ENDOCRINOLOGY

ENDOCRINE SYSTEM Mechanis Utilizes G Causes

Network of ductless glands that secrete m of proteins and 2 transcription of
nd
•
hormones directly into the blood. action messenger genes
• Considered to be the regulatory system of the Final Activate Synthesizes new
body. Effect existing intracellular
• It is regulated by means of control of hormone intracellular enzymes
synthesis rather than by degradation enzymes via
phosphorylatio
2 PHYSIOLOGIC REGULATORY SYSTEMS n
• Endocrine system Examples • Insulin • Aldosterone
• Nervous system • Glucagon • Cortisol
• Neuroendocrine System • Growth • Sex hormone
hormone • Vitamin D
TYPES OF GLANDS
• Endocrine HORMONE REGULATION
• secretes substance into the HORMONE SECRETION REGULATION
bloodstream • Negative-Feedback: limits final products (e.g.,
• Exocrine Insulin and Blood Glucose)
• secretes substance onto a surface, • an increased in product results to
usually through a duct decrease activity of the system and
the production rate
MAJOR GLANDS OF ENDOCRINE SYSTEM
• Pituitary Gland
• Thyroid Gland • Positive-Feedback: increases final products
• Parathyroid Gland (e.g., Oxytocin during breastfeeding and
• Adrenal Gland delivery, estrogen-induced LH and FSH surge
• Pancreas during ovulation)
• Reproductive Glands (ovaries & testes) • increased in product will result in the
• Thymus Gland elevation of the activity of the system
• Pineal Gland and production rate

HORMONE HORMONE RECEPTOR REGULATION

• Chemical signals produced by specialized cells
secreted into the bloodstream and carried to
a target tissue.
• they play an important role in growth and
development
• regulated by feedback mechanism: negative
and positive
• Major function: To maintain the consistency of
chemical composition of extracellular and
intracellular fluids and control metabolism,
growth, fertility and responses to stress.
• Upregulation: increase in receptor number or
sensitivity (e.g., uterus: estrogen upregulating
estrogen receptor (its own receptor) and LH
receptor)
• Downregulation: decrease in receptor number
or sensitivity (e.g., uterus: progesterone
downregulating progesterone receptors (its
own receptors) and estrogen receptor)

PROTEIN- LIPID HORMONE

HORMONE (LIPID-SOLUBLE)
(WATER-
SOLUBLE)
Location Cell membrane Nuclear/cytoplasmi
of receptors c receptor
receptor

Seminar 2 lizel
→ Hypothalamus will secrete your releasing hormone • ex. glycoprotein (FSH, HCG, TSH,
with anterior pituitary hormones and the endocrine erythropoietin) and polypeptides (ACTH, ADH,
gland will secrete its hormones. Hormone will go to its GH, angiotensin, calcitonin)
receptor on different target tissues.
→ Negative feedback (red line) when there is an Steroids
increase in the hormone it will signal the anterior • Water insoluble (hydrophobic) and circulate
pituitary and hypothalamus to stop the secretion of bound to a carrier protein
the releasing hormone and stimulating hormone • cholesterol as common precursor usually they
→ Positive feedback (green line) increase in product are produced in adrenal glands, ovaries, testis,
will lead to elevation of the activity signaling the placenta
anterior pituitary to the production rate of stimulating • ex. aldosterone, cortisol, estradiol,
hormone progesterone, and Vitamin B3

TYPES OF HORMONE ACTIONS Amines

• Endocrine • Derived from an amino acid and they are
• secreted in one location and releases intermediary between steroid and protein
into blood circulation hormones
• binds to specific receptor to a • epinephrine, norepinephrine, T3T4
physiologic response
• Paracrine HYPOTHALAMUS
• secreted in endocrine cells and • Portion of the brain located in the wall and
releases in interstitial spaces floor of the third ventricle.
• binds to adjacent cells and affects the • It is above the pituitary gland and is connected
binding receptor to the posterior pituitary by the infundibulum
• Autocrine (Pituitary stalk).
• secreted into endocrine and • It is the link between the nervous system and
sometimes releases in interstitial the endocrine system.
spaces • The supraoptic and paraventricular nuclei
• binds to specific receptor on the cell produce vasopressin and oxytocin.
of origin to self regulate function • Neurons in the anterior portion release the
• Juxtacrine following hormones (hypophyseal hormones)
• secreted in endocrine cell, acts on • Thyrotropin-releasing hormone (TRH)
immediately adjacent cell by direct cell • Gonadotropin-releasing hormone (Gn-
to cell contact RH)
• Intracrine • Growth hormone releasing hormone
• secreted in endocrine cells and (GH-RH)
remained as well as function inside the • Prolactin-inhibiting Factor (PIF)
synthesize of origin
• Exocrine RESPONSE PATTERN
• secreted in endocrine cells and OPEN-LOOP NEGATIVE FEEDBACK MECHANISM
releases into lumen of GUT
• Neurocrine
• secretes in neurons and releases into
extracellular spaces
• Neuroendocrine
• secreted in neurons and releases from
nerve endings

• Hypothalamus releases TRH and that

CLASSIFICATION OF HORMONE ACCDG TO
stimulates anterior pituitary and releases TSH
COMPOSITION OR STRUCTURES.
then thyroid gland will release T3, T4
Peptides and Proteins
pagsobrang dami ng ng T3 and T4 you can
• water soluble and not bound to carrier protein.
have negative feedback mechanism.
• synthesize and stored in the cell in a form of
• For T3 and T4 you have an open loop negative
secretory granules and cleaves as needed
feedback mechanism

