Management of Adrenal Failure

Question 1

How is Cushing’s treated?

Answer 1

First work out if its pituitary, adrenal or ectopic

Metyrapone or ketoconazole (inhibit steroid biosynthesis)

Question 2

How does metyrapone work?

Answer 2

Inhibits 11B hydroxylase, no cortisol or aldosterone produced
Synthesis arrested at 11-deoxycortisol stage
11-deoxycortisol has no neg. feedback on hypothalamus and pituitary

Question 3

How does ketoconazole work?

Answer 3

Blocks 17 hydroxylase reducing cortisol levels

Question 4

Does 11 deoxycortisone have negative feedback?

Answer 4

No

Question 5

Who is metyrapone given to? When and why?

Answer 5

Control Cushings prior to surgery (they have poor wound healing so this helps with surgery recovery)
Control Cushings after radiotherapy

Question 6

What are side effects of metyrapone?

Answer 6

Excess 11 deoxycortisone= hypertension, low K

Excess testosterone= hirtuism

Question 7

Who is ketoconazole given to? What must we also do?

Answer 7

Control Cushings prior to surgery
Make sure to check liver function as it can damage the liver (check clinically and biochemically)
Taken orally

Question 8

What are surgical options for Cushing’s?

Answer 8

Pituitary surgery (transspenoidal hypophysectomy)
Bilateral adrenalectomy (take out both adrenal glands)
Unilateral adrenalectomy for adrenal mass

Question 9

What is Conn’s syndrome? What happens to aldosterone levels?

Answer 9

Benign adrenal tumor of zone glomerulosa

Excess aldosterone= hypertension and hypokalaemia

Question 10

How is Conn’s diagnosed?

Answer 10

Primary hyperaldosteronism

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

Question 11

How is Conn’s treated?

Answer 11

Spironolactone or epleronone

Question 12

How does spironolactone work?

Answer 12

Converted to several metabolites inc. canrenone, a competitive antagonist of mineralocorticoid (aldosterone) receptor
Blocks Na resorption and K secretion in kidney tubules

Question 13

What are side effects of spironolactone?

Answer 13

Menstrual irregularities (agonist at progesterone receptor)
Gynaecomastia (antagonist at androgen receptor)

Question 14

How does epleronone work?

Answer 14

Mineralocorticoid antagonist

Less binding to androgen and progesterone receptors compared to spironolactone

Question 15

What are phaeochromocytomas? What hormone do they effect and how?

Answer 15

Tumors of adrenal medullas that secrete catecholamines

Question 16

How does phaeochromocytoma present?

Answer 16

Hypertension (especially in young people is uncommon so think phaeo/cushings/conn’s)
Episodic severe hypertension- can cause myocardial infarction or stroke (due to large burst of adrenaline)
Panic attacks
High adrenaline can cause ventricular fibrillation and death

Question 17

How can we differentiate between phaeochromocytoma and Cohn’s?

Answer 17

Phaeo= episodic sever hypertension

Question 18

What do you have to treat phaeos as?

Answer 18

A medical emergency

Question 19

How is phaeo treated?

Answer 19

Surgery but cant do this straight away as tumor cannot be touched
First step= give alpha blocker (e.g. phenoxybenzamine) after saline (to prevent severe BP fall)
IV fluid as alpha blockade commences
Beta blocker to prevent tachycardia
Once crisis is over then do surgery (weekend before massively block with alpha and beta blockade)

Question 20

Do phaeos have to be in the adrenal?

Answer 20

No, they can be extra adrenal and make adrenaline anyways