Adrenal Disorders

Question 1

What are the clinical features of Cushing’s

Answer 1

Excess cortisol (zona fasciculata)

Thin skin
Hypertension and hypokalaemia
Easy bruising, striae 
Moon face
Proximal myopathy 
Immunosuppression 
Centripetal obesity 
Osteoporosis, diabetes

Question 2

What are the causes of cushing’s

Answer 2

Excessive steroid use
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol

Question 3

What are the investigations done to determine the cause of Cushing’s syndrome

Answer 3

24hr urine collection for urinary free cortisol
Blood diurnal cortisol levels
Low dose dexamethasone suppression test

Question 4

When are cortisol levels highest and lowest

Answer 4

Highest at 9am and lowest at midnight if asleep

Question 5

Describe the low dose dexamethasone suppression test

Answer 5

Dexamethasone - artificial steroid
0.5mg 6 hourly for 48 hours
Normal people will suppress cortisol to 0 and those with Cushing’s will fail to do so

Question 6

What are the diagnostic cutoffs for Cushing’s diagnosis

Answer 6

Basal cortisol of 800nM (9am)

End of low does dexamethasone suppression test of 690nM

Question 7

How is Cushing’s treated pharmaceutically

Answer 7

Enzyme inhibitors of steroid biosynthesis

Metyrapone and ketoconazole

Question 8

What is the mechanism of action for metyrapone

Answer 8

Inhibition of 11beta-hydrolyxase, arresting steroid synthesis in the zone fasciculata (and reticularis) at the 11-doexycortisol stage

Question 9

What does 11b-hydroxylase do

Answer 9

Catalyses conversion of 11-deoxycorticosterone to corticosterone
Catalyses conversion off 11-deoxycortisol to cortisol

Question 10

What are the biochemical effects of metyrapone

Answer 10

Cortisol synthesis decreases
ACTH secretion increases
Plasma deoxycortisol increases

Question 11

What are the uses of metyrapone

Answer 11

Control of Cushing’s prior to surgery

Control of Cushing’s symptoms after radiotherapy (which is slow)

Question 12

Describe the use of metyrapone for controlling Cushing’s before surgery

Answer 12

Improves patients symptoms and promotes better post-op recovery (better wound healing, less infection)
Adjust the oral dose according to cortisol, aiming for mean serum cortisol 150-300 nmol/L

Question 13

What are the unwanted actions of metyrapone

Answer 13

Deoxycortisone accumulates in the glomerulosa, having aldosterone-like activity
Leads to salt retention and therefore hypertension
Hirutism

Question 14

What is the mechanism of action for ketoconazole

Answer 14

Blocks production of glucocorticoids, mineralocorticoids and sex steroids by inhibiting cytochrome P450
High conc. - inhibits steroidogenesis

Question 15

What are the uses of ketoconazole

Answer 15

Treatment and control of Cushing’s symptoms prior to surgery
Orally active
(Antifungal agent (withdrawn due to hepatotoxicity))

Question 16

What are the unwanted actions of ketoconazole and how are they controlled

Answer 16

Liver damage - monitor the liver function weekly. clinically and biochemically

Question 17

What are the non pharmaceutical methods of treating Cushing’s

Answer 17

Depends on cause
Pituitary surgery (trans-sphenoidal hypophysectomy)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

Question 18

What are the causes of Conn’s syndrome

Answer 18

Benign adrenal cortical tumour (zona glomerulosa)
Aldosterone in excess
Hypertension and hypokalaemia

Question 19

How is Conn’s syndrome diagnosed

Answer 19

Primary hyperaldosteronism

Renin-angiotensin system suppressed (except secondary hyperaldosteronism)

Question 20

How is Conn’s syndrome treated pharmaceutically

Answer 20

Receptor blocking drugs (MR antagonist)

Spironolactone and epleronone

Question 21

What are the uses of spironolactone

Answer 21

Primary hyperaldosteronism (Conn’s)

Question 22

How does spironolactone work

Answer 22

Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptors
Blocks sodium resorption and potassium excretion in the kidney tubules = potassium sparing diuretic

Question 23

What are the unwanted actions of spiromolactone

Answer 23

Menstrual irregularities (stimulates progesterone receptor)
Gynaecomastia (inhibits the androgen receptor)

Question 24

Describe epleronone

Answer 24

Drug used to treat Conn’s
Mineralocorticoid receptor antagonist
Similar affinity to the MR compared to spironolactone
Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated

Question 25

What are phaeochromocytomas

Answer 25

Tumours of the adrenal medulla that secrete catecholamines (A/NA)
10% extra-adrenal (sympathetic chain)
10% malignant
10% bilateral

Question 26

What are the clinical features of phaeochromocytomas

Answer 26

More common in certain inherited conditions
Hypertension in young people
Episodic severe hypertension (after abdominal palpation) - can cause MI or stroke
High adrenaline can cause ventricular fibrillation and death

Question 27

Describe how phaeochromocytomas are managed

Answer 27

Alpha blockade (+IV fluid)
Beta blockade in addition to prevent tachycardia
Eventually surgery