Seminar 2 lizel
 • the increase in hormone can directly send
signal to your anterior pituitary and also to
hypothalamus, signaling that there is an
increase in your thyroid hormone
PULSATILITY
• Pulse frequency of secretion
• INCREASING the frequency of GnRH pulses ‒
reduces the gonadotroph secretory response
decreasing the pulse frequency, increases the
amplitude of the subsequent LH impulse.
CYCLICITY
• Nervous system ‒ regulates this function
• Hormone secretion is dependent on the time
of the day.
• Ex. ACTH ‒ peak occurs in the morning
HYPOPHYSIOTROPIC HORMONES
ANTERIOR PITUITARY GLAND
• Derived from oral ectoderm (Rathke Pouch)
• Basophilic Cells: FSH, LH, ACTH, TSH,
MSH
• Acidophilic Cells: GH, Prolactin
POSTERIOR PITUITARY
• Derived from neural ectoderm (neural
outgrowth of Hypothalamus)
• Pituicytes store and secrete: Vasopressin
(ADH), Oxytocin
ANTERIOR PITUITARY GLAND
(ADENOHYPOPHYSIS)
• Is the true endocrine gland
• It regulates the released and production of
hormones such as prolactin, growth hormone,
gonadotropins (FSH and LH), TSH and ACTH.
• Hormones secreted by anterior lobe are either
peptides or glycoproteins.

5 TYPES OF CELLS BY IMMUNOCHEMICAL TEST

• Somatotrophs
• secretes growth hormone
• Lactotrophs or mammotrophs
• secretes prolactin
PINEAL GLAND • Thyrotrophs
• Attached to the midbrain • secretes TSH
• It secretes melatonin that decreases the • Gonadotrophs
pigmentation of the skin • secretes LH and FSH
• Secretions are controlled by nerve stimuli • Corticotrophs
• secretes POMC (Proopiomelanocortin)

• Midbrain HYPOTHALA ANTERIOR TARGET TARG

• Melatonin MIC PITUITARY ORGAN ET
• Nerve stimuli HORMONE HORMONE HORMONE ORGA
• Sleep wake cycle N
GHRH (+) GH IGF-1 Liver,
PITUITARY GLAND (HYPOPHYSIS) Somatostatin (Somatotro (Somatome muscl
• small egg shaped gland located at the base of (-) pin) din) e,
the brain beneath the hypothalamus bone,
• master gland kidney
• divided into 2 lobes: anterior & posterior , etc.
• located in sphenoid bone (Sella turcica or TRH (+) TSH T3, T4 Thyroi
turkish saddle) d
gland
CRH (+) ACTH GC (main), Adren
• Known as the master gland along with al
• Located in a small cavity in the sphenoid bone MC and cortex
of the skull called the Sella turcica or turkish weak
saddle androgens
• Connected by the infundibular stalk to the GnRH (+) FSH, LH Estrogen, Gonad
median eminence of the hypothalamus Progestero s
• All pituitary hormone have circadian rhythms. ne,

Seminar 2 lizel
 Testostero DISORDERS
ne GH DEFICIENCY (GHD)
PIH/Dopamin Prolactin --- Breast • Idiopathic growth hormone def.
e (-) • MC cause of GH deficiency in children
• In children with pituitary dwarfism,
(+) stimulation normal proprotions are retained and
(-) inhibition show no intellectual abn.
• Pituitary adenoma
ADENOHYPOPHYSIS HORMONES • MC etiology in adult-onset GH def.

ACROMEGALY
• Due to overproduction of GH

DIAGNOSTIC TEST:
GH DEFICIENCY
• Patient preparation - complete test; 30 min
before extracting blood
• Fasting serum (specimen; GH)
• Screening test: Physical activity test (Exercise
GROWTH HORMONE/SOMATOTROPIN
test)
• Most abundant of all pituitary hormones
• Result of the test: Elevated serum GH
• Controlled by GH-RH and somtostatin.
• Confirmatory Test:
• Structurally similar to prolactin and human
• Gold Standard: Insulin tolerance test
placental lactogen.
• Arginine Stimulation: 2nd confirmatory
• Secretion is erratic and occurs in short burst.
test
• Overall metabolic effect is to metabolize fat
• 24 hours or night time monitoring; pag
stores while conserving glucose.
hindi tumaas it confirms GH
• major stimulus deep sleep
deficiency
• major inhibitor stomatostatin
• >5 ng - adult
• >10 ng - children
DIRECT ACTIONS INDIRECT ACTIONS (VIA
IGF-1)
ACROMEGALY
• ↑ Plasma glucose • ↑ Bone length and
• Screening Test: Somatomedin C or insulin-like
(diabetogenic) thickness (pubertal
growth factor (IGF-1)
• ↑ Protein growth spurt)
• Confirmatory: Glucose Suppression Test ‒
deposition and lean • ↑ Protein synthesis
OGTT (75g glucose)
body mass in muscles and other
• blood is collected every 2 hours
• ↑ Lipolysis organs and ↑ lean
• ↑ IGF-1 body mass
GIGANTISM
• Anti-aging effects • ↑ Organ size
• hypersecretion of GH during childhood
REGULATION OF GH SECRETIONS
ACROMEGALY
FACTORS FACTORS • hypersecretion of GH during adulthood
INCREASING GH DECREASING GH
SECRETION SECRETION FEATURES:
• Starvation • Hyperglycemia • coarse facial features
• Hypoglycemia • High fatty acid levels • soft tissue thickening (lips)
• Low fatty acid levels • Aging • spade like hands
• Exercise • Obesity • protruding jaw (prognathism)
• Excitement • Somatostatin • Sweating
• Trauma • Exogenous GH • impaired glucose tolerance or DM
• Testosterone • Somatomedins (IGF)
• Estrogen GONADOTROPINS
• GHRH • Follicle Stimulating Hormone (FSH)
• Deep sleep • Luteinizing Hormone (LH)

