Adrenal disorders

Question 1

When should you sample the cortisol of someone when you suspect it to be too high?

Answer 1

At night.

Difficult to get it for those who are night workers as diurnal rhythm has shifted

Question 2

What is it called if you have too much Cortisol?

Answer 2

Cushing’s syndrome (source is adrenal)

Question 3

What are the clinical features of Cushing’s syndrome?

Answer 3

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

Question 4

What are the causes of Cushing’s disease?

Answer 4

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

Question 5

What is the most common cause of Cushing’s Syndrome?

Answer 5

Taking too much steroids

Question 6

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

Answer 6

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

Question 7

How would you carry out a dexamethasone suppression test?

Answer 7

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
9am cortisol - 800nM
End of LDDST should be 0 normally, 680nM

Question 8

What are the pharmacological manipulations for Cushing’s?

Answer 8

Enzyme inhibitors

Receptor blocking drugs

Question 9

What drugs are inhibitors of steroid biosynthesis?

Answer 9

metyrapone, ketoconazole

Question 10

What are the actions of Metyrapone?

Answer 10

Inhibition of 11-hydroxylase enzyme.
steroid synthesis in zona fasciculata inhibited at the 11-deoxycortisol stage.
11-deoxycortisol has no negative feedback on the hypothalamus and pituitary gland.

Question 11

How would you use Metyrapone?

Answer 11

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 12

Why do you get osteoporosis & thin skin in Cushing’s?

Answer 12

Cortisol suppresses protein synthesis and stimulates fat synthesis.

Question 13

Why do you get salt retention and hypertension ?

Answer 13

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

Question 14

What are the unwanted effects of Metyrapone?

Answer 14

Hypertension

Hirsutism

Question 15

What is the mechanism of action for Ketoconazole?

Answer 15

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

Question 16

What enzyme does ketoconazole inhibit?

Answer 16

17-hydroxylase

Question 17

What are the unwanted side effects of ketoconazole?

Answer 17

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

Question 18

What is the treatment for Cushing’s?

Answer 18

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

Question 19

What is Conn’s syndrome?

Answer 19

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

Question 20

What does Aldosterone do?

Answer 20

Controls blood pressure, sodium and potassium.

Question 21

What diagnoses Conn’s syndrome?

Answer 21

Primary hyperaldosteronism

Renin - angiotensin system should be suppressed (exclude secondary hyperaldosteronism

Question 22

What are the drugs for the treatment of Conn’s syndrome?

Answer 22

Spironolactone, epleronone

Question 23

What is the action of Spironolactone?

Answer 23

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).

Question 24

What are the unwanted side effects of Spironolactone?

Answer 24

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

Question 25

What is the action of Epleronone?

Answer 25

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 26

What are Phaeochromocytomas?

Answer 26

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

Question 27

What happens in Phaeochromocytomas?

Answer 27

Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions
release of adrenaline is very sudden and occure via a neural pathway.

Question 28

What are the clinical issues associated with Phaeochromocytomas?

Answer 28

Severe hypertension can cause myocardial infarction or stroke
High adrenaline can cause ventricular fibrillation + death
Thus this is a medical emergency

Question 29

What is the management for Phaeochromocytomas?

Answer 29

Dangerous to operate due to chance of anaesthetic causing hypertensive crisis, so you;
Alpha blockade is first therapeutic step.
Patients may need intravenous fluid as alpha blockade commences
Beta blockade added to prevent tachycardia