Metyrapone

Metyrapone (trade name Metopirone) is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).

Mechanism

Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels.

Uses

Metyrapone can be used in the diagnosis of adrenal insufficiency. Metyrapone 30 mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220 nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore if 11-deoxycortisol levels do not rise and remains less than 7 µg/dl (202 nmol/l) and ACTH rises, then it is highly suggestive of adrenal insufficiency, if neither 11-deoxycortisol nor ACTH rise it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus.