Improved single-dose metyrapone test

One dose of metyrapone (1.5 g) administered at 6 AM, with subsequent measurement of plasma ACTH, 11-deoxycortisol, or 17-hydroxycorticosteroids (17-OHCS) (cortisol + 11-deoxycortisol) at noon and 2 PM allowed an accurate assessment of the pituitary-adrenal reserve. Eighteen subjects with a normal pituitary-adrenal reserve were studied before and after the administration of this single metyrapone dose. By noon, plasma ACTH rose from a premedication value of 39 +/- 22 (SD) to 193 +/- 104 pg/ml and 11-deoxycortisol, from 0.0 +/- 0.3 (SD) to 9.0 +/- 2.7 microgram/dl. By 2 PM, plasma 17-OHCS had increased from a premedication value of 5.0 +/- 1.5 (SD) to 16.0 +/- 1.8 microgram/dl. The differences between pre- and postmedication values were statistically significant for all indices measured (P less than 0.001). No overlap was found between values before and after metyrapone. This protocol eliminates the need for metyrapone administration every 4 h over a 24-h period. It offers the advantage of low dose and low toxicity. The integrity of the pituitary-adrenal axis can be demonstrated by measuring either plasma ACTH and 11-deoxycortisol or even 17-OHCS 6 to 8 h after the administration of this single metyrapone dose.