Adrenocortical Steroids

Question 1

Of hormones produced by adrenal cortex, which produces negative FB to hypothalamus?

Answer 1

only Glucocorticoids

Question 2

What controls mineralcorticoid levels?

Answer 2

-K and Angiotensin II

plus ACTH to a lesser extent

Question 3

What controls glucocorticoids and androgens from adrenal glands?

Answer 3

ACTH

Question 4

what is the rate-limiting step in the synthesis of hormones from the adrenal cortex?

Answer 4

conversion of cholesterol to pregnenolone

Question 5

cortisol

Answer 5

has both GC and MC activity

• DOA 8-12 h
• replacement therapy and emergencies (chronic or acute adrenal insufficiency)

Question 6

prednisolone

Answer 6

increased GC and decreased MC activity
-DOA 12-36 h
systempic anti-inflammatory effects and immunosuppressive effects

Question 7

fludrocortisone

Answer 7

increased MC activity

-DOC for replacing MC

Question 8

dexamethasone

Answer 8

• no MC activity

- systemic anti-inflammatory and immunosuppressive effects, used when water retention is undesirable

Question 9

uses of GC in non-adrenal d/o

Answer 9

• lung maturation before birth
• suppressing immune system for organ transplantation
• rx of childhood ALL (with methotrexate)
• suppress immune system for symptomatic rx of inflammatory and/or immune d/o

Question 10

SE of GC

Answer 10

• few when used topically or systemically for 2 weeks of high doses:
• hyperglycemia/glycosuria
• increased PRO breakdown
• increased risk of infections
• myopathy
• osteoporosis
• behavioral changes
• cataracts
• ulcers
• sodium and fluid retention, loss of K (not all due to MC effect)
• hypertension
• growth retardation in children
• suppression of HPA

Question 11

effects of w/d from GC

Answer 11

• flare up of underlying disease being rx

- adrenal insufficiency

Question 12

minimizing SE of GC

Answer 12

• consider risk/benefit ratio
• use smallest dose possible and check periodically
• alternate day admin: alleviates suppression of the HPA axis
• administer together with newer immunosuppressants
• modify diet: high K, low Na, high PRO, incr Vit D and Ca

Question 13

use of mineralocorticoids

Answer 13

-only useful as rx of adrenal insufficiency

Question 14

SE of fludrocortisone

Answer 14

• Fluid and electrolyte abnormalities

- HTN

Question 15

rx acute adrenal insufficiency

Answer 15

-GC and MC

Question 16

rx chronic adrenal insufficiency

Answer 16

-GC and MC or GC + salt

Question 17

Congenital adrenal hyperplasia -1

Answer 17

-alteration in CYP21A2 [21B hydroxylase), effects progesterone conversion to 11-deoxycorticosterone and 17 alpha OH progesterone –> 11-desoxycortisol. result: CRH, ACTH high bc dec GC and MC. Elevated androgens

Question 18

CAH-2

Answer 18

• alteration in CYP11B1 (11B hydroxylase)

- end up with elevated 11-deoxycorticosterone, which acts as mineralcorticoid and inc androgens. dec cortisol.

Question 19

treatment of CAH

Answer 19

• GC replacement therapy and to inhibit ACTH production by pituitary
• MC and salt as replacement therapy when CAH-1
• MC antagonists and salt restriction in CAH 2
• antiandrogens to coutneract virilizing effects of increased androgen prod

Question 20

primary aldosteronism causes

Answer 20

• adrenal adenoma, hyperplastic adrenals, or malignant tumors
• common cuase of secondary HTN

Question 21

primary alderosteronism rx

Answer 21

• rx with spironolactone, antagonist of the mineralocorticoid receptor (also an androgen antagonist)
• eplenrenone, mineralocorticoid antagonist with no anti-androgen activity

Question 22

Cushing’s syndrome

Answer 22

• increased cortisol prod due to primary adrenal defect or increased ACTH secretion (pituitary or other tissues)
• hyperglycemia, HTN, fat redistribution, muscle wasting

Question 23

rx for cushing’s syndrome

Answer 23

• surgery or irradiation followed by replacement therapy

- drugs that block adrenocortical steroid synthesis

Question 24

aminoglutethimide

Answer 24

• inhibits conversion of cholesterol to pregnenolone

- blocks adrenocortical steroid synthesis

Question 25

ketoconazole

Answer 25

-inhibits many steps in adrenocortical steroid synthesis

Question 26

metyrapone

Answer 26

-inhibitor of 11B hydroxylase (CYP 11B1)

Question 27

etomidate

Answer 27

-inhibitor of 11B hydroxylase (CYP 11B1)

Question 28

abiraterone

Answer 28

-inhibitor of 17alpha-hydroxylase (CYP17A1)

Question 29

RU486

Answer 29

-progesterone and glucocorticoid antagonist

Question 30

dexamethasone as a diagnostic agent

Answer 30

in cushing’s syndrome, administering dexamethasone with suppress HPA.

• tests if axis is working
• origin of cushing’s. it will suppress cortisol if syndrome is d/t increased ACTH by pituitary. it will NOT suppress cortisol if syndrome is d/t primary adrenocortical hyperfunction or ACTH secretion by tumor or other tissues

Question 31

cushing’s disease

Answer 31

increased ACTH secretion by pituitary