Lecture 2 - Prolactinoma, acromegaly,

GABA and cholinergic pathways have what role on PRL release

inhibitory

prl regulation

@ hypothalamus, inhibitory

VIP, serotonin and histidine methionine effect on PRL

stimulatory

rhythm secretion PRL

pulsatile - biggest during rem

most common pituitary tumour

prolactinoma

who gets microprolactinoma

young women

immunohistochemistry for prolactinoma

positive for PRL

clinical manifestations prolactinoma women

hypogonadism (by inhibiting pulsatile secretion GnRH) - poor quantity periods or amenorrhea, galactorrhea, infertility, hot flashes, atrophic vaginitis, osteoporosis

clinical manifestations prolactinoma men

no libidio, sex dynamics disorders, azoospermia, gynecomastia

clinical manifestations prolactinoma in both sexes

neuro-opthalmological syndrome

tumour size based on serum prl level

>100 ng/ml - microadenoma

>200 ng/ml - macroadenoma

PRL >40 with prolactinoma means

in context of other hypothalamo-pituitary disorders

how to confirm dg hyperprolactinemia

1st then 2nd PRL levels

hook effect

false neg prl

evolution prolactinoma

untreated hypogonadism - osteoporosis

macroprolactinomas → neuro, ophthalmo +rhinorrhea complications

treatment prolactinoma

dopa agonists - reduces prl + tumour mass

• bromocriptine, cabergoline

excision - if resistance to meds or macro + wants pregnancy

temozolomide - if aggressive

what to give as treatment in case you can’t take bromocriptine

quinagolide

SE dopa agonists

nausea, postural hypotension, drowsiness, depression

SE of high doses of cabergoline and pergolide

valvulopathies

length of treatment depending on prolactinoma size

micro - 2-3y

macro - longer

how to treat hyperPRL in psych patients

no dopa agonists

olanzapine, clozapine and quetiapine - antipsychotics that don’t raise PRL

aripiprazole

estro-progestatives

GHRH stimulates

gh + prl

neg vs positive feedback GHRH

neg - IGF-1, GH (these elevate somatostatin)

pos - serotonin, y-aminobutiric acid

nonsense mutations of GHRH-R gene cause what

rare familial form of GH deficiency

somatostatin role

inhibitis secretion insulin, glucagon, cholecystokinin

synthetic analogs of somatostatin are used to treat

acromegaly, carcinoid or pancreatic tumours

bio effects of GH-IGF-1 axis

promotion bone growth

stimulation calcitrol

growth visceral organs

increased glomerular filtration

stimulates hair growth, sweat glands, dermis thickening

acromegaly occurs due to

gh + ghrh excess

clinical manifestations acromegaly if prepubertal or after closing growth cartilages

prepubertal - gigantism

after - acromegaly

clinical manifestations acromegaly

insidious onset (delay 10-15y)

• gh excess

• tumoural mass

• pitutary insufficiency

hypertrophy of extremities and vocal cords are manifestations of

gh excess

skin manifestations gh excess

thick, hyperhidrosis, cutis verticis gyrata, acanthosis nigricans

musculoskeletal manifestations gh excess

acroparesthesias, arthralgias, osteoarthritis

resp manifestations gh excess

narcolepsy, sleep apnea syndrome

visceromegaly and _____ occurs in gh exces

increased risk malignant colon polyps

cardiovasc manifestations gh excess

lvh, htn, hf

metabolic manifestations acromegaly

dm, hyperinsulinemia + resistance, decrease renin, increase aldosterone, thyroid hypertrophy, hypercalciuria, hypertriglyceridemia, macrogenitosomia

best screening test for acromegaly

serum conc IGF-1 >300ng/ml, glucose tolerancetest

confirmation of dg of GH hypersecretion

gh dosing during ogtt

confirmation of acromegaly dg is done by

imaging, neuro-ophthalmological exam

treatment acromegaly

transsphenoidal excision tumour

drugs if persistent gh secretion postop - octreotide (synthetic analogue somatostatin), lanreotide, gh r antagonists, pegvisomant, dopa agonists

radio

effects gh r antagonists

reduce igf-1, slight growht tumour, increases liver enzymes + lipodystrophy @ injection site