Adrenal Pathophysiology

Question 1

Cushing’s syndrome

Answer 1

having excess cortisol secretion regardless of cause or source

Question 2

The most common cause of Cushing’s

Answer 2

iatrogenic from exogenous glucocorticoid use

Question 3

3 Pathologic derangements of Cushing’s

Answer 3

loss of diurnal variation of cortisol secretion, autonomy from central ACTH control (loss of feedback inhibition), excess cortisol secretion

Question 4

T/F Iatrogenic Cushing’s is ACTH independent

Answer 4

T

Question 5

Most common Cushing’s ACTH dependent

Answer 5

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

Question 6

Most common ectopic ACTH syndromes

Answer 6

lung cancers

Question 7

Most common ACTH independent Cushing’s other than iatrogenic

Answer 7

Adrenal adenoma, adrenal carcinoma

Question 8

Target of cortisol action

Answer 8

glucocorticoid nuclear receptor

Question 9

Where is the glucocorticoid receptor?

Answer 9

almost all cells

Question 10

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

Answer 10

long time –> nuclear transcription affected

Question 11

3 metabolic derangements due to excess glucocorticoids

Answer 11

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

Question 12

Effects of fat metabolism: fat deposition pattern

Answer 12

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

Question 13

Effects of cortisol excess

Answer 13

impaired immunity, increased clotting factors, cataract formation, proximal myopathy, osteoporosis, fat redistribution, htn, PE, thin skin, bruising, striae, acne, hirsutism, mood lability

Question 14

ACTH dependent Cushing’s is characterized by _________

Answer 14

bilateral adrenal hyperplasia

Question 15

Excess of cortisol on mineralocorticoid and androgens

Answer 15

htn, hypokalemia, increased testosterone in females, abnormal menses

Question 16

Severe hypokalemia is associated more with _____ ACTH production

Answer 16

ectopic

Question 17

T/f negative feedback is still somewhat intact in ACTH dependent Cushings

Answer 17

T –> pituitary adenoma cells do not listen to the feedback but the feedback is still there

Question 18

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

Answer 18

F –> more worried about malignant adrenal tumor

Question 19

ACTH independent Cushing’s has high/low ACTH

Answer 19

low ACTH because negative feedback from elevated cortisol is still intact

Question 20

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

Answer 20

measure late night salivary cortisol

Question 21

How do we test autonomy form ACTH control?

Answer 21

1mg dexamethasone suppression test

Question 22

How do we measure cortisol excess?

Answer 22

24h urinary free cortisol

Question 23

What does the DST indicate?

Answer 23

inappropriate cortisol secretion but does not tell you the source –> normally should be low b/c DST should negative feedback on cortisol production

Question 24

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

Answer 24

3

Question 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?

Answer 25

pituitary adenoma

Question 26

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

Answer 26

adrenal

Question 27

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

Answer 27

pituitary or ectopic source

Question 28

ACTH is suppressed if source is ___

Answer 28

exogenous glucocorticoids

Question 29

Tx of adrenal adenoma

Answer 29

remove adrenal/cortex

Question 30

Tx of pituitary adenoma

Answer 30

trans sphenoidal hypophysectomy

Question 31

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

Answer 31

T --> might need to steroid taper as well

Question 32

Addison's

Answer 32

primary adrenal failure --> cortisol deficiency

Question 33

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

Answer 33

90

Question 34

Clinical marker of Addison's/Cortisol deficiency

Answer 34

elevated ACTH

Question 35

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

Answer 35

T

Question 36

What laboratory findings would you expect with Addison's

Answer 36

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

Question 37

Clinical findings in Addison's

Answer 37

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

Question 38

Addison's etiology

Answer 38

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

Question 39

Waterhouse-Friderichsen syndrome

Answer 39

meningococcemia caused hypotension and bleeding into adrenals

Question 40

Drugs that can cause addison's

Answer 40

aminoglutethimide, ketoconazole, etomidate, rifampin, phenytoin

Question 41

Most common autoimmune Ab in Addison's

Answer 41

21 hydroxylase Ab

Question 42

Dx of Addison's

Answer 42

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

Question 43

T/F if hypotensive with strong clinical suspicion of Addisons, should start treating immediately while assaying

Answer 43

T --> give dexamethasone becuase wont interfere with cortisol assay

Question 44

Addisonian Crisis

Answer 44

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

Question 45

Etiology of addisonian/adrenal crisis

Answer 45

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

Question 46

Tx for adrenal crisis

Answer 46

saline IV, dexamethasone, monitor electrolytes and bp

Question 47

Primary hyperaldosteronism

Answer 47

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

Question 48

Pituitary apoplexy

Answer 48

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

Question 49

Primary hyperaldosteronism and potassium

Answer 49

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

Question 50

Screening for primary hyperaldosteronism

Answer 50

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

Question 51

Diff Dx of Primary hyperaldosteronism

Answer 51

benign adrenal adenoma or bilateral adrenal hyperplasia

Question 52

Dx of Primary hyperaldosteronism

Answer 52

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

Question 53

Tx of Primary hyperaldosteronism

Answer 53

surgical resection for unilateral, mineralocorticoid antagonist if bilateral

Question 54

T/F adrenal adenomas often cause androgen excess

Answer 54

F --> efficient at secreting cortisol

Question 55

Androgen excess in men

Answer 55

reduced gnrh

Question 56

Androgen excess in women

Answer 56

hirsutism, baldness, menstrual irregularity

Question 57

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

Answer 57

T

Question 58

Pheocromocytoma

Answer 58

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

Question 59

T/F pheocromocytomas are associated with familial syndromes

Answer 59

T --> 15%

Question 60

T/F pheocromocytomas are associated with familial syndromes

Answer 60

T --> 15%