Adrenal pathophys Flashcards

1
Q

adrenal zone producing aldosterone

A

zona glomerulosa (outermost)

  • deficient in 17 alpha hydroxylase (no cortisol or androgens)
  • not regulated by ATCH
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2
Q

adrenal zones producing androgens and cortisol

A

zona fasiculata and reticularis (innermost zone of the cortex)
- regulated by ATCH, atrophies in its absence, hypertrophies in its excess

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3
Q

adrenal zone producing catecholamines

A

medulla

- NE –> E conversion

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4
Q

key enzymes of steroid biosynthesis

A
  • CYP11A, B1, B2

- - Cyp P450 scc, c11, aldo

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5
Q

adrenal androgens

A

androstendione
DHEA
DHEA sulfate

these have very little direct biological affect, converted to T and DHT in periphery

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6
Q

factors that affect cortisol secretion

A

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
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7
Q

regulation of aldosterone

A
  • RAAS system, most directly renin

- renin is measured to indicate primary or secondary (kidney-related) aldosterone issues

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8
Q

adrenal insufficiency clinical presentation

A

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
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9
Q

adrenal insufficiency causes

A

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
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10
Q

type 1 polyglandular autoimmune syndrome

A
  • rare
  • infancy
  • recessive AIRE mutation

sx:

  • apleenism
  • candidiasis susceptibility
  • hypO-PTH
  • Addison’s
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11
Q

type 2 polyglandular autoimmune syndrom

A
  • more common
  • usually adults
  • polygenic

sx (2+):

  • Addison’s
  • T1DM
  • Hashimoto’s thyroiditis (hypO-T3/T4)
  • premature ovarian failure
  • pernicious anemia
  • vitiligo
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12
Q

ACTH stim test primary and secondary adrenal insufficiency

A
  • 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
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13
Q

Cushing’s syndrome

A
  • 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%
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14
Q

Cushing’s disease

A
  • subset of Cushing’s syndrome
  • d/t excess pituitary ACTH
  • ~80%
  • 5:1 F>M
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15
Q

pseudo-Cushing’s

A
  • 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
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16
Q

initial testing for glucocorticoid excess

A
  • overnight dexamethasone screening test

- ACTH

17
Q

definitive testing hypercortisolism

A
  • 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)
18
Q

mineralocorticoid excess clinical picture

A
  • recent onset htn
  • – esp 30-50 y/o, F>M 2:1
  • refractory htn
  • volume expansion
  • edema
  • hypO-K
  • metabolic ALKalosis
19
Q

primary aldosteronism ddx

A

most common:

  • adenoma (typically unilateral)
  • bilateral hyperplasia
  • can be distinguished by CT or MRI

others:

  • carcinoma
  • glucocorticoid-suppressible hyperaldosteronism
20
Q

secondary hyperaldosteronism ddx

A

usually
- renovascular htn

rarely
- renin tumors

21
Q

tx mineralocorticoid excess

A
  • surgery usually definitive, where applicable (tumors)

- aldosterone antagonists: aldactone, eplerenone

22
Q

catecholamine excess clinical picture

A
  • 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

23
Q

ddx catecholamine excess

A
  • usually adrenal pheochromocytoma
  • exogenous intake
  • extra-adrenal tumor/pheo
24
Q

dx pheochromocytoma

A
  • 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
25
Q

tx pheo

A
  • surgery
  • pre-op alpha antagonists x1-2 week
  • beta blockers x days or during surgery; if before alpha, unopposed alpha –> worsening htn
26
Q

exogenous cortisol tx adjustment during stress, surgery, illness

A

increase, as body cannot physiologically increase on its own

27
Q

MEN1

A
  • hyper-PTH
  • facial angiofibromas
  • gastrinomas, insulinomas
  • pituitary adenomas (prolactin > GH > non-func > ACTH)
  • carcinoid tumors
  • adrenal adenomas
  • sub-Q lipomas
  • collagneomas
28
Q

MEN2A

A
  • hyper-PTH
  • medullary thyroid cancer
  • pheochromocytoma

most common MEN2

29
Q

MEN2B

A
  • medullary thyroid cancer
  • pheo
  • marfanoid
  • lips, tongue, conjunctiva neuromas
  • intestinal ganglioneuromas w/ constipation and diarrhea
  • (no hyper-PTH)
30
Q

order of zones of cortex

A

“GFR”
glomerulosa - mineralocorticoids
fasiculata - androgens, corticosteroids
reticularis - androgens, corticosteroids

31
Q

chromaffin cells

A

adrenal medula

epi, NE production

32
Q

yellow adrenal tumors

A

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
33
Q

autoimmune adrenalitis

A

most common cause of Addison’s disease in developed countries (TB worldwide)

histology

  • immune infiltrates
  • collapsed connective tissue
  • irregularly shrunken
  • intact medulla
34
Q

TB adrenalitis

A

most common cause of Addison’s disease worldwide

histology
- caseating granulomas