Metyrapone

Metyrapone is a medication that inhibits the enzyme 11β-hydroxylase (CYP11B1) in the adrenal cortex, blocking the final steps of cortisol and corticosterone synthesis. By preventing conversion of 11-deoxycortisol to cortisol, metyrapone lowers cortisol levels and reduces negative feedback on the hypothalamic–pituitary–adrenal axis. In a person with an intact pituitary, ACTH secretion increases in response, and precursors such as 11-deoxycortisol accumulate.

It is used primarily as a diagnostic tool to assess the hypothalamic-pituitary-adrenal axis, notably in the metyrapone test. After administration, morning serum 11-deoxycortisol and ACTH are measured to determine whether ACTH can rise in response to decreased cortisol. The test aids in differentiating primary from secondary adrenal insufficiency and evaluating pituitary function. Metyrapone is also used therapeutically in some cases of Cushing's syndrome or other forms of hypercortisolism, particularly when surgery is not feasible or other medical therapies are unsuitable. In such cases, it may be employed to reduce cortisol production while planning definitive treatment, with glucocorticoid replacement as needed.

Adverse effects relate to the accumulation of mineralocorticoid precursors and cortisol axis disruption. These can include hypertension, edema, and hypokalemia; fatigue, nausea, and vomiting; rash; and, in some individuals, hirsutism or acne due to increased adrenal androgen production. There is a risk of adrenal crisis if cortisol deficiency is not adequately managed or therapy is stopped abruptly. Drug interactions may occur with other steroids or medications affecting steroid metabolism.

Metyrapone is taken orally and is marketed under various brand names, including Metopirone. It is prescription-only and used in specialized endocrinology settings. Safety during pregnancy is not well established and use requires careful risk–benefit assessment.