6. Hyperadrenal disorders

Question 1

Features of Cushing’s Syndrome

Answer 1

Caused by having too much cortisol

• Can be caused by a tumour in the pituitary that’s making ACTH
• Can also rarely be due to a benign tumour of the adrenal gland
• Cortisol switches protein synthesis off and fat syntheisis on
• Get bruising because proteins for healing arent available
• Get fat deposition- ‘moon face’ and ‘buffalo hump’
• Stretch marks- putting on a lot of fat quickly
• Weaker

Question 2

Clinical features of Cushing’s

Answer 2

• Too much cortisol
• Centripedal obesity
• Moon face and buffalo hump
• proximal myopathy
• Hypertension and hypokalaemia- due to cortisol binding to receptors in the kidney (retain Na+ and K+)
• red striae, thin skin and easy bruising
• Osteoperosis, diabetes

Question 3

Causes of Cushing’s

Answer 3

Can be EXOGENOUS or ENDOGENOUS:​

Exogenous:

1. Taking too many steroids by mouth: cortisol type steroid cause loss of protein and more fat- glucocortisoid over use is more common cause than tumour. BUT bodybuiling steroids (testosterone) causes opposite effects

Endogenous:

1. Pituitary dependant Cushing’s disease
2. Ectopic ACTH from cancer
3. Adrenal adenoma making cortisol

Question 4

THREE tests to determine the cause of Cushing’s disease

Answer 4

1. 24 hour urine collection for urinary free cortisol
2. Blood diurnal cortisol levels
3. Low dose dexamethasone suppression test (gold standard)- will have high levels of cortisl after suppression

Question 5

Dangers of undiagnosed Cushing’s disease

Answer 5

Patients can become immunocompromised since they can’t heal and synthasise proteins- develop sepsis

Question 6

Problems with cortisol measurement

Answer 6

Cortisol is high in the morning and low when you go to sleep- diurnal- stress of blood test is another confounding factor

• To overcome this we do a 24 hour urine collection for urinary free cortisol

People with cushing’s loose their diurnal rythm and have high cortisol at all times

Question 7

Low dose demaxamethasone suppression test

Answer 7

Dexamethasone is an artificial steroid

You take a blood test before giving it, then you give the dexamethasone and at the end of that, normal people will have ZERO cortisol (because you don’t need more steroid) the pituitary will not produce ACTH since the system is saturated with steroid

People with cushing’s will still have high cortisol

• 0.5mg, 6 hourly for 48 hours

Question 8

Treatment of cushing’s (dependant for each cause)

Answer 8

1. Pituitary surgery (transphenoidal hypophysectomy)
2. Bilateral adrenalectomy (removal of both adrenal glands to prevent further cortisol production)
3. Unilateral adrenalectomy for adrenal mass (adrenal lump in one gland)

ALL treatments are proceeded by use of ALPHA blockers- this is because high blood pressure is an urgent issue due to VASONSTRICTION

Question 9

Pheneochromocytoma

Answer 9

A tumour of the adrenal medulla that leads to the production of loads of catecholamines

Question 10

Metrapyone mechanism of action

Answer 10

Inhibits 11b-hydroxylase

This slows down the cortisol synthesis pathway and thus can be used as a tretament for Cushing’s

Reduces production of cortisol and corticosterone

No negative feedback by 11-deoxycortisone so ACTH accumulates

Question 11

Uses of metrapyone

Answer 11

• Control of Cushing’s syndrome prior to surgery- patients are not good surgery candidates since they are predisposed to urgery wit thin skin (dose is according to serum cholesterol- should be between 150-300 nmol/L)
• Control of Cushing’s after radiotherapy

Question 12

Metrapyone effect on aldosterone production

Answer 12

11B-Hydroxylase (inhibited by metrapyone) is also relevant in the aldosterone production- converts 11-deoxycorticosterone to corticosterone

Inhibition leads to accumulation of 11-deoxycorticosterone and 11-deoxycortisone

These have mineralocorticoid properties- acts like aldosterone

causes salt retention and hypertension so cant use it long term

Question 13

Effect of metyrapone on sex steroid production

Answer 13

Since metyrapone blocks two arms of the pathway it funnels all production towards sex steroid synthesis

It causes an increase in adrenal androgens- can cause hirtuism

Question 14

Ketoconazole mechanism of action

Answer 14

Inhibits cytochrome P450 SCC (side chain cleavage) enzymes, thus blocking the production of glucocorticoids, mineralocorticoids and sex steroids

Question 15

Uses and unwanted actions of Ketoconazole

Answer 15

Uses: Cushings syndrome treatment and control of symptoms prior to surgery (orally active)

Unwanted actions:

• Nausea, vomiting, abdominal pain
• Alopecia
• Liver damage (could be fatal)
• Ventricular tachycardias
• Gnaecomastia, oligospermia, impotence

Question 16

Conns syndrome characteristics

Answer 16

Benign adrenocorticol tumour in the zona glomerulosa makes aldosterone in excess

Causes patients to retain sodium and lose potassium

HYPOTENSION and HYPOKALAEMIA

Question 17

Diagnosis of Conn’s syndrome

Answer 17

To identify primary hyperaldesteronism:

• If the patient has high blood pressure and low potassium levels on blood test

To identify Phyperaldo specific to Conn’s:

• Measure the aldosterone, if it is high, measure the renin, this should be supressed by the excess aldosterone

Question 18

Conns syndrome treatment

Answer 18

Medicine use, removal of tumour

to stop the effects of excess aldosterone you give mineralocorticoid receptor antagonist- SPIRINALACTONE

Question 19

Spironolactone mechanism

Answer 19

Converted to several active metabolites including CANRENONE, a competative antagonist of the mineralocorticoid receptor

Na+ reabsorption and K+ excretion in the kidney tubules

It is a potassium sparing diuretic

With bilateral adrenal hyperplasia, you may need to remove both adrenals (but dont want to do this to preserve cortisol production) In this case you use long term spirinalactone

Question 20

Unwanted actions of spirinalactone

Answer 20

Spirinalactone is a very non-specific so there are lots of side-effects;

• Causes menstrual irregularities (progesterone receptor antagonist)
• Causes gynaecomastia in men (androgen receptor antagonist)
• GI tract iritation

Question 21

Eplerenone effect

Answer 21

• Also a MINERALOCORTICOID RECEPTOR ANTAGONIST
• Has fewer side-effects than spironolactone so used more frequently
• More specific so interferes less with progesterone and androgen receptors
• MORE LIKELY TO BE USED LONG TERM

Question 22

Characteristics of phaechromoctoma

Answer 22

Tumours of the adrenal medulla which secrete catecholamines (adrenaline and noradrenaline)

Adrenaline gives you a rapid effect- causes a massive rise in blood pressure (300/150)

Causes sudden onset of panic, anxiousness, tachycardia and hypertension

Question 23

Clinical features of phaechromocytoma

Answer 23

If you see episodic severe hypertension in young people, phaeochromocytoma is a possibility

Could result in VENTRICULAR FIBRILLATION

Built up release could be tiggered after abdominal palpation or if there is a trauma

can cause myocardial infarction or stroke

Can also cause sudden cardiac death so is a medical emergency

Question 24

Management of Phaeochromocytoma

Answer 24

Eventually need surgery, but also requires careful preparation to prevent a hypertensive crisis which can be triggered by anaesthetic

First give an alpha blocker (May have to give IV fuids)

Now give beta blockade to prevent tachycardia