ENDOCRINE

o is a network of ductless glands that secrete hormones directly to blood

o considered to be regulatory system of the body

HORMONES

o Chemical signals produced by specialized cells secreted into the blood

stream and carried to a target tissue
o Play important role in growth and development Feedback mechanism:
o Regulates metabolic activity …
o Major function: maintain constancy of chemical POSITIVE FEEDBACK
Composition of extracellular fluids, and control Increase of product result of a system =
Metabolism, growth, fertility and responses to
Elevation of the activity of the system
Stress.
and the production rate
Types of hormone actions
NEGATIVE FEEDBACK
 Juxtacrine Hormone  direct cell-to-cell contact Increase of product of a system
 Autocrine Hormone  self-regulation =
 Paracrine Hormone  interstitial space  adjacent cell Decrease activity of the system and the
 Endocrine Hormone  blood circulation  specific receptor
 Neurocrine Hormone  neurons  extracellular space
production rate
 Intracrine Hormone inside endocrine cells, remain in origin
 Neuroendocrine Hormone  neurons  nerve endings
 Exocrine Hormone  gut

CLASSIFICATION OF HORMONE ACCORDING TO COMPOSITION OR STRUCTURE

A.Peptides
-They cannot cross the cell membrane due to their large molecular size
and thus; produce their effects on the outer surface of the cell
-Water soluble and not bound to carrier protein
a.1 Glycoproteins
-FSH, HCG, TSH, EPO
a.2. Polypeptides
-ACTH, ADH, GH, angiotensin, calcitonin, cholecalcitonin,gastrin,
glucagon, insulin, MSH, oxytocin, PTH, prolactin, somatostatin

B. Steroids
-Lipid molecules, cholesterol is their common precursor
-Produced by Placenta, Adrenal glands, Testes and Ovaries
-Water insoluble and bound to a carrier protein
-ex. Aldosterone, cortisol, estradiol, progesterone, testosterone,
activated vitamin D3

C. Amines
-derived from amino acids, intermediary between steroid and protein
hormones.
-ex. Triiodothyronine,Epinephrine, Norepinephrine, thyroxine
 HYPOTHALAMUS
 LOCATION: brain, wall and floor of third ventricle. Above PG,
Connected to posterior pituitary by infundibulum.
 Link between nervous system and endocrine system.
 Supraoptic:vasopressin (ADH) ; Paraventicular nuclei: oxytocin
 Hypophyseal hormones: TRH____________, GnRH_______________,
GH-IH___________________, GH-RH___________, PIF______________

* The endocrine system is a finely integrated system whereby the hypothalamus, the
pituitary, and target glands continually communicate through feedback inhibition and
stimulation to control all aspects of metabolism, growth, and reproduction. By
understanding this interplay, and carefully manipulating these systems via provocative
and suppressive stimuli, it is possible to characterize an underlying abnormality and
provide directed treatment.

ENDOCRINE GLANDS
PINEAL GLAND
o Attached in midbrain
o Secretion are controlled by ___________.
o Hormone : Melatonin ________________________________________________.

PITUITARY GLAND
o A.k.a “MASTER GLAND”
o Located in small cavity in sphenoid bone of the skull called
____________ or ____________.
o All pituitary hormones have circardian rythms.

a. ANTERIOR PITUITARY( Adenohypophysis)

 True endocrine gland
 Hormones are either peptide or glycoprotein
 Hormones: PRL, GH, FSH, LH, TSH, MSH, ACTH

Types of cells by immunochemical testing:

1. Somatotrphs secretes growth hormone
2. Lactotrophs or mammotrophs secretes prolactin
3. Thyrotrophs secretes TSH
4. Gonadotrophs secretes LH and FSH
5. Corticotrophs secretes proopiomelanocortin(POMC)

o The hypothalamus coordinates with the anterior pituitary by synthesizing its own
trophic hormones that are specific for each of the cell population. These
trophic hormones pass through infundibular stalk to the _____________.