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 • Important markers in diagnosing: • leads to bilateral adrenal hyperplasia and
• Fertility cortisol overproduction
• Menstrual cycle disorder • Obesity!!!
• Present in blood of both male and female at
all ages
• FSH: Spermatogenesis (males) ADDISON S DISEASE
• LH: Synthesis of hormone • secondary (ACTH) or tertiary (CRH) adrenal
• for male - testosterone insufficiency
• for female - ovulation • hyposecretion of glucocorticoids and
• Elevated FSH: Diagnosis of Premature aldosterone
menopause (45 to 50 years old)
• After Menopause: Increase FSH and LH PROLACTIN (PRL)
• lack of estrogen (have a protective • acts directly on mammary glands
mechanism for female decreasing the • controls the initiation and maintenance of
frequency of having a heart disease) lactation
• induces ductal growth, development
INFERTILITY of breast lobular alveolar system and
• lack of FSH and LH in both male and female synthesis of specific milk proteins
• inability to conceive after 1 year of • requires priming by estrogens, progestins,
unprotected intercourse corticosteroids, thyroid hormones, and insulin
• Men: 1-20ng/mL
THYROID STIMULATING HORMONE (TSH) • Women: 1-25 ng/mL
• AKA thyrotropin • major inhibitor prolactin: dopamine
• main stimulus of the uptake of iodide (iodide, • who secrete dopamine: hypothalamus
necessary for the production of T3 and T4) • if have prolactin excess: will have
• Increases: hypogonadism
• size of thyroid follicular cells • usually where can we see increase prolactin:
• release of thyroxine from thyroid infertility and pituitary adenoma and if have
colloid follicles amenorrhea and galactorrhea also
• uptake of iodide by thyroid cells from acromegaly and renal failure and patient with
ECF cirrhosis and picos
• thyroxine biosynthesis • usually highest level during sleep: 4am to 8am
• differentiates pituitary (2 ) hypothyroidism and 8pm to 10pm
from primary hypothyroidism
GALACTORRHEA
ADRENOCORTICOTROPIC HORMONE (ACTH) • inappropriate production of breast milk
• acts on the adrenal cortex to stimulate growth • due to hypersecretion of PRL
and secretion of corticosteroids • symptoms: irregular menstruation,
• follows circadian rhythm menopausal symptoms, milk discharges,
• elevated during times of stress difficulty in getting erection, breast
• single chain peptide without disulfide bond tenderness and enlargement
• it is produce in response to slow serum
cortisol AMENORRHEA
• due to low cortisol level sign to that ACTH • absence of menstrual cycle in females
increase • due to hypersecretion of PRL
• responsible for the regulation for adrenal
androgen synthesis IMPOTENCE
• since it follows cardigan rhythm. the ACTH is • inability to attain penile erection in males
usually high between 6am to 8am • due to hypersecretion of PRL
• lowest is 6pm to 11pm
• usually found in addison s disease ectopic 3 FORMS OF CIRCULATING PROLACTIN:
tumors or after protein meals during • Non-glycosylated monomer ‒ major form of
samgyusal prolactin
• Big prolactin - consists of dimeric and trimeric
CUSHING S DISEASE glycosylated form
• hypersecretion of ACTH
Seminar 2 lizel
 • Macro-prolactin ‒ which is less physiologically
active form
SPECIMEN CONSIDERATION
• Collect 3-4 hours after the patient awakes •
Highest level: 4-8am; 8-10pm
SUMMARY:
• GH: growth of bone and soft tissues
• PRL: for lactation
• TSH: release of thyroid hormone
• FSH: growth of the follicle (female) and initial
wave of spermatogenesis (male)
• LH: ovulation and final follicular growth
(female)
• ACTH: release of cortisol
POSTERIOR PITUITARY GLAND
• Oxytocin or pitocin: for contraction of uterus
and ejection of milk primed with estrogen
• ADH or arginine vasopressin or pitressin:
permeability of kidney tubules
** for what are these hormones?
oxytocin:
• oxytocin usually secreted in a association with
carrier protein
• stimulate the contraction of the uterus called
ferguson reflex
• oxytocin also play roles in hemostasis at the
placental site following delivery
• stimulates contraction during delivery and
lactation
ADH:
• usually act on what part of kidney
• distal convoluted tubules and
collecting tubules
• major function is to maintain osmotic
homeostasis throughout the regulation of
water balance
• it decreases the production of urine by
promoting reabsorption of water by renal
tubules and to maintain water homeostasis
• urine decrease and promote absorb of water
OXYTOCIN
• Major effect: smooth muscle contraction
• Stimulates contraction of the gravid uterus
• Contributes directly to uterine contractions
during labor on the myometrium and
promotes prostaglandin secretion
• Hemostasis at the placental site after delivery
• HL: 3-5 minutes
• Useful test in some pregnant women in
predicting pre-term labor
• Oat cell carcinoma of the lung and
adenocarcinoma of the pancreas
Seminar 2
ARGININE VASOPRESSIN
• Maintain osmotic homeostasis by regulating
water balance
• Nonapeptide that acts on the DCT and
collecting tubules of the kidneys
• Urine/serum/plasma osmolality and thirst may
stimulate ADH secretion
• 5-10% drop in blood volume and blood
pressure triggers (baroreceptors) the release
