Introduction to Clinical Medicine

(ICM)
Case Studies
Diseases of the Endocrine System

Prepared by
Robert W. Wilhoite M.D.
Edited by
Patrice Thibodeau, M.D.
 Case # 1
• A 51 year old women consults with her physician because of a
progressive weight gain of 20 pounds, increasing fatigue and
difficulty concentrating over the last 2 months. At times she
finds it difficult to tolerate the cold Maine temperatures.

Thought Questions
• What is on the problem list?
• What are you thinking? What is your differential?
 Case # 1
• A 51 year old women consults with her physician because of a
progressive weight gain of 20 pounds, increasing fatigue and
difficulty concentrating over the last 2 months. At times she
finds it difficult to tolerate the cold Maine temperatures.
• 3 months ago she experienced increased anxiety, difficulty
sleeping, palpitations and increased sweating that lasted for a
few weeks. She believes she may be going through menopause.

Thought Question
• What other history questions would you like to ask to help
narrow the differential?
 Other questions
• “Did you have a respiratory illness before the start
of your initial symptoms?”
– had URI infection about 3.5 months ago
• “Did you recently give birth?”
– Has not given birth recently.

• What are you thinking now? Can you narrow

down your differential?
• What would you like to do on exam?
 Case # 1
• A 51 year old women consults with her physician because of a
progressive weight gain of 20 pounds, increasing fatigue and
difficulty concentrating over the last 2 months. At times she
finds it difficult to tolerate the cold Maine temperatures.
• 3 months ago she experienced increased anxiety, difficulty
sleeping, palpitations and increased sweating that lasted for a
few weeks. She believes she may be going through menopause.
• Physical exam reveals an obese woman in no acute distress.
Temp is 98.8. Her skin is cool and dry, her hair coarse and
brittle. There is some puffiness of the skin beneath the infra-
orbital area. Palpation of the neck suggests an increase in the
size of her thyroid gland and it is described as slightly tender.
 Problem List
• Transient palpitations, anxiety, sleep issues,
heat intolerance after a URI
• Recent weight gain, fatigue , cold intolerance,
dry coarse hair, infraorbital edema
• Mildly enlarged and slightly tender thyroid
gland

• DDx? What initial labs would you get?

 Initial laboratory findings
– WBC 10.5 (slightly elevated)
– Hgb 13.5 (N)
– Basic metabolic profile - normal

– Any other labs?

 Other Labs
• TFT’s (TSH, FT4)
– pending
• ESR
– slightly elevated at 38 (0-20 is nml)
 Thought Questions
• What is your primary diagnosis?
– Transient hyperthyroidism followed by hypothyroidism from a
thyroiditis.
• What forms of hypothyroidism causes a painful thyroiditis?
– DeQuervain’s or subacute granulomatous thyroiditis (most common and
occurs after viral illness)
– Suppurative thyroiditis (immunocompromised patient, staph or strep)
– Radiation induced thyroiditis (from radioactive iodine)
• What forms of hypothyroidism cause painless thyroiditis?
– Hashimoto’s thyroiditis (rarely painful, usually painless)
– Drug induced thyroiditis-from treatment for HepB/C (INF-a)
– Postpartum thyroiditis and Silent thyroiditis which are variants of
Hashimoto’s thyroiditis
• What form of thyroiditis does this patient most likely have?
– DeQuervain’s thyroiditis
 Thought questions
• What are the phases of this disease?
– Thyrotoxic phase, hypothyroid phase, recovery phase.
• What would you expect the TSH and FT4
to be in this patient presently? 3 mos ago?
– Elevated TSH and low FT4 now
– Elevated FT4/T3 and low TSH 3 mos ago
• Should you image this patient? Check
antibodies?
– RAIU and Ultrasound are not necessary
– Antibodies not necessary
 Thought question
• If you did get a RAIU scan, what would you
expect to see?
– Hyperthyroid phase
• preformed hormones are being secreted, no new
hormone production due to inflammation, thus
RAIU is low or undetectable.
– Hypothyroid phase
• The RAIU during the hypothyroid phase returns to
normal or is even increased as a result of the rise in
TSH.
 Thought questions
• How would you treat this patient?
– NSAIDs
– If patient has marked local or systemic
symptoms then glucocorticoids (40-60mg
prednisone)
– May need levothyroxine replacement if the
hypothyroid phase is prolonged and patient
symptomatic
Normal Thyroid Gland
Close up
“ C” Cells
Subacute Granulomatous thyroiditis
Hashimoto’s disease
 Positive immunofluorescent stain for
anti-thyroid peroxidase (TPO) antibody
 Case # 1
Final diagnosis

DeQuervain’s disease
Hypothyroidism
 Case #2
• This 38 year old woman, the CEO of a major computer systems
company, states that she has not felt well for several months.
• She has been unable to sleep at night because of her strong heart
beat and irregular pulse. She has lost 18 pounds over the past four
months and currently describes herself as a “nervous wreck!”

