Lecture 7 - Pituitary-adrenal axis, adrenocortical insufficency, CAH

most cortisol is bound to

most cortisol is bound to

CBG (prednisolone), some to albumin (DXM)

androgens (DHEA) metabolism

mostly free

cortisol and adrenal androgens metabolism is done thru

hydroxylation

Addisons

primary adrenocortical insufficiency

adrenal hyperplasia, adrenoleukodystrophy and adrenomyeloneuropathy are types of

congenital causes of adrenocortical insufficiency

tb, hiv and cmv are causes of

adrenocortical insufficiency

when is there an inflammatory form of adrenocortical insufficiency

autoimmune

autoimmune polyglandular syndromes

1. APECED - Addisions

2. Schmidt Addison

acute ICSR is caused by

hemorrhagic/thrombosis adrenal veins → adrenocortical insufficiency

waterhouse-friderichsen syndrome

meningococcal sepitcemia causing vascular origin of adrenocortical insufficnecy

symptoms hypoadrenalism

fatigue, anorexia, postural dizzy, salt craving, arthralgia, amenorrhea, decrease libido, melanodermia. hypotension, auricular calcification, dry + pruritic skin, no body hair

labs hypoadrenalism

hyponatremia, hyperkalemia, relative lymphocytosis, eosinophilia

decreased basal cortisol

basal hypoglycemia in kids

4 steps autoimmune hypoadrenalism

1. increased renin

2. low cortisol response to acth stimulation tests

3. increase basal ACTH

4. decrease cortisol

what is a strong negative prognosis in the evolution of hypoadrenalism

adrenal crisis

substitution treatment overdose in hypoadrenalism

clinical signs hypercorticism, osteoporosis

treatment hypoadrenalism

short acting - oral hydrocortisone

long acting - prednisone/solone, dexamethasone

mineralocorticoids (fludrocortisone)

when should you increase treatment in hypoadrenalism

severe trauma (DXM)

stressful situations (glucocorticoids)

surgery (HHS)

treatment monitoring in hypoadrenalism

glucocorticoids - clinically

mineralocorticoids - bp in recumbent + supine, electrolytes, renin

why does acute adrenal insufficiency happen in a primary adrenal insufficiency

didn’t increase glucocorticoids during illness, vomiting

causes of acute adrenal insufficiency

undiagnosed + stress

after bilateral adrenal hemorrhage/infarction

cessation long standing corticoid therapy + decompensating secondary hypoadrenalism

after pituitary infarction/apoplexy

clinical signs adrenal crisis

hypotension, dehydration, hypovolemic shock

abd pain

fever

confusion

coma, death

labs acute adrenal crisis

hyponatremia, hyperkalemia, hypoglycemia, acidosis, lymphocytosis, eosinophilia

treatment acute adrenal insufficiency

iv saline dextrose/glucose + hydrocortisone

transition to oral gc

atb if persistent fever

congenital adrenal hyperplasia pathophysio

21 hydroxylase deficiency

3 phenotypes of congenital adrenal hyperplasia

• salt wasting form - @ d5, electrolyte + fluid loss, sexual ambiguity in female, macrogenitosomy in males

• simple virilizing form - @ birth

• late onset form - virilization in teens

StAR deficiency

male pseuodohermaphroditism, adrenal lipoid hyperplasia, severe prognosis

11 b-hydroxylase deficiency

htn and virilization in girls (elevated testosterone)

17 a-hydroxylase deficiency

htn, lack pubertal dev

labs 21 hydroxylase dericiency

elevated steroids upstream + decrease downstream - 17 OH progesterone high, late onset has high acth

adrenal hypertrophy in US

increased testosterone + progesterone

CYP21A2 mutations

treatment congenital adrenal hyperplasia in kids vs adults

neonate + child - hydrocortisone, fludrocortisone, monitorization by hormones + bone maturation/growth velocity, surgery ext genitalia

adults - dxm, prednisolone, monitoring hormones, fludrocortisone

late onset - OCs (for bradymenorrhea), antiandrogens (for hirsutism), glucocorticoids (for fertility)

when is there poor prognosis in congenital adrenal hyperplasia

salt-wasting and hypoadrenalism forms

complications men w/ 21 hydroxylase deficiency

testis remnants, spermatogenesis impairment, infertility

complications females with congenital adrenal hyperplasia

anovultion, infertility, aggressive behaviour

testicular adrenal rest tumours (TART)

21 hydroxylase deficiency in males causing masses of tissue leading to obstruction + infertility, may regress during glucocorticoid therapy