Management of adrenal pathway dysfunction

Question 1

what investigations are used to determine the cause of cushing’s syndrome?

Answer 1

24h collection urinary free cortisol
9am cortisol
dexamethasone suppression test (acts like cortisol, and any cause of cushing’s will fail to suppress cortisol)

Question 2

what is the treatment for Cushing’s?

Answer 2

enzyme inhibitors –> inhibit cortisol synthesis

receptor blocking drugs –> aldosterone receptor antagonists, used in Conn’s syndrome

Question 3

what is conn’s syndrome?

Answer 3

excess aldosterone - tumour of zona glomerulosa

Question 4

give 2 examples of enzyme inhibitors to inhibit cortisol synthesis

Answer 4

metyrapone, ketoconazole

Question 5

what does metyrapone do?

Answer 5

inhibits enzyme 11- hydroxylase

Question 6

aldosterone receptor antagonists give 2 examples

Answer 6

spironolactone, eplerenone

Question 7

which drug inhibits 11beta hydroxylase? What does it do?

Answer 7

metyrapone, inhibits cortisol synthesis

Question 8

How do you adjust the dose of metyrapone? Aim for what mean serum concentration of cortisol?

Answer 8

according to cortisol –> 150-300nmol/L

Question 9

which of these in excess has side effects? What?

1. 11-deoxycortisol
2. 11-deoxycortisone

Answer 9

2 - acts like aldosterone, in excess leads to high BP, low potassium

Question 10

what are the side effects of metyrapone?

Answer 10

high BP, low potassium due to elevated levels of 11-deoxycortisone

Question 11

When should metyrapone be used?

Answer 11

Control of Cushing’s syndrome prior to surgery

Control of Cushing’s symptoms after radiotherapy - which is slow to take effect

Question 12

Ketoconazole is used for what?

Answer 12

treatment and control of symptoms of cushing’s syndrome prior to surgery

Question 13

potential side effects of ketoconazole? What monitoring should be done?

Answer 13

liver damage, liver function tests weekly

Question 14

What surgical treatment should be used for a pituitary tumour causing cushing’s?

Answer 14

pituitary surgery (transsphenoidal hypophysectomy)

Question 15

What surgical treatment should be used for bilateral adrenal tumours?

Answer 15

bilateral adrenalectomy

Question 16

What surgical treatment should be used for one adrenal mass?

Answer 16

unilateral adrenalectomy

Question 17

what are the clinical effects of Conn’s syndrome?

Answer 17

high BP, high sodium, low potassium

Question 18

which medications can be used for conn’s syndrome?

Answer 18

spironolactone, epleronone

Question 19

how does spironolactone work?

Answer 19

converted to canrenone in the body, which is a competitive antagonist of the mineralocorticoid receptor

Question 20

how does epleronone work?

Answer 20

mineralocorticoid antagonist

Question 21

how is epleronone different to spironolactone?

Answer 21

less binding to androgen and progesterone receptors, so better tolerated

Question 22

what does a mineralocorticoid antagonist do?

Answer 22

blocks sodium reabsorption and potassium secretion

Question 23

what are the unwanted actions of spironolactone?

Answer 23

• menstrual irregularities (+ progesterone receptor)

- gynaecomastia (- effects on androgen receptor)

Question 24

what is the name given to tumours of the adrenal medulla which secrete catecholamines?

Answer 24

phaeochromocytomas

Question 25

what are catecholamines?

Answer 25

adrenaline and noradrenaline

Question 26

how do you measure adrenaline levels?

Answer 26

measure in urine/blood: metanephrine, VMA (breakdown products of adrenaline)

Question 27

why do we measure metanephrine and VMA instead of adrenaline?

Answer 27

adrenaline doesn't last long enough

Question 28

``` intermittent episodes high BP panic attacks headache sweating vomiting palpitations dizziness nervousness pallor ``` are all signs of?

Answer 28

phaeochromocytomas

Question 29

how does the medulla release adrenaline?

Answer 29

stores and releases in one go

Question 30

which disease do the effects of phaeochromocytomas mimick?

Answer 30

hyperthyroidism

Question 31

which disease is a cause of hypertension in young people?

Answer 31

phaeochromocytoma

Question 32

what can episodic severe hypertension lead to?

Answer 32

MI or stroke

Question 33

If you palpate the abdomen of someone with a phaeochromocytoma, what can happen?

Answer 33

lots of adrenaline released in response to palpation, leading to severe hypertension

Question 34

How can high adrenaline cause death?

Answer 34

ventricular fibrillation

Question 35

management of phaeochromocytomas?

Answer 35

- admit to hospital and give IV fluid - alpha blockers and beta blockers - only after giving these drugs do you do surgery to remove adrenal gland

Question 36

what do alpha blockers and beta blockers help with in someone with a phaeochromocytoma?

Answer 36

alpha - block receptors causing hypertension | beta - prevent tachycardia

Question 37

why do we need to give alpha and beta blockers before performing surgery to remove a phaeochromocytoma?

Answer 37

touching adrenal gland can lead to a severe adrenaline rush, so need to block these effects

Question 38

what percentage of phaeochromocytomas are 'paragangliomas' and what does that mean?

Answer 38

10% - tumours of sympathetic chain rather than adrenal gland

Question 39

what percentage of phaeochromocytomas are malignant?

Answer 39

10%