2/13 Adrenal Gland - Lubitz Flashcards
adrenal gland
adrenal cortex (“gfr” & “deeper you go, sweeter it gets)
- zona glomerulosa → mineralocorticoids (salt)
- zona fasciculata → glucocorticoids (sugar)
- zona reticularis → androgens (sex)
- androstenedione, DHEA
adrenal medulla → catecholamines
- norepi, epi, dopamine
endocrine causes of HTN
adrenal diseases
- Cushing’s Syndrome (hypercortisolism)
- thick violaceous striae, buffalo hump/dorsocervical fat pad, supraclavicular fat pad, abd obesity, moon facies, ecchymoses, hirsutism, acne
- Conn’s Syndrome (hyperaldosteronism)
- pheochromocytoma
this type of HTN is curable with surgery
Cushing’s syndrome
signs/sx
- DM, HTN
- abnl fat deposition: central obesity, moon facies, dorsocervical and supraclavicular fat pads
- skin abnormalities
- violaceous striae, easy buising, acne, hirsutism
- psych abnormalities
- menstrual irregs, decr lebido in men
- myopathy
- osteoporosis
- inf (reactivated TB, candidiasis, etc)
regulation of ACTH and cortisol
hypothal: CRH → pit: ACTH → adrenal: cortisol
- circadian pattern of release (highest cortisol in early am); sleep-wake cycle can alter release pattern
- incr cortisol seen in physio and patho states
- physio: stress, strenuous exercise, preg
- patho: pseudo-Cushing’s, ACTH-dep CD, ACTH-indep CD, exogenous ACTH
pseudo-Cushing’s syndrome
NOT primary overproduction of ACTH
instead, some stressor triggering overproduction of CRH/ACTH/cortisol
- exercise
- pregnancy
- uncontrolled diabetes
- sleep apnea
- pain
- alcoholism
- psych disorders
- stress
- extreme obesity
tx: TREAT UNDERLYING CONDITION!!!
Cushing’s Syndrome
dx
- 24h urine free cortisol
- dexamethasone suppression test (low dose)
- high dose test used to see where ACTH is coming from
- midnight cortisol
- midnight salivary cortisol
etiologies of Cushing’s Syndrome
ACTH-dependent (either form pit or from ectopic source)
- Cushing’s Disease (pit) 68
- ectopic ACTH syndrome (ex. sm cell lung cancer)
ACTH-independent (low ACTH, from adrenal glands)
- adrenal adenoma 10
- adrenal carcinoma 8
- micronodular hyperplasia
- macronodular hyperplasia
**MEDICATION (most common cause of Cushing’s)
- oral, IM, inhaled, skin cream (rare)
Cushing’s Syndrome localization
Cushing’s Disease : from pituitary
Cushing’s Syndrome : from any source (even exogenous)
primary adrenal : over prod of cortisol
- will actually dampen CRH and ACTH production through neg feedback
sooo. ..measure plasma ACTH to diagnose location - if ACTH low → issue is adrenal glands (ACTH independent disease)
- if ACTH high → issue is either pituitary or ectopic (ACTH-producing tumor)
to differentiate between pituitary or ectopic…
CRH stimulation test
- no change in ACTH → ectopic source
- shrink/decr in pit gland activity → pituitary source
high dose dexamethasone suppression test
- no change in ACTH → ectopic source
- depression of ACTH/cortisol prod → pituitary source
bilat inf petrosal sinus sampling (measure amt of ACTH in sinus vs in periphery)
- more ACTH in periph → ectopic source
dexamethasone suppression tests
low dose
- 1mg dex at 11pm, pl cortisol check at 8am
- if pt has Cushing’s Syndrome (any cause), AM cortisol will not be suppressed
high dose
- 8gm dex at 8am
- if pt has Cushing’s Disease (pit source), AM cortisol will be suppressed to 50% baseline
- if ectopic production, cortisol UNSUPPRESSED
- if pt has Cushing’s Disease (pit source), AM cortisol will be suppressed to 50% baseline
ectopic ACTH production
- oat cell (sm cell) lung carcinoma
- thymoma
- pancr islet cell carcinoma
- carcinoid tumors (lung, gut, pancreas, ovary)
- thyroid medullary carcinomas
- pheochromocytoma and others
Conn’s Syndrome
(primary mineralocorticoid excess)
etiology
clinical pres
- bilat adrenal hyperplasia 60
- aldosterone producing adrenal adenoma 40
- adrenal carcinoma 1
- glucocorticoid remediable hyperaldosteronism
presentation
- HTN
- hypoK
- metabolic acidosis
RAAS system graphic
remember: NO ROLE FOR THE PITUITARY
dx of primary hyperald
tx
- HIGH aldosterone level w LOW renin level
- salt loading (oral or IV) to try to suppress aldosterone
- localization
- CT scan of adrenal glands; adrenal vein sampling
tx
- unilateral adenoma? surgical resection
- cant operate? medical tx
- bilat hyperplasia? medical tx
medical therapy = SPIRONOLACTONE (aldosterone antagonist)
- anti-androgen (side effect: gynecomastia in men)
- also used for PCOS for this effect!
