Metyrapone dosing

Other tests that can help determine the etiology include the high-dose dexamethasone suppression test, plasma ACTH test, metyrapone stimulation test, corticotropin-releasing hormone stimulation test or inferior petrosal sinus sampling. 

Two further communications [31,32] reported that prednisolone stearoylglycollate, in substantial doses, was the least potent anti-inflammatory steroid (among the representative series studied) with respect to pituitary-adrenal inhibition. The order of increasing suppressive potency in this test was prednisolone stearoylglycollate, prednisolone, triamcinolone, dexamethasone, betamethasone. Techniques used in the comparative evaluations included the metyrapone test and gas-liquid chromatography. 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

To the extent that there was a significant reduction of the 11-deoxycortisol response in PTSD in the absence of an attenuated ACTH response, this would indeed support the idea of a reduced adrenal output. However, the trend for an ACTH response suggests that part of the failure to achieve statistical significance may have also occurred because of Hmited power, particularly given the lack of evidence for increased ambient ACTH levels in PTSD relative to normal controls. Dose-response studies using the higher vs lower dose of metyrapone should certainly be conducted to further address this critical issue. 

Increased ACTH levels to high dose metyrapone Yes No... 

Metyrapone is commonly used in tests of adrenal function. The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion. A dose of 300-500 mg every 4 hours for six doses is often used, and urine collections are made on the day before and the day after treatment. In patients with Cushing s syndrome, a normal response to metyrapone indicates that the cortisol excess is not the result of a cortisol-secreting adrenal carcinoma or adenoma, since secretion by such tumors produces suppression of ACTH and atrophy of normal adrenal cortex. 

Metyrapone (m). 2-methyl-l,2-bis-(3-pyridyl)-l-propanone, continues to be used clinically for determining the pituitary s ability to secrete ACTH. The adrenal response to the drug as measured by the secretion of F and S is found to depend on the pituitary reserve of ACTH and the degree of dose-dependent inhibition of lip-hydroxylase39. The failure to include the increased secretion of DOC leads to a low value for the inhibition of the enzyme. The varied M response seen in liver disease may result from altered metabolism of the drug. NADPH does not reverse the M inhibited conversion of P to B, 18-OH B and Aldo by mouse adrenal quarters. ... 

Pretreatment with cyproheptadine 4 mg every 6 hours, 2 days before and throughout a standard metyrapone test (750 mg every 4 hours for 6 doses), redueed the metyrapone-induced urinary 17-hydroxycorticosteroid response in 9 healthy subj ects by 32%, and also reduced the serum 11 -deox-... 

The drag metyrapone (2-methyl-l,2-di(pyridin-3-yl)propan-l-one) has been used for decades to inhibit cortisol biosynthesis, primarily through its inhibition of P450clip [83]. Metyrapone is a relatively weak inhibitor, requiring several grams per day in 3 divided oral doses. Etomidate (ethyl 1 -(1 -phenylethy 1)-1 H-iraidazole-5-car-... 

Urinary Steroid Dynamics After a Single Dose of Metyrapone Acta Endocrinol. (Copenhagen) 77 (2) 221-240 (1974) CA 82 40247k... 

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