01-13 Acromegaly and Hyperprolactinemia Flashcards
Acromegaly —case presentation: clinical and biochemical manifestations —GH: action and regulation of secretion —What causes acromegaly? —Treatment: physiological basis Amenorrhea-glactorrhea —case presentation: manifestations —differential diagnosis —treatment: physiological basis Relevance of the pituitary developmental scheme
Clinical Manifestations of Acromegaly
—clothes/shoes/rings don't fit —lantern jaw —coarse facies —wide doughy hands —large tongue —space between teeth —insulin resistance (from excess GH) —HTN
Lab Findings in Acromegaly
—insulin resistance or DM on OGTT w/ simultaneous GH (which in nl people is suppressed by glucose, but would be elev here)
—sky high IGF
—low testosterone/estrogen w/o appropriate rise in FSH and LH (i.e. normal or low levels of FSH/LH)
What causes acromegaly?
Either:
—excessive hypothalamic release of GHRH
—primary neoplasm of the ant. pituitary (often occur by random somatic mutation)
How does GHRH signal?
somatotrophs have a GPCR that binds GHRH
—increases [cAMP]
—cell proliferation and increased GH release
**mutations are often constitutive activation of this receptor
How is GH regulated?
Stress, environmental stims and endogenous rhythms control hypothalamic release of GHRH
Hypothal: GHRH ↑s GH, Somatostatin ↓s
Ant Pit: GH is released → Liver → IGF release
—IGF-1 inhib feedback to liver, ant pit; positive feedback to somatostatin neurons in hypothal
—GH feedback: inhibits GHRH neurons and positive feedback to somatostatin neurons in hypothalamus
Tx options for acromegaly
1. Surgery —small: transnasal adenectomy —large: subfrontal craniotomy 2. Radiation 3. Medical —octreotide (long-acting somatostatin analog) —dopaminergic
Clinical Manifestations of Hyperprolactinemia
—Lab Manifestation
CLINICAL Women —galactorrhea (30-80%) —menstrual ∆s —inferitility
Men —impotence (most common) —galactorrhea (<30%) —visual field ∆s —EOM paralysis —h/a —ant pit dysfxn
LAB —check hCG (pregnancy is #1 cause of amenorrhea!) —TSH: normal (or low if TRH-mediated) —LH: low —FSH: low —Prolactin: sky high
DDx of hyperprolactinemia
—Think through acix
Hypothalamic: tumor, infiltration (e.g. sarcoidosis)
Pituitary dz:
—prolactinoma
—acromegaly; TSH-oma
—stalk compression
Neurally-mediated
—breast stim or chest wall lesion (suckling reflex)
Drugs
—anything anti-dopaminergic (psych, metoclopramide)
Primary Hypothyroidism
Chronic Renal Failure
How does hyperprolactinemia suppress sex steroidogenesis?
mechanical
—prolactinoma pushes against the other cells in the ant. pit.
hormonal
—prolactin inhibits GnRH release
Treatment
—rationale for tx
Options
RATIONALE
—infertility, osteoporosis, mass effect
OPTIONS
—surgery
—med: long-acting dopaminergics (b/c DA from hypothal inhibits prolactin release); actually will shrink size
—radiation
Recurrence
“Prolactinomas tend to recur, even after ‘successful’ surgery”
Names of the two dopamine agonists we learned
bromocriptine and cabergoline
Effect of TRH on Prl
TRH stimulates Prl
