count (CBC), which may be ordered for a variety of
reasons.
The white blood cell (WBC) count indicates the number of white blood cells in a
441
sample of blood. This count provides a clue to the presence of illness. White blood
cells are made in the bone marrow and protect the body against infection and aid in
the immune response. If an infection develops, white blood cells attack and destroy
the bacteria, fungus, or virus causing the infection.
How is it used?
Conditions or medications that weaken the immune system, such as HIV infection or
chemotherapy, cause a decrease in white blood cells. The WBC count detects
dangerously low numbers of these cells.
The WBC count is used to suggest the presence of an infection or leukemia. It is also
used to help monitor the body’s response to various treatments and to monitor bone
marrow function.
When is it ordered?
A WBC count is normally ordered as part of the complete blood count (CBC), which
is ordered for a wide variety of reasons. A WBC count also may be ordered to
monitor recovery from illness. Counts that continue to rise or fall to abnormal levels
indicate that the condition is getting worse. Counts that return to normal indicate
improvement.
An elevated number of white blood cells is called leukocytosis. This can result from
bacterial infections, inflammation, leukemia, trauma, or stress.
A decreased WBC count is called leukopenia. It can result from many different
situations, such as chemotherapy, radiation therapy, or diseases of the immune
system.

Eating, physical activity, and stress can cause an increased WBC count.
Pregnancy in the final month and labor may be associated with increased WBC levels.
If you have had your spleen removed, you may have a persistent mild to moderate
increased WBC count.
The WBC count tends to be lower in the morning and higher in the late afternoon.
WBC counts are age-related.
On average, normal newborns and infants have higher WBC counts than adults. It is
not uncommon for the elderly to fail to develop leukocytosis as a response to
infection.
There are many drugs that cause both increased and decreased WBC counts.
442
Zinc Protoporphyrin
Also known as: ZPP, ZP, Free Erythrocyte Protoporphyrin, FEP

Why get tested?
To screen for and monitor chronic exposure to lead; to detect iron deficiency in
children; sometimes to help diagnose certain porphyrias (inherited conditions that
affect the production of heme)
When to get tested?
If you have been chronically exposed to lead, as part of a program to monitor lead
exposure, and/or if your doctor suspects lead poisoning; as part of a screening
program for iron deficiency in children and adolescents; if a doctor suspects a patient
has a porphyria.
The zinc protoporphyrin (ZPP) test is a blood test that can identify a disruption in the
formation of heme. Heme is an essential component of hemoglobin, the protein in red
blood cells (RBCs) that carries oxygen from the lungs to the body’s tissues and cells.
The formation of heme occurs in a series of enzymatic steps that conclude with the
insertion of an iron atom into the center of a molecule called protoporphyrin. If there
is not enough iron available, or if ferrochelatase (the enzyme responsible for the
incorporation of iron) is blocked, then protoporphyrin combines with zinc instead of
iron to form zinc protoporphyrin. Since it cannot transport oxygen, ZPP serves no
useful purpose in the RBCs that contain it.
The term ZPP is sometimes used interchangeably with free erythrocyte

protoporphyrin (FEP). In reality, about 90% of protoporphyrin in red blood cells is
ZPP, while the remainder is present as FEP (not bound to zinc). The testing method
for ZPP measures both substances, and the results may be reported as either ZPP or
FEP.

