Hyper adrenal disorders

Question 1

Cushing’s CF

Answer 1

caused by too much cortisol

centripetal obesity
moon face 
buffalo hump - interscapular fat pad
proximal myopathy
striae, thin skin and easy bruising
diabetes, osteoporosis
hypertension and hypokalaemia

Question 2

Causes of Cushing’s syndrome

Answer 2

Cushing’s disease - pituitary tumour
Oral steroids
Ectopic ACTH from lung cancer
Adrenal adenoma producing ACTH

Question 3

Why do patients become become hypertensive and hypokalaemic

Answer 3

Cortisol binds to receptors in the kidneys that causes them to retain sodium and excrete potassium

Question 4

Cortisol levels through the day

Answer 4

high in the morning

low when you sleep

Question 5

Why are blood tests not used to measure cortisol levels

Answer 5

Pain/ stress causes increase in cortisol

Question 6

Investigations to determine Cushing’s syndrome

Answer 6

1) 24 hour urine collection for free cortisol in the urine
2) Blood diurnal cortisol levels - should be low at midnight. If it is high, it’s suspicious
3) Low dose dexamethasone suppression test. Cushing’s will have high cortisol after test.

Question 7

How does the low dose dexamethasone suppression test work

Answer 7

Normal person: The extra steroid is detected by the pituitary so ACTH is turned off and within hours will have 0 cortisol

Cushing’s disease: cortisol doesn’t decrease because tumour keeps releasing ACTH

Question 8

Treatment of Cushing’s

Answer 8

Depends on cause:

• Pituitary surgery - transphenoidal hypophysectomy
• ## Unilateral / Bilateral adrenalectomy

Question 9

Medical treatment of Cushing’s

Answer 9

Metyrapone

Ketoconazole

Question 10

How Metyrapone works

Answer 10

Inhibits 11-beta-hydroxylase. Blocks cortisol synthesis

Question 11

Negative aspects of metyrapone

Answer 11

11-beta-hydroxylase is involved in 2 parts of the pathway

It leads to an accumulation of 11-deoxycoticosterone and 11-deoxycortisol

11-deoxycoticosterone has mineralocorticoid properties – can cause hypertension and salt retention

blocking 2 limbs of pathway, all precursors funnel towards sex steroid synthesis –> hirsutism in women

Question 12

Uses of metyrapone

Answer 12

control of cushing’s prior to surgery (decrease chance of infection, better wound healing)

Control of Cushing’s after radiotherapy (slow)

Question 13

Uses of ketoconazole

Answer 13

Treatment of Cushings

- used to control Cushing’s before surgery

Question 14

How ketoconazole works

Answer 14

Blocks cytochrome P450 SCC enzymes - blocking production of glucocorticoids, mineralocorticoids and sex steroids

Question 15

Negative aspects of metyrapone

Answer 15

Nausea, vomiting, abdominal pain
Alopecia
Gynaecomastia, impotence, decreased libido
LIVER DAMAGE (could be fatal)

Question 16

Conn’s is

caused by

Answer 16

primary hyperaldosteronism

benign tumour in the adrenal cortex (zona glomerulosa makes aldosterone)

Question 17

Clinical features of Conn’s

Answer 17

Hypertension and hypokalaemia

Question 18

Diagnosis of Conn’s

Answer 18

Measure BP- high
Do blood test then if potassium high, suspect Conn’s
If aldosterone levels are high, RAAS suppressed - renin will be turned off
Measure the renin - should be low

High BP; low potassium; low renin

Question 19

Treatment for Conn’s

Answer 19

Give a mineralocorticoid receptor antagonist -
Spironolactone –

Or Epleronone – similar affinity to MR as spironolactone but less binding to progesterone and androgen receptors so is better tolerated

then surgery to remove tumour

Question 20

MOA of spironolactone

Answer 20

Spironolactone is converted into active metabolites e.g. canrenone - competitive antagonist for MR

blocks Na reabsorption and K excretion in kidney. Is a potassium sparing diuretic

Question 21

Why do you need to first give someone medication (spironolactone before taking them in for surgery)

Answer 21

Want to reduce their BP because giving general anaesthetic to someone with high BP has added dangers

Question 22

People with bilateral adrenal hyperplasia are given what treatment

Answer 22

LT spironolactone

Question 23

Pharmacokinetics of sprionolactone

Answer 23

Oral
Highly protein bound and metabolised in liver
Daily dose / divided doses

Question 24

Unwanted actions of spironolactone

Answer 24

very non-specific
progesterone receptor agonist–> menstrual irregularities

androgen receptor antagonist –> gynaecomastia in men

can cause GI irritation
Also renal/ hepatic disease

Question 25

Patients needing a LT MR antagonist are more likely to be put on and why

Answer 25

Eplerenone due to its more specific binding to MR so has fewer side effects

Question 26

Phaechromocytoma caused by

Answer 26

Tumours of the adrenal medulla

Secretion of catecholamines (NA and A)

Question 27

Phaechromocytoma CF

Answer 27

Episodic severe HT in young people
stress/post abdominal palpation in big one/trauma –> increase in BP and release of lots of adrenaline

Severe HT can cause MI or stroke
Can cause ventricular fibrillation - sudden cardiac death

Question 28

Management of phaeochromocytoma

Answer 28

Can’t directly give anaesthetic –> will cause adrenaline release

first give alpha blocker (IV fluid) –>blocks receptors to which adrenaline binds

Then beta blocker –> prevent tachycardia

then surgery to remove tumour