ANTERIOR PITUITARY HORMONES

Growth Hormone(GH)/ Somatotropin

o Most abundant of all pituitary hormones
o Controlled by GH-RH(release) and somatostatin (frequency and duration of
secretory pulse)
o Structurally similar to _________ and ______________.
o Overall metabolic effect is to metabolize fat while conserving glucose.
o Major stimulus: deep sleep
o Somatostatin:___________
 o Physiologic stimuli: stress, fasting and high protein diet
o GH suppressor: glucocorticoid and elevated fatty acid
o Increased: acromegaly, chronic malnutrition, renal disease, cirrhosis
and sepsis
o FASTING REFERENCE VALUE: <___ng/mL

**Disorder:
o GH deficiency(GHD)
A. Idiopathic growth hormone deficiency
-most common cause of GH def. in children
-pituitary dwarfism, normal proportions are retained and show no
intellectual abnormalities
B. Pituitary adenoma
-most common etiology in adult-onset GH deficiency
o Acromegaly
-is due to overproduction of GH >50 ng/mL

SCREENING TEST CONFIRMATORY TEST

GH DEFICIENCY  Physical  Insulin Tolerance
activity(exercise Test(gold standard)
test)  Arginine stimulation
 Result: elevated test
serum GH (2nd confirmatory
 If fails confi. test)
Must be made  Result: fail to
rise>5 ng/ml (A)
>10 ng/ml(c)
*GHD in childhood is defined by
failure of serum GH to reach
defined levels when atleast 2
diff. pharmacologic stimulus are
used.
ACROMEGALY  Somatomedin C/  Glucose suppression
Insulin Growth Test-OGTT 75g glucose
Like Factor 1(IGL-  Blood is collected
1) every 30 mins. For 2
 IGF 1 produce by hours; fasting!
the liver
 IGF 1 low in GHD

 Gonadotropins- Follicle Stimulating Hormone (FSH) and Leutinizing Hormone (LH)

o important markers in diagnosing fertility and mestrual cycle disorder
o present in both gender in all ages
o FSH aids in spermatogenesis
o LH helps _____________ to produce testosterone(male), and it is
necessary for ovulation and final follicular growth(female)
o LH acts in __________ to cause synthesis of androgens, estrogens,
and progesterone

 Thyroid Stimulating Hormone(TSH)/Thyrotropin

o Stimulus for iodine uptake of thyroid gland
o Stimulates thyroid hormone production

 Adenocorticotropic Hormone(ACTH)
 o Single chained peptide without disulfied bond
o Production is response to low _________;regulator of adrenal androgen
synthesis
o Deficiency of ACTH lead to atrophy of 2 zones in adrenal
cortex(glomerulosa and reticularis)
o Higest: 6-8 am; Lowest: 6-11pm
o Increased: Addison’s dse’, ectopic tumor and protein rich diet

 Prolactin
o Pituitary lactogenic hormone, a stress hormone, a direct effector
hormone
o Initiation and maintenance of lactation
o Inhibited by _________
o Highest: 4AM and 8AM, and 8PM and 10PM
o Increased: Menstrual irregularity, infertility, amenorrhea,
galactorrhea, PCOS
o Excess leads to _________
o Physiologic stimulus: exercise, sleep, stress, pain, coitus, pregnancy,
nipple stimulation
o Ref value M: 1-20 ng/ml F:1-25 ng/ml
o Elevation of prolactin level due to physiologic and pharmacological
stimulus rarely exceed ______ ng/ml

* Prolactin levels can be elevated as the result of a variety of pharmacologic and

physiologic stimuli; however, values greater than 200 ng/mL are almost always
associated with the presence of a ______________.

b. Posterior Pituitary Gland (Neurohypophysis)

 Capable of releasing hormone but not producing
 Its hormones are synthesized by the _____________, therefore
produced by CNS
 Release of hormone is due to serum osmolality or suckling

 Oxytoxin
o Very similar to ADH, secreted in association of carrier protein
o Stimulates the contraction of gravid uterus_________________
o Released in response to neural stimulation of receptor of birth canal
and uterus and touch receptor of breast
o Stimulates muscle contraction during deliver and lactation-with bursts
of oxytoxin with anticipation of nursing and baby cry

 Anti-Diuretic Hormone (ADH)/ Arginine Vasopressin

o Acts on distal convoluted tubules(DCT) and Collecting duct by wate
reabsorption
o Major function: maintain osmotic homeostasis by regulating water balance
o Stimulus: _____________ plasma osmolality (>295 mOsm/kg),
decreased blood vol.(increses BP)
o Promotes factor VII and vWF release
o Rise in effective osmolality shrinks the hypothalamic
osmoreceptor cells, w/c then stimulate ADH production in the
____________ and ___________
**Disorder
Diabetes Insipidus deficiency of ADH (=severe polyuria>3L urine/day)

