hyperadrenal disorders

Question 1

what are the clinical features of Cushing’s?

Answer 1

• too much cortisol
• centripetal obesity
• moon face
• buffalo hump
• proximal myopathy
• hypertension and hypokalaemia
• red striae, think skin
• osteoporosis and diabetes

Question 2

what are the causes of Cushing’s?

Answer 2

• taking too many steroids
• pituitary dependant Cushing’s disease
• ectopic ACTH (lung cancer)
• adrenal adenoma

Question 3

what investigations should you carry out to determine cause?

Answer 3

1. urinary free cortisol
2. blood diurnal cortisol analysis
3. low-dose decamethasone suppression test

Question 4

what would the blood diurnal cortisol analysis show in normal people/cushing’s people?

Answer 4

Normal: cortisol high in morning and low at night

Cushing’s: cortisol high all time

Question 5

what would the low-dose dexamethasone suppression test should in normal/ Cushing’s?

Answer 5

normal: dexamethasone suppresses cortisol to zero due to feedback inhibition
Cushing’s: any cause will fail to suppress

Question 6

what are the 2 types of Cushing’s treatment?

Answer 6

• drugs: metyrapone, Ketoconazole

- surgery

Question 7

what is the MoA of metyrapone?

Answer 7

• inhibits 11 beta hydroxylase
• blocks production of cortisol but raises ACTH secretion
• steroid synthesis in zona fasciculata is stopped at 11-deoxycortisol stage

Question 8

what are the uses of metyrapone?

Answer 8

• control of Cushing’s prior to surgery

- control of Cushing’s after radiotherapy

Question 9

what are the unwanted actions of metyrapone?

Answer 9

• hypertension (deoxycortisone accumulates in zona glomerulosa which has aldoesterone like activity)
• Hirsutism: inc. androgen production

Question 10

what is the MoA of ketoconazole?

Answer 10

inhibits steroidogenesis

Question 11

what are the uses of ketoconazole?

Answer 11

• treatment and control of symptoms prior to surgery

- orally active

Question 12

what are the unwanted actions?

Answer 12

liver damage

Question 13

what is Conn’s syndrome?

Answer 13

• benign adrenal cortical (zona glomerulosa) tumour
• produces aldosterone in excess
• leads to hypertension and hypokalaemia

Question 14

what is the treatment of Conn’s?

Answer 14

• aldosterone receptor antagonists (Spironolactone)

- surgery

Question 15

what is the MoA of spironolactone?

Answer 15

• spironolactone converted to several active metabolites including canrenone (competitive antagonist of MR)
• blocks Na reabsorption and K excretion

Question 16

what are the unwanted effects of spironolactone?

Answer 16

• menstrual irregularities via progesterone receptor

- gynaecomastia via androgen receptor

Question 17

what is epleronone?

Answer 17

• also a MR antagonist

- less binding to androgen and progesterone receptors compared to spironolactone so better tolerated

Question 18

what are phaechromocytomas?

Answer 18

• tumours of adrenal medulla

- which secrete catecholamines

Question 19

what are the clinical features of these?

Answer 19

• hypertension in young people

- episodic severe hypertension

Question 20

what is the treatment of these?

Answer 20

• alpha blockade is first step (give IV fluids as BP will drop)
• beta blockade is added to prevent tachycardia