Adrenal Gland

Question 1

Causes of Cushing’s

Answer 1

Taking too many steroids
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
adrenal adenoma secreting cortisol

Adrenal cortex tumour

Question 2

Cushing’s investigation

Answer 2

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

Dexamethasone - normal will suppress cortisol to zero, Cushing’s fail to suppress

Question 3

Cushing’s medication

Answer 3

Excess cortisol

Inhibitors of steroid biosynthesis
metyrapone; ketoconazole

Question 4

Conn’s treatment

Answer 4

Excess aldosterone

MR antagonist:
spironolactone, epleronone

Question 5

Metyrapone mechanism

Answer 5

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.

Control Cushing’s before surgery for better recovery and after radiotherapy

Question 6

Metyrapone side effects

Answer 6

Hypertension on long-term administration

Hirsutism

Question 7

Ketoconazole mechanism

Answer 7

main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity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

Block 17 alpha hydroxylase - inhibit cortisol production

Control Cushing’s prior to surgery

Question 8

Ketoconazole side effects

Answer 8

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

Question 9

Treatment of Cushing’s

Answer 9

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

Question 10

Conn’s syndrome

Answer 10

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

Question 11

Conn’s syndrome : diagnosis

Answer 11

Primary hyperaldosteronism

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

Low renin and high aldosterone

Question 12

Spironolactone mechanism

Answer 12

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 13

Spironolactone side effects

Answer 13

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

Question 14

Epleronone

Answer 14

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 15

Phaeochromocytomas

Answer 15

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

Increased heart rate and hypertension
Holds adrenaline and then releases it all in one go

Question 16

Clinical features of a phaeo

Answer 16

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

Question 17

Management of phaeo

Answer 17

Eventually need surgery, but patient needs careful preparation as anaesthetic can precipitate a hypertensive crisis

Alpha blockade is first therapeutic step.
Patients may need intravenous fluid as alpha blockade commences

Question 18

Tumour of adrenal medulla

Answer 18

Phaeochromocytomas