Major Types of DI
A. True DI a.k.a
o Deficiency in ADH with normal ADH receptor
o Failure of PG to secretes ADH

B. Nephrogenic DI
o Normal ADH but abnormal ADH receptor
o Failure
Diagnostic testoffor
Kidney
DI: to respond to ADH (congenital or acquired
Overnight water Deprivation Test
Fasting (8-12 hours)
Neurogenic: ADH level LOW=kidney acts rapidly to conserve H2O
Nephrogenic:ADH Level N/HIGH=administration od ADH has little or no effect in
reabsorption

Syndrome Of Inappropriate Anti-Diuetic hormone Secretion (SIADH)

o Sustained production of ADH in the absence of a known stimuli=dcrease
urine volume, low plasma osmolality, N or elevated Urine Na levels

THYROID GLAND
o Butterfly-shaped(2 lobes = connected by the isthmus)
o Follicle, fundamental structural unit of thyroid gland
Follicular cells Secrete T3 and T4
Parafollicular or C Secrete calcitonin
cells
o Iodine is the most important element in biosynthesis of thyroid hormones
o TSH stimulates thyroid hormone synthesis
o Protein bound hormone are metabolically inactive
o Protein bound to thyroid hormone do not enter cells and are considered to be
biologically inert and function as storage sites for circulating Thyroid hormone
o _____________, are metabolically inactive product of T4 metabolism.
o Iodine intake below________ is an indication of deficiency of hormone secretion
o FUNCTION OF TH: Development of CNS, and mental development. Tissue growth, Heat
production, Carbohydrates and Protein metabolism, energy conservation and
control of O2 consumption

Major Thyroid Hormone

 Triiodothyronine(T3)
o The most active Thyroid hormonal activity_________
o is produced from deiodination of T4 to T3(particularly in liver
and kidney)
o Principal application is for diagnosing T3 thyrotoxicosis
o Better indicator of recovery from hyperthyroidism and recurrence of
hyperthyroidism
o Ref value: 60-160 ug/dl(adult); 105-245 ug/dl(children 1-14)

 Tetraiodothyronine(T4)
o Principal secretory product
o Prohormone of T3
o All circulating originates in thyroid gland
o Elevated thyroxine inhibits TSH and vice versa
o Ref val: 5.5-12.5 ug/dl(adult) 11.8—22.6(children)
 THYROID HORMONE BINDING PROTEIN
Thyroid Binding
Globulin(TBG)
Thyroid Binding PreAlbumin
(Transthyretin)
Thyroid Binding Albumin
Transports 70-75 of TT4, and majority of
T3
Transports 15-20% of TT4
No affinity for T3
Transports T3 and 10% of T4

THYROID AUTOANTIBODIES
Thyroid autoantigens Thyroperoxidase(TPO) involve in hashimoto’s dse’
Thyroglobulin (Tg)
TSH Receptor(TSHR) involve in grave’s dse’

**Disorder

a. Hyperthyroidism, excess circulating thyroid hormone

 Primary Hyperthyroidism  T3 and T4;  TSH
 Secondary Hyperthyroidism  T3 and T4;  TSH
S&S: Tachycardia, tremors, weight loss, heat intolerance, emotional lability
and menstrual cycle changes
T3 Thyrotoxicosis -group of syndrome caused by high levels of free thyroid hormone
(Plummer’s disease) - T3, N-T4,  TSH
Graves’ disease -feature: exophthalmos and pretibial myxedema
(Diffuse toxic goiter) -Most common cause of thyrotoxicosis (autoimmune)
-Women > Men
-Anti-TSH receptor
Riedel’s thyroiditis -Thyroid turns to woody or stony-hard mass
Subclinical -No symptoms
hyperthyroidism -N-T3 and T4;  TSH
Subacute -Painful thyroiditis
granulomatous/ -Neck pain, low-grade fever
Subacute -(-) anti-TPO,  ESR and Tg
nonsuppurative/ De
Quervain’sthyroditis

b.Hypothyroidism, issuficient amount of thyroid hormone available to

tissue, treated with ___________________________.