• What are your thoughts? DDx?

• Any other questions?
• What are you looking for on exam?
 Case #2
• This 38 year old woman, the CEO of a major computer systems
company, states that she has not felt well for several months.
• She has been unable to sleep at night because of her strong heart
beat and irregular pulse. She has lost 18 pounds over the past four
months and currently describes herself as a “nervous wreck!”
• Physical exam reveals a thin woman in no acute distress although
she finds it difficult to remain calm during the interview and exam.
Her temperature is 99.8.
• There is some mild peri-orbital edema and she tends to stare at her
physician in a prominent fashion.
• Palpation of her neck suggests bilateral nontender enlargement of
her thyroid gland but no lymphadenopathy. A bruit is heard when
listening over the thyroid gland.
• ?Problem list?
 Problem List
• Weight loss
• Periorbital edema
• Peculiar stare
• Tachycardia
• Non tender thyroid gland enlargement
• Thyroid bruit

• DDx? Labs?
 Initial laboratory findings
– WBC 8,500 (N)
– Hgb 13.5 (N)
Basic metabolic profile = normal
 Thought questions
• What is your principal working diagnosis?
– Hyperthyroidism (Graves disease)
• What additional laboratory tests would you order?
– TSH, FT4 and T 3
• What do you expect the labs to be in a patient with
Grave’s disease?
– Elevated FT4 +/- T3, depressed TSH
• What antibodies might you check?
– TSI and TRAB
• What other disease states may be associated
with Graves disease?

– Pernicious anemia
– Mysthenia gravis
– Diabetes mellitus
Thyroid gland hyperplasia
Scalloping effect in thyroid gland hyperplasia
 Treatment for Graves?
• Give beta blocker (ie atenolol) for symptomatic
relief of adrenergic symptoms in patient with
thyrotoxicosis
• Anti-thyroid meds (PTU and methimazole)
– Methimazole preferred, once a day dosing and less side effects
– If patient pregnant*, PTU is used in first trimester (check preg
test!!)
• May need radioactive iodine ablation or surgery if
does not go into remission
– I-131 for ablation
 Case # 2

Final diagnosis

Grave’s Disease
 Case # 3
• A 36 year old man seeks his physician’s attention
because of severe right costo-vertebral angle pain
which is not relieved by NSAID’s. Because his
physician is on vacation and because of the severity of
his pain, he goes to the local ER seeking help.

• What are you thinking?

• Any other questions?
 Case # 3
• A 36 year old man seeks his physician’s attention
because of severe right costo-vertebral angle pain
which is not relieved by NSAID’s. Because his
physician is on vacation and because of the severity of
his pain, he goes to the local ER seeking help.
• When questioned, he describes a colicky type pain
which radiates down to his right groin. On the way to
the hospital he vomited twice. He believes he may have
seen blood in his urine today. Has not had any fevers.

• What are you thinking?

• What PE would you like?
 Case # 3
• A 36 year old man seeks his physician’s attention because of severe
right costo-vertebral angle pain which is not relieved by NSAID’s.
Because his physician is on vacation and because of the severity of
his pain, he goes to the local ER seeking help.
• When questioned, he describes a colicky type pain which radiates
down to his right groin. On the way to the hospital he vomited
twice.
• Physical exam reveals an agitated man in severe
distress. His face is flushed and he is unable to remain
quiet during the examination, frequently attempting to
change position. He has + CVA tenderness.

• What causes CVA tenderness?

• Problem List?
 Problem List
• Vomiting
• Right costal-vertebral angle pain
• Colicky nature of pain
• Radiation down right groin
• Patient in distress from pain and unable to
sit still

• What labs?
 Initial Lab Findings
– WBC 18,500 (H)
– Hgb 15 (N)
– Differential shift to the left
– Glucose 100
– Sodium 150 (H)
– Potassium 3.8 (N)
– Bicarbonate 26 (N)

Thoughts to explain the labs?

