Anterior Pituitary Flashcards
1
Q
Pituitary Embryology
A
- 2 lobes form separately
-
Anterior lobe from outpocket of Rathke’s pouch of floor of primitive oral cavity (ectoderm)
**Can have Rathke pouch cysts b/n 2 lobes
- Posterior lobe from outpocket of diencephalon (neuroectoderm) - off developing 3rd ventricle
2
Q
Anterior Pituitary Portal Circulation
A
- Hypophysial-portal circulation - superior hypophysial artery –> hypothalamus capillary bed (on median eminence) –> hypothalamic-hypophysial veins –> anterior lobe capillaries –> cavernous sinus veins
- Carry hormones directly from hypothalamus to pituitary in high conc
- Since this runs thru stalk … transection or pressure on stalk can disrupt flow –> dec hormones carried to anterior and dec axonal flow to posterior
3
Q
6 Hormones Released from Anterior Pituitary (+ hypothalamus hormone and cell type of ea)
A
- 3 Polypeptides
- GHRH –> GH (from somatotropes)
- Dopamine –> inhibits Prolactin (from lactotropes)
- CRH –> ACTH (from corticotropes)
- 3 Glycoproteins (dimers - all have same alpha but diff beta)
- GnRH –> FSH and LH (both from gonadotropes)
- TRH –> TSH (from thyrotropes)
4
Q
What effects does GH normally have?
A
- Indirect Effects - stimulate liver and other tissues to make IGF-1 (insulin-like GF)
- IGF-1 stimulates proliferation of chondrocytes for bone growth
- Stimulates myoblast differentiation/proliferation
- Stimulates AA uptake and protein synthesis in muscle and other tissues
- Direct Metabolism Effects
- Protein anabolism / dec protein oxidation
- Fat utilization / TG breakdown and oxidation of FA
- Maintain blood glucose w/ anti-insulin activity (suppresses insulin’s ability to inc glucose uptake) and enhances glucose synthesis in liver
5
Q
What stimulated GH?
A
- GHRH from hypothalamus –> somatotrophs
- GHRH binds its receptor –> inc cAMP –> act Pit-1 –> GH transcription
- Ghrelin - peptide secreted from stomach; binds somatotrophs to stimulate GH secretion
- Binds separate secretagogue receptor to inc secretion but no effect on synthesis
- Low blood glucose - stimulates GH release
- Inc in stress, exercise, hypoglycemia, protein intake, sex hormones, alpha adrenergics and Ach
6
Q
What inhibits GH?
A
- Somatostatin released from hypothalamus –> inhibits GH release from anterior pituitary
- Somatostatin binds SRIF receptor –> dec cAMP –> dec Pit-1 –> dec GH transcription
- IGF-1 neg feedback by inhibiting somatotrophs and inc somatostatin
- GH itself neg feedback by inhibiting somatotroph
- Dec w/ obesity, glucocorticoids, hyperglycemia, high free FAs, hypothyroid, old age, beta adrenergics
7
Q
GH Timing / Distribution
A
pulsatile secretion
low basal conc
sleep > wake
higher in puberty
lower in obese
8
Q
GH Def in Kids v Adults
A
- GH def in kids - short stature & subnormal growth rate
- GH def in adults - inc fat mass, dec muscle mass/strengh, dec exercise capacity, inc cholesterol (usually only suspect in adults if hypothalamic problems or other pituitary def)
9
Q
How is GH evaluated?
A
- CANNOT just measure GH in serum
- Meas IGF-1 levels in kids
- ITT (insulin tolerance test) - IV insulin –> hypoglycemia; then look at inc in GH in 30-60 min (>5 ng/ml inc in kids and > 10 in adults) OR
- Look for inc GH w/ GHRH + arginine; GH should inc by > 4 ng/ml
10
Q
What is the role of prolactin?
