Metyrapone can be used in the diagnosis of
adrenal insufficiency. Metyrapone 30 mg/kg, maximum dose 3,000 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 remain less than 7 μg/dL (202 nmol/L) and
adrenocorticotropic hormone (ACTH) rises, then it is highly suggestive of
adrenal insufficiency. If neither 11-deoxycortisol nor ACTH rise, it is highly suggestive of an impaired
hypothalamic–pituitary–adrenal axis at either the
pituitary or
hypothalamus. The metyrapone test may aid in verifying the cause of
Cushing's syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH-producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone. Metyrapone is used for the medical control of hypercortisolism in Cushing's syndrome (ACTH dependent or independent). The aim for medical treatment is to achieve pre-operative control of hypercortisolism, or for control of residual disease persisting post-operatively (TSS, adrenalectomy). It is not for long term definitive treatment/cure, only as an adjunct (surgery is the aim for cure in most causes of Cushing's syndrome). Metyrapone hence acts by inhibiting adrenal steroidogenesis. One side effect is hirsutism (in women) because of the excess androgen precursors created. The other commonly used agent for medical treatment of Cushing's is
ketoconazole (an anti-fungal agent), though it is not FDA approved for Cushing's. This does not exhibit the side effect of hirsutism, but does carry a high risk of hepatoxicity and other serious side effects.
Levoketoconazole, an enantiomeric form of ketoconazole, is FDA approved to treat Cushing's and carries a lower risk of hepatoxicity and other serious side effects compared to ketoconazole. ==Pharmacology==