ADH
• example: decrease blood volume and
blood pressure means not enough
fluids in the blood circulation therefor
ADH will increase instead of releasing
a lot of fluid through urination the
distal convoluted tubule and collecting
tubules will absorb more water to
increase BV and BP
• Responsible for the maintenance of blood
volume, pressure and tonicity
• Basal plasma vasopressin: 2.3-3.1pg/uL
• Diagnostic test: Overnight water deprivation
test
POLYURIA
• deficient ADH production or action
• Hypothalamic DI
• Nephrogenic DI
• Psychogenic or primary polydipsia
SYNDROME OF INAPPROPRIATE ADH SECRETION
(SIADH)
• autonomous sustained production of AVP in
the absence of known stimuli for its release
• malignancy, CNS diseases, pulmonary
disorders drug therapies
• decreased urine volume, increased sodium
concentration and urine osmolality
• why increase sodium concentration: increase
diuretic hormone so there will be a increase in
water reabsorption
• if there is increase water reabsorption there
will be increase sodium reabsorption
SIADH
• Occurs when there is uncontrolled secretion
of ADH without any known stimulus for such
release
• ADH is release even though the blood volume
is normal or increased and plasma osmolality
is low
• the usual stimuli, the dehydration or decrease
blood volume or if have high salt ingestion
there will be increase blood osmolality
therefor, osmoreceptor in your hypothalamus
will trigger the posterior pituitary to increase
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 ADH secretion therefor there will be water PARAFOLLICULAR CELLS (C-CELLS):
retention by kidney and another is thirst, so • Calcitonin
you are going to drink water that leads to • regulation of calcium
increase blood volume and decrease blood
osmolality which is negative feedback FUNCTION OF THYROID HORMONE
response • For tissue growth
• Mental development
HYPOPITUITARISM • Development of the central nervous system
• Panhypopituitarism • Elevated heat production
• Tumors • Control of Oxygen consumption
• Trauma • Influence carbohydrates and protein
• radiationtherapy metabolism
• infarction • Energy conservation
• infection
• familial MAJOR THYROID HORMONE:
• idiopathic TRIIODOTHYROINE (T3)
• Monotropic hormone deficiency • Most active thyroid hormonal activity
• Almost 75-80% is produced form T4
TRUE DIABETES INSIPIDUS (Deiodination)
• Hypothalamic/neurogenic/cranial/central • Best indicator of recovery from
diabetes insipidus hyperthyroidism as well as recurrence of
• Deficiency of ADH with normal ADH receptor, hyperthyroidism
due to hypothalamic or pituitary disease
• Failure of the pituitary gland to secrete ADH TETRAIDOTHYRONINE (T4)
• Large volume of urine is excreted (3-20L/day) • Principal secretory product
• Prohormone for T3 production
NEPHROGENIC DIABETES INSIPIDUS • Good indicator: thyroid secretory rate
• Normal ADH with abnormal ADH receptor ‒ • Elevated Thyroxine: causes inhibition of your
renal resistance to ADH action TSH
• Failure of the kidneys to respond to normal or • TSH will be inhibited
elevated ADH levels
• Treatment: Desmopressin (dDAVP) THYROID HORMONE BINDING PROTEINS
• Urine output: >2.5 L THYROXINE-BINDING GLOBULIN (TBG)
• Diagnostic test: water deprivation test • Transport majority of T3
• Transport 70-75% of total T4
THYROID GLAND
• located in front of the lower neck THYROXINE-BINDING PREALBUMIN
• bow tie or butterfly-shaped gland (TRANSTHYRETIN)
• Follicles: structural units of thyroid • Transport 15-20% of total T4
• Colloid: homogenous viscous fluid consisting • T3 has no affinity for prealbumin
mainly of a glycoprotein
• iodine complex called thyroglobin THYROXINE-BINDING ALBUMIN
• secretes T3 and T4 and calcitonin • Transport T3 and 10% of T4
• thyroglobulin is a glycoprotein that acts as
preformatrix containing tyrosyl group and it is THYROID AUTOANTIBODIES RESPONSIBLE FOR
stored in the follicular colloid of the thyroid AUTOIMMUNE THYROID DISORDER:
gland • Thyroperoxidase - encountered during
HASHIMOTO s Disease
TYPES OF CELLS: • Thyroglobulin
FOLLICULAR CELLS: T3 AND T4 • TSH receptor - associated with GRAVE s
• control the rate at which cells burn fuels from Disease
food for energy
• CNS activity and brain development GOITER
• cardiovascular stimulation, bone and tissue • an enlarged thyroid gland which is a symptom
growth and development of many thyroid disorders (hypo, hyper, or
• GI regulation and sexual maturation euthyroid state)
Seminar 2 lizel
CRETINISM
• hyposecretion of thyroid hormones during
fetal life or infancy
• Iodine deficiency
MYXEDEMA
• hypothyroidism during the adult years
• describe as peculiar non-pitting swell of the
skin, the skin becomes infiltrated by
mucopolysaccharide
• puffy face and weight gain, dery and yellow
skin also possible anemia
HASHIMOTO S DISEASE
• acquired hypothyroidism in later childhood
due to development of autoantibodies to
thyroid tissue components
• also called chronic autoimmune thyroiditis
• most common cause primary hypothyroidism
• thyroid gland retain lymphoid tissue and
lymphoid tissue produces t lymphocytes,
autoantibodies and will bind to the cell
membrane of the follicular cells causing cell
