Endo 6 - Hyperadrenal disorders

Question 1

Cushings syndrome is caused by too much?

Answer 1

Cortisol

Question 2

What are 6 clinical features of Cushings?

Answer 2

1. Centripetal obesity
2. Moon face and buffalo hump
3. Proximal myopathy
4. Hypertension and hypokalaemia
5. Red striae/thin skin / bruising
6. Osteoporosis / diabetes

Question 3

What are 4 causes of Cushings?

Answer 3

1. Taking too many steroids (exogenous)
2. Pituitary dependent Cushings
3. Ectopic ACTH from lung cancer
4. Adrenal adenoma secreting cortisol

Question 4

Name 3 investigations to determine the cause of Cushings syndrome

Answer 4

1. 24h urine collection measuring urinary free cortisol
2. Blood diurnal cortisol levels
3. Low dose dexamethasone suppression test

Question 5

In someone with Cushings, what is the diurnal cortisol rhythm like?

Answer 5

It is high all the time

Question 6

What are the results of giving low dose dexamethasone ?

Answer 6

If normal = cortisol suppressed to 0

Any cause of Cushings = failure to suppress cortisol to 0

Question 7

What is Conns syndrome?

Answer 7

Excess aldosterone

Question 8

What medication is given to treat patients with Cushings syndrome?

Answer 8

Steroid biosynthesis inhibitors -

Ketoconazole, metyrapone

Question 9

Where in the adrenal cortex are aldosterone, cortisol and oestradiol produced?

Answer 9

Aldosterone - zona glomerulosa

Cortisol - zona fasciculata

Oestradiol - zona reticularis

Question 10

How does metyrapone work?

Answer 10

It inhibits 11-B-hydroxylase

Which causes an accumulation of 11-deoxycortisol

Also causes increased ACTH secretion

Question 11

What are the uses of metyrapone?

Answer 11

1. Control Cushings syndrome before surgery

2. Control Cushings syndrome after radiotherapy

Question 12

What are 2 side effects of metyrapone?

Answer 12

1. Increased salt retention and hypertension due to 11-deoxycortisone (Arrested) accumulating in z.glomerulosa
2. Increased adrenal androgen production - hirsutism in women

Question 13

What is the mechanism of action of ketoconazole

Answer 13

Ketoconazole = anti fungal

Blocks production of glucocorticoids, mineralocorticoids and sex steroids

Question 14

What are the uses of ketoconazole

Answer 14

Treatment and management of Cushings Syndrome prior to surgery

It is a tablet

Question 15

What is the unwanted action of ketoconazole

Answer 15

Liver damage - could be fatal.

MUST CHECK LIVER FUNCTION REGULARLY

Question 16

What surgical treatments are there for Cushings?

Answer 16

1. Pituitary surgery
2. Bilateral adrenalectomy
3. Unilateral adrenalectomy

Question 17

Conns syndrome is due to XS aldosterone. What does this cause

Answer 17

1. Hypertension and hypokalaemia

Question 18

If primary hyperaldosteronism (Conns), how is it diagnosed?

Answer 18

High aldosterone, low renin = Conns

RAS system suppression = exclude secondary hyperaldosteronism

Question 19

How is Conns syndrome treated?

Answer 19

Block Mineralocorticoid (MR) receptor - MR antagonist

e.g. Spironolactone, epleronone

Question 20

Spironolactone - mechanism of action

Answer 20

Converted into canrenone = competitive MR antagonist

Blocks Na resorption and K excretion in kidney tubules (K sparing diuretic) - combats effects of increased aldosterone

Question 21

What are the unwanted action of spironolactone?

Answer 21

1. Menstrual irregularities (progesterone agonist)

2. Gynaecomastia (androgen receptor antagonist)

Question 22

Epleronone - mechanism of action

Answer 22

1. MR antagonist

2. Less binding to progesterone/androgen receptors = less side effects and better tolerated

Question 23

What are phaeochromocytomas?

Answer 23

Adrenal medulla tumours - which secrete catecholamines

Question 24

What are the clinical features of a phaeo?

Answer 24

1. Hypertension in young people
2. Episodic severe hypertension attacks
3. More common in certain inherited conditions

Question 25

What are the problems with phaeo?

Answer 25

1. Severe hypertension - can cause MI or stroke | 2. High Adrenaline - can cause VF / death

Question 26

How are phaeos managed?

Answer 26

1. Alpha blockade 2. Give IV as alpha blockade commences 3. Beta-blocker to prevent tachycardia 4. Surgery

Question 27

What is the 10% rule of phaeochromocytomas?

Answer 27

1. 10% extra-adrenal 2. 10% malignant 3. 10% bilateral Phaeos = very very rare