Hyperadrenal disorders

Question 1

What is Cushing’s syndrome due to?

Answer 1

Too much cortisol

Question 2

Clinical features of Cushing’s

Answer 2

Synthesize too much fat and break down too much protein
Get really obese with weak muscles - centripetal obesity
Thin skin that tears so red marks - striae
Buffalo hump
Proximal myopathy
Bruising
Moon face
Osteoporosis
Diabetes

Question 3

What causes Cushing’s

Answer 3

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

Question 4

Investigations for Cushing’s syndrome

Answer 4

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

Question 5

When is cortisol usually highest and lowest?

Answer 5

cortisol usually highest at 9am and lowest at midnight if asleep. Follows circadian rhythm.

Question 6

What is dexamethasone

Answer 6

Artificial cortisol that lasts a long time

Question 7

How is dexamethason suppression test administrated

Answer 7

0.5mg every 6 hours for 48 hours

Question 8

What shows cushing’s syndrome in a dexamethason supression test?

Answer 8

Normally will suppress cortisol to zero as that is a lot of steroid but ANY cause of Cushing’s will fail to suppress

Question 9

How would you approach too much cortisol medically?

Answer 9

Inhibitors of steroid biosynthesis: metyrapone, ketoconazole

Question 10

Why do you really want to lower cortisol before a surgery to remove the source permanently

Answer 10

Patients have thin skin, easy bruising and there is a lot of bleeding. Cortisol suppresses the immune system and increases risk of infection.

Question 11

How does metyrapone work?

Answer 11

It inhibits 11 beta hydroxylase which stops corticosterone and cortisol production from cholesterol

Question 12

What are uses of metyrapone?

Answer 12

Control of Cushing’s syndrome prior to surgery - improve patient symptoms and promotes better post op recovery
Control Cushing’s syndrome after radiotherapy (which is usually slow to take effect)

Question 13

What are the issues with metyrapone?

Answer 13

Hypertension on long term administration

Hirsutism

Question 14

How does metyrapone cause salt retention and hypertension

Answer 14

It would lead to a build up of the product before the use of 11 beta hydroxylase - such as 11 deoxycorticosterone which has a mineralocorticoid activity which leads to salt retention and hypertension

Question 15

How does metyrapone cause hirsutism

Answer 15

Due to the other two brances of cholesterol conversion being blocked, funnels it into sex steroid production so more androgen production so causes hirsutism in women

Question 16

What is hirsutism

Answer 16

condition of unwanted, male-pattern hair growth in women. Hirsutism results in excessive amounts of dark, course hair on body areas where men typically grow hair — face, chest and back

Question 17

What is the main use of ketoconazole?

Answer 17

Antifungal agent that was withdrawn in 2013 because of risk of hepatotoxicity

Question 18

How does ketoconazole work?

Answer 18

It blocks 17 alpha hydroxylase which is higher up than metyrapone

Question 19

What is the unwanted action of ketoconazole?

Answer 19

Liver damage that is possibly fatal therefore must monitor liver function weekly, clinically and biochemically

Question 20

What are ways of curing Cushing’s?

Answer 20

Depends on cause:
Pituitary surgery - transsphenoidal hypophysectomy
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

Question 21

What is Conn’s syndrome?

Answer 21

Benign adrenal cortical tumour of outer zone of adrenal gland - zona glomerulosa leading to XS aldosterone

Question 22

What are symptoms of Conns

Answer 22

Hypertension and hypokalaemia

Question 23

How do you diagnose Conn’s

Answer 23

If aldosterone very high but renin surpressed - conns

Just measure them

Question 24

What is the treatment of Conn’s syndrome?

Answer 24

Block the receptor that the hormone works by - MR antagonist eg spironolactone or eplerenone

Question 25

What is the mechanism of action of Spironolactone?

Answer 25

It is converted into several active metabolites including cenrenone, a competitive antagonist of the mineralocorticoid receptor that blocks Na+ resorption and K+ excretion in the kidney tubules (potassium sparing diuretic)

Question 26

What are the unwanted actions of spironolactone?

Answer 26

Menstrual irregularities (+ progesterone receptor) 
Gynaecomastia (- androgen receptor) bc not very specific

Question 27

What is a phaeochyromocytomas

Answer 27

A tumour of adrenal medulla which secretes catecholamines that leads to episodic release of adrenaline or noradrenaline that is more common in certain inherited condition

Question 28

What are clinical features of phaeochyromocytomas

Answer 28

Blood pressure shoots up crazy numbers
Sweating
Headache
Sick
Sudden dizziness
Sudden anxiety
Hypertension in young people
Episodic severe hypertension after abdominal palpation

Question 29

How can phaeochyromocytomas cause sudden death

Answer 29

The severe hypertension can cause myocardial infarction or stoke and the high adrenaline can cause ventricular fibrillation and death THUS is a MEDICAL EMERGENCY

Question 30

What is the management for phaeochyromocytomas

Answer 30

Alpha blockade is the first therapy step, patients may need intravenous fluid as alpha blockade commence - may have very severe drop on BP. The beta blockade added to prevent tachycardia

Question 31

What percentage of phaeochyromocytomas are malignant? What percentage bilateral? how common are they? What percentage extra adrenal?

Answer 31

10% extra adrenal - sympathetic chain
10% malignant
10% bilateral
Phaeos are v. rare