lysis and inflammatory reaction and there will
be a presence of enlarge thyroid gland in a
form of goiter
• have High TSH and positive + for
thyroperoxidase enzyme TPO
GRAVE S DISEASE
• hyperthyroidism with peculiar edema behind
the eyes called exophthalmos which causes
the eye to protrude
• hypersecretion of thyroid stimulating
immunoglobulins (TSIs)
• aka Diffuse toxic goiter
• most common cause of thyrotoxicosis
• there is production of autoantibodies
in a form of TSH receptor
autoantibodies
• these autoimmune disease in which
antibody are produce will activate your
TSH receptor
• clinical findings: bulging eye and pretibial
myxedema
• diagnostic test: TSH receptor antibody test
SERUM FREE TRIIODOTHYRONINE
• measures the amount of free triiodothyronine
(T3) in blood
• used to evaluate and manage disorders of the
thyroid gland
• related tests: TSH, FT4
• Adults:1.4-4.4pg/mL(0.22-
6.78pmol/L)
Seminar 2
• N>37weeks(cordblood):15-
391pg/dL(0.2-6pmol/L)
• Pregnancy,1st:211-383pg/dL(3.2-
5.9pmol/L)
• Pregnancy,2nd:196-338pg/dL(3-
5.2pmol/L)
• Pregnancy,3rd:196-338pg/dL(3-
5.2pmol/L)
DIRECT EQUILIBRIUM DIALYSIS
• uses undiluted serum dialyzed for 16-18 hours
at 37 C
• dialysate is then analyzed directly using RIA
• 2-128 ng/L (2.6 to 165 pmol/L)
• reference method or direct method for FT3
and FT4
TRIIODOTHYRONINE MEASUREMENT
• measures the level of total T3 in blood
• used to evaluate and manage thyroid
dysfunction, including hyperthyroidism •
related tests: FT4, T3 uptake
• Adults: 60-181 ng/dL (0.92-2.78
nmol/L)
• Pregnancy (last 5 mos): 116-247
ng/dL (1.79-3.8 nmol/L)
SERUM TOTAL T4 COMPETITIVE IMMUNOASSAY
• measures the total amount of thyroxine/T4
(both free and CHON bound)in blood
• uses barbital buffers (vs TBPA) and 8-anilino-
1- naphthalene-sulfonic acid (vs TBG)
• Adults: 4.5-10.9 μg/dL (58-140
nmol/L)
TSH IMMUNOASSAY
• measures the amount of thyroid stimulating
hormone (TSH) in blood
• using chemiluminescence w/ low detection
limit
• related tests: T3 and T4
• Adults: 0.5-4.7μunits/L
• Pregnancy (1st) :0.3-4.5μunits/L
• Pregnancy (2nd): 0.5-4.6μL
• Pregnancy (3rd): 0.8-5.2μL
• increase TSH:
• primary hypothyroidism
• Hashimoto s disease
• thyrotoxicosis due to primary tumor
• TSH antibodies
• thyroid hormone resistance
• decrease TSH:
• primary hyperthyroidism
• secondary and tertiary
hypothyroidism
• treated Grave s disease
lizel
 • euthyroid sick disease Thyroxine binding globulin (TBG)
• overreplacement of thyroid hormone • Use to CONFIRM results of FT3 and FT4 or
in hypothyroidism abnormalities of TT4 and THBR test\
• most important thyroid function test • Distinguish:
• best detemethod for detecting clinical • Hyperthyroidism: normal TBG
significant thyroid dysfunction is TSH • Euthyrodism: increase TBG
• Hormonal Effect: Estrogen increases TBG,
THYROTROPIN RELEASING HORMONE (TRH) Androgens decreases of TBG
STIMULATION TEST • Increased: euthyroidiam and hypothyroidism
• injection of TRH and measurement of the and pregnancy
output of TSH • Decreased: using anabolic steroids and
• used in the diagnosis of combined pituitary- nephrosis
thyroid disorders
• differentiates 2 hypothyroidism and 3 other test:
hypothyroidism FINE NEEDLE ASPIRATION: evaluate thyroid nodules
• measures the relationship between TRH and recombinant human tsh: thyroid cancer
TSH tanned erythrocyte hemagglutination : measure
• to differentiate euthyroid and hyperthyroid antithyroglobulin antibodies
patient serum calcitonin : tumor markers - thyroid metastasis
• also to detect thyroid resistant syndrome (MTC)
• increase during hypothyroidism pentagastrin test: MTC medullary thyroid carcinoma
• decrease during hyperthyroidism disorders T3 T4 TS FT4 rT Tg T
H 4 B
radioactive iodine uptake
G
• Measure the ability of thyroid gland to
trap iodine Grave s INC INC DE INC IN INC N
• Helpful: disease C C
• Hyperthyroidism
• high uptake: metabolically active gland Primary N/ DE IN DE DE N/ N
• High uptake + TSH deficiency = autonomous hypothyroi DE C C C C DE
thyroid activity dism C C
Thyroglobulin (Tg) Assay
• Postoperative marker of thyroid cancer Hashimoto N/ N/ IN N/ DE N/ N
• Monitoring course of metastatic thyroiditis DE DE C DE C DE
or recurrence of Thyroid cancer C C C C
• Differentiate:
• Subacute thyroiditis: increase thyroglobulin Nonthyroid DE N/ V V N/I N N
(tg) al illness C DE NC
• Thyrotoxicosis factitia: decrease thyroglobulin C
(tg)
Thyroid INC INC N/I INC IN INC N
• increased: untreated metastatic thyroid
hormone r NC C
cancer also nodular goiter and
esistance
hyperthyroidism
• reference test: double antibody radio
Neonatal DE DE IN DE DE N/ N
immunoassay RIA also elisa and IRMA
hypothyroi C C C C C DE
dism C
T3 uptake
• Measure the number of available
binding sites of the thyroxine- binding
proteins. PARATHYROID GLAND
• Does not measure: T3; reflects: TBG • four tiny glands attached to the thyroid
• Inversely related to TBG: there will be • releases PTH
decrease uptake result in elevated tbg • actions directed to bone, kidney and
• increased: TBG intestines
• decreased: T3 uptake • controls calcium and phosphate
• reference value = 25 - 35 % metabolism with the help of calcitonin

