Adrenal Steroids - Khan

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