adrenal pathophys

Question 1

AIRE-deficiency causes autoimmune polyendocrine snydrome type 1 (APS-1)

Answer 1

addisons disease

Question 2

chronic low levels of cortisol and aldosterone

Answer 2

addisons disease

Question 3

addisons disease causes

Answer 3

APS-1
metastatic tumors
medication induced (ketoconazole, phenytoin)

Question 4

chronic primary adrenal insufficiency

Answer 4

addisons disease

Question 5

caused by hypercortisolism or chronic GC use

Answer 5

cushing syndrome

Question 6

cushing syndrome causes

Answer 6

iatrogenic cushing syndrome- chronic use of steroids
adrenal atrophy

pituitary cushings disease- tumor in anterior pituitary releases high levels of ACTH
bilateral adrenal hyperplasia

adrenal cushing syndrome- tumor in anterior adrenal cortex secretes cortisol independently of ACTH
nodular hyperplasia

paraneoplastic cushing syndrome- cancer outside of HPA axis secrets ACTH

Question 7

MOA- inhibits adrenal and gonadal steridogenesis at high doses

Answer 7

ketoconazole

Question 8

MOA- decrease cortisol, corticosterone, aldosterone

Answer 8

11B-hydroxylase inhibitors:
metyrapone (metopirone)
etomidate (amidate)
isturisa (osilodrostat)

Question 9

MOA- inhibits steroidogenesis
decreases cortisol production

Answer 9

adsrenolytic agent:
mitotane (lysodren)

Question 10

MOA- antagonist for GC and progesterone receptors
may increase ACTH and cortisol production

Answer 10

mifepristone (korlym)

Question 11

MOA- doapime receptor agonist
inhibits ACTH secretion

Answer 11

cabergoline

Question 12

MOA- inhibits ACTH and GC secretion
decreases glucagon and insulin secretion

Answer 12

somatostatin analog:
pasireotide (signifor)

Question 13

MOA- MC receptor antagonist
competitively inhibits aldosterone
increases excretion of water and sodium
decreases potassium excretion and BP

Answer 13

spironolactone (aldactone)

Question 14

MOA- decrease sodium reabsorption in renal collecting tubules and ducts
decrease potassium excretion

Answer 14

epithelial sodium channel blockers:
amiloride
triamterene (dyrenium)

Question 15

cortisol synthesis

Answer 15

hypothalamus releases CRH in response to stress, this stimulates the release of ACTH from corticotroph cells
ACTH binds to MC2R on zona fasciculate cells of the adrenal cortex, when stimulated it synthesizes and releases cortisol

Question 16

glands for cortisol synthesis

Answer 16

adrenal cortex: aldosterone, cortisol, testosterone, estrogen
adrenal medulla: EPI, NE (catecholamines)

Question 17

EPI and NE release in response to

Answer 17

ACh

Question 18

aldosterone is released in response to

Answer 18

angiotensin 2 and potassium
ACTH

stimulates mineralocorticoid receptor

Question 19

cortisol is released in response to

Answer 19

ACTH

stimulates glucocorticoid receptor

Question 20

testosterone and estrogen are released in response to

Answer 20

FSH and LH

stimulates androgen receptor and estrogen receptor

Question 21

enzymes involved in cortisol synthesis

Answer 21

11B-hydroxylase
21-hydroxylase
aldosterone synthase
17,20 lyase
aromatase

Question 22

glucocorticoid receptor activation

Answer 22

cortisol enters cell and binds to an inactive GR, binding causes a conformational change and HSPs dissociation, activation of receptor

Question 23

regulation of gene expression

Answer 23

the cortisol-GR complex binds to GREs (DNA sequence) GR can up regulate or down regulate gene expression depending on the gene and co-regulatory proteins involved
it recruits coactivators and coexpressors that influence RNA polymerase 2 activity

Question 24

prednisolone structure

Answer 24

double bonds

Question 25

mifepristone structure

Answer 25

double bonds methyl substituted ethyne group dimethylamine

Question 26

spironolactone structure

Answer 26

dihydrofuranone spiro center thither ketone

Question 27

fludrocorticoid structure

Answer 27

fluorine