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Flashcards in Adrenal Pathophysiology Deck (60):
1

Cushing's syndrome

having excess cortisol secretion regardless of cause or source

2

The most common cause of Cushing's

iatrogenic from exogenous glucocorticoid use

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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

4

T/F Iatrogenic Cushing's is ACTH independent

T

5

Most common Cushing's ACTH dependent

pituitary adenoma secreting ACTH followed by ectopic ACTH syndrome (tumor outside pituitary)

6

Most common ectopic ACTH syndromes

lung cancers

7

Most common ACTH independent Cushing's other than iatrogenic

Adrenal adenoma, adrenal carcinoma

8

Target of cortisol action

glucocorticoid nuclear receptor

9

Where is the glucocorticoid receptor?

almost all cells

10

How long will effects of disease last after a cure for Cushings?

long time --> nuclear transcription affected

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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

12

Effects of fat metabolism: fat deposition pattern

dewlap, buffalo hump, supraclavicular fat pads, moon facies --> central lipogenesis + muscle loss

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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

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ACTH dependent Cushing's is characterized by _________

bilateral adrenal hyperplasia

15

Excess of cortisol on mineralocorticoid and androgens

htn, hypokalemia, increased testosterone in females, abnormal menses

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Severe hypokalemia is associated more with _____ ACTH production

ectopic

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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

18

T/F frank/marked virilization of a woman is sign of Cushing's

F --> more worried about malignant adrenal tumor

19

ACTH independent Cushing's has high/low ACTH

low ACTH because negative feedback from elevated cortisol is still intact

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How do we measure loss of diurnal variation of cortisol secretion?

measure late night salivary cortisol

21

How do we test autonomy form ACTH control?

1mg dexamethasone suppression test

22

How do we measure cortisol excess?

24h urinary free cortisol

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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

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Cushing's is more likely if urinary cortisol is > ___X upper limit of normal

3

25

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

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Plasma ACTH should be low if Cushing's is from ___ source

adrenal

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Plasma ACTH should be normal/elevated if Cushing's is from ___

pituitary or ectopic source

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ACTH is suppressed if source is ___

exogenous glucocorticoids

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Tx of adrenal adenoma

remove adrenal/cortex

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Tx of pituitary adenoma

trans sphenoidal hypophysectomy

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T/F symptoms of hypercortisolism can take a year to resolve

T --> might need to steroid taper as well

32

Addison's

primary adrenal failure --> cortisol deficiency

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Typically ___% of cortex is destroyed prior to presentation of Addison's

90

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Clinical marker of Addison's/Cortisol deficiency

elevated ACTH

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T/F in Addision's all adrenal hormones can be lost

T

36

What laboratory findings would you expect with Addison's

hyponatremia (low aldosterone) and hyperkalemia (no K+ exchange), and hypertension (no cortisol and no mineralocorticoids)

37

Clinical findings in Addison's

hyperpigmentation, weight loss, muscle/joint pain, fatigue, nausea, hypoglycemia

38

Addison's etiology

autoimmune destruction (60% of cases), infectious (TB, fungus, HIV), bilateral hemorrhage/infarct, metastatic cancer, drugs

39

Waterhouse-Friderichsen syndrome

meningococcemia caused hypotension and bleeding into adrenals

40

Drugs that can cause addison's

aminoglutethimide, ketoconazole, etomidate, rifampin, phenytoin

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Most common autoimmune Ab in Addison's

21 hydroxylase Ab

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Dx of Addison's

early morning cortisol and ACTH (low cortisol, high ACTH), cosyntropin simulation testing, hypotension

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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

44

Addisonian Crisis

acute deficiency in cortisol and mineralocorticoids --> hypotension, shock, fatigue, fever, abdominal pain, hypoglycemia

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Etiology of addisonian/adrenal crisis

primary adrenal failure, acute illness, acute withdrawal of glucocorticoids, pituitary apoplexy

46

Tx for adrenal crisis

saline IV, dexamethasone, monitor electrolytes and bp

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Primary hyperaldosteronism

mineralocorticoid excess --> hypertension, hypokalemia, mild hypernatremia, metabolic alkalosis, muscle weakness can occur

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Pituitary apoplexy

large pituitary adenomas infarct -->acute headache and loss of normal pituitary function due to hemorrhage

49

Primary hyperaldosteronism and potassium

potassium may fall to severely low levels --> may be normal but usually severe K wasting

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Screening for primary hyperaldosteronism

persons under 30 with htn and no obesity/family hx // unexplained hypokalemia and hypertension //resistant htn

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Diff Dx of Primary hyperaldosteronism

benign adrenal adenoma or bilateral adrenal hyperplasia

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Dx of Primary hyperaldosteronism

early morning aldosterone:renin ratio (>20 usggestive), inappropriate aldosterone secretion after salt loading, CT/MRI

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Tx of Primary hyperaldosteronism

surgical resection for unilateral, mineralocorticoid antagonist if bilateral

54

T/F adrenal adenomas often cause androgen excess

F --> efficient at secreting cortisol

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Androgen excess in men

reduced gnrh

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Androgen excess in women

hirsutism, baldness, menstrual irregularity

57

T/F cushing's can cause elevated testosterone and dhea-s

T

58

Pheocromocytoma

tumor that secretes catecholamiens in adrenal medulla (chromaffin cells) --> tachycardia, HTN, headache, sweating

59

T/F pheocromocytomas are associated with familial syndromes

T --> 15%

60

T/F pheocromocytomas are associated with familial syndromes

T --> 15%