Seminar 2 lizel
 TYPES OF CELLS: LABORATORY METHOD FOR PTH:
• CHIEF CELLS PTH LEVEL MEASUREMENT:
• synthesize and secrete hormone PTH • overnight fasting
• Intact PTH: 10-65 pg/mL
• PTH N-terminal (includes intact PTH): 8-24
• OXYPHIL CELLS pg/mL
• non secretory cell • PTH C-terminal (includes C-terminal, intact
• seen only after puberty PTH, and midmolecule): 50-330 pg/mL

PARATHYROID HORMONE (PTH; RELATED TESTS:

PARATHORMONE) • Calcium, Phosphorus and Creatinine
• Only hormone produced by parathyroid gland
• Secreted by Chief cells ADRENAL GLAND
• Most important regulator of blood calcium • a triangular gland on top of the kidney •
level
ADRENAL CORTEX:
INCREASES CIRCULATING BLOOD LEVEL OF • outer part
CALCIUM BY • produces cortocosteroids for regulation of
• Indirectly increasing number and activity of salt & water balance, response to stress,
osteoclasts metabolism, immune system, & sexual
• Inhibiting bone formation by osteoblasts development & function
• Enhancing calcium reabsorption in renal
tubules ADRENAL MEDULLA:
• Increasing conversion of vitamin d to its active • inner part
form • consists of Chromaffin cells
• Increasing excretion of phosphate by kidneys • produces catecholamines from tyrosine
• Promoting absorption of calcium in digestive
tract MINERALOCORTICOIDS (ALDOSTERONE)
• responsible for fluid and electrolyte balance
CONTROL OF SECRETION: • sodium reabsorption and water retention
• Secretion of PTH is dictated by blood levels of • maintain osmolality
ionized calcium
• High calcium plasma level inhibits HORMONE HALF-LIFE
secretion and calcium is deposited in Aldosterone 20 minutes
bone Corticosterone 60-90 minutes
• Low calcium plasma level stimulates DHEA 7-22 hours
secretion Epinephrine 2 minutes
Norepinephrine 2 minutes
CLINICAL SIGNIFICANCE OF PTH Renin 15 minutes
• Tetany: hypoparathyroidism and deficiency of
calcium GLUCOCORTICOIDS (CORTISOL & CORTISONE)
• abnormally high PTH values may indicate • enhances glucose production from CHONs,
primary, secondary, or tertiary acting as insulin antagonist
hyperparathyroidism, chronic renal failure, • (cortisol): only hormone to inhibit the anterior
malabsorption syndrome, and vitamin D pituitary secretion of ACTH by negative
deficiency feedback
• primary hyperthyroidism • follows circadian rhythm like ACTH
• most common cause of hypercalcemia • (cortisone): reacts with stress
• phosphaturia • stimulate lipolysis, provide resistance to stress
• presence of parathyroid adenoma and depress immune responses
• secondary hyperparathyroidism • urinary metabolite: 17-hydroxycorticosteroids
• decrease calcium level
SEX HORMONES/ANDROGENIC STEROIDS
• hyperplasia all 4 glands
• Estrogen, progesterone,
dehydroepiandrosterone (DHEA),
androstenedione, and testosterone

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 • Male: development of sexual characteristics, • Low-dose Dexamethasone
usually insignificant Suppression Test
• Female: influence female sex drive, pubic hair, • Midnight Plasma Cortisol
axillary hair growth • CRH Stimulation Test
• Midnight Salivary Cortisol Test: screening test
ADRENAL MEDULLA : SECRETIONS • Buffalo hump, hyperglycemia, hypertension,
• Epinephrine (70%) increased cholesterol
• Norepinephrine (30%) • Screening Test
• Dopamine • 24 hour Urine Free Cortisol Test
• mobilize energy stores and prepare • Overnight Dexamethasone
the body for muscular activity and Suppression Test
stressful conditions (increase heart
rate and BP, and increase blood sugar) ADDISON S DISEASE
• Urinary metabolite: vanillyl mandelic acid • primary adrenal insufficiency
(VMA) • due to progressive dysfunction or destruction
of the gland
DISEASES ASSOCIATED WITH HORMONES OF THE • symptoms: fatigue, weakness, weight loss, GI
ADRENAL GLAND disturbances, postprandial hypoglycemia
HYPERALDOSTERONISM • hyposecretion of adrenal hormones
• hypersecretion of aldosterone
• 1 : due to an adenoma, hyperplasia(Conn s CONGENITAL ADRENAL HYPERPLASIA
disease), adrenal carcinoma, glucocorticoid (ADRENOGENITAL SYNDROME)
suppressible aldosteronism • congenital absence or deficiency of one or
• greatly affects electrolyte balance (metabolic more of the biosynthetic enzymes needed in
alkalosis) cortisol biosynthesis
• hypernatremia and hypokalemia • hyperplasia: ACTH stimulation because of low
• 2 : stimulus outside the adrenal gland (excess levels of cortisol
production of renin • ambiguous genitalia for girls, and precocious
• Confirmatory Test: puberty for boys
• Saline Suppression Test
• Oral Loading Sodium Test VIRILISM OR HIRSUTISM
• Aldosterone • elevated plasma testosterone in women as a
• most potent mineralocorticoids result of ovarian or adrenal tumor (virilizing
• steroid hormone regulate with water adenoma)
and electrolytes • Excessive hairiness on women
• sodium chloride, potassium
• regulate blood pressure GYNECOMASTIA
• excessive growth (benign) of the male
HYPOALDOSTERONISM mammary glands due to an adrenal tumor
• deficient aldosterone production (feminizing adenoma) which secretes
• deficiency of 21 hydroxylase feminizing hormone (estrogen)
• seen in Addison s disease, kidney disease-2
(hyporeninemic hypoaldosteronism), enzyme PHEOCHROMOCYTOMA
defects, acquired due to heparin therapy or • tumor of the adrenal medulla that is a cause
surgery of hypertension
• hyperkalemia and hyponatremia • Screening Test: plasma metanephrines and
• destruction of adrenal gland and deficiency of normetanephrines
glucocorticoids • 50-30 years old
• hypertension, tachycardia, headache,
CUSHING S SYNDROME sweating
• hypersecretion of cortisol (ACTH • overproduction of catecholamines
independent)
• due to primary adrenal disease like adenoma NEUROBLASTOMA
• features: truncal obesity, moon face, • fatal malignant condition in children in which
hypertension, hirsutism cancer of the nervous system causes excess
• Confirmatory Test production of norepinephrine

