Adrenal steroids Flashcards
Metabolic effects of glucocorticoids
Gluconeogenesis, amino acid release through muscle catabolism, inhibition of peripheral glucose uptake, lipolysis
Why does aldosterone have higher affinity for aldosterone receptors than cortisol does?
11B-hyrodxysteroid dehydrogenase converts cortisol –> cortisone
Fludrocortisone
Synthetic mineralcorticoid
Use of glucocorticoids
Dx Cushing’s, tx adrenal insufficiency and CAH, tx inflammatory, allergic and immunological disorders
Dexamethasone suppression test is negative: Pituitary adenoma or ectopic ACTH?
Ectopic ACTH
High ACTH and High cortisol: ACTH dependent or ACTH independent?
ACTH dependent
Aminoglutethimide: Tx and action
Cushing’s: blocks conversion of cholesterol–> pregnenolone
Ketoconazole: Tx and action
Cushing’s: nonselective inhibitor of adrenal and gonadal steroid synthesis
Mitotane: Tx and action
Cushing’s: nonselective cytotoxic action on adrenal cortex
Metyrapone: Tx and action
Cushing’s: selective inhibitor of 11-hydroxylation, decreases cortisol production
Metyrapone test
If pituitary function is normal, ACTH (& 11-deoxycortisol) should increase d/t metyrapone induced decrease in cortisol
Mifepristone: Tx and action
Cushing’s: glucocorticoid receptor antagonist at high concentration; doesn’t bind to MC receptor
SE of Mifepristone
GC resistance, fatigue, nausea, headache, hypokalemia (high levels act as mineralcorticoids), arthalgias, edema, endometrial thickening, ADRENAL INSUFFICIENCY
Pasireotide: Tx and action
Cushing’s: somatostatin analog–> binds to somatostatin receptors–> blocks release of ACTH
SE’s of Pasireotide
Hyperglycemia and GI sx
Primary adrenal insufficiency: cause and levels
destruction of adrenal gland --autoimmune adrenalitis --infection --hemorrhage --tumor ↑ACTH ↓cortisol
Secondary adrenal insufficiency
↓ pituitary ACTH production:
–suppression from exogenous GC therapy
–hypopituitarism
↓ACTH ↓cortisol
Sx’s of primary adrenal insufficiency
weakness, fatigue, NVD, weight loss, skin pigmentation, hypotension, hyponatremia, hyperkalemia, anemia
Sx’s of seconday adrenal insufficiency
Same as primary but NO hyperpigmentation (b/c ACTH not elevated)
Adrenal Crisis sx’s
common in primary adrenal insufficiency; volume depletion, NV, hyperkalemia, hyponatremia
Cortrosyn test for adrenal insufficiency
Synthetic ACTH used to stimulate adrenal glands; low cortisol is abnormal
Tx of chronic primary adrenal insufficiency
Glucocorticoid replacement: hydrocortisone 15-20mg morning, 5-10mg afternoon
–hydrocortisone for illness or surgery
Mineralcorticoid replacement: fludrocortisone 0.05-0.2 daily
Tx of adrenal crisis
LOTS of IV fluids (0.9% NaCl solution) plus IV glucocorticoid (dexamethasone or hydrocortisone) NOOO hypotonic saline
Tx of primary aldersteronism
spironlactone (AR blocker w/antiandrogenic effects) or eplerenone (less antiandrogen)
21-hydroxylase deficiency
no conversion of 17-hydroxyprogesterone–> 11-deoxycortisol–> ↓glucocorticoids and mineralcorticoids (which ↑ACTH) and ↑androgens
Sx’s of 21-Hydroxylase def
Virilization (clit enlargement, labial fusion, sexual ambiguity) Salt wasting and hypotension
Tx for 21-hydroxylase def
Steroids: dexamethasone, prednisone, hydrocortisone
Fludrocortisone for salt-wasting
Nonendocrine uses of steroids
suppress inflammatory and immune responses
Toxicity of corticosteroids
iatrogenic Cushing’s, adrenal insufficiency from withdrawal, insomnia, behavior changes, peptic ulcers, pancreatitis
