Hellekant Adrenal Cortex Physiology and Pharm

Question 1

What zone of the adrenal cortex produces aldosterone?

Answer 1

Glomerulosa

Question 2

What zone of the adrenal cortex produces glucocorticoids?

Answer 2

Fasiculata

Question 3

What zone of the adrenal cortex produces androgens?

Answer 3

Reticularis

Question 4

What causes the release of CRH? Where is it released from?

Answer 4

Stress and circadian rhythm cause CRH release from hypothalamus

Question 5

What promotes the production of aldosterone?

Answer 5

Angiotensin II (due to low BP), high K+, and high levels of ACTH

Question 6

What is the difference between aldosterone and cortisol in the HPA axis?

Answer 6

Cortisol has a negative feedback; aldosterone does not

Question 7

What cells does CRH bind? What is the receptor type CRH binds?

Answer 7

Binds Gs receptor on corticotrophs in the anterior pituitary

Question 8

CRH increases synthesis of what?

Answer 8

Preprohormone POMC - which is cleaved into ACTH and MSH and lipotropin

Question 9

What is POMC cleaved into?

Answer 9

ACTH, MSH, lipotropin

Question 10

How do melanocytes in the skin cleave POMC?

Answer 10

Into MSH, but not ACTH

Question 11

What cells synthesize ACTH?

Answer 11

Corticotrophs

Question 12

ACTH binds what receptor in adrenal cortical cells?

Answer 12

Melanocortin-2 receptor (MC2R)

Question 13

What kind of receptor is melanocortin receptor type 2? What binds it?

Answer 13

Gs coupled receptor; ACTH binds it

Question 14

ACTH binding MC2R promotes what?

Answer 14

Synthesis of side-chain cleavage enzyme (CYP11A) in adrenal cortex

Question 15

What is the function of the enzyme CYP11A1?

Answer 15

Conversion of cholesterol to pregnenolone

Question 16

What is the rate limiting step in adrenal steroid synthesis?

Answer 16

CYP11A - p450scc enzyme converting cholesterol to pregnenolone

Question 17

What receptor can ACTH bind on melanocytes?

Answer 17

Melanocortin 1 receptor

Question 18

Where in the cell are glucocorticoid receptors found?

Answer 18

Cytosol

Question 19

Where are mineralocorticoid receptors found?

Answer 19

Kidney, colon, sweat glands, heart, hippocampus, brown adipose

Question 20

Mineralocorticoid receptor has affinity for what?

Answer 20

Equal affinity for mineralocorticoid and glucocorticoids

Question 21

How to mineralocorticoid responsive tissues regulate the equal affinity of glucocorticoids and mineralocorticoids for the MR?

Answer 21

Mineralocorticoid responsive tissues (eg kidney) convert cortisol to inactive cortisone so there is no effect from cortisol

Question 22

What is the inactive form of cortisol?

Answer 22

Cortisone

Question 23

What is the active form, cortisol or cortisone?

Answer 23

Cortisol

Question 24

What increases the level of corticotropin binding globulin?

Answer 24

Estrogens and pregnancy

Question 25

What is the function of 11 beta hydroxylase 2?

Answer 25

Converts active glucocorticoid to inactive steroid (eg cortisol converted to cortisone)

Question 26

What tissues convert active glucocorticoids to inactive steroids?

Answer 26

Kidney, colon, salivary glands, placenta, fetus

Question 27

What enzyme can convert inactive steroids to active steroids?

Answer 27

11 beta hydroxylase type 1

Question 28

What tissues convert inactive steroid to active steroids?

Answer 28

Liver adipose, lung, vascular tissue, CNS, macrophages

Question 29

What is cushing disease?

Answer 29

Excess ACTH secretion, usually due to pituitary adenoma, resulting in hypercorticolism

Question 30

What is cushing syndrome?

Answer 30

Iatrogenic or due to primary glandular excess production of cortisol (adrenal tumors); increased cortisol, decreased ACTH

Question 31

What are the levels of ACTH and cortisol in cushing disease?

Answer 31

Both elevated

Question 32

What are the levels of ACTH and cortisol in cushing syndrome?

Answer 32

Elevated cortisol, decreased ACTH

Question 33

17 alpha hydroxylase is important in synthesis of what?

Answer 33

Glucocorticoids and androgens

Question 34

What region of the adrenal cortex lacks 17 alpha hydroxylase?

Answer 34

Zona glomerulosa; expresses aldosterone synthase instead

Question 35

What are the hormone level changes seen in congenital 21 hydroxylase def?

Answer 35

Decreased mineralocorticoids and glucocorticoids; elevated androgens; increased ACTH

Question 36

11 beta hydroxylase deficiency effects the adrenal cortex hormone levels how?

