Cushing’s disease - Adrenal axis

Cushing’s disease

Definition

In 1932, Harvey Cushing described pituitary adenomas as a cause of adrenocortical excess.

Incidence/prevalence

80% of Cushing’s syndrome are due to a pituitary cause.

Age

Any age, peak 20–40 years.

Sex

8F : 1M

Aetiology

In virtually all patients, an ACTH-secreting pituitary adenoma is found, occasionally the cause is hypothalamic oversecretion of corticotrophin releasing hormone (CRH).

Pathophysiology/clinical features

As for Cushing’s syndrome. Unlike patients with ectopic ACTH syndrome, patients with pituitary adenomas rarely have hypokalaemia, weight loss, anaemia or hyperpigmentation.

Macroscopy

Bilateral adrenocortical hyperplasia twice the size of normal, with thickening of zona reticularis and the zona fasciculata. The zona glomerulosa appears normal, because mineralocorticoid production is controlled primarily by the renin–angiotensin system.

Microscopy

The pituitary tumour is normally a microadenoma. The cells contain ACTH and its related peptides.

Investigations

As for Cushing’s syndrome.

Management

The treatment of choice is transsphenoidal hypophysectomy. Irradiation is used post-surgery, for patients where complete resection was not possible. Drugs which inhibit adrenal cortisol synthesis are often used as adjunctive therapy, e.g. ketoconazole, metyrapone and aminog-lutethimide. Their disadvantage is that they increase ACTH secretion so this enzyme inhibition is overcome and the clinical effect is short-lived.

Bilateral adrenalectomy is still used if the adrenals have become semi-autonomous, however it must be followed by pituitary treatment (e.g. irradiation) as otherwise the pituitary adenoma can progress to cause hyperpigmen-tation, local pressure effects and Nelson’s syndrome (an ACTH-secreting tumour of the pituitary which enlarges post-bilateral adrenalectomy).