Adrenal Disorders 2

Question 1

What could a tumour in the adrenal gland lead to?

Answer 1

Too much cortisol
Increase the amount of fat you store and reduces protein sore ; switches off protein synthesis
If you injure, you bruise and don’t heal
Fat deposited in random places
Skin tears as there is not enough protein
Muscles become weaker

Question 2

What are clinical features of Cushing’s

Answer 2

Too much cortisol
Centripetal obesity
Moon face and buffalo hump
Proximal myopathy
Hypertension and hypokalaemia
Red striae, thin skin and bruising
osteoporosis, diabetes

Question 3

What are causes of Cushing’s

Answer 3

Taking too many steroids e.g. pregnenolone

Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
adrenal adenoma secreting cortisol

Question 4

What investigations can you do to determine the cause of Cushing’s syndrome

Answer 4

24 h urine collection for urinary free cortisol
Blood diurnal cortisol levels
(cortisols usually highest at 9am and lowest at midnight, if asleep)
Low dose dexamethasone suppression test

Question 5

What is the low dose dexamethasone suppression test

Answer 5

0.5 mg 6 hourly for 48 hrs
Dexamethasone = artificial steroid

Normals will suppress cortisol to zero
Any cause of Cushing’s will fail to suppress

Question 6

What is medication that can be given for Cushings

Answer 6

Enzyme inhibitors
Receptor blocking drugs

Metyrapone
Ketoconazole
Osilodrostat

Question 7

What can be used in Cushings syndrome to combat excess cortisol

Answer 7

Inhibitors of steroid biosynthesis:
metyrapone - Inhibition of 11b-hydroxylase
ketoconazole

Question 8

What can be used in Conn’s syndrome to combat excess aldosterone

Answer 8

MR antagonist:
spironolactone, epleronone

Question 9

What is the action and mechanism of metyrapone

Answer 9

Inhibition of 11b-hydroxylase

steroid synthesis in the zona fasciculata [and reticularis] is arrested at the 11-deoxycortisol stage

11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland.

Question 10

When is metyrapone used

Answer 10

Control of Cushing’s syndrome prior to surgery.
- adjust dose (oral) according to cortisol (aim for mean serum cortisol 150-300 nmol/L)
- improves patient’s symptoms and promotes better post-op recovery (better wound healing, less infection etc)
Control of Cushing’s symptoms after radiotherapy (which is usually slow to take effect)

Question 11

Side effects of metyrapone?

Answer 11

Hypertension on long-term administration-deoxycorticosterone accumulates in z. glomerulosa; it has aldosterone-like (mineralocorticoid) activity, leading to salt retention and hypertension.

Hirsutism-Increased adrenal androgen production
in women

Question 12

What is the mechanism of ketoconazole and what are its uses

Answer 12

main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity

at higher concentrations, inhibits steroidogenesis – off-label use in Cushing’s syndrome

Mainly blocks
17a hydroxylase,
inhibiting cortisol
production

treatment and control of symptoms prior to surgery for Cushings
- orally active

Question 13

What are the side effects to ketoconazole

Answer 13

Liver damage - possibly fatal - monitor liver function weekly, clinically and biochemically

Question 14

How is Cushing’s treated?

Answer 14

Depends on cause
Pituitary surgery (transsphenoidal hypophysectomy)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

Question 15

What is Conn’s syndrome

Answer 15

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

Question 16

What does aldosterone do?

Answer 16

Controls blood pressure, sodium and lowers potassium

Question 17

What is the diagnosis of Conn’s syndrome?

Answer 17

Primary hyperaldosteronism

Renin - angiotensin system should be suppressed (exclude secondary hyperaldosteronism)

Question 18

What is the mechanism of spironolactone

Answer 18

Primary hyperaldosteronism (Conn’s syndrome)

Converted to several active metabolites, including canrenone, a competitive antagonist of the mineralocorticoid receptor (MR).

Blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic).

Orally active
Highly protein bound and metabolised in the liver

Question 19

What are the side effects of spironolactone

Answer 19

Menstrual irregularities (+ progesterone receptor)
Gynaecomastia (- androgen receptor)

Question 20

What is epleronone

Answer 20

Also a mineralocorticoid receptor (MR) antagonist
Similar affinity to the MR compared to spironolactone
Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated

Question 21

What is Phaeochromocytomas

Answer 21

These are tumours of the adrenal MEDULLA which secrete catecholamines
(adrenaline and nor-adrenaline)

Question 22

What are the clinical features of

Answer 22

Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions

Severe hypertension can cause myocardial infarction or stroke

High adrenaline can cause ventricular fibrillation + death

Thus this is a medical emergency