Answer 36

Low aldosterone, but elevated 11-deoxycorticosterone (weak mineralocorticoid), low cortisol, elevated sex hormones

Question 37

What CAH results in low aldosterone and cortisol, but high BP?

Answer 37

11 beta hydroxylase def; 11-deoxycorticosterone increases BP

Question 38

What CAH results in low cortisol and androgens, but elevated aldosterone?

Answer 38

17 alpha hydroxylase def

Question 39

What is Addison disease?

Answer 39

Adrenal insufficiency

Question 40

What are the symptoms of adrenal insuff?

Answer 40

Fatigue, anorexia, diarrhea, hyperpigmentation

Question 41

What is tetracosactide?

Answer 41

Synthetic ACTH

Question 42

What is the short ACTH stimulation test?

Answer 42

Give tetracosactide, measure cortisol one hour later; if increased above normal or 2x, adrenal gland is functioning

Question 43

When do you do the long ACTH stimulation test?

Answer 43

If the short test reveals cortisol is subnormal

Question 44

How is the long ACTH stimulation helpful in diagnosis?

Answer 44

Differentiates between primary and secondary adrenal insufficiency

Question 45

If tetracosactide is administered multiple times, and the cortisol level is measured at 1, 4, 8, and 24 hours and at all time points the cortisol levels are decreased, what is the diagnosis?

Answer 45

Primary adrenal insuff (Addison disease for example)

Question 46

If tetracosactide is administered multiple times, and the cortisol level is measured at 1, 4, 8, and 24 hours and there is a delayed but normal increase in cortisol, what is the diagnosis?

Answer 46

Secondary corticoadrenal insufficiency

Question 47

What does high levels of cortisol in the urine confirm?

Answer 47

Hypercortisolism

Question 48

If late night saliva test reveals increased cortisol, what does this mean?

Answer 48

Hypercortisolism

Question 49

How can hypercortisolism be tested?

Answer 49

24 hr urine measure of free cortisol; late night salivary cortisol; low dose dexamethasone test

Question 50

Once hypercortisolism is established, what is the next test?

Answer 50

Plasma ACTH levels are obtained

Question 51

What is the high dose dexamethasone used for?

Answer 51

High dose dexamethasone suppresses ACTH production by a pituitary adenoma (serum cortisol is lowered) but will not suppress ectopic ACTH

Question 52

If cortisol is still elevated after a high dose dexamethasone test, what is the cause?

Answer 52

Ectopic ACTH production

Question 53

What is cushing disease?

Answer 53

Cushing syndrome caused by pituitary tumor secreting ACTH

Question 54

What can the CRH stimulation test be used for?

Answer 54

Distinguish between pituitary tumors vs ectopic/adrenal tumors Pituitary tumors are responsive to CRH; ectopic and adrenal show no response

Question 55

What is the active form? Prednisolone or prednisone?

Answer 55

Prednisolone

Question 56

What happens when prednisone is the substrate for 11 beta hydroxydehydrogenase?

Answer 56

Prednisone (inactive) is converted to prednisolone (active)

Question 57

What is fludrocortisone?

Answer 57

Mineralocorticoid

Question 58

Why do glucocorticoids increase susceptibility to infection?

Answer 58

Lymphocyte levels decrease (T cells > B cells)

Question 59

What are the hematologic effects of glucocorticoids?

Answer 59

Lymphocytes, basophils, eosinophils decreased, neutrophils increased, erythrocytes increased

Question 60

What effect do glucocorticoids have on the CNS?

Answer 60

Lowers seizure threshold; behavioral changes

Question 61

What are the effects of glucocorticoids on the GI system?

Answer 61

Increased gastric acid and pepsin; decrease Ca++ absorption

Question 62

What is pasireotide? What is it used for?

Answer 62

Somatostatin analog; used for suppression of ACTH

Question 63

What is cabergoline?

Answer 63

D2 analog

Question 64

What is mifepristone?

Answer 64

Glucocorticoid receptor antagonist

Question 65

What is mitotan?

Answer 65

Glucocorticoid receptor antagonist

Question 66

What enzyme is inhibited by ketoconazole?

Answer 66

Cyp11A1

Question 67

What is the MOA of etomidate?

Answer 67

Inhibits 11 beta hydroxylase CYP11B1

Question 68

What is metyrapone?

Answer 68

Inhibits 11 beta hydroxylase CYP11B1 in adrenal gland

Question 69

Pituitary tumors that secrete ACTH usually express what receptors?

Answer 69

SST and D2

Question 70

What can mitotane be used for the treatment of?

Answer 70

Adrenal carcinoma