Want any other labs?
If so which? And Why?
 Initial Lab Findings
– WBC 18,500 (H)
– Hgb 15 (N)
– Differential shift to the left
– Glucose 100
– Sodium 150 (H)
– Potassium 3.8 (N)
– Bicarbonate 26 (N)
– Phosphorous 2.8 (L) (3.0-4.5)
– Calcium 12.5 (H) (8.5-10.2)
– Urinalysis 10 rbc/hpf
 Thought questions
• From the laboratory tests given which
values are most significant?
– Serum phosphorous = 2.8
– Serum calcium = 12.5
• What is the likely cause of this man’s pain?
– Renal calculi
 Types of kidney stones
• Calcium oxalate or phosphate
– Most common
– Radio-opaque
• Struvite
– Made up of magnesium, ammonium and phosphate
– Usually associated with proteus UTI
– Radio-opaque - e.g. staghorn calculus
• Uric acid
– Associated with gout, dehydration and high protein diet
– Radio-lucent
• Cystine
– Uncommon; associated with genetic disorder cystinuria
– Faintly radio-opaque
 What are the causes of
hypercalcemia?
• Primary Hyperparathyroid disease (multiglandular
hyperplasia/adenoma from MEN1 or 2A; adenoma, cancer)
• Tertiary Hyperparathyroid dz (due to severe chronic renal
failure) (will discuss more later)
• Vitamin D intoxication
• Drugs – thiazides*, lithium
• Milk-alkali syndrome*
• Granulomatous disease – e.g. sarcoidosis, TB
• Endocrine disorders –hyperthyroidism*
• Prolonged bed rest –increased mobilization from bone
• Malignancy–ectopic PTH production, PTHrp humoral
hypercalcemia, osteolytic mets
 What are the symptoms of
hypercalcemia?
• Most common is asymptomatic: discovered on lab testing
done for other reasons
• Kidney stone pain and hematuria (gross or microscopic)
• Bone fractures (from affects of high PTH on bone turnover)
• Abdominal pain, nausea, vomiting and anorexia
• Constipation, polyuria, polydipsia, nocturia**
• Emotional changes - depression, mental confusion, mental
status changes, memory loss, psychosis

• Why does this patient have elevated Na?**

“Stones, Bones, Abdominal Groans,
Thrones and Psychic overtones.”
 Thought Questions
• What additional tests would you order:
– Parathyroid hormone level (PTH)
– Kidney stone study (ie non-contrast helical CT scan)

– Result: PTH is elevated and the CT shows multiple

stones in the R ureter.

• What is your primary diagnosis?

– Primary hyperparathyroidism causing calcium kidney
stones
 What are the functions of
PTH?
• Increase in serum calcium levels by
• Resorption of calcium from bones - Activate osteoclasts to
remove Ca from bone
• Increase tubular reabsorption of Ca in the kidney
• Increase absorption of Ca from the gut by converting vitamin
D to its active form (25 to 1,25 dihydroxycholcalciferol) within
the kidney which increases absorption of Ca from the gut
• Increase excretion of phosphorous
 What are the causes of
hypocalcemia?
• Hypoparathyroidism
• Post-thyroidectomy*
• Chronic magnesium deficiency
– Low levels inhibit PTH release
• Vitamin D deficiency
• Pancreatitis
– Fatty saponification
• Renal insufficiency
– Hyperphosphatemia **
– Lack of nephron mass available to hydroxlate vit. D
 What are the symptoms of
hypocalcemia?
• Muscle cramps
• Tetany
• Paresthesias – perioral and
acral
• Chvostek’s sign
– twitching of lips with
tapping anterior to the ear
• Trousseau's sign
– carpal spasm ( BP cuff
for 2minutes)
Normal parathyroid gland
Parathyroid adenoma
Parathyroid gland hyperplasia
 What organs may be involved in a
patient with hyperparathyroidism?
• Skin – calciphylaxsis with ischemic changes
• Kidney – renal calculi
• Bones – painful bones – fractures
• Abdominal groans – peptic ulcer, pancreatitis
• Psychic moans – depression, lethargy
• Heart – dystrophic calcification of valves
 Disorders of the Parathyroid Gland
• Primary hyperparathyroidism (high PTH, high calcium)
– Adenoma, hyperplasia, carcinoma
• Secondary hyperparathyroidism (high PTH and low calcium):
– Chronic renal failure
• Decreased phosphate excretion =  serum Phos
• Increased phosphorous depresses serum ionized Ca
• Decreased calcium stimulates parathyroid gland to produce more
PTH to normalize the Ca and to decrease the Phos levels
– Vit D deficiency
• Decreased Ca gut absorption
• Low calcium stimulates PTH secretion
• Tertiary hyperparathyroidism (high PTH, high calcium) from
long standing poorly treated CRF*
 Case # 3
Final diagnosis