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 • high urine excretion of AVA or VMA or both • distinguish whether the cause is adrenal (low
and dopamine cortisol and aldosterone production) or
pituitary (low ACTH production)
LABORATORY MEASUREMENT OF SOME • cortisol should be increased by
HORMONES SECRETED BY THE ADRENAL GLAND twofold to threefold within 60 minutes
ALDOSTERONE MEASUREMENT • fasting (8 hrs)
• measures the amount of aldosterone in blood
• related tests: sodium and potassium ADRENAL ANTIBODY TEST
• test is done in the morning • detects antiadrenal antibodies, which attack
• position affects the result: seat upright the body's own adrenal gland, in blood
• alcohol intake • used to diagnose and monitor patients
• supine, normal-Na diet: 2-9 ng/dL (55- suspected to have autoimmune adrenocortical
250 pmol/L) insufficiency (the autoimmune form of
• upright, normal-Na diet: 2 to 5x supine Addison's disease)
value • related test: ACTH
• supine, low-Na diet: 2 to 5x supine • Adults: Negative at 1:10 dilution
value
PANCREAS
URINE FREE CORTISOL MEASUREMENT (UFC) • lying immediately beneath the stomach
• measures the amount of cortisol in urine • both an exocrine and an endocrine gland
• 24-hour urine collection (follow usual diet &
drink TYPES OF TISSUES:
• fluids as you ordinarily would) • Acini
• avoid drinking alcohol before and during the • secretes digestive juices into the
urine collection intestine
• normal:<2% of cortisol is seen in urine
• >120 μg/day is diagnostic
• RIA (adults): 20-70 μg/day (55-193 • Islets of Langerhans
nmol/24 hrs) • secretes hormones directly into the
• HPLC (adults): ≤50 μg/day (≤138 blood
nmol/24 hrs)
HORMONES
SERUM CORTISOL MEASUREMENT • Glucagon: glycogenolysis and
• amount of cortisol in blood gluconeogenesis • Insulin: glycogenesis,
• used to help diagnose adrenal gland glycolysis, lipogenesis
dysfunction caused by conditions such as • Somatostatin
Addison's disease and Cushing's syndrome
• related test: ACTH DISEASES ASSOCIATED WITH HORMONES OF THE
• pregnancy (FE) PANCREAS
• 8 AM to noon: 5-25 μg/dL (138- DIABETES MELLITUS
690nmol/L) • deficiency of insulin or defects in insulin
• 8 PM to 8 AM: 0-10 μ g/dL (0-276 receptors
nmol/L)
HYPERINSULINISM
DEXAMETHASONE SUPPRESSION TEST • hypersecretion of insulin
• 1 mg at midnight • may be due to a tumor, insulinoma
• Serum cortisol is measured the following day
(8:00 GLUCAGONOMA
• AM) • hypersecretion of glucagon by a tumor
• suppressed to <5 μg/dL or 140 nmol/L
SOMATOSTATINOMA
ACTH STIMULATION TEST • hypersecretion of somatostatin by a tumor
• cosyntropin test or tetracosactide test
• small amount of synthetic ACTH is injected,
and the
• amount of cortisol or Aldosterone is measured
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 LABORATORY MEASUREMENT OF SOME
HORMONES SECRETED BY THE PANCREAS
INSULIN C-PEPTIDE MEASUREMENT
• measures the level of a by-product of the
hormone insulin called C-peptide in blood
• used to know how much insulin is being
produced in the body
• fasting specimen
• Adults: 0.5 - 2.0 ng/mL (0.17 - 0.66
nmol/L)
ANTI-INSULIN ANTIBODY TEST (RIA)
• measures the amount of antibodies to insulin
• used when insulin resistance in diabetes is
• suspected
• determination of the binding of 125I-Tyr-Al4-
insulin to the serum fraction precipitated by
PEG
• related test: Insulin C-peptide
• <8.2% binding
GLUCAGON IMMUNOASSAY (RIA)
• glucagon competes with 125I tracer for
binding sites
• amount of 125I is measured and is inversely
proportional to the concentration of glucagon
• Fasting: 60-200 pg/mL
GONADS
• main source of sex hormones
TESTES: ANDROGENS (TESTOSTERONE)
• produce sperm
• sexual development (muscle enlargement,
growth of body hair, voice changes, male
sexual drive)
OVARIES: LOCATED IN THE PELVIS
• produce eggs
• secrete estrogen and progesterone and
relaxin
• for sexual development (breast
enlargement, distribution of fats),
menstruation, pregnancy
DISEASES ASSOCIATED WITH HORMONES
SECRETED BY GONADS
FEMALE PSEUDOHERMAPHRODITISM
• genetically female but whose phenotypic
characteristics are, to varying degrees, male
• exposure to androgens before the 12th week
of gestation
PRECOCIOUS PUBERTY
Seminar 2
• development of secondary sexual
characteristics in girls < 8 yrs old and boys < 9
years old
• premature hair and breast development
KALLMANN SYNDROME
• most common form of hypogonadotropic
hypogonadism due to deficiency of GnRH
• both seen in males and females
