Adrenal Pathophysiology Flashcards
Cushing’s syndrome
having excess cortisol secretion regardless of cause or source
The most common cause of Cushing’s
iatrogenic from exogenous glucocorticoid use
3 Pathologic derangements of Cushing’s
loss of diurnal variation of cortisol secretion, autonomy from central ACTH control (loss of feedback inhibition), excess cortisol secretion
T/F Iatrogenic Cushing’s is ACTH independent
T
Most common Cushing’s ACTH dependent
pituitary adenoma secreting ACTH followed by ectopic ACTH syndrome (tumor outside pituitary)
Most common ectopic ACTH syndromes
lung cancers
Most common ACTH independent Cushing’s other than iatrogenic
Adrenal adenoma, adrenal carcinoma
Target of cortisol action
glucocorticoid nuclear receptor
Where is the glucocorticoid receptor?
almost all cells
How long will effects of disease last after a cure for Cushings?
long time –> nuclear transcription affected
3 metabolic derangements due to excess glucocorticoids
hyperglycemia, muscle loss, lipogenesis and insulin resistance
carbohydrate metabolism stimulates gluconeogenesis –> hyperglycemia, fat metabolism increases lipogenesis –> insulin resistance, protein catbolism from increased gluconeogenesis —> muscle loss
Effects of fat metabolism: fat deposition pattern
dewlap, buffalo hump, supraclavicular fat pads, moon facies –> central lipogenesis + muscle loss
Effects of cortisol excess
impaired immunity, increased clotting factors, cataract formation, proximal myopathy, osteoporosis, fat redistribution, htn, PE, thin skin, bruising, striae, acne, hirsutism, mood lability
ACTH dependent Cushing’s is characterized by _________
bilateral adrenal hyperplasia
Excess of cortisol on mineralocorticoid and androgens
htn, hypokalemia, increased testosterone in females, abnormal menses
Severe hypokalemia is associated more with _____ ACTH production
ectopic
T/f negative feedback is still somewhat intact in ACTH dependent Cushings
T –> pituitary adenoma cells do not listen to the feedback but the feedback is still there
T/F frank/marked virilization of a woman is sign of Cushing’s
F –> more worried about malignant adrenal tumor
ACTH independent Cushing’s has high/low ACTH
low ACTH because negative feedback from elevated cortisol is still intact
How do we measure loss of diurnal variation of cortisol secretion?
measure late night salivary cortisol
How do we test autonomy form ACTH control?
1mg dexamethasone suppression test
How do we measure cortisol excess?
24h urinary free cortisol
What does the DST indicate?
inappropriate cortisol secretion but does not tell you the source –> normally should be low b/c DST should negative feedback on cortisol production
Cushing’s is more likely if urinary cortisol is > ___X upper limit of normal
3
You suspect Cushing’s in apt. Urine cortisol is elevated and cortisol is elevated after DST. ACT is normal. What is hte source of Cushing’s?
pituitary adenoma
Plasma ACTH should be low if Cushing’s is from ___ source
adrenal
Plasma ACTH should be normal/elevated if Cushing’s is from ___
pituitary or ectopic source
ACTH is suppressed if source is ___
exogenous glucocorticoids
Tx of adrenal adenoma
remove adrenal/cortex
Tx of pituitary adenoma
trans sphenoidal hypophysectomy
T/F symptoms of hypercortisolism can take a year to resolve
T –> might need to steroid taper as well
Addison’s
primary adrenal failure –> cortisol deficiency
Typically ___% of cortex is destroyed prior to presentation of Addison’s
90
Clinical marker of Addison’s/Cortisol deficiency
elevated ACTH
T/F in Addision’s all adrenal hormones can be lost
T
What laboratory findings would you expect with Addison’s
hyponatremia (low aldosterone) and hyperkalemia (no K+ exchange), and hypertension (no cortisol and no mineralocorticoids)
Clinical findings in Addison’s
hyperpigmentation, weight loss, muscle/joint pain, fatigue, nausea, hypoglycemia
Addison’s etiology
autoimmune destruction (60% of cases), infectious (TB, fungus, HIV), bilateral hemorrhage/infarct, metastatic cancer, drugs
Waterhouse-Friderichsen syndrome
meningococcemia caused hypotension and bleeding into adrenals
Drugs that can cause addison’s
aminoglutethimide, ketoconazole, etomidate, rifampin, phenytoin
Most common autoimmune Ab in Addison’s
21 hydroxylase Ab
Dx of Addison’s
early morning cortisol and ACTH (low cortisol, high ACTH), cosyntropin simulation testing, hypotension
T/F if hypotensive with strong clinical suspicion of Addisons, should start treating immediately while assaying
T –> give dexamethasone becuase wont interfere with cortisol assay
Addisonian Crisis
acute deficiency in cortisol and mineralocorticoids –> hypotension, shock, fatigue, fever, abdominal pain, hypoglycemia
Etiology of addisonian/adrenal crisis
primary adrenal failure, acute illness, acute withdrawal of glucocorticoids, pituitary apoplexy
Tx for adrenal crisis
saline IV, dexamethasone, monitor electrolytes and bp
Primary hyperaldosteronism
mineralocorticoid excess –> hypertension, hypokalemia, mild hypernatremia, metabolic alkalosis, muscle weakness can occur
Pituitary apoplexy
large pituitary adenomas infarct –>acute headache and loss of normal pituitary function due to hemorrhage
Primary hyperaldosteronism and potassium
potassium may fall to severely low levels –> may be normal but usually severe K wasting
Screening for primary hyperaldosteronism
persons under 30 with htn and no obesity/family hx // unexplained hypokalemia and hypertension //resistant htn
Diff Dx of Primary hyperaldosteronism
benign adrenal adenoma or bilateral adrenal hyperplasia
Dx of Primary hyperaldosteronism
early morning aldosterone:renin ratio (>20 usggestive), inappropriate aldosterone secretion after salt loading, CT/MRI
Tx of Primary hyperaldosteronism
surgical resection for unilateral, mineralocorticoid antagonist if bilateral
T/F adrenal adenomas often cause androgen excess
F –> efficient at secreting cortisol
Androgen excess in men
reduced gnrh
Androgen excess in women
hirsutism, baldness, menstrual irregularity
T/F cushing’s can cause elevated testosterone and dhea-s
T
Pheocromocytoma
tumor that secretes catecholamiens in adrenal medulla (chromaffin cells) –> tachycardia, HTN, headache, sweating
T/F pheocromocytomas are associated with familial syndromes
T –> 15%
T/F pheocromocytomas are associated with familial syndromes
T –> 15%
