Cushing's syndrome

Question 1

What causes it?

Answer 1

Persistently and inappropriately elevating circulating glucocorticoid levels.

Most cases result from administration of synthetic steroids or ACTH for the treatment of medical conditions e.g. Asthma.

Spontaneous Cushing’s syndrome is rare and two-thirds of cases result from excess ACTH secretion from the pituitary gland.

Alcohol excess mimics Cushing syndrome clinically and biochemically (pseudo-Cushing’s syndrome). The pathogenesis is incompletely understood but the features resolve when alcohol is stopped.

Question 2

What is the difference between Cushing’s syndrome and Cushing’s disease?

Answer 2

Cushing’s disease must be distinguished from Cushing’s syndrome. The latter is a general term which refers to the abnormalities resulting from a chronic excess of glucocorticoids whatever the cause, whereas Cushing’s disease specifically refers to excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary (usually microadenoma, less often cortophin hyperplasia).

Question 3

How does it present?

Answer 3

Obesity: fat distribution is typically central, affecting the trunk, abdomen and neck (buffalo hump).

Plethoric complexion with a moon face.

The skin bruises easily and is thin, there are purple striae on the abdomen, breast and thighs. Pigmentation occurs with ACTH-dependent cases.

Patients with ectopic production of ACTH tend to have rapidly progressive symptoms and have evidence of the primary tumour.

Question 4

Signs on examination?

Answer 4

Moon face
Plethora
Depression/psychosis
Acne
Hirsutism
Frontal balding
Thin Skin
Bruising
Poor wound healing
Pigmentation
Skin infections
Hypertension
Pathological fractures (especially vertebrae and ribs). Osteoporosis. Kyphosis. Buffalo hump. 
Central obesity
Striae
Oedema
Proximal myopathy
Proximal muscle wasting
Glycosuria.

Question 5

Investigations

Answer 5

The 48-hour low dose dexamethasone suppression test is the most reliable screening test. Normal individuals supress plasma cortisol. In most people urinary free cortisol is raised.

Adrenal CT or MRI will detect adrenal adenomas and carcinomas.

Pituitary MRI will detect some, but not all, pituitary adenomas.

Plasma ACTH levels are low or undetectable in adrenal gland disease.

Can also do a corticotrophin-releasing hormone test. An exaggerated plasma ACTH response to exogenous CRH suggests pituitary-dependent Cushing’s disease.

Question 6

Treatment

Answer 6

Surgical removal is indicated for most pituitary (usually a trans sphenoid approach) and adrenal tumours and may be appropriate for many cases of ectopic ACTH-producing tumours.

Drugs which inhibit cortisol