S&S: Bradycardia, weight gain, coarsened skin, cold intolerance and mental
dullness
o Primary Hypothyroidism  T3 and T4 TSH
-causes: ablation of thyroid gland
-other causes: surgical removal, radioactive iodine
for hyperthyroidism treatment, radiation exposure and
drugs such as lithium
Hashimoto’s disease -Most common cause of 1’ hypothyroidism
(Chronic autoimmune -Thyroid is replaced by a nest of lymphoid tissue (T cells)
thyroiditis) Goiter
-lab result: (+) anti-TPO and  TSH
Myxedema coma -Severe form of 1’ hypothyroidism
-Peculiar nonpitting swelling of the skin
-Skin is infiltrated by mucopolysaccharides
“Puffy” face, thin eyebrows
  Congenital hypothyroidism (Cretinism)
o Secondary Hypothyrodism
-defect in development or function of
- T3 and T4;  TSH the gland
-due to pituitary destruction -Mental
or retardation (child)
adenoma
-Screening: T4 ; Confirmatory: TSH
o Tertiary hypothyroidism
-due to hypothalamic disease  Subclinical hypothyroidism
- T3 and T4;  TSH; TRH - N-T3 and T4;  TSH

THYROID FUNCTION TEST

TRH stimulation test -Most specific and sensitive test for diagnosing
thyroid disease
-Differentiates euthyroid and hyperthyroid patients
who both have undetectable TSH levels
-__________ borderline cases and euthyroid Graves’
disease
: 1’ hypothyroidism
: Hyperthyroidism
TSH test -_________________thyroid function test
-most clinically sensitive assay for detection of
primary thyroid disorder
-differentiates primary to secondary hypothyroidism
-increase: 1’ hypothyroidism, hashimoto’s
thyroiditis, thyroqtoxicosis due to Pituitary tumor,
TSH antibodies and thyroid hormone resistance
-decrease:1’hyperthyroidism, 2’ and 3’ hypothyroidism
Treated grave’s dse, euthyroid sick dse’, thyroid
hormone replacement therapy
Radioactive Iodine -Measure the ability of the thyroid gland to trap
Uptake (RAIU) _______
-helpful in establishing cause of hyperthyroidism
Thyroglobulin (Tg) -____________________ marker of thyroid cancer
assay -: Untreated and metastatic differentiated thyroid
cancer, hyperthyroidism
-: Hypothyroidism, thyrotoxicosis factitia
Reverse T3 (rT3) -Assess borderline or conflicting laboratory results
-___ major circulating thyroid hormone
Free Thyroxine Index -Indirectly assesses the level of FT4 in blood
(FTI or T7) -Equilibrium relationship of bound T4 and FT4
-Reference method: Equilibrium dialysis
FT4I = TT4 x T3U(%) or TT4 x THBR
100
TT3, FT3, FT4 -FT4 test: differentiates drug induced TSH elevation
and hypothyroidism
-TT3 or FT3: confirm hyperthyroidism
-Reference method (FT4): Equilibrium dialysis
T3 Uptake test -Measures the number of available binding sites of
the __________________________
-Does not measure level of T3 in serum but reflects
serum level of TBG
 TBG =  T3U
 TBG =  T3U
TBG test -Confirm results of FT3 or FT4 or abnormalities in
 the relationship of TT4 and THBR test
Estrogen: _TBG
Androgen: _TBG
Fine-needle -Most accurate tool in the evaluation of
aspiration _______________
Recombinant Human -Test patients w/ thyroid cancers for the presence of
TSH residual or recurrent dis.
Tanned Erythrocyte -Test for anti-Tg disorders
Hemagglutination
method
Serum calcitonin -Marker for familial medullary thyroid carcinoma
test
** FT4 and TSH are both Best indicators of thyroid status
** FT3 and FT4 are more specific indicators of thyroid function than meas. of
total hormone and is not affected by TBG

*Abnormal values of T3 and T4 must be evaluated with TBG measurement

* Euthyroid sick syndrome is acutely ill but without thyroid disease- T3 and
T4

 Calcitonin

PARATHYROID GLAND
o Location: Near thyroid capsule, sometimes within thyroid gland;mayalso
be found between the hyoid bone in the neck and mediastinum
o Maybe found 2,4 or 8
o Smallest endocrine gland
o Hormone: Parathyroid hormone(hypercalcemic hormone)

 Parathyroid hormone
 Prevents hypocalcemia by regulating blood calcium
 Preserves calcium and phosphate with in normal range
 Promotes bone resorption and increase renal reabsorption of
calcium
 Activates vitamin D to vitamin D3
 Depends on calcium level in the blood

