hyperadrenal disorders

Question 1

What are the clinical features of Cushing’s?

Answer 1

Too much cortisol.

Centripetal obesity.

Moon face + buffalo lump

proximal myopathy.

Hypertension and hypokalaemia.

red striae, thin skin and bruising.

Osteoporosis, diabetes.

Question 2

What can cause Cushing’s syndrome?

Answer 2

Taking too many steroids.

Pituitary dependent Cushing’s disease.

Ectopic ACTH from lung cancer.

Adrenal adenoma secreting cortisol.

Question 3

What investigations can be done to determine cause of Cushing’s syndrome?

Answer 3

24hr urine collection for urinary free cortisol.

Blood diurnal cortisol levels.

(cortisol usually highest at 9am, lowest at midnight if asleep).

Low dose dexamethasone suppression test.

Question 4

What effect does Cushings have of the diurnal rhythm of cortisol?

Answer 4

Cortisol is always high and doesn’t fluctuate according to time of day or sleeping/waking.

Question 5

How does the dexamethasone suppression test work?

Answer 5

0.5mg 6 hourly for 48 hours.

Normal person will have no cortisol afterwards.

Any form of Cushing’s will fail to suppress.

Question 6

How might Cushing’s be treated?

Answer 6

Enzyme inhibitors.

Receptor blocking drugs.

Pituitary surgery.

Bilateral adrenalectomy.

Unilateral adrenalectomy for adrenal mass.

Question 7

Name two important inhibitors of cortisol synthesis.

Answer 7

metyrapone, ketoconazole.

Question 8

outline the mechanism of action of metyrapone.

Answer 8

Inhibition of 11 beta-hydroxylase.

steroid synthesis in zona fasciculata arrested at 11-deoxycortisol stage.

Question 9

What are the effects of metyrapone administration?

Answer 9

Cortisol and corticosterone synthesis blocked.

ACTH secretion increased.

Plasma 11 deoxycortisol increased.

Question 10

How is Cushing’s syndrome controlled before surgery?

Answer 10

Adjust dose of metyrapone acccording to cortisol levels (aiming for 150-300nmol/L) - improve patient’s symptoms and promote better post-op recovery.

Question 11

Why is metryapone used after radiotherapy?

Answer 11

Control symptoms of Cushing’s syndrome till radiotherapy takes effect.

Question 12

What are the effects of high 11-deoxycorticosterone as a result of blocked corticosterone synthesis due to metryapone?

Answer 12

Accumulation in z. glomerulosa. Aldosterone like activity –> Salt retention and hypertension.

Question 13

What other effect might metyrapone have?

Answer 13

Increased adrenal androgen production in women.

Question 14

What are the unwanted actions of metyrapone?

Answer 14

Hypertension with long term administration.

Hirsutism.

Question 15

What are the main uses of ketoconazole?

Answer 15

Mainly antifungal agent.

At high concentrations inhibits steroidogenesis of cortisol.

Question 16

What is the mechanism of action of ketoconazole?

Answer 16

Inhibit cytochrome P450 - inhibit synthesis of aldosterone, corticosterone, cortisol, androgens.

Question 17

What are the uses of ketoconazole?

Answer 17

Treatment and control of symptoms of Cushing’s prior to surgery.

Question 18

What are the unwanted actions of ketoconazole?

Answer 18

Liver damage.

Question 19

What is Conn’s syndrome?

Answer 19

Excess aldosterone.

Benign adrenal cortical tumour.

Hypertension ans hypokalaemia.

Question 20

How is Conn’s syndrome diagnosed?

Answer 20

Blood test - high aldosterone, low renin.

Question 21

How is Conn’s syndrome treated with drugs?

Answer 21

Blocking of aldosterone receptor.

e.g. spironolactone, epleronone.

Question 22

What is the mechanism of action of spironolactone?

Answer 22

Converted to several active metabolitesm, e.g. canrenone - a competitve antagonist to mineralocorticoid receptor.

Blocks Na+ resorption and K+ excretion in kidney tubules.

Question 23

What are the unwanted actions of spironolactone?

Why?

Answer 23

Menstrual irregularities (progesterone receptor agonist)

Gynaecomastia (androgen receptor antagonist)

Not specific for mineralocorticosteroid receptor.

Question 24

How is epleronone different to spironolactone?

Answer 24

Less binding to androgen and progresterone receptors.

Question 25

What are phaeochromocytomas?

Answer 25

Tumours of adrenal medulla which secretes catecholamines - secrete NA and A

Question 26

What are the clinical features of a phaeo?

Answer 26

Hypertension in young people - can cause MI or stroke.

episodic severe hypertension (after abdominal palpation).

More common in certain inherited conditions.

Question 27

What is a potential complication of high adrenaline?

Answer 27

ventricular fibrillation + death.

Question 28

How is phaeo managed?

Answer 28

Surgery needed, but careful anaesthetic preparation due to potential hypertensive crisis - block effects of adrenaline.

Question 29

How can the effects of adrenaline be blocked prior to phaeo surgery?

Answer 29

Alpha blockade is first therapeutic step.

Patients may need IV fluid as alpha blockade commences.

Beta blockades added to prevent tachycardia.

Question 30

What % of phaeos are extra-adrenal, malignant, bilateral?

Answer 30

10%