Parathyroid gland adenoma

Renal calculi

Treatment?
 Case # 4
• This 39 year old woman has noted a gradual
increase in her weight over the past six months.
She gained 30 pounds. Associated with this has
been an increase in her lower back pain as well
as some muscle weakness.
• Physical exam reveals a woman who exhibits
predominantly a central obesity with her
peripheral extremities remaining thin. Her skin
is dry and wrinkled with some slight hirsutism
of her upper lip and chin. There is no
hyperpigmentation. Blood pressure is 165/90.
 Case # 4
• This 39 year old woman has noted a gradual
increase in her weight over the past six months.
She gained 30 pounds. Associated with this has
been an increase in her lower back pain as well
as some muscle weakness.
• Physical exam reveals a woman who exhibits
predominantly a central obesity with her
peripheral extremities remaining thin. Her skin
is dry and wrinkled with some slight hirsutism
of her upper lip and chin. There is no
hyperpigmentation. Blood pressure is 165/90.
• Problem List?
 Problem List
• Weight gain
• Back pain
• Muscle weakness
• Truncal obesity
• Hirsutism
• Hypertension

• DDx? Labs?
 Initial laboratory findings
– WBC 8,000
– Hgb 15.0
– Plasma glucose 200 (N < 100)
– Serum sodium 149 (N = 135-145)
– Serum potassium 1.8 ( N = 3.5 – 5.0)

– Interpretation of labs?
 Problem List
• Weight gain
• Back pain
• Muscle weakness
• Truncal obesity
• Hirsutism

• Hyperglycemia
• Hypernatremia
• Hypokalemia
 What is your differential
diagnosis?
• Cushing’s syndrome
– ACTH - Dependent
• Cushing’s disease – pituitary adenoma
• Ectopic sources: lung, pancreas, thyroid
– ACTH - Independent
• Idiopathic adrenal hyperplasia, adenoma, carcinoma
• Exogenous steroid use
• Hyperaldosteronism

• What historical questions might you ask to help

you with ddx? Other PE components?
• Why does patient have back pain?
 What additional lab tests would
you order?
• Establish elevated cortisol (2 of the following need to be abnormal)
• Late night salivary cortisol (need to perform twice)
• 24 hour urine cortisol (need to perform twice)
• Low dose dexamethasone suppression test
• Next measure ACTH levels to establish dependent vs
independent – ACTH Cushing Syndrome (CS)
• ACTH levels < 5 pg/ml indicate Independent ACTH CS (ie adrenal hyperplasia)
• ACTH levels > 20 pg/ml indicate dependent ACTH from ectopic source or Cushing’s
disease
– Can do Head MRI first and if negative, do the high dose dexamethasone
suppression test to distinguishes cause. See previous lecture notes.
• Locate lesion
– Head MRI
– Thin section CT or MRI of adrenals
• If negative, order labs to rule out hyperaldo (renin, aldosterone)
Classic findings in patient with
Cushing syndrome?
– Hypertension
– Weight gain
– Secondary diabetes –due to gluconeogenesis
– Truncal obesity
– Moon facies
– Buffalo hump – fat in posterior neck and shoulders
– Hirsutism – increased androgens
– Fragile skin – poor wound healing
– Purple striae
– Hyperpigmentation in patients with Cushing’s Disease
(high ACTH; ACTH dependent)
– Osteoporosis/bone fractures
Normal Adrenal glands
 Adrenal
Atrophy

Normal

Bilateral cortical
hyperplasia
Adrenal
cortical
adenoma
Pituitary gland adenoma
(Cushing’s disease)
 Case # 4

Final diagnosis

Cushing’s syndrome due to a

adrenal cortical adenoma.

Treatment?
 Case # 5
• This 62 year old man has a past history of benign prostatic
hypertrophy. More recently he has been seen by his
physician over the past six months because of persistent
hypertension. Today BP is 190/110. His original diagnosis
was essential hypertension. Despite continued treatment
with ACE-I, beta-blockers and diuretics he has remained
hypertensive.
• More recently he has complained of severe episodic
headaches during attempts to urinate, some nocturia and a
general weakening of the musculature of his extremities.
• Physical exam revealed a BP of 192/110 and some atrophy of
the muscles of his legs. Fundoscopy exam shows no evidence
of papilledema. Motor exam is 4/5 diffusely.

