Cushing's syndrome

Question 1

What is Cushing’s syndrome?

Answer 1

Signs and symptoms that develop after prolonged abnormal elevation of cortisol

Question 2

What is Cushing’s disease?

Answer 2

The specific condition where a pituitary adenoma (tumour) secretes excessive ACTH

Question 3

Name 5 features or symptoms of Cushing’s syndrome

Answer 3

• Round “moon” face
• Central Obesity
• Abdominal striae
• Buffalo Hump (fat pad on upper back)
• Proximal limb muscle wasting
• Hypertension
• Cardiac hypertrophy
• Hyperglycaemia (T2DM)
• Depression
• Insomnia
• Osteoporosis
• Easy bruising and poor skin healing

Question 4

Name 2 causes of Cushing’s syndrome

Answer 4

• Steroid medication (patients on long term high dose steroid medications)
• Cushing’s disease
• Paraneoplastic Cushing’s
• Adrenal tumour

Question 5

1) What is paraneoplastic cushing’s?
2) What is the commonest cause?

Answer 5

1) When excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release
2) Small cell lung cancer

Question 6

What is the test of choice for the diagnosis of Cushing’s syndrome?

Answer 6

Dexamethasone suppression test

Question 7

1) How does this test work?
2) How is this test performed?

Answer 7

1) A patient is given a low dose test. If this is normal Cushing’s syndrome can be excluded. If it’s abnormal a high dose test can be used to differentiate between causes
2) Patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night and their cortisol and ACTH is measured in the morning. The intention is to find out whether the dexamethasone suppresses their normal morning spike of cortisol

Question 8

What is the normal response in the low dose dexamethasone suppression test?

Answer 8

Dexamethasone suppresses the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. The hypothalamus responds by reducing the CRH output. The pituitary responds by reducing the ACTH output. The lower CRH and ACTH levels result in a low cortisol level

Question 9

In the high dose dexamethasone suppression test, will cortisol and ACTH be suppressed or not suppressed in a pituitary adenoma, and why?

Answer 9

Cortisol and ACTH will be suppressed as the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol

Question 10

In the high dose dexamethasone suppression test, will cortisol and ACTH be suppressed or not suppressed in an adrenal adenoma, and why?

Answer 10

Cortisol not suppressed but ACTH will be. In an adrenal adenoma, the cortisol production is independent from the pituitary. Therefore cortisol is not suppressed but ACTH is due to negative feedback to the hypothalamus and the pituitary gland

Question 11

In the high dose dexamethasone suppression test, will cortisol and ACTH be suppressed or not suppressed in paraneoplastic Cushing’s/ectopic ACTH, and why?

Answer 11

Both won’t be suppressed as ACTH production is independent of the hypothalamus.

Question 12

Name an option for the treatment of Cushing’s syndrome

Answer 12

• Remove the underlying cause i.e. surgery or stop drugs
• Remove both adrenal glands and give replacement steroid hormones for life if surgical removal isn’t possible

Question 13

Name a cause of pseudo-cushings disease

Answer 13

• Excessive alcohol intake
• HIV
• Depression

Question 14

What metabolic abnormality can be caused by Cushing’s syndrome and how?

Answer 14

Hypokalemic metabolic acidosis (cortisol at high levels can stimulate the effects of aldosterone - increased potassium and subsequent bicarbonate excretion)