20) Endocrine Flashcards
3 major classes of hormones
Polypeptide hormones
Steroid hormones
Hormones derived from
amino acids
polypeptide hormone half-life is usually…
short (<30 min)
affect targets via second messenger system
polypeptide hormones
amino acid based hormones
steroid hormones are derived from…
cholesterol
basic carbon skeleton structure for steroid hormones
cyclopentaoperhydrophenanthrene
half-life of steroid hormones
30-90 min
forms of circulating steroid hormones
- bound to carrier proteins
- unbound; able to promote physiological response
examples of steroid hormones
Aldosterone
Cortisol
Estradiol (E2)
Progesterone
Testosterone
hormones derived from tyrosine
T3
T4
epinephrine
norepinephrine
hormones derived from tryptophan
melatonin
serotonin
T4 half-life
7-10 days
free catecholamine half-life
<1 min
hormones derived from amino acids
Dopamine
Epinephrine (also adrenaline)
Norepinephrine (noradrenalin)
Serotonin
Thyroxine (T4)
Triiodothyronine (T3)
act on endocrine glands to release their hormones
tropic hormones
act on endocrine tissue to promote growth and function
trophic hormones
2 major classes of hormone receptors
membrane (protein hormones; 2nd messenger)
nuclear (steroid & thyroid hormones)
releasing factor
peptide synthesized by the hypothalamus and released into the portal circulation to affect pituitary hormone synthesis and secretion
affects hypothalamus release of releasing factor
levels of circulating target hormone
cortisol negative feedback
corticotrophin-releasing hormone (CRH) - hypothalamus
ACHT - anterior pituitary
thyroid hormone negative feedback
thyrotrophin-releasing hormone (TRH) - hypothalamus
TSH - anterior pituitary
gonadal steroids negative feedback
gonadotropin-releasing hormone (GnRH) - hypothalamus
FSH, LH - anterior pituitary
2 types of assays for measuring hormones
- competitive immunoassays: Ag competes with hormone for sites; hormone-Ag complex forms, inversely proportional to hormone level
- immunometric assays: Ab used to “sandwich” hormone; complex is directly proportional to hormone level
8pm ——– is approximately 50% of 8am levels
cortisol
autonomy
syndromes of hormone excess (tumors)
overproduction is not suppressed by feedback
examples of protein-bound hormones in circulation
cortisol
T4
heterogeneity
hormones that circulate in blood as multiple distinct immunologic forms
ex) PTH
tropic hormone and target hormone both increased or decreased
secondary hyper/hypofunction
tropic hormone is first cause
tropic hormone and target hormone in opposite directions
primary hyper/hypofunction
target hormone is first cause
standard low levels of activity during total rest
sufficient for dx when disease is severe
basal levels
stimulation or suppression tests are required when…
excess or deficiency is not severe/definitive
used to document hyposecretion
explain
stimulation tests
challenge with tropic hormone, determine if target hormone increases
used to document hypersecretion
explain
suppression tests
synthetic target hormone is given, determine if tropic hormone decreases
hormones of posterior pituitary
ADH
oxytocin
hormones of anterior pituitary
ACTH
FSH
LH
GH
Prolactin
TSH
AKA somatotropin
GH
Gh functions
promote growth, cause changes in electrolyte metabolism, stimulate uptake of nonesterified fatty acids by muscle, and accelerates fat mobilization from adipose tissue
secretion is pulsatile, with greatest levels at night (onset of sleep)
GH
Diagnosis of deficiency is usually made by provocative stimuli. (Exercise, insulin-induced hypoglycemia, and other pharmacologic tests that increase hormone)
GH
Most validated test to distinguish pituitary-sufficient patients from those with adult GH deficiency