TESTICULAR FEMINIZATION SYNDROME
• Androgen insensitivity syndrome
• defect in androgen action
• males w/ female habitus & develop breast
tissue • blind vagina with rudimentary testes
LABORATORY MEASUREMENT OF SOME
HORMONES SECRETED BY THE GONADS
ESTRONE MEASUREMENT
• measures the amount of estrone in blood •
note pregnancy and menstruation
• Prepubertal children 1-10 yrs:<56
pmol/L
• Adult males: 55-240 pmol/L
• Adult females (menstrual phase):
• Early follicular phase: 55-555
pmol/L
• Luteal phase: 55-740 pmol/L
• Pregnant: increases 10-fold from 24th
to 41st wk
PROGESTERONE RIA
• Mab1-Progesterone-Mab2125I
• Male: 0.6-2.11 ng/mL
• Female:
• Follicular: 0.70-1.78 ng/mL
• Ovulatory: 0.79-3.95 ng/mL
• Luteal: 4.57-17.56 ng/mL
• Menopause: 0.43-2.13 ng/mL
SERUM ESTRADIOL MEASUREMENT
• used for conditions such as amenorrhea, early
puberty or hypogonadism
• related tests: FSH, LH, testosterone, PRL •
vegetarian
• Postmenopausal: <59 pg/mL (217
pmol/L)
• Menstruating Adult Female
• Follicular phase: <20-145
pg/mL (184-532 pmol/L)
• Midcycle peak: 112-443
pg/mL (411-1,626 pmol/L)
• Luteal phase: <20-241 pg/mL
(184-885 pmol/L)
• Adult Male: <20 pg/mL (184 pmol/L)
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TOTAL TESTOSTERONE EIA
• measure the total amount of testosterone
• uses salicylates or sulfactants, pH alterations,
• temperature changes, and competing steroids
• related tests: FSH, LH, PRL, free testosterone
• Adult M (morning): 9.36-37.1 nmol/L
• Adult F (morning): 0.21-2.98 nmol/L
• Pregnant: 3 to 4 times normal
• Postmenopausal: 0.28-1.22 nmol/L
• RIA (125I)
OTHER
PLACENTA
• Estrogen: prepares uterine endometrium for
pregancy
• Estradiol, estriol, estrone
• Progesterone: prepares uterus for pregnancy,
the
• breast for lactation and maintains the
• endometrium
• HCG (trophoblast): maintains progesterone in
early pregnancy
• similar alpha subunit to LH, FSH, TSH
• HPL: stimulates estrogen and progesterone
production by corpus luteum
• similar to growth hormone and PRL
• produce placenta, measured urine and
serum, amniotic fluid
• stimulate development of mammary
gland
GIT
• Gastrin: G cells (antrum)
• causes secretion of HCl, pepsin,
pancreatic enzymes by
• parietal cells: relaxes iliocecal sphincter
• Secretin:S cells (duodenum)
• stimulates secretion of watery alkaline
pancreatic
• fluid, decreases gastric acid secretion
• Cholecystokinin or pancreazymin: I cells
(duodenum)
• stimulates gallbladder contraction,
augments secretin
• Vasoactive intestinal peptide (VIP):
• relaxes and vasodilates gut smooth
muscles
• Gastric Inhibitory Peptide (GIP):
• inhibits gastric acid and pepsin
secretion and motility, and stimulates
secretion of intestinal juice & insulin
• Enterogastrone:
• inhibits gastric acid production and
mobility
• Motilin: M cells (duodenum and jejunum)
Seminar 2
• diminishes speed of gastric emptying
and stimulates secretion of pancreas
• gastric acid secretion and pepsin;
stimulates HCO -
OTHER LABORATORY METHODS:
• RIA- radio immunoassay
• ELISA ‒ enzyme-linked immunosorbent assay
• Test applicable for target glands
• IRMA- immunoradiometric assay
• FPIA- Fluorescent polarization immunoassay
• EIA- enzyme immunoassay
OTHER LABORATORY METHODS:
• Porter Silber Fluorometric Method: 17-OHCS
• Zimmermann reaction: 17-KS
• Kober reaction: urine estrogen
• Dexamethasone Suppression Test (DST):
Cortisol test in depression
• RIA, FPIA
• GC and HPLC: catecholamines
DEXAMETHASONE SUPPRESSION TESTS
• Investigates suspected overactivity of
hypothalamic-pituitary-adrenal axis
• Low dose: 1 mg orally at 23:00 and
cortisol measurement at 8:00 or 9:00
• Normal: Cortisol <50 nmol/L
• High dose: 8 mg
• Suppressed ACTH: Cushing s
• No suppression: malignant
ACTH production
SYNACTHEN TESTS
• check the function of the adrenal glands
(cortisol)
• Short synacthen test
• Long synacthen test
THYMUS GLAND
• lies in the upper part of the thoracic cavity
• important in the immune system, especially
• early in life
• secretes thymosin
• helps in the development of of WBCs
(T cells)
PINEAL GLAND/BODY
• small pinecone shaped located in the middle
of the brain
• secretes melatonin
• decreases the secretion of LH and
FSH by decreasing the release of
hypothalamic releasing hormone
(inhibits functions of reproductive
system)
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 • plays an important role in the onset of
puberty
• Regulates sleep and wake cycle

Seminar 2 lizel