• What other history do you want? What PE findings do

you want to know about?
 Problem List

• BPH
• Hypertension not responsive to treatment
• Episodic headaches with urination
• Atrophy of muscles and motor weakness

• DDx?
 What is your differential
diagnosis?
• Pheochromocytoma
• Hyperaldosteronism
• Thyrotoxicosis
• Anxiety
• RAS
• Drug use (amphetamines, cocaine)

• Labs?
 Initial laboratory findings
• Serum sodium - normal
• Serum potassium - normal
• Bicarbonate – normal
• BUN/Cr – normal

– Interpretation?
 Which is/are less likely based
on these labs?
• Pheochromocytoma
• Hyperaldosteronism
• Thyrotoxicosis
• Anxiety
• RAS
• Drug use (amphetamines, cocaine)
 Problem List

• BPH
• Hypertension not responsive to treatment
• Episodic headaches with urination
• Atrophy of muscles and motor weakness
• NML BMP
 Thought Questions
• What other tests would you order?
– TSH, T3, FT4 to rule out hyperthyroidism
– Drug screen for cocaine or amphetamines if suspicious
– Aldosterone and Renin –r.o. hyperaldosteronism ( ie aldo
high, renin low, aldo/renin > 20)
– To rule in/out pheo usually establish biochemical
confirmation before imaging
• 24 hour urinary tests for fractionated metanephrines* and
catecholamines* used if low index of suspicion*
• plasma metanephrines if high index of suspicion*
 Thought Questions
• What additional tests would you order to rule in/out
pheochromocytoma?
– Abdominal CT with contrast for location of tumor or
– T2 weighted MRI with gadolinium contrast
• optimal for detecting pheochromocytoma and is somewhat better
than CT for imaging extra-adrenal pheochromocytoma
(paragangliomas)
 Back to the patient
• A noncontrast CAT scan of abdomen was miskakenly done
in this case before biochemical confirmation
– Resultsa possible mass in the right adrenal gland.
– The mass was resected and the upcoming microscopic slides are
representative of the lesion.

• Now what are you thinking? Which of the following is less

likely?
– Pheochromocytoma
– Hyperaldosteronism
– Thyrotoxicosis
– Anxiety
– Drug use
 Pheochromocytoma
• “the rule of 10”…Debunked??
– 10 % are malignant
– 10% are bilateral
– 10 % are extra-adrenal
– 10% are seen in children
– 10 % show calcification within the tumor
– 10 % are familial
 Typical findings in a patient
with a pheochromocytoma
• Classic triad
– episodes of palpitations, HA and profuse sweating with
either episodic HTN or persistent HTN likely pheo
– May last > 15 minutes without relief with meds

• Complains of stress and anxiety attacks with feeling

of impending doom

• Episodes are worse with exercise, positional change,

urination.* (Why does this man have HA with
urination?)
 Nomenclature
• Pheochromocytomas
– Catecholamine-secreting tumors that arise
from chromaffin cells of the adrenal medulla
– typically secrete a greater quantity of
epinephrine than norepinephrine.
• Paragangliomas
– Catecholamine-secreting tumors that arise from
chromaffin cells of the sympathetic ganglia
("extra-adrenal pheochromocytomas“)
– predominantly produce norepinephrine
 Nomenclature
• Because the tumors have similar clinical
presentations and are treated with similar
approaches, many clinicians use the term
"pheochromocytoma" to refer to both adrenal
pheochromocytomas and catecholamine-secreting
paragangliomas.
• However, the distinction between
pheochromocytoma and paraganglioma is an
important one because of implications for
associated neoplasms, risk for malignancy, and
genetic testing.
 Name disorders associated with
pheochromocytomas
• All of which have autosomal dominant
inheritance
– von Hippel-Lindau (VHL) syndrome
– multiple endocrine neoplasia type 2 (MEN2)
– neurofibromatosis type 1 (NF1)
 Treatment
• Complete tumor removal is the goal
• Begin patient on alpha blocker (ie phenxybenzamine)
• Can start beta blockers for persistent tachycardia, but
because beta blockers can induce a paradoxical
increase in blood pressure in the absence of alpha
blockade, they should be administered only after
effective alpha blockade.
• May use calcium channel blockers, ARB or ACE I if
need more blood pressure control.
• Be careful during surgery as manipulation of tumor
may cause a hypertensive crisis.
Pheochromocytoma
Zellballen
 Pathology Thought Questions
• Following resection of the tumor, what stain
would your order to support your diagnosis?
– Dichromate fixative
• Why?
– The tumor cells have an affinity for chromic
acid which oxidizes catecholamines to melanin.
Dichromate staining
 What other tumors secrete
catecholamines?
• Found in children
• Neuroblastomas
Neuroblastoma – liver metastases
Neuroblastoma
Right adrenal gland
Neuroblastoma
Rosette formation - neuroblastoma
 Case # 5
Final diagnosis