insulin-induced hypoglycemia stimulation test
acromegaly characteristics (4)
middle-aged pts
elongation and enlargement of bones
somatotrope adenomas
cosecretion of prolactin
pituitary gigantism characteristics (3)
children
elevated GH before long bones are finished growing
linear growth
produced by lactotrophs of pituitary
prolactin
function of prolactin
initiate and sustain lactation
control of osmolality, fat and carbohydrate metabolism,
calcium and vitamin D metabolism, fetal lung development, and steroidogenesis
levels are controlled by dopamine, which inhibits it; if dopamine is absent, levels rise
prolactin
sensitive indicator of pituitary disease; first to rise during pituitary infiltrative disease/compression
prolactin
Anovulation (infertility)
Amenorrhea and galactorrhea
Galactorrhea alone
Oligospermia or impotence in males
hyperprolactinemia
function of ADH
maintaining water homeostasis and electrolyte balance
retain water, increase BP
functions of oxytocin
Stimulates the contraction of the estrogen-primed uterus (positive feedback)
Also stimulates the lactating mammary gland
Role in mother-infant bonding
Useful as a therapeutic agent in inducing labor
pitocin
2 types of DI
central
nephrogenic
suspected if urine osmo > plasma osmo without increased urine Na
SIADH
areas of adrenal gland and hormones produced (4)
Outermost layer (zona glomerulosa)–Produces aldosterone
Broad lipid-filled (zona fasciculata)–Produces cortisol
Dense compact cells (zona reticularis)–Secrete androgens
Adrenal medulla; lies below the zona reticularis–Produces catecholamines
catecholamines
adrenal medulla hormones
epinephrine
norepinephrine
dopamine
other sites of catcholamine production
Neurons of the sympathetic nervous system, CNS, chromaffin cells found in abdomen and neck
Methoxyhydroxyphenylglycol (MHPG)
Vanillylmandelic acid (VMA)
Homovanillic acid (HVA
metabolites of catecholamines
Initiate their respective biological actions via specific cell-membrane receptors:
α-adrenergic and β-adrenergic receptors
norephinephrine: α-adrenergic receptors
epinephrine: β-adrenergic receptors
functions of norepinephrine
Vasoconstriction, decreased insulin secretion, sweating, and stimulation of glycogenolysis in the liver and skeletal muscle
functions of epinephrine
Vasodilation, stimulation of insulin release, increased cardiac contraction rate, relaxation of smooth muscle in the intestinal tract, enhanced lipolysis, bronchodilation
may be significant in drug treatment of mental disorders (Parkinson’s disease and tardive dyskinesias)
dopamine
Catecholamine-producing tumors of the neurochromaffin cells
pheochromocytoma
neuroblastomas
↑ VMA
↑ Metanephrines
Normal Dopamine
Normal HVA
pheochromocytoma
Catecholamine elevation may be induced by stress, upright posture, exercise, hypoglycemia, cold temps, and mental states of anxiety or anger
pheochromocytoma
Malignant neoplasm of neural crest origin
Common in pediatric patients
neuroblastoma
↑ VMA
↑ Urinary Catecholamines
↑ Dopamine
↑ HVA
neuroblastoma
specimen handling for pheochromocytoma and neuroblastoma tests
24hour urine properly collected and preserved with hydrochloric acid to maintain acid pH, stored at -80°C
major glucocorticoid
cortisol
functions of cortisol
promotes gluconeogenesis, glycogenesis, lipolysis
decreases glucose use
suppresses immune system
anti-inflammatory
CBG
coristol-binding globulin
explain RAAS
Renin (secreted by renal cells) acts on its substrate to produce angiotensin I, which is rapidly converted to angiotensin II in the lung by angiotensin-converting enzyme. Angiotensin II stimates aldosterone production.
Aldosterone acts on the renal distal tubules to
increase sodium retention and volume repletion, thus shutting off renin.