**Disorder

Primary -physiologic defective: Parathyroid gland

hyperparathyroidism -Most common cause of hypercalcemia
-due to presence of parathyroid adenoma
- If goes undetected  severe demineralization
(osteitis fibrosacystica)
Clinical features:__ PTH and iCa2+(Hypercalciuria)
*Phosphaturia Hypophosphatemia
Secondary -develops in response to Ca2+
hyperparathyroidism -there is diffuse hyperplasia of all 4 glands
Causes: Vit. D deficiency and chronic renal failure
Clinical features ___PTH and __ Ca2+
Tertiary -Occurs w/ 2’ hyperparathyroidism ( Ca2+)
hyperparathyroidism -Autonomous function of hyperplastic PT glands or PT
adenoma
- PO4
-Calcium phosphates precipitate in soft tissues
Hypoparathyroidism -due to accidental injury of the PT glands (neck)
during surgery
-other cause: _____________ parathyroid destruction
 PTH =  Ca2+

**Hyperparathyroidism results to:_____________ why?

**low PTH causes elevated bicarbonate reabsorption:____________
*The best method for PTH measurement involves the use of antibodies that
detect both the amino-terminal fragment and intact PTH

ADRENAL GLAND
o Pyramid like shape gland above the kidney
o Composed of outer adrenal cortex(________) and inner adrenal
medulla(____________)
 Adrenal cortex
 Secretes steroid hormone and is a major site for steroid
hormone production
 Cortical hormone are composed of basic structure known
as_________________________________, a 17-carbon skeleton from
____________________
 Synthesized from LDL
 Secretion of adrenal androgens and glucocorticoid is regulated
by ACTH w/c is under control of Hypothalamic _______________

Layers of Adrenal Cortex

 Zona Glomerulosa(outer)10% principal source of mineralcoticois

 Zona Fasciculata(middle)75% Glucocorticoid synthesis and DHEA
 Zona Reticularis(inner) 10% Androstenedione and
Dehydroepiandrosterone (weak androgens)
 Cortisol

o Principal glucocorticoid
o Synthesis regulated by ACTH; mostly bound to glycoprotein and
transcortin
o Stimulates ____________ in the liver resulting hyperglycemia
o The only adrenal hormone that inhibit the secretion of ACTH
o Anti-inflammatory and immunosuppressive
o Diurnal:  6-8AM /  10PM-12AM
o The liver degrades all glucocorticoid to metabolites
o Urinary metabolites: 17-OHCS _______________________and
17-KGS___________________________

**Disorder

 Cushing’s syndrome (Hypercortisolism)

o Group of clinical and metabolical disorder characterized by
adrenocortical hyperfunction
 o Primarily caused by excessive production of cortisol and ACTH and
overuse of corticosteroids
o S&S extreme obesity(Buffalo hump), Hyperglycemia,
Hypertension,Hypercholesterolemia,  Lymphocytes

Screening tests 1. 24-hour urine free cortisol test

(Cushing’s) 2. Overnight dexamethasone suppression tests = Most widely
used (1mg)
3. Salivary cortisol test
Confirmatory tests 1. Low-dose dexamethasone suppression test (0.5mg)
(Cushing’s) 2. Midnight plasma cortisol
3. CRH stimulation test

PATIENTS PREPARATION

 Midnight saliva cortisol: It is recommended that the patient avoid -

_________ on the day of specimen collection
 Midnight plasma cortisol: hospital admission is required for atleast
___, insertion of a line for IV access before 10 pm, and patient should
be sleeping at the time of the blood collection

*HPLC-MS-current reference method for measuring urinary free cortisol

*the 24 hr urinary free cortisol is reflection of the unbound circulating

cortisol that is freely filtered by glomerulus

 Hyporcortisolism

Addison’s disease -Primary adrenal insufficiency

(Primary -excess cortisol production- 90%destruction of
hypocorticolism) adrenal cortex
Clinical feature: Cortisol and aldosterone, renin;
 ACTH
(+) Hyperpigmentation
Secondary -Secondary adrenal insufficiency
hypocorticolism -Due to hypothalamic-pituitary insufficiency
Clinical feature:  ACTH and cortisol, (-)
hyperpigmentation

Screening test: ____________________________

Confirmatory test: ________________________

*Corsyntropin is synthetic cortisol and aldosterone stimulator

*8 am-9 am plasma cortisol <3 ug/dl is indicative of __________________ and
does not required additional testing.
*Random cortisol of<10 ug/dl is strongly suggestive of adrenal insufficiency
*17-OHCS and 17-KS are increased when ACTH stimulation is excessive