Pheochromocytoma
 Case # 6
• This 57 year old woman with a PMHx significant
for asthma presents with progressive and easy
fatigability. She also gives a history of anorexia,
weight loss, nausea, arthralgias and myalgias.
More recently she has noticed increasing
difficulty in walking and an increased
pigmentation of her skin over sun exposed areas.
• Physical exam reveals a cachectic appearing
woman whose blood pressure is 94/50. She
appears pale and her eyes appear to be shrunken
in their sockets. Motor strength is 4/5 diffusely.
 Problem List
• Progressive fatigue
• Weight loss, anorexia, nausea
• Myalgias, arthralgias, difficulty walking
• Skin pigmentation
• Cachexia
• Hypotension
• Sunken eyes
• Pale
• DDx? Other history questions? PE? Labs?
 Initial laboratory findings
• WBC 4,000 (N)
• Hgb 11 (L) (Nml is 12-16)
• RBC indices normocytic, normmochromic
• Serum sodium 126 (N=135-145)
• Serum potassium 6.0 (N= 3.5 –5.0)
• Serum glucose 60 (N= 70-110)
• Bicarbonate 20 (N=23-28)
• Interpretation?
 Problem List
• Progressive fatigue
• Weight loss
• Difficulty in walking
• Skin pigmentation
• Cachexia
• Hyponatremia
• Hyperkalemia
• Metabolic acidosis
• Hypoglycemia
• Normocytic anemia (anemia of chronic disease)
 Thought Questions
• What is your primary differential diagnosis?
• Causes of adrenal insufficiency
• What are causes of adrenal insufficiency?
– Primary adrenal insufficiency (Addison’s dz)
• Autoimmune adrenalitis - (most common)
• Infectious (TB, fungal, viral, syphilis)
• Hemorrhage (Waterhouse-Friderichsen syndrome-
infectious cause, trauma) or infarction
• Invasion by metastasis or lymphoma
 Causes of adrenal insuff cont’d
• Primary adrenal insufficiency (Addison’s dz)(see prev slide)
• Secondary adrenal insufficiency
– decreased ACTH pituitary production
• Pituitary macroadenoma (crowding out ACTH porduction)
• Pituitary surgery or radiation
• Sheehan’s syndrome/Pituitary apoplexy (pituitary infarction)
• Infections
• Head trauma
• Infiltrative diseases (Sarcoidosis)
• Craniopharyngioma, etc
• Tertiary - decreased corticotropin releasing hormone (CRH)
• Hypothalamic dysfunction as reviewed
– Abrupt withdrawal of exogenous glucocorticoids*
 Lab results review
• Hyponatremia
• Hyperkalemia
• Metabolic acidosis
• Hypoglycemia
• Normocytic anemia (anemia of chronic disease)

• How do you explain these lab results in this patient?

 Explanation of Lab Results
• Sodium
–  (low aldosterone = lose Na)
• Potassium
–  (low aldosterone = retention of K)
• Bicarbonate
–  (low aldosterone = H + not excreted)
• BP
–  (hypotension from loss of free water with naturesis)
• Skin pigmentation*?
– Cortisol deficiency leads to an increase in
proopiomelanocortin (ACTH-MSH-etc)
 Which kind of adrenal
insufficiency?
• Primary, Secondary or Tertiary adrenal
insufficiency? Why?
– Only see the hyperpigmentation in primary
adrenal insufficiency (Addison’s) and not in
secondary or tertiary because the
proopiomelanocortin is only elevated in
primary disease from elevation of ACTH-MSH
(POMC).
 How do you confirm the diagnosis
of adrenal insufficiency?
• First establish cortisol deficiency
– Check 8 am cortisol levels
• If < 3ug/dL then likely adrenal insufficiency
• If > 18 ug/dL then unlikely adrenal insufficiency
• Need to do a cosyntropin stim test for nondiagnostic levels of 3-18 ug/dL.
(explained in next slide and also reviewed in previous lecture)
• If cortisol is low, establish whether primary or secondary/tertiary cause
– Measure plasma ACTH levels
• If ACTH is high  primary cause****
• If ACTH is low  secondary / tertiary cause

