Effects of Metyrapone and Corticotropin Infusion on Cortisol Disappearance Rate in Man

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Abstract
Eleven normal subjects underwent iv metyrapone stimulation tests. The adrenal effect was evaluated on the basis of specific determinations of the changes in cortisol and compound S concentrations in the blood over a period of 12 hr. Only the results of the first 60 min are reported in the present paper. At 8 am the concentrations of plasma cortisol and plasma compound S were 14.0 ± 3.4 (sd) and 0.44 ± 0.25 (sd) μg/100 ml, respectively. At 9 am 4.2 ± 1.6 (sd) and 2.51 ± 1.57 (sd), respectively. In all subjects a pronounced and significant decrease in the half-life of endogenous cortisol was observed, compared with the calculated normal minimum value. The increase in plasma compound S concentration was significant within the first 60 min. It is reasonable to explain the acceleration in the cortisol disappearance rate by an extra-adrenal metyrapone effect alone. Activation of feedbackinduced corticotropin release is probably induced simultaneously and could be a contributory factor. In order to clarify this, 11 patients who had previously undergone bilateral adrenalectomy, were studied. The disappearance rate for exogenously administered cortisol is visualised in three curve sections, i.e. before metyrapone, during metyrapone and during metyrapone and corticotropin infusions. Significant changes in slope coefficients and the corresponding half-life values for the individual curve sections are indicated. The conclusion reached from this study confirms the theory that increased cortisol disappearance rate during metyrapone administration is an isolated extraadrenal metyrapone effect. However the mechanism governing this remains so far unexplained.

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