Management of adrenal failure

Question 1

What are the clinical features of cortisol?

Answer 1

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

Question 2

What are the 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 is Cushing’s diagnosed?

Answer 3

24 h urine collection for urinary free cortisol
Blood diurnal cortisol levels
(cortisol’s usually highest at 9am and lowest at midnight, if asleep)
Low dose dexamethasone suppression test

Question 4

How does the Low dose dexamethasone suppression test work?

Answer 4

Potent glucocorticoid should suppress cortisol

Give 1/2 mg 6 hourly for 48 hours

Cortisol would be zero the next day if normal

Does not tell you what type of Cushing’s they have

Question 5

What drugs can be given to treat Cushing’s?

Answer 5

Enzyme inhibitors

Receptor blocking drugs

Question 6

Which drugs inhibit steroid biosynthesis?

Answer 6

Metyrapone

Ketoconazole

Question 7

What is the action of Metyrapone?

Answer 7

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.

Question 8

How do we control cortisol prior to surgery?

Answer 8

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)

Question 9

What are the side effects of metyrapone?

Answer 9

high blood pressure

high testosterone

Question 10

What was the main use of Ketoconazole?

Answer 10

main use as an antifungal agent – although withdrawn in 2013 due to risk of hepatotoxicity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 11

What is the mechanism of action for Ketoconazole?

Answer 11

Inhibition of 17-hydroxylase

Question 12

Summarise the invasive treatments for Cushing’s?

Answer 12

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

Question 13

Summarise the medical treatments for Cushing’s?

Answer 13

Metyrapone

Ketoconazole

Question 14

What are the side effects of Ketoconazole?

Answer 14

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

Question 15

What causes Conn’s syndrome?

Answer 15

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

Question 16

How do you diagnose Conn’s syndrome?

Answer 16

Primary hyperaldosteronism

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

Question 17

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

Answer 17

spironolactone, epleronone

Question 18

What is the mechanism of action for spironolactone?

Answer 18

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).
Therefore also used by cardiologists as a hypertensive

Question 19

What are the side effects of spironolactone?

Answer 19

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

Question 20

What are the main features of epleronone?

Answer 20

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 21

What are phaeochromaocytomas?

Answer 21

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

Question 22

What are the effects of phaeochromaocytomas?

Answer 22

Blood pressure elevation
Increased cardiac output
BMR elevation
Bronchodilation
Glycogenolysis 
Hyperglycaemia
CNS excitability

Question 23

What are the clinical features of phaeochromaocytomas?

Answer 23

Intermittent episodes of high BP (after abdominal palpitation)

As the tutor gets bigger they will have more attacks

Hypertension in young people

More common in certain inherited conditions

Question 24

When do patients with phaeochromaocytomas present?

Answer 24

They just think they are having unexplained panic attacks

It is only when they collapse that the tumour is discovered

Question 25

What can phaeo’s cause?

Answer 25

Hypertension in young people
Episodic severe hypertension (after abdominal palpation)
More common in certain inherited conditions

Question 26

How do you manage a phaeo?

Answer 26

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

Needs to prepped for surgery

Question 27

How to prep a patient for a phaeo surgery?

Answer 27

Alpha blockade is first therapeutic step

Patients may need intravenous fluid (to maintain BP) as alpha blockade commences

Beta blockade added to prevent tachycardia

Question 28

What happens the weekend before a surgery for phaeo?

Answer 28

High does alpha blockade in hospital

By the surgery they have absolutely no adrenal function

Question 29

What are some key facts about phaeochromocytoma’s?

Answer 29

10 % extra-adrenal (sympathetic chain)
10 % malignant
10 % bilateral
Phaeo’s are extremely rare