Adrenal pathophys Flashcards
adrenal zone producing aldosterone
zona glomerulosa (outermost)
- deficient in 17 alpha hydroxylase (no cortisol or androgens)
- not regulated by ATCH
adrenal zones producing androgens and cortisol
zona fasiculata and reticularis (innermost zone of the cortex)
- regulated by ATCH, atrophies in its absence, hypertrophies in its excess
adrenal zone producing catecholamines
medulla
- NE –> E conversion
key enzymes of steroid biosynthesis
- CYP11A, B1, B2
- - Cyp P450 scc, c11, aldo
adrenal androgens
androstendione
DHEA
DHEA sulfate
these have very little direct biological affect, converted to T and DHT in periphery
factors that affect cortisol secretion
physiologic:
- episodic CRH –> ACTH –> cortisol
- circadian
homeostatic:
- fasting (contributes to bg control)
- physical stress
- illness
- surgery
- trauma
- starvation
- psychological stress
- severe anxiety
- depression
- mania
pathologic:
- CNS and pituitary disorders
- Cushing’s syndrome
- liver disease
- chronic renal failure
- alcoholism
- tumors such as pheochromocytomas
regulation of aldosterone
- RAAS system, most directly renin
- renin is measured to indicate primary or secondary (kidney-related) aldosterone issues
adrenal insufficiency clinical presentation
sx:
- fatigue
- vomiting
- diarrhea
- abd pain
- anorexia w/ weight loss
- malaise
- muscle/joint pain
- depression
dx:
- hypO-Na
- hypER-K
- hypoglycemia
- lymphocytosis (high)
- eosinophilia
- normochromic anemia
- plasma ATCH depends on primary or secondary
adrenal insufficiency causes
deficient production of glucocorticoids or mineralocorticoids
destruction or dysfunction of cortex (primary; Addison’s)
- previously most often d/t TB
- now d/t autoimmune adrenalitis, which is often comorbid w/ other autoimmune endocrine disease
- also metastasis (SCLC, melanoma), TB, fungal, hemorrhage
deficient ATCH (secondary) - often d/t glucocorticoid tx
type 1 polyglandular autoimmune syndrome
- rare
- infancy
- recessive AIRE mutation
sx:
- apleenism
- candidiasis susceptibility
- hypO-PTH
- Addison’s
type 2 polyglandular autoimmune syndrom
- more common
- usually adults
- polygenic
sx (2+):
- Addison’s
- T1DM
- Hashimoto’s thyroiditis (hypO-T3/T4)
- premature ovarian failure
- pernicious anemia
- vitiligo
ACTH stim test primary and secondary adrenal insufficiency
- insufficient stim in primary, since already max stim, unresponsive
- insufficient stim in secondary, since chronic ACTH deficiency has led to atrophy, hypO or unresponsive
- either way poor response predicts deficiency on “gold standard” HPA axis tests, i.e. insulin-induced hypOglycemia, metyrapone
- partial ACTH deficiency/decreased pituitary reserve or recent onset of secondary would lead to normal test, since atrophy has not occurred
Cushing’s syndrome
- chronic glucocorticoid excess d/t any cause
possible causes:
- Cushing’s disease (excess ACTH) ~80%
- ectopic ACTH e.g. tumor ~10%, often lacks classic clinical features d/t relatively recent onset; poor prognosis d/t most frequently being a result of metastatic disease
- primary adrenal tumors ~10%
Cushing’s disease
- subset of Cushing’s syndrome
- d/t excess pituitary ACTH
- ~80%
- 5:1 F>M
pseudo-Cushing’s
- suspected Cushing’s d/t signs of hypercortisolism
- abnormal dev suppression test - but false positive
d/t diseases causing hyper stress states
- alcoholism
- anorexia nervosa
- severe neuropsych incl depression, anxiety, mania
- withdrawal
initial testing for glucocorticoid excess
- overnight dexamethasone screening test
- ACTH
definitive testing hypercortisolism
- urinary free cortisol, 24 h
- late-night serum or salivary cortisol (absence of diurnal rhythm in Cushing’s)
- full dex suppression - dex q6h for 2 days, 24h urine collection at day 0 and day 2
- – low dose for hypercortisolism
- – high-dose to distinguish Cushing’s disease (pituitary; suppressible w/ high dose) vs ectopic ACTH (remains high)
mineralocorticoid excess clinical picture
- recent onset htn
- – esp 30-50 y/o, F>M 2:1
- refractory htn
- volume expansion
- edema
- hypO-K
- metabolic ALKalosis
primary aldosteronism ddx
most common:
- adenoma (typically unilateral)
- bilateral hyperplasia
- can be distinguished by CT or MRI
others:
- carcinoma
- glucocorticoid-suppressible hyperaldosteronism
secondary hyperaldosteronism ddx
usually
- renovascular htn
rarely
- renin tumors
tx mineralocorticoid excess
- surgery usually definitive, where applicable (tumors)
- aldosterone antagonists: aldactone, eplerenone
catecholamine excess clinical picture
- htn, generally paroxysmal, widely fluctuating
triad:
- headache
- palpitations
- sweating
other:
- flushing
- anxiety
- nausea
- fatigue
- weight loss
- abd and hest pain
may be precipitated by stress, exercise, anesthesia, or tyramine intake
ddx catecholamine excess
- usually adrenal pheochromocytoma
- exogenous intake
- extra-adrenal tumor/pheo
dx pheochromocytoma
- urinary cat: metanephrine, normetanephrine
- – high NE usually indicates extra-adrenal tumor, since NE not produced in adrenals
- CT or MRI
- – f/u w/ 131-I-MIBG PET or DOTA TATE for extra-adrenal pheo
tx pheo
- surgery
- pre-op alpha antagonists x1-2 week
- beta blockers x days or during surgery; if before alpha, unopposed alpha –> worsening htn
exogenous cortisol tx adjustment during stress, surgery, illness
increase, as body cannot physiologically increase on its own
MEN1
- hyper-PTH
- facial angiofibromas
- gastrinomas, insulinomas
- pituitary adenomas (prolactin > GH > non-func > ACTH)
- carcinoid tumors
- adrenal adenomas
- sub-Q lipomas
- collagneomas
MEN2A
- hyper-PTH
- medullary thyroid cancer
- pheochromocytoma
most common MEN2
MEN2B
- medullary thyroid cancer
- pheo
- marfanoid
- lips, tongue, conjunctiva neuromas
- intestinal ganglioneuromas w/ constipation and diarrhea
- (no hyper-PTH)
order of zones of cortex
“GFR”
glomerulosa - mineralocorticoids
fasiculata - androgens, corticosteroids
reticularis - androgens, corticosteroids
chromaffin cells
adrenal medula
epi, NE production
yellow adrenal tumors
yellow d/t being lipid rich
primary adrenocortical adenoma
- a cause of Cushing’s syndrome
pheochromocytoma
- excess catecholamines
- can also be brown, hemorrhagic, or necrotic
- excess chromaffin cells
autoimmune adrenalitis
most common cause of Addison’s disease in developed countries (TB worldwide)
histology
- immune infiltrates
- collapsed connective tissue
- irregularly shrunken
- intact medulla
TB adrenalitis
most common cause of Addison’s disease worldwide
histology
- caseating granulomas
