Quantitation of the accelerating effect of metyrapone on cortisol metabolism

Quantitation of the accelerating effect of metyrapone on cortisol metabolism has been made by determination of the metabolic clearance rate (MCR) of exogenous cortisol during a metyrapone load. Six adrenalectomized patients were studied. The slope of cortisol concentrations in plasma was determined after intravenous administration of 0-3 mg cortisol/kg b.w. with or without metyrapone 17-5 mg/kg b.w./h. In all six patients studied, the MCR of cortisol increased during metyrapone load from an average of 12-3 +/- 5-0 (SD) l/h to 29-6 +/- 15-7 (SD) l/h or corrected for body weight 3-0 +/- 1-1 (SD) ml/kg b.w./min to 7-1 +/- 2-5 (SD) ml/kg b.w./min. The discrepancy discovered in clinical practice between the relatively small rise in plasma total corticosteroid concentration and the greater increase in urinary excretion of corticosteroid metabolites during the metyrapone test may be explained by the findings in this study.