Steroid Pharm

Question 1

3 zones of adrenal gland

Answer 1

glomerulosa, fasciculata, reticularis. G makes aldosterone, F makes cortisol, R makes cortisol and androgens

Question 2

negative feedback loop for cortisol

Answer 2

stressors cause hypothal to release corticotropin-releasing hormone, which causes anterior pituitary to release ACTH, which causes adrenal cortex to release cortisol. cortisol inhibits all of the steps

Question 3

11B hydroxysteroid dehydrogenase Type 2

Answer 3

converts cortisol to cortisone so it can’t bind to the receptors

Question 4

molecular alterations give rise to differences in:

Answer 4

affinity for mineralocorticoid vs glucocorticoid receptor. extent of protein binding. stability/half-life. generally significantly greater glucocorticoid effect than naturally occurring cortisol

Question 5

fludrocortisone

Answer 5

synthetic mineralocorticoid. similar structure to aldosterone

Question 6

primary vs. secondary adrenocortical insufficiency

Answer 6

primary: anatomic destruction of adrenal gland. secondary: decreased pituitary production of ACTH.

Question 7

types of secondary adrenal insufficiency

Answer 7

iatrogenic: suppression from exogenous glucocorticoid therapy. or hypopituitarism.

Question 8

signs and symptoms of primary adrenal insufficiency

Answer 8

weakness, fatigue, nausea, vomiting, diarrhea, salt craving, anorexia, vitiligo, hypotension, pigmentation of mucous membranes, skin pigmentation, weight loss

Question 9

what causes the hyperpigmentation in primary adrenal insufficiency?

Answer 9

high levels of ACTH, specifically the melanocyte-stimulating hormone sequence within ACTH molecule.

Question 10

signs and symptoms of secondary adrenal insufficiency

Answer 10

same as primary AI, just no hyperpigmentation (ACTH is low not high). near normal aldosterone levels

Question 11

what test do you use to diagnose adrenal insufficiency

Answer 11

cosyntropin test. if cortisol above 18, normal. if lower than 18, abnormal. cosyntropin is expected to cause increased secretion of cortisol from a functioning adrenal cortex.

Question 12

acute adrenal insufficiency “adrenal crisis”

Answer 12

most common in patients with primary adrenal insufficiency. life threatening, requires immediate treatment. hypotension, nausea, vomitting, hyperkalemia and hyponatermia. support with large amounts of IV fluids that ARENT hypotonic. then give high dose IV glucocorticoid, taper to maintenance dose

Question 13

treatment of chronic adrenal insufficiency

Answer 13

stress-dosing: when patient is ill increase the glucocorticoid dose for a few days, do not increase mineralocorticoid.

Question 14

congenital adrenal hyperplasia

Answer 14

deficient adrenal corticosteroid synth due to mutations of genes involved with adrenal steroidgenesis. most common form is 21-hydroxylase deficiency

Question 15

how to diagnose neonatal vs. late onset CAH due to 21-hydroxylase deficiency

Answer 15

for neonatal, will have high level of 17-OH-progesterone. for late onset, use cosyntropin test.

Question 16

21-hydroxy deficiency treatment

Answer 16

steroids: dexameth, prednisone, hydrocortisone. in salt wasting, need fludrocortisone as well.

Question 17

cushing’s syndrome types

Answer 17

ACTH dependent: pituitary adenoma, ectopic ACTH production.

ACTH independent: adrenal adenoma, adrenal carcinoma

Iatrogenic cushing’s syndrome

Question 18

cushings syndrome signs and symptoms

Answer 18

weight gain, menstrual irreg, hirsutism, psychiatric dysfunction, backache, muscle weakness, fractures, obesity, moon face, hypertension, bruising, ankle edema, etc

Question 19

diagnosis of cushings

Answer 19

give ACTH. check 24 hour cortisol excretion in urine. can do a low dose dexameth overnight suppression test. midnight salivary cortisol level.

Question 20

ACTH dependent vs Independent cortisol/ACTH values

Answer 20

high both = ACTH dependent process.

low ACTH and high cortisol: ACTH independent process.

Question 21

medical treatment of cushings

Answer 21

aminoglutethimide (blocks conversion of cholesterol to pregnenolone), ketoconazole (inhibits adrenal and gonadal steroid synth), mitotane. mitotane has bad side effects.

Question 22

metyrapone

Answer 22

selective inhibitor of 11-hydroxylation. interferes with cortisol and corticosterone synth.

Question 23

mifepristone

Answer 23

glucocorticoid receptor antagonist activity at higher concentrations. indicated to control hyperglycemia secondary to hypercortisolism

Question 24

pasireotide

Answer 24

for cushings disease. somatostatin analog. blocks release of ACTH. causes hyperglycemia and GI symptoms.

Question 25

primary aldosteronism

Answer 25

increased aldosterone, decreased renin. hypertension. hypokalemia. treat unilateral adenoma with surgery, bilateral with spironolactone or eplerenone.

Question 26

toxicity of corticosteroids

Answer 26

continued use of supraphysiological steroid doses resulting in iatrogenic cushing’s syndrome. withdrawal of steroid therapy resulting in adrenal insufficiency.

Question 27

glucocorticoid withdrawal syndrome

Answer 27

anorexia, nausa, vomiting, weight loss, headache, fever, joint pain, hypotension posturally. occuring in setting or normal or high plasma cortisol levels. suggests steroid dependence.