 Congenital Adrenal Hyperplasia

o Deficiency of enzymes that is necessary for cortisol synthesis
o For diagnosis of hirsutism and virilization measurement of serum
Total Testosterone and DHEA-S would be a great help
o Definitive Test:17-OHP measurement of amniotic fluid and
____________________________________-most preferred
 21-hydroxylase -most common
-leads to hirsutism in women and
other symptoms caused by excess
androgen levels such as
virilisation;infertility and
amenorrhea
-DEFECTIVE GENE: CYP21
11 β-hydroxylase -2nd most common
-virilization and hypertension
-DEFECTIVE GENE: CYP11B1
3β-hydroxysteroid dehydrogenase- -Pseudohermaphroditism in female
isomerase infants, and incomplete
masculinization in male infants
-DEFECTIVE GENE:HSD3B2
17-hydroxylase deficiency -Inability to convert 17-
hydroxypregnenolone to DHEA and
17a-hydroprogesterone to
androstenedione
-DEFECTIVE GENE: CYP17

 It is frequently unnecessary to perform an adrenocorticotropic

hormone stimulation test in critically ill patients. A random cortisol of
greater than 25 μg/dL (700 nmol/L) during stress makes it highly
unlikely that the patient is adrenally insufficient.

 Aldosterone(Aldo)
 Most potent mineralcorticoid(electro regulating hormone)
 Steroid hormone that helps regulates water, electrolytes and blood
pressure
 Main determinant of K+ renal excretion
  retention of Na+ and Cl- in reneal tubular epithelium and
excretion of  K+ and H+ ; at night
 Synthesis controlled primarily by renin-angiotensin system

**Disorders

Conn’s disease -caused by aldosterone-secreting adrenal adenoma

Primary -associated with plasma aldosterone and plasma
hyperaldosteronism renin.
-symptoms: hypertension, hypokalemia, mild
hypernatremia and metabolic alkalosis
Screening test: Plasma Aldo conc./Plasma renin
activity ratio (PAC/PRA ratio)
-(+): >30 suggestive
-(+): >50 ratio diagnostic
Confirmatory test:
-Saline suppression test
-Oral sodium loading test
-Fludrocortisone suppression test
Captopril challenge test

-(+): >5 ng/dL aldosterone

Secondary -result of excessive production of renin
Hyperaldosteronism -accompanied by plasma levels of aldosterone and
 renin

SECONDARY HYPERALDOSTERONISM THAT RESULTS IN HYPOKALEMIA

Liddle’s syndrome -Pseudohyperaldosteronism

-Resembles 1’ aldosteronism clinically
-congenital disorder characterized by increase ENaC
act. In collecting duct
 Aldosterone
(-) Hypertension
Bartter’s syndrome -Bumetanide-sensitive chloride channel mutation
-autosomal recessive disorder, defect in NaCl
reabsorption in thick ascending loop of henle
 Aldosterone and Renin
Gitelman’s syndrome -Thiazide-sensitive transporter mutation
-defect in NaCl reabsorption in DCT
 Aldosterone

Hypoaldosteronism -Destruction of the adrenal glands

-Glucocorticoid deficiency
-21-hydroxylase deficiency
TEST: a. Furosemide stimulation test or upright
posture (+): Low aldo levels
b. Saline suppression test:(+) high aldo
*postural stimulation test is an ___________________
*Urine samples for aldo are assayed using ____________ and extraction
*Florinef is synthetic _____________

 Weak Androgens/Adrenal Androgens•

o Serve as precursor for production of more potent androgens and
estrogen in tissue
o Bound to steroid hormone binding globulin (SHBG)
o DHEA(converted to estrone; the principal adrenal androgen) and
Androstenedione
o Excessive production of __________ leads to virilisation
o To confirm measurement of excessive androgen level: measure
__________________ and ____________________

ADRENAL MEDULLA
-Composed primarily of _____________ that secretes catecholamines(________
precursor)
- Norepinephrine/Epinephrine ---(Monoamine oxidase and Catechol-0-methyl-
transferase)--->Metanephrines and VMA
-____________________ converts epinephrine to metanephrine, norepinephrine to
normetanephrine and dopamine to methoxytyramine, all of which in turn can be
oxidized to VMA and MAO
-____ RATIO of norepinephrine to epinephrine

