adrenals

Question 1

what is Cushing’s syndrome

Answer 1

too much cortisol (hypersecretion of cortisol from adrenal cortex)

Question 2

clinical features of Cushing’s disease

Answer 2

too much cortisol, centripetal obesity (lemon on sticks), moon face and buffalo hump, proximal myopathy, hypertension and hypokalaemia, red striae (not making protein), thin skin (poor wound healing), bruising, osteoporosis, diabetes

Question 3

4 causes of Cushing’s syndrome

Answer 3

taking too many steroids (glucocorticoids; most common cause), pituitary dependent (Cushing’s disease), ectopic ACTH from lung cancer, adrenal adenoma secreting cortisol

Question 4

what is done to determine cause of Cushing’s syndrome

Answer 4

24 hour urine collection for urinary free cortisol; blood diurnal cortisol levels; low dose dexamethaone suppression test

Question 5

diurnal rhythm of cortisol: normal vs Cushing’s

Answer 5

normal: usually highest at 9am and lowest at midnight, if asleep; Cushing’s: remain high (so at 9am normal level, but when asleep still very high)

Question 6

what is a low dose dexamethaone suppression test: normal vs Cushing’s

Answer 6

0.5mg 6 hourly for 48 hours of artificial steroid; normal: suppress cortisol to zero; Cushing’s: failure to suppress (for all causes)

Question 7

diagnosis of Cushing’s using low dose dexamethaone suppression test (LDDST)

Answer 7

basal (9am) cortisol of 800 nM; at end of LDDST, 680 nm

Question 8

Cushing’s treatment

Answer 8

pharmacological manipulation of steroids

Question 9

2 examples of pharmacological manipulation of steroids to treat Cushing’s syndrome

Answer 9

enzyme inhibitors, receptor blocking drugs

Question 10

which 2 drugs are used to inhibit cortisol biosynthesis to treat Cushing’s syndrome before operation (wound healing and recovery)

Answer 10

metyrapone, ketoconazole

Question 11

how does metyrapone treat Cushing’s syndrome before operation

Answer 11

inhibits 11B-hydoxylase used in steroid biosynthesis (converts 11-deoxycortisol to cortisol; also convertes 11-deoxycorticosterone to corticosterone); causes build up of intermediates as no negative feedback

Question 12

where does steroid synthesis occur in adrenals, and is subequently arrested at 11-deoxycortisol stage

Answer 12

zona fasciculata (and reticularis)

Question 13

when is metyrapone used to control Cushing’s syndrome

Answer 13

prior to surgery or after radiotherapy (usually slow to take effect, so used to provide symptomatic relief in interim)

Question 14

why is metyrapone used to control Cushing’s syndrome prior to surgery and how is the dose adjusted

Answer 14

improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc.); adjust oral dose according to cortisol levels in blood

Question 15

effects of metyrapone on ACTH secretion, plasma deoxycortisol levels and adrenal andorgen production in women

Answer 15

all increase due to build up of intermediates, with latter causing hirsutism

Question 16

effect of deoxycorticosterone accumulation in zona glomerulosa following metyrapone treatment

Answer 16

aldosterone-like (mineralocorticoid) activity, so leads to salt retention and hypertension

Question 17

2 unwanted actions of metyrapone

Answer 17

hypertension on long-term admission, hirsutism (unwanted, male-pattern hair growth in women)

Question 18

how does ketoconazole treat Cushing’s syndrome

Answer 18

inhibits steroidogenesis at higher concentrations by inhibiting 17a-hydroxylase (so blocks production of all glucocorticoids, mineralocorticoids and sex steroids)

Question 19

uses of ketoconazole to treat Cushing’s syndrome and administration

Answer 19

similar to metyrapone (control of symptoms prior to surgery); orally active

Question 20

unwanted action of ketoconazole when treating Cushing’s syndrome, and how is this risk mitigated

Answer 20

liver damage (possibly fatal); liver function monitored weekly, clinically and biochemically

Question 21

what does Cushing’s syndrome treatment depend on

Answer 21

cause of syndrome

Question 22

treatment for Cushing’s disease

Answer 22

pituitary surgery (transsphenoidal hypophysectomy)

Question 23

other treatments for Cushing’s syndrome

Answer 23

bilateral adrenalectomy, unilateral adrenalectomy for adrenal mass