acromegaly, gigantism and dwarfism

what hormones have a negative feedback on the release of GH

somatostatin (in the hypothalamus) and insulin like growth factor (in the liver)

excessive secretion of GH usually due to a pituitary somatotroph (cells in anterior pit that produce GH) that happens in adulthood only (40-45yo avg onset), after the epiphyseal closure

acromegaly

what is the onset like for acromegaly

insidious onset w slow progression (dx takes like a year)

acromegaly sx

acral (facial bones/lips/nose/tongue) overgrowth, soft tissue overgrowth, skin thickening

enlarged jaw, hands, and feet (inc glove and shoe size over time)

coarse facial features w big nose and frontal bones

macroglossia (big tongue)

deepening of the voice (enlargement of soft tissues of pharynx and larynx)

hand paresthesias

headaches and visual changes due to pressure from the adenoma

cardiovasc disease (HTN, cardiomyopathy)

type 2 Dm (inc gluconeogenesis and lipolysis)

arthropathies and back pain

single BEST test for acromegaly dx

serum Insulin like growth factor-1

normal serum IGF-1 when screening for acromegaly means what

strong evidence against acromegaly

unequivocal serum IGF-1 when screening for acromegaly or gigantism what can we do next on top of that to confirm

oral glucose tolerance test (measures serum GH before and after)

what is the most specific test to dx acromegaly and gigantism

oral glucose tolerance test (pos= over 1 after 2hrs)

if a pt has high IGF-1 or unequivocable IGF-1 and high GH after oral glucose tolerance test (shows inadequate suppression) whats the last step to dx acromegaly or gigantism

pituitary MRI (see if its extra-pituitary acromegaly or a GH-secreting pituitary adenoma)

whats the surgical tx for acromegaly

endoscopic transphenoidal surgery

if we cant do surgery on the acromegaly pt what meds can we give

somatostatin analog (octreotide, ianreotide), dopamine agonist (cabergoline), competitive GH receptor agonist (pegvisomant)

what are the tx goals for a pt w acromegaly

lower serum IGF-1 and Gh concentrations back to normal (improves sx and soft tissue growth and reverses metabolic abnormalities like T2D but cant reverse bony changes)

GH excess that occurs before the fusion of the epiphyseal growth plates AKA happens in kids

gigantism

what is the NORMAL pathway for GH release

hypothalamus releases GHRN (pos feedback) and somatostatin (neg feedback) to the anterior pit → GH released → IGF-1 released → grow

what are some causes of gigantism

either too much GHRH in hypothalamus, too much GH in pituitary all on its own, or too little somatostatin (too little neg feed back)

gigantism sx

often around 13 but earlier in girls

big hands and feet

coarsening of the facial features

excessive sweating

progressive macrocephaly

adenomas (associated w amenorrhea in girls and sx of tumor compression in boys)

dramatic linear growth

gigantism surgical tx

endoscopic transphenoidal surgery

gigantism tx if we cant do surgery

dopamine analog (bromocriptine), somatostatin analog (octreotide), competitive GH agonist (Pegvisomant)

what causes dwarfism

growth hormone decifiency

diagnostic tests for dwarfism

serum IGF-1, Xray for bone age, growth hormone provocation

dwarfism tx

recombinant growth hormone (start as young as possible) (very safe and effective, few ADR)

theraputic monitoring every 4-6mo for height velocity, IGF-1 and bone age