Norepinephrine -Primary amine

-produced by sympathetic ganglia
-highest concentration found in CNS
-acts as neurotransmitter in both CNS and SNS
Metabolites:
-3-methoxy-4-hydroxyphenylglycol (MHPG) = Major
metabolite
 -VMA
Epinephrine -Secondary amine
-Most abundant medullary hormone
-“Flight or fight hormone” WHY?
________________________________
-increases glucose metabolism
Metabolites:
-Vanillylmandelic acid (VMA) = ___________________
-Metanephrines
-Normetanephrines
-HVA
Dopamine -Primary amine
-From the decarboxylation of 3,4-
Dihydroxyphenylalanine (DOPA)
-major intact catecholamine present in urine
-Major metabolite: Homovanillic acid (HVA)

**Disorder
 Pheochromocytoma
 Tumor or adrenal medulla or sympathetic ganglia
 Due to overproduction of cathecolamines
 Commonly seen in 3rd to 5th decade of life
 Classic “Spells”: tachycardia, headache, chest tightness,
sweating, hypertension
Screening test -Plasma metanephrines and normetanephrines by HPLC(4-
fold increased)
Confirmatory test -24 hr urinary excretion of metanephrines and
normetanephrines(^)
patient preparation: avoid caffeine, nicotine, alcohol and acetaminophen,
minoamine oxidase inhibitors, and tricyclic antidepressants for at least 5 days
before testing

PHARMACOLOGIC TEST
Clonidine Test -differentiates ______________(not
suppressed) to ________________
(decrease in catecholamine levels) or
those individual with borderline
elevation in urinary test
-only used if plasma catecholamines
are > 1000 pg/ml
Glucagon Stimulation Test -used if pheochromocytoma is highly
suggestive
-used for individuals with normal
blood pressure and when
catecholamines are only modestly
elevated

 Neuroblastoma
 Is a fatal malignant condition in children resulting to excessive
production of norepinephrine
 (+) high urinary excretion of HVA or VMA or both, and dopamine

Clonidine test Differentiates:

Pheochromocytoma (Catecholamines not suppressed) from
 Neurogenic hypertension (50% decreased in
catecholamines)
Neuroblastoma Norepinephrine (Children)
 urinary HVA, VMA or both and dopamine
* The chromatographic measurement of plasma free metanephrines
and normetanephrines is the best screening test for pheochromocytoma. The
patient should avoid caffeine, alcohol and
acetaminophen, monoamine oxidase inhibitors, and tricyclic
antidepressants for at least 5 days before testing.

*____________________ is preferred method of blood collection to eliminate

anxiety of venepuncture.

*24 urine creatinine test ______________________________________ (0.8 g/day)

REPRODUCTIVE HORMONES

 Ovaries: converts testosterone to estradiol and adrostenedione to

estrone
 Major transport protein: ____________________, ___________________ and
albumin
 Testosterone
 Principal androgen hormone in the blood(most potent male androgen)
 Synthesized by the___________, also derived from _____________
 Functions: growth, development of the reproductive system,
prostate and external genitalia
 Peak: 8 am; lowest:8pm
 Gradual reduction at age of __

TYPES OF TESTICULAR INFERTILITY (HYPOGONADISM)

PRETESTICULAR INFERTILITY
(secondary hypogonadism)
TESTICULAR INFERTILITY
(primary hypogonadism)
POST-TESTICULAR INFERTILITY
OTHER DISORDER OF SEXUAL DEVELOPMENT
TESTISCULAR FEMINIZATION SYNDROME
SERTOLI CELL-ONLY SYNDROME
KALLMAN’S SYNDROME
-Due to hypothalamic or pituitary
lesions
-N or decrease levels: Testosterone,
FSH, LH
-it maybe congenital or acquired
-decrease: testosterone
-increase: FSH, LH
-It is due to disorder of sperm
transport and function
-N testosterone, FSH, LH
-most severe form of androgen resistance
syndrome
-physical development pursues female
phenotype
Lab test: N testosterone; FSH, LH
-Lack of germ cells
-Testicular biopsy for confirmation
-Clinical Feature: small testes ,  FSH,
azoospermia, N testosterone
-inherited x-linked recessive trait
manifest as hypogonadism during puberty
 -assoc defect: anosomia, midline defect

 Dehydroepiandrosterone (DHEA)
 Principal androgen formed by adrenal cortex;weak androgen
 Valuable in assessing adrenal cortical function
 Estrogen
 Carbon 18 steroid that has a phenol A ring
 From structural alteration of testosterone
 Not produced by ovaries after menopause
 Functions: promotion of breast development, maturation of external
genitalia, deposition of body fat and termination f linear growth