• ****Plasma aldosterone and plasma renin activity should be checked if

suspect primary adrenal insufficiency
– Low aldosterone and high PRA (plasma renin activity)
 Nondiagnostic am Cortisol level
Cosyntropin (ACTH) stim test
• Measure baseline serum cortisol and ACTH levels
• Administer 250 ug of synthetic ACTH
• Measure cortisol levels at 30 and 60 minutes
– Serum cortisol level > 18 ug/dl indicates a normal
response and thus helps rule out adrenal insufficiency
– If there is no increase in cortisol levels after the injection
of ACTH adrenal insufficiency (primary or secondary)
• Then use result of ACTH level to help determine if the adrenal
insufficiency is primary or secondary as noted in previous slide.
 Adrenal
Atrophy
Addison’s

Normal

Bilateral cortical
hyperplasia
Waterhouse-Fredrichson Syndrome
Adrenal hemorrhage
 Case 6
Final diagnosis
Primary acute adrenal
insufficiency

Tx?
 Case # 7
• This 46 year old man gives a history of
persistent hypertension (190/120) which
has failed to respond to appropriate
medications. Despite this he has
experienced little in the way of symptoms
except for increased muscle weakness,
excessive thirst and nocturia.
• Physical exam reveals no retinopathy or
abdominal bruit.
 Problem List
• Refractory hypertension
• Muscle weakness
• Polydypsia
• Nocturia

• DDx?
 What is your differential diagnosis?
– Poor HTN med compliance
– Idiopathic hypertension
– Primary Hyperaldosteronism ( i.e. Conn’s syndrome)
– Secondary Hyperaldosteronism
• Renovascular HTN (Renal artery stenosis)(but no bruit)
• CRF, Cirrhosis, nephrotic syndrome)
– Pheochromocytoma
– ADH deficiency (but this would not explain the HTN!)
– DM Type II (but this would not explain the HTN)
– Hyperthyroidism
– Cushing syndrome

What labs would you order?

 Initial Lab Finding
• Serum sodium 157
• Serum potassium 3.0
• Bicarbonate 33 
• Glucose nml

• Interpretation? What disease gives these

BMP findings?
 Thought Questions

• What additional tests would you order?

– Plasma renin activity (PRA)
– Aldosterone and plasma aldosterone/plasma renin ratio
– 24 hour urine fractionated metanephrines and
catecholamines (if have low suspicion for pheo) or
plasma metanephrines (if have high suspicion for
pheo).
 Thought Questions
• What is your principal diagnosis to explain all
the problems?
– Primary Hyperaldosteronism
• What are the causes of primary
hyperaldosteronism? (Conn’s syndrome)
– Bilateral adrenal hyperplasia
– Aldosterone producing adrenal adenoma
– May be due rarely to an adrenal carcinoma
• What is the action of aldosterone?
– Increased sodium retention (causing HTN from sodium
retention)
– Increased potassium and hydrogen ion excretion 
hypokalemia and metabolic alkalosis
– Suppression of renin production  decreased PRA
 What are the causes of secondary
hyperaldosteronism?
• Due to a peripheral abnormality that causes the
kidney to misperceive a fall in BP which
inappropriately activates the RAAS which then
increases the levels of renin.
• Decreased renal perfusion – renal artery stenosis
• Chronic renal failure, nephrotic syndrome, cirrhosis
• Arterial hypovolemia and edema – CHF, cirrhosis
• Pregnancy – due to estrogen-induced increase in
plasma renin
 Typical findings in Primary
Hyperaldosteronism
• Muscle weakness and fatigue from low K
• Hypernatremia
• Metabolic alkalosis
• Suppressed Renin
• Elevated Aldosterone
Plasma renin: Normal = 1-3 ng/ml/hr
Plasma aldosterone: Normal = 3-9 ng/ml
 General info
• Primary aldosteronism accounts for 1% of
all causes of HTN
• Function of aldosterone – acts on distal
tubules to inc. reabsorption of Na and
excretion of K
• Plasma renin is low in primary hyperaldo
because retained Na feeds back to JGA and
decreases renin release.
 Case # 7

Final diagnosis

Adrenal adenoma
with
Primary hyeraldosteronism
 Case # 8
• This 38 year old woman complains of
progressive anorexia, nausea, vomiting
and irritability. A week ago she had a
seizure, the cause of which remains
unexplained.
• Physical exam reveals some papilledema
noted on fundoscopy exam.
• Problem List?
 Problem List
• Anorexia
• N/V
• Seizure
• Papilledema

