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What are the regulators of cortisol secretion from the pituitary and hypothalamus?
Pituitary- ACTH
Hypothalamus- CRH
What is the regulator of mineralocorticoid secretion?
Angiotensin II
What is the rate limiting step of adrenal steroid biosynthesis?
Conversion of cholesterol into pregnenolone (C27-C21)
What is the precursor of ACTH?
POMC
What is the precursor of MSH?
POMC
What is the difference between cortisol and cortisone, prednisone and prednisolone?
Cortisone and prednisone are the inactive forms. They must be converted into cortisol and prednisolone in the liver.
What are the effects of glucocorticoids on carbohydrate metabolism?
increase glucose metabolism
What are the effects of glucocorticoids on fat metabolism?
increase fat metabolism
redistribution of fats
What are the effects of glucocorticoids on bone, CVS, eye, and CNS?
bone- increase osteoclast activity
CVS- HTN/ raise BP
eye- cataracts
CNS- mood swings
What is the function of aldosterone?
Na+ and water reabsorption, K+ excretion
What is primary adrenal insufficiency and its cause?
Primary adrenal insufficiency is also known as Addison’s disease and is decreased synthesis of cortisol, aldosterone, and sex hormones. Its cause is autoimmune destruction of the adrenal gland.
What are the signs/symptoms of primary adrenal insufficiency?
hypotension, hyperkalemia, hyperpigmentation, weakness/fatigue
What is the cause of hyperkalemia and hyperpigmentation in primary adrenal insufficiency?
hyperkalemia- bc aldosterone isn’t produced
hyperpigmentation- bc of extra MSH
What is secondary adrenal insufficiency and its cause?
Secondary adrenal insufficiency is due to anything not in the adrenals. Could be a tumor in the HT, pituitary, or more commonly ABRUPT WITHDRAWL of glucocorticoids.
Why are hyperkalemia and hyperpigmentation NOT seen in secondary adrenal insufficiency?
hyperkalemia- because adrenal gland is not damaged, and aldosterone can still be made and secreted
hyperpigmentation- because decreased pituitary stimulation= low POMC= low ACTH and MSH
What are the causes of Cushing’s syndrome?
exogenous—> glucocorticoids
endogenous—> tumors/cancer in adrenal or pituitary gland
What makes fludrocortisone different from cortisone? What benefit does that change cause?
Fludrocortisone has a 9a-F that cortisone does not. This increases mineralocorticoid activity by 300-800 times!!!!
What is the indication for fludrocortisone use? Which hormone deficiency is corrected?
Indication- primary adrenal insufficiency/ Addison’s disease
aldosterone hormone deficiency is corrected
What is the cause of adrenal insufficiency from prolonged glucocorticoid administration?
HPA suppression
List the steroid synthesis inhibitors:
ketoconazole
etomidate
mitotane
metyrapone
List the inhibitors of ACTH secretion:
cabergoline
pasireotide
What is the name of the progesterone antagonist?
mifepristone
How does mifepristone work?
It’s a GC receptor antagonist so cortisol can’t bind
What is hyperaldosteronism?
abnormal secretion of aldosterone from hyperplastic gland or tumor
How is hyperaldosteronism treated?
spironolactone or surgery
What are the ADRs of spironolactone?
hyperkalemia
gynecomastia/ endocrine effects
What is the cause of gynecomastia from spironolactone?
spironolactone blocks androgen receptors and that makes androgen convert to estrogen = boobs