3 forms

Estrone E1 -most abundant in post-menopausal

women
Estradiol E2 -most potent estrogen secreted by the
ovaries
-abundant in pre-menopausal women,
low in menopausal stage
-synthesized from testosterone
-precursor of E1 and E3
-negative feedback for FSH
Estriol E3 -metabolite of estradiol
-found in maternal urine
-major estrogen excreted by placenta
when pregnant
-preferred specimen:plasma

 Progesterone
 Carbon 21 compound from steroid family
 Produce by corpus luteum
 The prime excretory product of ovary
 Responsible for luteal cell cycle-
 Prepare ________ for pregnancy and ______ for lactation
 Metabolites: pregnanediols, (most easily measured) pregnanediols,
pregnanalones
Markers for Down AFP
Syndrome Unconjugated Estriol *ovaries also produce androgens like
hCG androstenedione, dehydroandrostenedione,
Inhibin A testosterone, dihydrotestosterone
Karyotyping or FISH Test for Down syndrome
typing (amniotic fluid) *when one of the 4 markers of down syndrome
Tests for menstrual Estrogen is abnormal,_______________ should be
cycle dysfunction and Progesterone
performed.
anovulation FSH
LH
*________________ or ______________ is test
for down syndrome using amniotic fluid as
specimen

* The measurement of day 2–3 follicle-

stimulating hormone is a good
indicator of follicular reserve; a day 21–22
progesterone is used to
assess whether cycles are ovulatory.
Tests for female Hcg
infertility PRL
FT4
TSH
FSH
LH
Estradiol
Progesterone
Tests for male Semen analysis
infertility Testosterone
FSH
LH

PANCREAS
 Digestive gland in gastrointestinal system
 Exocrine gland: synthesizes digestive enzymes
 Endocrine gland: synthesis of hormones
 Alpha cells: 20-30% glucagon
 Beta cells: 60-70% insulin
 Delta cells: 2-8% somatostatin

MISCELLANEOUS HORMONES
 Human Chorionic Gonadotropin (HCG)
 produced by trophoblast cells of placenta during pregnancy
 dimeric molecule (alpha and beta subunit that confers antigenic
individuality
 serves to maintain progesterone production in the early pregnancy
 the intact HCG is predominant form throughout pregnancy
 for serum assay, an antibody is directed separately to beta
subunit and intact HCG
 for urine assay, an antibody is directed separately to alpha and
beta subunit
 > 5 mIU/ml ____________________________

 Human Plancental Lactogen

 Functionall, structurally similar to GH and PRL
 Can be measured in Urine, serum or amniotic fluid
 Important in diagnosing intrauterine growth retardation

 Gastrin
 Secreted by G cells (stomach)
 Stimulates parietal cells to secrete HCl
 Stimulus: Amino acid
 Zollinger-Ellison syndrome
 Pernicious anemia

 •Serotonin
 Derived from hydroxylation and decarboxylation of tryptophan
 Synthesized by argentaffin cells (GIT)
 Binds to platelet and released during coagulation
 Metabolite: 5-HIAA (ehrlich’s aldehyde test (+)purple)
 Somatostatin
 GH inhibiting hormone, also inhibit: glucagon, insulin
  Found in GIT, hypothalamus, delta cells of islet of Langerhans in
pancrease
 Inhibin A
 Reproductive hormone which inhits ___ activity

Other related diseases

primary amenorrhea Menstruation having never occurred
Secondary amenorrhea Absence of menses for 6 months
Cushing’s disease Abnormal increased secretion of ACTH
Cushing’s syndrome Chronic excessive production of cortisol by the adrenal
cortex
-Large doses of glucocorticoids
-Pituitary tumor (ACTH) = most common cause
Gynecomastia Development of breast tissue in males
Hirsutism Excessive hair growth w/ a male distribution pattern in a
female
Most common endocrine disorder in women
Mullerian agenesis Congenital malformation or absence of the fallopian tubes,
uterus or vagina
N-FSH, LH and testosterone
Nonthyroidal illness Illness that do not directly involve the thyroid gland
Sipples syndrome (MEN Medullary carcinoma of the thyroid
II) Pheochromocytoma
Parathyroid adenoma
Stein-Leventhal Mild hirsutism w/ normal menses to excessive hirsutism w/
syndrome amenorrhea
Thyroid stones A.k.a. thyroid crisis
Life-threatening
Uncontrolled thyrotoxicosis