Cushing's syndrome

Question 1

Cushing’s Syndrome vs Cushing’s Disease?

Answer 1

Syndrome: used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol

Disease: specific condition where a pituitary adenoma secretes excessive ACTH. Cushings disease causes a cushings syndrome, not vice versa

Question 2

Causes of Cushing’s syndrome

Answer 2

• Exogenous steroids(in patients on long term high dose steroid medications)
• Cushing’s disease(apituitary adenomareleasing excessiveACTH)
• Adrenal Adenoma(a hormone secreting adrenal tumour)
• Paraneoplastic Cushing’s → when excess ACTH is released from a cancer (not from pituitary) and stimulates excessive cortisol release. Small cell lung cancer is the most common cause of paraneoplastic Cushing’s.
• alcohol excess can mimic cushing’s disease (pseudo cushing’s syndrome)*

Question 3

What is in excess in Cushing’s

Answer 3

Cortisol

ACTH dependent or independent

Question 4

ACTH dependent causes

Answer 4

Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia

ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes

Question 5

ACTH independent causes

Answer 5

iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)

Question 6

Pseudo-Cushing’s

Answer 6

mimics Cushing’s

often due to alcohol excess or severe depression

causes false positive dexamethasone suppression test or 24 hr urinary free cortisol

insulin stress test may be used to differentiate

Question 7

Risk factors

Answer 7

• high levels of stress
• Alcohol excess → pseudo cushings syndrome

Question 8

Clinical presentation: cushings

Answer 8

round in the middle with thin limbs

• round “moon” face
• central obestiy
• abdominal striae → central obesity has caused stretch marks on the skin
• buffalo hump (fat pad on upper back)
• proximal limb muscle wasting

high levels of stress horomone:

• hypertension
• cardiac hypertrophy
• hyperglycaemia and type 2 diabetes
• depression
• insomnia

extra effects:

• osteoporosis
• easily burising and poor skin healing
• hyperpigmentation as increased ACTH is capable of binding to melanocyte-stimulating hormone receptors (MSH)

Question 9

General findings consistent with Cushing’s syndrome

Answer 9

A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.

Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels.

Question 10

Tests to confirm Cushing’s syndrome

Answer 10

The two most commonly used tests are:

overnight dexamethasone suppression test:
- this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
- patients with Cushing’s syndrome do not have their morning cortisol spike suppressed

24 hr urinary free cortisol

Question 11

First-line localisation test?

Answer 11

9am and midnight plasma ACTH (and cortisol) levels.

If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma

Question 12

High-dose dexamethasone suppression test

Answer 12

The high-dose dexamethasone suppression test may be used to localise the pathology resulting in Cushing’s syndrome. This test may be interpreted as follows:

Cortisol: not suppressed, ACTH: suppressed = Cushings syndrome due to other causes (eg adrenal adenomas)

Cortisol: suppressed, ACTH: suppressed = Cushing’s disease (ie pituitary adenoma - ACTH secretion)

Cortisol: not suppressed, ACTH: not suppressed = Ectopic ACTH syndrome

Question 13

Other tests?

Answer 13

CRH stimulation
if pituitary source then cortisol rises
if ectopic/adrenal then no change in cortisol

Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion.

An insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’s.

Question 14

Treatment of Cushing’s syndrome?

Answer 14

The main treatment is to remove the underlying cause (surgically remove the tumour)

• Trans-sphenoidal(through the nose) removal of pituitary adenoma
• Surgical removal of adrenal tumour
• Surgical removal of tumour producing ectopic ACTH

If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the patient replacement steroid hormones for life.