3 adrenal androgens, precursors to each other
Dehydroepiandrosterone (DHEA)
Androstenedione
Testosterone
stimulates hypothalamus to produce CRH
stress
no diurnal variation in cortisol
adrenal disorders such as adenomas and Cushing’s
primary adrenal insufficiency
Addison’s disease
Destructive events in the hypothalamus or pituitary gland that result in a decreased ability to secrete ACTH (secondary) or CRH (tertiary)
secondary or tertiary adrenal insufficiency
sx of Addison’s
- bronzing of skin
- postural HTN
- hypoglycemia
- changes in body hair
- GI disturbances
- weakness/muscle wasting
- weight loss
- hyponatremia
- hyperkalemia
test used to dx Addison’s
ACTH stimulation test (Cortrosyn test)
normal response to ACTH stimulation test
> 20ug/dL of cortisol from the baseline
test used to dx secondary/tertiary adrenal insufficiency
Metyrapone stimulation
2 types of adrenal hyperfunction
- Cushing’s syndrome: primary, low ACTH
- Cushing’s disease: secondary, high ACTH
70% cases caused by pituitary tumor
Cushing’s disease (secondary)
Elevated levels of cortisol due to either medications or the presence of an adrenal tumor (adrenal adenoma)
Cushing’s syndrome (primary)
17-OHCS test (urine)
Cushing’s
measures cortisol metabolites
Sensitive indicator of Cushing’s because the increase is rapid as soon as plasma cortisol exceeds the binding capacity of CBG
urine free cortisol
sx of Cushing’s
- buffalo hump
- moon face
- weight gain, thin extremities, edema
- purple striae
- male gynecomastia
- facial acne
- hyperglycemia
- personality changes
- amenorrhea, hirsutism
- osteoporosis
used initially to establish true hypersecretion of cortisol
low dose dexamethasone suppression test
used to differentiate diagnosis of an ACTH-secreting pituitary adenoma
high-dose dexamethasone suppression test
adrenal aldosterone-producing adenoma
Conn’s syndrome
hyperaldosteronism responsive to surgery
Conn’s syndrome
adrenal hyperplasia, treated with drugs
idiopathic hyperaldosteronism
differentiate Conn’s syndrome from IHA
Posture stimulation
- Conn’s/APA: Declining values on standing
- IHA: Normal postural rise
Most reliable: Adrenal bilateral vein catheterization and measuring serum aldosterone
Renal artery stenosis or renin-producing juxtaglomerular cell tumor of the kidney
causes secondary hyperaldosteronism
hallmark of secondary hyperaldosteronism
↑ urinary aldosterone in the presence
of ↑ plasma renin activity
enlarged adrenal glands at birth
decreased cortisol and aldosterone
congenital adrenal hyperplasia (CAH)
21-hydroxylase deficiency (most common)
11-hydroxylase deficiency (2nd most common)
congenital adrenal hyperplasia (CAH)
increased 17-OH progesterone, andostenedione, testosterone, estriol
congenital adrenal hyperplasia (CAH)
causes virilization
sx of congenital adrenal hyperplasia
water wasting
dehydration with hypotension
hyponatremia
hyperkalemia
virilization
failure to thrive
proteins that carry sex hormones
sex-hormone binding globulin (SHBG)
cortisol-binding globulin (CBG)
albumin
C18 sterol compounds
estrogens
Steroid hormone with 21 carbons
progesterone
Basal body temperature rises after… due to…
ovulation
progesterone
any of the C19 sterols synthesized from cholesterol in the testes and adrenal glands
androgens
Primarily secreted by Leydig cell in male testes and female ovaries
testosterone
primary precursor of natural estrogens
DHEA (androgen)
test used to establish hypogonadism in males
hCG Stimulation Test
hCG should make testosterone —
↑
Responsible for secretion of both gonadotropic hormones, LH and FSH
GnRH
binds to Leydig cell receptors to enhance conversion of cholesterol to testosterone
LH
activates the seminiferous tubules for sperm production (in males)
FSH
Male has XXY chromosomes (47 karyotype), infertile, small testicles, sparse facial and body hair, reduced muscle mass, and enlarged breasts, low IQ
Klinefelter’s syndrome
deficiency of GnRH during embryonic development in both males and females. Characterized by hypogonadism and lost sense of smell (anosmia).
Kallmann’s syndrome
Defect in androgen receptor gene (testosterone level is normal/elevated)
Female body build and development of breast tissue, intra-abdominal testes
Androgen Insensitivity Syndrome (AIS)
reduced efficiency of the conversion of testosterone to the more potent DHT.
Males are born with ambiguous genitalia
5a-Reductase Deficiency (5-ARD)
↑ testosterone:DHT ratio
5a-Reductase Deficiency (5-ARD)
Increased estrogen:androgen ratio in males
gynecomastia
3 types of gynecomastia
- Transient: 60-90% of all newborns from estrogen crossing the placenta (males and females)
- Puberty: 50-70% of healthy boys.
