Cushing's Syndrome

Question 1

Cushing’s Disease vs Cushing’s Syndrome

Answer 1

Cushing’s Syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol.

Cushing’s Disease is used to refer to the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH

Question 2

Cushing’s Syndrome Causes

Answer 2

Too much ACTH:

• Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
• ectopic ACTH production (5-10%): e.g. small cell lung cancer

Too much cortisol:

• Exogenous iatrogenic steroids
• adrenal adenoma (5-10%)
• adrenal carcinoma (rare)
• Carney complex: syndrome including cardiac myxoma

Question 3

Clinical Features

Systemic features

Answer 3

Round in the middle with thin limbs:

• Round “moon” face
• Central Obesity
• Abdominal striae
• Buffalo Hump (fat pad on upper back)
• Proximal limb muscle wasting

ACTH dependent: skin hyperpigmentation

Systemic Features

• Hypertension
• Cardiac hypertrophy
• Hyperglycaemia (Type 2 Diabetes)
• Depression
• Insomnia
• Osteoporosis
• Easy bruising and poor skin healing

ABG: hypokalaemic metabolic alkalosis

Question 4

First line tests used to diagnose Cushing’s Syndrome

Answer 4

24 HOUR URINARY FREE CORTISOL

Overnight LOW DOSE (1mg) DEXAMETHASONE SUPPRESSION TEST
- normal response = negative feedback causing low CRH, ACTH and cortisol levels

Question 5

Second line tests (i.e. localisation tests)

Answer 5

MIDNIGHT AND 9AM ACTH LEVEL MEASUREMENTS
- If ACTH is suppressed then ACTH independent cause is likely such as an adrenal adenoma
(so CT scan the adrenals)

HIGH DOSE (8mg) DEXAMETHASONE SUPPRESSION TEST
- In Cushing’s Disease (pituitary adenoma) the pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol.

• Where there is ectopic ACTH (e.g. from a small cell lung cancer), neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland.

CRH CORTICOTROPIN TEST
- Cortisol rises with pituitary adenoma but not ectopic ACTH

Question 6

Management

Answer 6

Surgically Remove tumour:

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

Medical:

• Bone protection: Bisphosphonate + Calcium + Vitamin D
• Metyrapone and ketoconazole if ectopic ACTH

[Tyra banks would laugh at you if you had central obesity and it would make you wish you were on a keto diet]

Question 7

Nelson’s Syndrome

Answer 7

enlargement of an adrenocorticotropic hormone-producing tumour in the pituitary gland, following surgical removal of both adrenal glands in a patient with Cushing’s disease

So patient presents with bitemporal hemnianopia and skin pigmentation