Adrenocortical Steroids Flashcards
Of hormones produced by adrenal cortex, which produces negative FB to hypothalamus?
only Glucocorticoids
What controls mineralcorticoid levels?
-K and Angiotensin II
plus ACTH to a lesser extent
What controls glucocorticoids and androgens from adrenal glands?
ACTH
what is the rate-limiting step in the synthesis of hormones from the adrenal cortex?
conversion of cholesterol to pregnenolone
cortisol
has both GC and MC activity
- DOA 8-12 h
- replacement therapy and emergencies (chronic or acute adrenal insufficiency)
prednisolone
increased GC and decreased MC activity
-DOA 12-36 h
systempic anti-inflammatory effects and immunosuppressive effects
fludrocortisone
increased MC activity
-DOC for replacing MC
dexamethasone
- no MC activity
- systemic anti-inflammatory and immunosuppressive effects, used when water retention is undesirable
uses of GC in non-adrenal d/o
- 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
SE of GC
- 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
effects of w/d from GC
- flare up of underlying disease being rx
- adrenal insufficiency
minimizing SE of GC
- 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
use of mineralocorticoids
-only useful as rx of adrenal insufficiency
SE of fludrocortisone
- Fluid and electrolyte abnormalities
- HTN
rx acute adrenal insufficiency
-GC and MC
rx chronic adrenal insufficiency
-GC and MC or GC + salt
Congenital adrenal hyperplasia -1
-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
CAH-2
- alteration in CYP11B1 (11B hydroxylase)
- end up with elevated 11-deoxycorticosterone, which acts as mineralcorticoid and inc androgens. dec cortisol.
treatment of CAH
- 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
primary aldosteronism causes
- adrenal adenoma, hyperplastic adrenals, or malignant tumors
- common cuase of secondary HTN
primary alderosteronism rx
- rx with spironolactone, antagonist of the mineralocorticoid receptor (also an androgen antagonist)
- eplenrenone, mineralocorticoid antagonist with no anti-androgen activity
Cushing’s syndrome
- increased cortisol prod due to primary adrenal defect or increased ACTH secretion (pituitary or other tissues)
- hyperglycemia, HTN, fat redistribution, muscle wasting
rx for cushing’s syndrome
- surgery or irradiation followed by replacement therapy
- drugs that block adrenocortical steroid synthesis
aminoglutethimide
- inhibits conversion of cholesterol to pregnenolone
- blocks adrenocortical steroid synthesis
ketoconazole
-inhibits many steps in adrenocortical steroid synthesis
metyrapone
-inhibitor of 11B hydroxylase (CYP 11B1)
etomidate
-inhibitor of 11B hydroxylase (CYP 11B1)
abiraterone
-inhibitor of 17alpha-hydroxylase (CYP17A1)
RU486
-progesterone and glucocorticoid antagonist
dexamethasone as a diagnostic agent
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
cushing’s disease
increased ACTH secretion by pituitary