- Adults: 50-80 yrs old from testicular failure or ↑ body fat
enhances the effects of FSH on a maturing follicle
estradiol
A glycoprotein hormone that is secreted during pregnancy by the placenta
hCG
hcG first detected in maternal serum — days following conception
6-9
Absence of menstruation by age 16, fail to develop secondary sex characteristics
primary amenorrhea
45 X karyotype (monosomy)
Non-functioning ovaries
By age 2, no eggs are left
Turner’s syndrome
46 XX or XY karyotype (Swyer Syndrome)
pure gonadal dysgenesis
menstruation ceases for at least 6 months
secondary amenorrhea
infrequent menstruation that occurs < 9 times/year
oligomenorrhea
Genetically female, but phenotypic male characteristics
Enzyme deficiency in pathway: 21-hydroxylase or 11β-hydroxylase which results in virilization
female pseudohermaphroditism
Characterized by infertility, hirsutism, obesity, irregular vaginal bleeding, and acanthosis nigricans (dark pigmentation of spiny layer of skin)
PCOS
Greater frequency of both hyperinsulinism & insulin resistance
PCOS
LH:FSH ration >2
PCOS
developmental anomaly of the placenta made up of trophoblastic tissue
Hydatidiform Mole
Leading cause of pregnancy-related, first-trimester death
ectopic pregnancy
main methods for measuring most hormones and metabolites
immunoassay techniques
chromatography
mass spectrometry
components of total testosterone measurement
- free (bioavailable)
- albumin-bound (bioavailable)
- SHBG-bound (unavailable)
Major circulating estrogen after menopause
estrone/E1
Most active of endogenous estrogens
estradiol/E2
Predominant urinary estrogen during pregnancy
estriol/E3
routinely used for identifying a fetus with Down Syndrome
unconjugated estriol/uE3
Any disruption in the biosynthetic pathway will lead to very low maternal serum ————– levels.
unconjugated estriol
produced exclusively during pregnancy by the fetal liver
unconjugated estetrol/E4
No Estrogen
↑↑ LH & FSH
menopause
basic function of thyroid
Control basal metabolic rate and calorigenesis through increased oxygen consumption in tissue
secretory units of the thyroid gland that contain colloid
follicles
Amorphous material composed of thyroglobulin (Tg) and iodinated thyroalbumin
colloid
—— is ingested and converted to ——- by the thyroid, which is attached to tyrosine residues to give…
iodide
iodine
monoiodotyrosine (MIT) and diiodothyronine (DIT)
2 MIT
T4
MIT + DIT
T3
Once produced, T3 & T4 are stored as ——- in the colloid
thyroglobulin
Only about 20% of —— is glandular, the rest is derived outside the thyroid gland through deiodination of —–, which takes place in the liver, kidney, and muscle
T3
T4
carriers of thyroid hormone
Thyroid-binding globulin (TBG)
Thyroid-binding prealbumin (TBPA)
Transthyretin (TTR)
Serum albumin
major biologically active thyroid hormone
T3
Causes an increase in number and size of follicular cells (hyperplasia) so they can trap more iodide to synthesize more thyroid hormones
TSH
bradycardia, hoarseness, cold sensitivity, dry skin, and muscle weakness
hypothyroidism
Diagnostic Test: Thyroid peroxidase (TPO) and antithyroglobulin antibodies
Hashimoto’s thyroiditis
hypothyroidism with ↑ TSH and goiter
Hashimoto
Causes mental and physical restriction (cretinism)
Must be detected early in newborns (first 3 months)
congenital hypothyroidism
Heat intolerance
Tachycardia
Weight loss
Weakness/tremors
Emotional lability/anxiety
hyperthyroidism
Thyroid Receptor Antibody (TRAb)
Thyroid-Stimulating Antibody (TSI)
Graves disease
Graves disease triad
Exophthalmic eye (Eye bulging)
Tremors
Weight Loss
TT4
T4 bound (99.97%)
FT4 index purpose
measures the degree of unsaturation of TBG
T3 is helpful in confirming diagnosis of —–thyroidism, but not —–thyroidism
hyper-
hypo-
does not reflect glandular secretion and often are normal
useful in patients who show equivocal signs and symptoms of thyroid dysfunction and when thyroid-function test results are not clearly diagnostic
Thyrotropin-Releasing Hormone Stimulation
Used clinically to differentiate nonthyroidal illness (NTI) from hypothyroidism
reverse T3
Directed against the thyroglobulin protein located within the thyroid colloid
Thyroglobulin Antibodies (TgAb)
Directed against a protein component of thyroid cell microsomes.
microsomal Ab
protection from radiation in nuclear disaster/atomic bomb
oral dose of potassium iodide before and/or after (<3-4 hours) exposure to saturate the thyroid-uptake system and prevent uptake of radioactive iodine
