Management of Adrenal Failure

Question 1

What is Cushing’s Syndrome?

What are the clinical presentations of Cushing’s syndrome?

Answer 1

Excess cortisol production

Moon face
Buffalo hump
Easy bruises
Central fat gain
Weak muscles - hard to stand up 
High BP, low K+ 

Excess cortisol turns off protein synthesis = turns off wound healing

Question 2

What are the 4 causes of Cushing’s?

Answer 2

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

Question 3

How can Cushing’s syndrome be diagnosed?

HINT: 3 different methods

Answer 3

24h urine collection to measure free cortisol - as cortisol follows a diurnal rhythm
Measure blood cortisol levels at different times of the day (measure from midnight to 9am and look for curve)
Give them a dose of dexamethasone (artifical steroid - potent glucocorticoid acting like cortisol), which should suppress ACTH - cortisol levels should be 0 the next day in normal individuals

Question 4

What happens in Cushing’s to the diurnal rhythm of cortisol?

Answer 4

The diurnal rhythm is lost (though that may happen due to stress)

Question 5

How can Cushing’s be treated with drugs that manipulate the biochemical pathway of cortisol production?

Answer 5

Treat excess cortisol production -

Drugs that inhibit cortisol synthesis: e.g. metyrapone, ketoconazole

Question 6

What is the function of metyrapone?

Answer 6

Inhibits 11-hydroxylase
As that is found in both pathways - aldosterone and cortisol
But 11DCS acts as aldosterone so not much of an issue

Question 7

What are the uses of metyrapone?

Side effects:

Answer 7

Used before surgery as if cortisol can be controlled pre-surgery, post-surgery results are better

Nausea, 11DCS = high BP and low K+, excess testosterone production too

Question 8

What is the function of ketoconazole?

Answer 8

Antifungal agent - inhibits enzymes in the steroid pathways (withdrawn in 2013 due to hepatotoxicity)

Mainly inhibits 17 Hydroxylase

Question 9

What are the uses of ketoconazole?

What are some side effects of ketoconazole?

Answer 9

Orally given pre-surgery to control cortisol levels = better post-op results

Liver damage - monitor liver function weekly

Question 10

How is Cushing’s syndrome treated?

Answer 10

Depends on the cause:
Treated pharmacologically (medications), or surgery: pituitary surgery, or bilateral / unilateral adrenalectomy

Question 11

What is Conn’s Syndrome?

Answer 11

Small benign adrenal cortical tumours

Excess aldosterone production = hypertension and hypokalaemia (low K+)

Question 12

How to diagnose Conn’s Syndrome?

Answer 12

Patients with high BP and low K+ - look for primary hyperaldosteronism by measuring renin levels to look for other high aldosterone causes (i.e. active renin-angiotensin system would mean secondary hyperaldosteronism)

Question 13

What is the treatment for Conn’s Syndrome?

Answer 13

Treat excess aldosterone production -

MR (mineralocorticoid receptor) antagonist e.g. spironolactone, epleronone

Question 14

What is the mechanism of spironolactone?

Answer 14

Blocks Na+ reabsorption and retains K+ in the kidney
Very good for heart failure as it removes Na+
Orally active, metabolised in the liver

Question 15

What are the side effects of spironolacyone?

Answer 15

Looks a bit like steroids - acts on progesterone receptors = menstrual irregulaties
Gynaecomastia - breasts become englarged in men (only a little)

Question 16

What is the mechanism of epleronone?

Answer 16

Works the same way as spironolactone

Less binding to androgen and progesterone receptors compared to spironolactone, so better tolerated

Question 17

What are Phaeochromocytomas (phaeo)?

Answer 17

Tumours of the adrenal medulla which secrete catecholamines (i.e. adrenaline and nor-adrenaline)

Sudden blast of adrenaline = panic attack, sweating, headache, vomiting, fight or flight response activated

Question 18

What can be measured in the urine or blood to look for phaeo?

Answer 18

Metanephrin = breakdown product of adrenaline = lasts for a long time 
Adrenaline = short half life = difficult to measure in blood / urine

Question 19

What are the effects of Phaeochromocytomas?

When do patient’s present / seek help?

Answer 19

Intermittently raised adrenaline attacks
As the tumour grows = sudden panic attacks
Patients seek help very late - i.e. when they collapse from a panic attack / high BP

Question 20

Why is it difficult to diagnose?

Answer 20

Symptom overlap = accused of anxiety

Misdiagnosed with thyroid issues but blood tests come back normal

Question 21

What are the clinical features of Phaeochromocytomas?

Answer 21

Hypertension in young people
Episodic severe hypertension - e.g. after abdominal palpitation
More common in certain inherited conditions

Severe hypertension = MI or stroke
High adrenaline can cause ventricular fibrillation + death
Medical emergency

Question 22

What is the treatment for Phaeochromocytomas?

Answer 22

Eventually need surgery but needs to prepped properly as they may have an hypertensive crisis

Alpha-blockage = block receptors that cause severe hypertension - BP drops v. suddenly (so hospital gives them plenty of fluids to reduce the sudden drop)

Then give beta-blocker to prevent tachycardia
Patients take it everyday, then they are put on the waiting list for surgery

Massively block the receptors just before the surgery to prevent hypertensive crisis = make sure they have no adrenal function

Adrenalectomy