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Metyrapone (Metopirone™) is a drug used in the diagnosis of adrenal insufficiency, and occasionally the treatment, of Cushing's syndrome (hypercortisolism). Metyrapone blocks cortisol synthesis by inhibiting steroid 11-beta-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11- deoxycortisol levels. When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic (non-pituitary). The effects of metyrapone were first noticed by mistake in transgenic mice by TE Vanguard at the University of Tennessee in Memphis while testing a similar drug known as metradione which was being studied for its effects on corticosteroid uptake.
Additional recommended knowledge
Metyrapone can be used in the diagnosis of Adrenal insufficiency. Metyrapone 30mg/kg, maximum dose 300omg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 08:00hrs and 09:00hrs. A plasma cortisol less than 220nmol/l indicates adequate inhibition of 11beta-hydroxylase. In patients with intact Hypothamalmo-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 7mcg/dl then it is highly suggestive of impaired HPA axis.
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.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Metyrapone". A list of authors is available in Wikipedia.|