adrenal Flashcards
adrenal gland is composed of
medulla- 10%
cortex- 90%
adrenal cortex is composed of
zona glomerulosa
zona fasciculata
zona reticularis
What happens in adrenal medulla
tyrosine is converted to epi and norepi in response to stress
what happens in zona glomerulosa
RAAS, aldosterone produced
what happens in zona fasciculata
cortisol
controlled by HPA, ACTH
what happens in zona reticularis
androgens
controlled by HPA, ACTH
the adrenal cortex synthesizes what 2 classes of steroids
and how many carbons do they have
corticosteroids (glucocorticoids and mineralocorticoids): 21 carbons
androgens: 19 carbons
main mineralocorticoid
aldosterone
main glucocorticoids
cortisol, corticosterone
endogenous cortisol= exogenous _________
hydrocortisone
hydrocortisone usefulness
1:1 anti-inflammatory:mineralocorticoid
useful for adrenal insufficiency: Addison’s, sepsis
prednisolone, prednisone modifications to cortisol
a double bond: increases anti-inflammatory effect
methylprednisolone modifications to cortisol
a methyl group: increase anti-inflammatory effect
high glucocorticoid activity useful for immunologic flares like MS, rejection
fludrocortisone modifications to cortisol
fluoro group: increases mineralocorticoid effect
useful for addison’s disease: treat hyperkalemia, hypotension
dexamethasone modifications to cortisol
has a methyl group, double bond, and fluoro group
NO mineralocorticoid at all
100% anti-inflammatory: good for meningitis or anti-emetic
main buckets: hyperfunction of adrenal gland
Cushing syndrome
Hyperaldosteronism
2 main buckets of cushing syndrome
ACTH dependent: Cushing DISEASE, or ectopic ACTH secretion by a nonpituitary tumor
ACTH independent: adrenocortical adenoma or carcinoma
broad 3 main steps for diagnosis of cushing syndrome
1: rule out iatrogenic causes
2: establish presence of hypercortisolism
3: determine if ACTH dependent or independent
how do you establish the presence of hypercortisolism
most common is the low dose dexamethasone test: give 1 mg dexamethasone PO btwn 11 pm-midnight, then draw levels at 8am. if dexamethasone is detectable and cortisol is high, diagnosed hypercortisolism
other options: 24hr urinary free cortisol conc, late night salivary cortisol conc
what if there is hypercortisolism but plasma ACTH is undetected
then it is adrenocorticol adenoma or carcinoma
what if there is hypercortisolism and plasma ACTH is elevated
it is ACTH-dependent Cushing syndrome so you need to get an MRI to look at pituitary
what if MRI is normal in ACTH-dependent Cushing Syndrome
then it is ectopic ACTH secreting non-pituitary tumor: check IPSS or JVS to completely rule out Cushing disease
what if MRI is abnormal in ACTH-dependent Cushing Syndrome
then it is probs Cushing DISEASE.
need to do a CRH test or a high dose dexamethasone test to confirm
CRH test
100 ug of ovine CRH (corticorelin) IV–> measure cortisol & ACTH every 15 minutes
if you have cushing disease you respond with a rise in cortisol and ACTH
high dose dexamethasone test
get baseline cortisol level
give dexamethasone 2 mg every 6 hr for 48h
if you having Cushing Disease your cortisol level decreases
treatment targets for cushing syndrome
- inhibit adrenal hormone synthesis
- destroy adrenocortical cells
- inhibit ACTH
- glucocorticoid receptor antagonist
drugs that are steroidogenesis inhibitors
ketoconazole
metyrapone
etomidate
what to know about ketoconazole
blocks cortisol & aldosterone
ANTI-ANDROGENIC ACTIVITY
side effects are elevated liver enzymes, gynecomastia, n/v, teratogenic
what to know about metyrapone
blocks cortisol (NOT ANDROGENS) so androgenic side effects like acne, hirsutism, edema, blood pressure, electrolytes–> usually give with ketoconazole to avoid those
what to know about etomidate
it is an anesthetic, causes adrenal suppression long term, usually reserved for rescue
what is the adrenolytic agent
mitotane
what to know about mitotane
it destroys cells; high doses of steroid replacement therapy are often needed
it is a CYP3A4 inducer, neuro & GI effects, avoid pregnancy/nursing
what is the glucocorticoid receptor antagonist
mifepristone
what to know about mifepristone
it terminates pregnancy
it is used to treat hyperglycemia in cushing syndrome
what is the somatostatin analog that targets ACTH
pasireotide
what to know about pasireotide
for cushing DISEASE
causes hyperglycemia/increased A1c, GI, hypotension
what are the kinds of hyperaldosteronism and what causes them
primary (adrenal gland): Conn syndrome, adrenal hyperplasia
secondary (stimulation of zona glomerulosa): pregnancy, excessive potassium, oral contraceptives, CHF, cirrhosis
how do you treat hyperaldosteronism
spironolactone
types of adrenal insufficiency and how you know which one it is
primary: adrenal steroid is decreased but ACTH and CRH are increased
secondary: adrenal steroid and ACTH are decreased. CRH is increased
tertiary: adrenal steroid, ACTH, and CRH are all decreased
diagnosis of adrenal insufficiency
abnormal cosyntropin stimulation test: measure serum cortisol levels at baseline and then 30-60 minutes after injection
if cortisol remains low and does not increase more than 10 ug/dL above the baseline, then adrenal insufficiency is diagnosed
addison’s (primary adrenal insufficiency) treatment
mineralocorticoid + glucocorticoidd
distinguishing feature of addison’s
hyperpigmentation in areas of increased friction
treatment of secondary/tertiary adrenal insufficiency
glucocorticoid ONLY
NO mineralocorticoid
what do you give for glucocorticoid replacement
hydrocortisone or cortisone: give in the AM and then 8 hrs later
monitoring for glucocorticoid replacement
body weight, postural BP, energy levels
glucocorticoid replacement: what to give before strenuous activities like exercise
extra 5-10 mg hydrocortisone
glucocorticoid replacement: what to give if there is febrile illness or injury
double the daily dose
glucocorticoid replacement: what to give if there is trauma, surgery, critically ill
10x the daily dose
what to give for mineralocorticoid replacement
fludrocortisone: 0.05-0.2 mg once daily
what to monitor for fludrocortisone
body weight, BP, ECG
side effects are GI, edema, HTN, hypokalemia, diabetes
how do you treat adrenal crisis
IV fluids with glucose
high dose IV glucocorticoids
