Metyrapone
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| Trade names | Metopirone |
| AHFS/Drugs.com | Consumer Drug Information |
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Oral |
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| Pharmacokinetic data | |
| Biological half-life | 1.9 ±0.7 hours. |
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| ECHA InfoCard | 100.000.188 |
| Chemical and physical data | |
| Formula | C14H14N2O |
| Molar mass | 226.274 g/mol |
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Metyrapone (trade name Metopirone) is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).
Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels.
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 remain 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.
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). This does not exhibit the side effect of hirsutism.
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Wikipedia