- K sparing diuretic
adrenal (cortex) insufficiency
types x3
dx: screening/confirmation
how to distinguish between primary and secondary adrenal insuff
- primary: Addison’s disease
- lose all three layers of cortex → loss of mineralocorticoid, glucocorticoid, androgens
- secondary (pituitary)
- loss of glucocorticoid >>> loss of androgen
- RAAS is intact (bc pituitary has no role here!!!)
- tertiary (hypothalmic)
dx
- screening: morning cortosol level (not good test)
-
confirmation: cortrosyn or cosyntropin stim test (synth ACTH)
- WONT tell you whether its a pit problem or an adrenal gland prob…why? if the issue is pit, why would the adrenals not respond to synth ACTH?
- if you dont have ACTH stimulating the adrenal gland daily, the adrenals deteriorate → i.e. won’t respond to synth ACTH in this case
- sooo…how do you tell if its primary or secondary?
- check ACTH level (not super helpful)
- check RAAS (check K - will be high in primary! in secondary, K will be ok)
adrenal insufficiency
key signs/sx
-
cortisol deficiency
- wt loss, fatigue, weakness
- anorexia, n/v, abd pain
- fasting hypoglycemia, inability to excrete free water
- decr responsiveness to catecholamines
-
mineralocorticoid deficiency (in PRIMARY)
- inability to conserve Na/waste K → hypoNa, hyperK, dehydration, hypotn, azotemia, decr CO
-
lack of androgenic steroids
- lack of axillary/pubic hair in women
-
excess ACTH and MSH (in PRIMARY)
- hyperpigmentation
why does adrenal insuff cause hyperpigmentation
ACTH made up 39 a.a.s
- regulates adrenal cortex, synth of adrenocorticosteroids
- alphaMSH (first 13 aa of ACTH) → stim melanocytes! darkens skin
therefore, overprod of ACTH can lead to hyperpig due to alphaMSH
etiology of primary adrenal insuff
- autoimmune (most common cause in U.S.)
- infectious
- hemorrhage
- metastatic disease
- drugs (either decr synth or incr catabolism)
- familial
adrenal hormone synthesis pathways
cholesterol → pregnenolone → progesterone (precursor for all 3 pathways)
- mineralocorticoid pathway → aldosterone
- glucocorticoid pathway → cortisol, hydrocortisone
- adrenal androgen pathway → androstenedione, DHEA
each layer of cortex makes the hormones it does due to more/less levels of the enzymes req for each pathway
congenital adrenal hyperplasia
most common type
dx
disorders of adrenal steroid biosynthesis tesulting in glucocorticoid and mineralocorticoid deficiencies
- bc of deficient cortisol synth, ACTH levels are increased → adrenal hyperplasia → overprod of steroids preceding blockage
- all AUTOSOMAL RECESSIVE
- “classic” syndrome at birth
- “non-classic” dx later
most common: CYP21 (21-hydroxylase) deficiency (95%)
- just makes a ton of male hormones
- dx: w HIGH levels of 17-hydroxyprogesterone level
11beta hydroxylase deficiency
- cant make cortisol
- make tons of DOC (most potent mineralocorticoid) → HTN, hypoK
- adrenal androgen excess
17alpha hydroxylase deficiency
- cant make cortisol
- mineralocorticoid excess
- adrenal androgen deficiency (males → pseudoherm)
