What are the causes of Cushing's Syndrome?

Excessive glucocorticoid administration (e.g for rheumatoid arthritis) is by far the most common cause of Cushing's syndrome. This should be readily diagnosed from a careful history.

The remaining cases are caused by organic conditions. These can be classified as:

  • ACTH-dependent Cushing's syndrome
    Excess ACTH stimulates the adrenal gland to over-produce cortisol
  • ACTH-independent Cushing's syndrome
    The adrenal gland autonomously produces excess cortisol as a result of a tumour or hyperplasia

ACTH-dependent Cushing's syndrome

Cushing's disease: Accounts for approximately 65% of organic cases. The most common cause is an ACTH-secreting microadenoma in the anterior pituitary. Rarely, macroadenomas are seen.

Ectopic ACTH syndrome: Involves tumours occurring outside the pituitary secreting ACTH, such as bronchial carcinoid tumours. They account for 14% of organic cases of Cushing's syndrome.

Ectopic CRH syndrome: This is very rare with tumours occurring outside the hypothalamus producing corticotrophin releasing hormone (CRH), which raises ACTH levels and therefore cortisol levels. They account for less than 1% of organic Cushing's syndrome.

ACTH-independent Cushing's syndrome

Adrenal adenoma: These are benign tumours of the adrenal gland secreting cortisol. They are generally larger than 2cm and are the most common cause of ACTH-independent Cushing's syndrome, accounting for 10% of organic causes of Cushing's.

Adrenal carcinoma: These are malignant tumours of the adrenal cortex producing, amongst other hormones, cortisol. Often androgens may be produced as well resulting in hirsuitism and virilisation of women. Normally they are large tumours, > 6cm in diameter. They are very rare in adults, accounting for 8% of organic causes of Cushing's, but occur more commonly in children.

Nodular hyperplasia: This is non-tumorous excessive growth of the adrenal gland. Where the resulting nodules secrete cortisol. The aetiology of this is still to be determined. It accounts for 2% of organic causes of Cushing's.

What are pseudo-Cushing's syndromes?

This is Cushing's syndrome associated with alcoholism and/or depression in patients. It accounts for 2% of the causes of Cushing's syndrome. Blood and urinary cortisol levels may be raised and a disturbed circadian rhythm is often seen. Stopping alcohol consumption or treatment of the depressive disorder will result in cortisol levels returning to normal.