Endo - Adrenal Disorder (overactive)

Question 1

What are the clinical features of Cushing’s Disease?

Answer 1

→ too much cortisol
→ centripetal obesity
→ moon face + buffalo hump
→ proximal myopathy
→ hypertension + hypokalaemia
→ red striae, thin skin, bruising
→ osteoporosis + diabetes

Question 2

What are the causes of Cushing’s Disease?

Answer 2

→ too many steroids
→ pituitary dependent Cushing’s disease
→ ectopic ACTH from lung cancer
→ adrenal adenoma secreting cortisol

Question 3

What investigations determine the cause of Cushing’s Syndrome?

Answer 3

→ 24 hour urine collection for urinary free cortisol
→ blood diurnal cortisol levels
→ low dose dexamethasone

Question 4

What is a low dose dexamethasone suppression test?

Answer 4

→ dexamethasone = artificial cortisol that has fluorine and can last ages
→ should suppress ACTH and cortisol in normal people
→ however, in Cushing’s, cortisol will still be produced

Question 5

What’s the difference between Cushing’s Syndrome and Cushing’s Disease?

Answer 5

cushing’s syndrome is having excess cortisol

cushing’s disease is having adrenal tumour

Question 6

When is cortisol the lowest according to the diurnal rhythm?

Answer 6

midnight

Question 7

Why does ectopic ACTH from lung cancer cause Cushing’s disease?

Answer 7

if lung cancer expresses protein that produces ACTH, it can stimulate adrenal glands to produce cortisol

Question 8

What is Cushing’s disease/syndrome?

Answer 8

too much cortisol

Question 9

What are the two ways in which steroids can be pharmacologically manipulated?

Answer 9

→ enzyme inhibitors

→ receptor blocking drugs

Question 10

What drugs inhibit cortisol biosynthesis?

Answer 10

→ metyrapone

→ ketoconazole

Question 11

What drugs inhibit aldosterone biosynthesis?

Answer 11

→ spironolactone

→ epleronone

Question 12

What is metyrapone’s mechanism of action?

Answer 12

→ inhibition of 11-beta-hydroxylase
→ steroid synthesis in the zona fasciculata is stopped at the 11-deoxycortisol stage
→ 11-deoxycortisol has no negative feedback effect in hypothalamus + pituitary gland

Question 13

What are the specific clinical uses of metyrapone?

Answer 13

→ control of Cushing’s syndrome prior to surgery

→ control of Cushing’s symptoms after radiotherapy (as it has very slow effects)

Question 14

What are the unwanted consequences of metyrapone?

Answer 14

→ hypertension on long-term administration

→ hirsutism

Question 15

What are the main uses of ketoconazole?

Answer 15

→ main use = anti-fungal agent

→ higher concentrations inhibits steroidogenesis

Question 16

What is the mechanism of action of ketoconazole?

Answer 16

blocks 17-alpha-hydroxylase, preventing production of cortisol

Question 17

What are the unwanted consequences of ketoconazole?

Answer 17

possibly fatal liver damage

Question 18

How do you treat Cushing’s Disease?

Answer 18

→ pituitary surgery
→ bilateral adrenalectomy
→ unilateral adrenalectomy for adrenal mass

Question 19

What is Conn’s disease?

Answer 19

too much aldosterone

Question 20

What can cause Conn’s disease?

Answer 20

benign adrenal cortisol tumour

Question 21

What are the clinical features of Conn’s syndrome?

Answer 21

→ hypokalaemia (low potassium)

→ hypertension

Question 22

How do you distinguish between primary and secondary hyperaldosteronism?

Answer 22

renin-angiotensin system should be suppressed for primary hyperaldosteronism?

Question 23

What are the main uses of spironolactone?

Answer 23

treats primary hyperaldosteronism before surgery

Question 24

What is the mechanism of spironolactone?

Answer 24

→ converted to several active metabolites, including canrenone (competitive antagonist of mineralocorticoid receptor)
→ blocks Na+ absorption and K+ excretion in kidney tubules

Question 25

What are the unwanted consequences of spironolactone?

Answer 25

→ menstrual irregularities

→ gynaecomastia (man boobs)

Question 26

What are the pharmacokinetics of spironolatone?

Answer 26

→ orally active

→ highly protein bound + metabolised in liver

Question 27

Why is a higher dose of epleronone given in comparison to spironolactone?

Answer 27

→ less binding to androgen and progesterone receptors compared to spironolactone
→ more highly tolerated

Question 28

What are spironolactone and epleronone examples of?

Answer 28

MR antagonists

mineralocorticoid antagonists

Question 29

What are tumours of the adrenal medulla called?

Answer 29

phaeochromocytomas

Question 30

What do phaeochromocytomas do?

Answer 30

secretes catecholamines (adrenaline + nor-adrenaline)

Question 31

What are the clinical features of a phaeo?

Answer 31

→ hypertension in young people
→ episodic severe hypertension (abdominal palpation)
→ more common in certain inherited conditions

Question 32

What are the consequences of some of the clinical features in a phaeo?

Answer 32

→ severe hypertension = myocardial infarction or stroke

→ high adrenaline = ventricular fibrillation + death

Question 33

How is phaeo managed?

Answer 33

→ eventually needs surgery

→ needs careful prep as anaesthetic can precipitate a hypertensive crisis

Question 34

How can phaeo be managed pharmacologically?

Answer 34

→ alpha blockade

→ beta blockade to prevent tachycardia

Question 35

How can phaeo be managed pharmacologically before surgery?

Answer 35

→ alpha blockade (patient may need IV fluids alongisde)

→ beta blockade to prevent tachycardia

Question 36

Why are IV fluids given when alpha blockades are given?

Answer 36

huge drop in blood pressure may be too much for body