In adults, ZPP is measured directly in a sample of whole blood taken by inserting a
needle into a vein in your arm. In children, it is often measured as the ZPP/heme ratio,
using a drop of blood from a fingerstick and an instrument called a
hematofluorometer. This instrument measures the fluorescence of ZPP and reports the
amount of ZPP per number of heme molecules.
How is it used?
Zinc protoporphyrin is ordered primarily to help detect iron deficiency in children and
to detect and monitor chronic exposure to lead in adults. Lead inhibits the action of
ferrochelatase, resulting in increased ZPP formation even when adequate amounts of
iron are present. ZPP is thought to be a better screening test for lead burden (the total
amount of lead being held by the body) than a lead concentration because lead levels
tend to vary day to day in the blood and because lead moves from the blood into
443
organs and bone. While blood samples for lead may be contaminated by any
environmental lead present at the time of collection, ZPP is not affected.
In the general adult population, ZPP may be ordered, along with a lead level, as part
of a screen for chronic lead exposure. Hobbyists that work with products containing
lead and people who live in older houses are examples of people who may be at an
increased risk of developing lead poisoning. This is because lead is usually ingested
or inhaled. Those who inhale dust that contains lead, handle lead directly and then eat,
or - in the case of children - eat paint chips that contains lead (common in houses built
prior to 1960) can have elevated levels of lead and ZPP in their body. In an industrial
setting, the Occupational Safety & Health Administration mandates the use of ZPP
and strongly recommends that a ZPP test be ordered every time that a lead level is
ordered to monitor an employee’s exposure to lead. Both are necessary because ZPP
will not reflect recent or acute lead exposure, and it does not change quickly when a
patient is removed from lead exposure. ZPP is best at detecting a person’s average
exposure to lead over the last 3-4 months.
The maximum lead concentrations considered safe in children have been set at a very
low level to minimize the negative impact of lead exposure on their development.
ZPP is not sensitive enough for use as a screening test in children, as values do not
rise until lead concentrations exceed the acceptable range. In this age group, blood
lead measurements should be done to detect exposure to lead.
In children, the ZPP/heme ratio is frequently ordered as an early indicator of iron
deficiency. It is one of the first signs of insufficient iron and will be elevated in most
young people before signs or symptoms of anemia are present. Those with an elevated
ZPP/heme ratio may require further testing to determine the cause. In some cases, a
patient may have both lead exposure and iron deficiency.
ZPP also is occasionally ordered to help diagnose porphyrias. These are a group of
rare inherited disorders that are caused by deficiencies in the enzymes necessary to
produce heme. Deficiency of an enzyme leads to a bottleneck and the buildup of
intermediate products that would normally be converted to heme. There are two
porphyrias in which very high concentrations of ZPP and other porphyrins accumulate
in red blood cells. The main symptom exhibited by these patients is extreme
sensitivity to sunlight.
When is it ordered?
ZPP is ordered along with a lead level when chronic exposure to lead is suspected,
when an employee is a participant in an occupational lead monitoring program, or
when someone has a hobby, such as stained glass working, that brings them into
frequent contact with lead. The ZPP/heme ratio is ordered as a screening test for iron
deficiency in children and adolescents and/or when iron deficiency is suspected.
Occasionally ZPP is ordered when a patient is sensitive to sunlight and the doctor
suspects a porphyria.
444
The ZPP concentration in whole blood is usually very low. An increase in ZPP
indicates a disruption of normal heme production, but is not specific as to its cause.
The main reasons for increases in ZPP are iron deficiency, lead poisoning and, in rare
cases, a porphyria. It is important that ZPP levels be evaluated in the context of a
patient’s history, clinical findings, and the results of other tests such as ferritin, whole
blood lead, and a CBC (complete blood count). It is possible that the patient may have
both iron deficiency and lead poisoning.
In cases of chronic lead exposure, ZPP reflects the average lead level over the
previous 3-4 months. However, the amount of lead currently present in the blood and
the burden of lead in the body (the amount in the organs and bones) cannot be
determined with a ZPP test. Values for ZPP rise more slowly than blood lead
concentration following exposure, and they take longer to drop after exposure to lead
has ceased.
An increase in the ZPP/heme ratio in a child is most often due to iron deficiency. If a
ZPP or ZPP/heme result is greatly increased and the patient is sensitive to sunlight,
then a porphyria may be present.

ZPP may be elevated in inflammatory conditions, infections, and several blood-
related diseases, but it is not generally used to monitor or diagnose these conditions.
Depending on the method used to test ZPP, other substances in the blood that
fluoresce, such as bilirubin and riboflavin, can produce false positive results. Falsely
low values may occur if the sample is not protected from light before testing.
ZPP isn't a test your doctor would typically order in the office to screen for iron
deficiency; rather, it is used mostly in the field by health departments for this purpose.
1. Besides ZPP and lead levels, what other tests might my physician order to
monitor exposure to lead?
If you are in an occupational setting where you are frequently exposed to lead, your
physician may order the following tests to evaluate your kidneys and red blood cell
production:
 BUN
 Creatinine
 Urinalysis
 CBC or hemoglobin and hematocrit
 Peripheral blood smear.
445

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5-HIAA 1

AFP Tumor Markers 13

Aldosterone and Renin 17

Vitamin B12 & Folate 58

BNP and NT-proBNP 78

Bone Marrow Aspiration and Biopsy 82

BRCA-1 and BRCA-2 87

Clostridium difficile toxin 92

Cardiac Biomarkers 104

Cardiac Risk Assessment 106

Catecholamines, Plasma and Urine 108

CD4 Count 114

Celiac Disease Tests 116

CF Gene Mutation Testing 121

Chemistry Panels 124

Complement Levels 143

Comprehensive Metabolic Panel 146

Creatinine Clearance 154

C-Reactive Protein 156

Diabetes-related Autoantibodies 166

Direct Antiglobulin Test (Direct Coomb’s test) 171

Testing for Drugs of Abuse 175

Epstein-Barr Virus Antibodies 178

Epidermal Growth Factor Receptor 183

Protein Electrophoresis Immunofixation Electrophoresis 190

Factor V Leiden and PT 20210 197

Fecal Occult Blood Test 200

Fetal fibronectin 203

GFR and EGFR 212

Gram Stain 218

Growth Hormone 219

HIV Antibody 240

HIV Genotypic Resistance Testing 242

HIV Viral Load 244

Hormone Receptor Status 251

Indirect Antiglobulin Test 265

Influenza Tests 268

Lipoprotein Subfraction Testing 291

Liver Panel 296

Lipoprotein little a 297

Lyme Disease 299

Methylmalonic Acid 306

Ova and Parasite Exam 313

p24 An gen 321

Pap Smear 322

Plasma Free Metanephrine 327

Platelet Count 330

Porphyrin Tests 332

Protein C and Protein S 347

Rheumatoid Factor 359

Respiratory Syncytial Virus 361

Sickle Cell 372

Stool Culture 376

Strep Throat 380

Susceptibility Testing 383

Sweat Test 386

TB Skin Test 392

Therapeutic Drug Monitoring 398

Total Protein and A/G Ratio 403

Triple Screen 408

Tumor Markers 416

Uric Acid 419