A
- Induces lobuloalveolar growth of mammary glands (alveoli are clusters that secrete milk)
- Stimulation of milk production after giving birth (prolactin + cortisol + insulin - stimulate transcription of milk genes)
11
Q
Prolactin Stimulation
A
- Stimulation of nipples and mammary glands in nursing (spinal reflex)
- Stimulated by TRH (so if hypothyroid and inc TRH then can have hyperprolactin)
- Stimulated by estrogen (inc in late pregnancy)
- Stress and exercise can also in prolactin levels
12
Q
Prolactin Inhibition
A
Hypothalamus TONICALLY INHIBITS prolactin secretion from anterior pituitary (mainly via dopamine)
So disconnect b/n 2 or use of dopamine blockers inc prolactin while dopamine agonists dec prolactin
13
Q
Prolactin Timing
A
Pulsatile
Sleep > wake
14
Q
Prolactin Evaluation
A
- Screen - serum prolactin
- Confirm - TRH stimulation test
15
Q
Symptoms of Hyperprolactinemia
A
- Mainly due to disruption of normal release of GnRH
- Female - menorrhea, galactorrhea (extra or spont secretion of milk)
- Male - hypogonadism, dec sex drive, dec sperm production, impotence
- Disrupts puberty
16
Q
2 Rare Causes of Prolactin Deficiency
A
- Post partum hemorrhage / necrosis of pituitary –> inability to lactate
- Congenital prolactin def - RARE Pit-1 mutation
17
Q
How is ACTH made?
A
POMC is a precursor protein cleaved into ACTH + beta-endorphin/met-enkephalin (opioid peptides) + melanocyte-stim-hormone
-SO … If cortisol def –> inc ACTH –> inc POMC –> more melanocyte stim hormone (hyperpigmentation)
18
Q
Role of ACTH
A
Stimulate adrenal cortex to release cortisol and adrenal androgens but little effect on ADH release
19
Q
ACTH Stimulation v Inhibition
A
- Stimulation
- Stress –> CRH –> ACTH (helps prevent shock in times of stress)
- Inhibition
- Glucocorticoids (exogenous and endogenous) inhibit CRH and ACTH (neg feedback)
20
Q
How to determine adrenal insufficiency v. ACTH def
A
- If cortisol def (adrenal failure) –> inc ACTH b/c no feedback
- If ACTH def –> cortisol and androgen def –> fatigue, muscle weakness, anorexia, wt loss, +/-hyponatremia/hypoglycemia BUT ADH okay so no dehydration or hyperkalemia
- Screen - low plasma cortisol (meas early in morning - higher)
- Confirm - ACTH stimulation (cortisol should inc by > 18 ug/dl); then can check serum ACTH to determine primary or secondary
- If cannot make ACTH - low cortisol and low ACTH
- If adrenal insufficiency - low cortisol but high ACTH
21
Q
ACTH Timing
A
diurnal; highest at 4 AM then decline and lowest at midnight
Why you do tests in AM
22
Q
TSH (role, timing and evaluation)
A
- Binds epithelial cells of thyroid gland –> synthesis and release of thyroid hormones
- Timing - secreted in circadian rhythm; peak b/n 9PM and 5AM
- Evaluation
- Screen - low free thyroxine
- Confirm - normal or low TSH level
23
Q
TSH Stimulation v Inhibition
A
- Stimulation - TRH
- Inhibition
- High levels of thyroid hormones (T3 and T4) in blood inhibit TRH (neg feedback loop)
24
Q
Hypothyroid
Hyperthryoid
TSH Def (+ symptoms)
A
- Hypothyroid (thyroid cannot make T3/T4)- inc TSH to comp
- Hyperthyroid (inc production of T3/T4)- TSH suppressed
- TSH def (secondary hypothyroidism) - low free thyroxine and low/normal TSH
- TSH symptoms = lack of energy, wt gain, cold intolerance, constipation (similar but less severe than primary hypothyroidism)
25
Q
LH
A
- Secretion of sex steroids from gonads
- Male - testosterone from Leydig cells in testes
- Female - testosterone from theca cells in ovaries THEN converted to estrogen by adjacent granulosa cells
- Named b/c pre-ovulatory LH surge in females –> proliferation of residual cells in ovulated follicles to form corpora lutea –> corpea lutea make progesterone and estradiol to maintain pregnancy
- LH needed to cont development and function of corpea lutea
- LH is very pulsatile (frequency of pulses changes w/ cycle)
26
Q
FSH
A
- Female - stimulates maturation of ovarian follicles
- Male - supports function of Sertoli cells which in turn support sperm cell maturation
27
Q
LH/FSH Stimulation v. Inhibition
A
- Stimulation
- GnRH
- Activin - hormone secreted by gonads that activates FSH release from pituitary
- Inhibition
- Sex steroids (estrogen, progesterone, testosterone) inhibit GnRH and LH/FSH secretion
- Inhibin -hormone secreted by gonads which inhibits FSH from pituitary
28
Q
LH/FSH Evaluation
A
- Screen - low FSH or LH in blood
- Confirm - end products (low estradiol in women and low testosterone in men)
29
Q
What happens w/ FSH or LH def? What are possible causes?