• DDx? Other historical questions? What electrolyte

imbalances can cause a seizure? Which is more
likely with the papilledema?
• What labs, imaging would you like? Why?
 Initial laboratory findings
– WBC 10,000 (N)
– Hgb 14.2 (N)
– Serum sodium 110 
– Serum potassium 3.5 Normal
– Plasma osmolality 210  (275-295)
– Urine osmolality increased

Can you explain her seizure based on these

labs?
 Case # 8
– Sodium 110 
– Serum osmo 210 
– Urine osmo 

• What is your interpretation of the laboratory

findings? Based on the laboratory findings
what is your diagnosis?
– SIADH
• Imaging?
 Imaging study?
• A chest x-ray shows a mass in the
right upper lobe of the lung.
• Significance?
– Small cell Ca of lung that secretes ectopic ADH
 Syndrome of Inappropriate
Secretion of ADH (SIADH)
• ADH acts on collecting tubules of the
kidney to increase water reabsorption
• Results in decrease serum osmolarity
• Which results in decrease serum sodium
concentration
• Cerebral edema occurs due to shift of fluid
from intravascular compartment to
intracellular compartment.
Other Diseases of the Posterior
Pituitary Gland
• Central diabetes insipidus
– A deficiency of vasopressin (ADH)
– Results in an inability to resorb and concentrate water
resulting in a chronic water diuresis, thirst and
polydipsia .
• Sodium 
• Serum osmolarity 
• Urine osmolarity 
– Will respond to desmopressin – a synthetic vasopressin
Other Diseases of the Posterior
Pituitary Gland
• Nephrogenic diabetes insipidus:
– Due to a lack of response of the collecting
tubules of the kidney to ADH
– Will not respond to desmopressin.
 Case # 8

Final diagnosis

Paraneoplastic syndrome:
Small cell carcinoma of the lung with
SIADH
 Case # 9
• This 23 year old girl is brought to the ER in a
semi-comatose state. Her mother states that
her daughter had the “flu” 5 days ago and
more recently has complained of increasing
thirst and increased volume of urination.
There is also a history of a ten pound weight
loss in the past month.
• Physical exam reveals a dehydrated patient
• Vital signs in dehydration? Other PE?
• Problem List?
 Problem List
• Semi-comatose state
• History of flu
• Polydypsia and polyuria
• 10 pound weight loss
• Dehydration

• DDx? Labs?
 Initial laboratory findings
• WBC 13,500 (H)
• Hgb 15.0 (N)
• Blood glucose 475 (H)
• Na 134 (L)
• K 3.0 (L)
• HCO3 11 (L)
• CL 96 (L)
• Urinalysis Positive glucose and ketones

What is your primary diagnosis?

Interpretation of labs and explanation?
 Thought Questions
• How do you explain her current physical
condition?
– She is suffering from diabetic ketoacidosis
• What other lab test would you like?
– ABG
• What would you expect?
– pH ?, PCO2, HCO3, O2?
 Thought Questions
• What are the underlying biochemical
mechanisms involved in this woman’s
condition?
 Pathogenesis of Diabetic Ketoacidosis
Underlying biochemical mechanisms
• Absolute deficiency of insulin (usually seen in Type I DM) and subsequent
increase in counter-regulatory hormones (ie cortisol, GH, epinephrine, glucagon)
• Cells unable to uptake and utilize glucose without insulin  inc blood glucose
• Liver attempts to compensate for loss of energy source (gluconeogenesis,
glycogenolysis, lipolysis) Inc blood glucose
• Liver uses free fatty acids as an alternative source of energy (ketogenesis)
• Liver mobilizes fatty acid from triglycerides through oxidation
• Results in formation of ketone bodies (acetone, betahyroxybutyrate and
acetoacetate)Released into the circulation = metabolic acidosis
• Hyperglycemia and ketone bodies promote osmotic diuresis dehydration
• The shift of fluid from the intracellular space to extracellular (vascular) space
caused by the hyperglycemia and increased osm will cause dilutional
hyponatremia.
• Potassium excess is caused by a shift of potassium from the intracellular to the
extracellular space causing initial hyperkalemia. Hydrogen ions also accumulate
extracellularly causing acidosis. (Total body depletion of K eventually results
causing low serum potassium as in our patient)
 Case # 9

Final diagnosis

Type I diabetes mellitus and DKA

Treatment?