A
- hypogonadism
- Fail to produce sperm in males and low testosterone (infertile); hot flashes and testicular atrophy
- Cessation of cycle in females (infertile); hot flashes and dec libido possible
- If pre- pubertal - impaired secondary sex characteristics, primary amenorrhea, eunuchoid habitus b/c delayed epiphyseal closure (arm span > ht)
- Causes of dec GnRH - illness, stress (inc cortisol), wt loss, starvation, inc prolactin (REVERSIBLE)
30
Q
What does an FSH or LH excess indicate?
A
- Usually gonadal failure (no feedback)
- can be from removal or gonads or gonad failure - post-menopause - man w/ Kleinfelter’s
31
Q
Pulsatile v Non-pulsatile GnRH
A
- If hypothalamus dysfunction but normal pituitary then give GnRH to stimulate ovulation / spermatogenesis (must be pulsatile w/ infusion pump)
- Long-term GnRH analogs NOT pulsatile (ex - leuprolide) down regulates the system; less LH/FSH to dec testes action in prostate cancer (medical orchidectomy) OR to dec ovary activity in endometrial cancer (medical oophorectomy)
32
Q
How do oral contraceptives work?
A
progestin (progesterone mimic) +/- estrogen to inhibit LH so no LH surge
33
Q
Kallmann’s Syndrome
A
- isolated hypogonadotropic hypogonadism (IHH) from mutation in neural cell adhesion protein that guides axon growth and allows GnRH neurons to migrate from origin to anterior hypothalamus (X-linked recessive)
- Auto dom form FGFR1 gene mutation in females
- X linked KAL-1 gene mutation in males
- Inability to smell, cleft palate, low plasma LH, testosterone/estrogen (missing certain axons)
34
Q
Hypopituitarism (what is it and how to treat)
A
- Need > 50% of 1 type of secretory cell to be lost to have detectable def / > 80% for severe basal loss
- Loss of pituitary cells «_space;loss of target cells themselves
(more mild symptoms) - If multitrophic (tumor) then common order - GH then LH/FSH then TSH then ACTH and PRL last (prolactin inc b/c no tonic inhibition)
- Can be rapid or slow onset
- Tx = replace target products NOT pituitary hormones themselves
- ACTH - hydrocortisone (inc dose in stress; give larger dose in morning than night)
- TSH - thyroxine (monitor w/ free T4)
- GH - synthetic GH (more in kids than adults)
- LH/FSH - estradiol + progesterone if reproductive age women (pill or patch); men get testosterone IM injections every 2 wks OR dermal gel OR patch
35
Q
8 Categories of Hypopituitarism Causes
A
- Sellar/parasellar lesions - mechanical pressure blocks blood flow –> less hormone delivery to anterior pituitary and ischemia of anterior pituitary; from cysts or tumors
- Iatrogenic - neurosurgery or radiation
- Infiltrate - sarcoidosis, Tb, mycoses, hemochromatosis (iron), histiocytosis; these usually involve hypothalamus (mets to brain are common b/c so vascular)
- Brain damage/trauma
- Infarction - Sheehan’s syndrome or spontaneous apoplexy (bleeding); usually bleed into anterior
- Autoimmune - lymphocytic hypophysitis
- Structural - pituitary hypoplasia, aplasia, ectopic location, empty sella (incomplete diaphragm sella or acquired)
- Congenital - absent transcription factors
- Prop1- TSH, GH, prolactin and gonadotropin
- Pit 1 - GH, prolaction, TSH
- TPIT/TBX19 - isolate ACTH def
