Extra-adrenal actions of metyrapone in man. Effects on plasma cortisol disappearance, growth hormone secretion and glucose metabolism.

Abstract

Extra-adrenal effects of high doses of oral metyrapone (6 g over 210 min) were investigated in 9 normal subjects. Plasma sugar increased markedly. Plasma cortisol fell dramatically from 12.3±1.7 μg/100 ml (mean±sem) at 0 min to 6.6±1.1 μg/100 ml at 30 min and to 3.0±0.6 μg/100 ml at 60 min. The disappearance half-time of endogenous cortisol from plasma, calculated over the 0–30 min period, averaged 32 min (range 22–49 min). This acceleration in the disappearance of cortisol from plasma was confirmed by control studies with labeled cortisol performed in 3 subjects. These data strongly suggest an extra-adrenal action of metyrapone upon cortisol catabolism and/or utilization. A significant increase in plasma levels of immunoreactive human growth hormone (IRHGH) was observed in spite of concomitant hyperglycemia; the maximal increment over basal level averaged 10.4±2.5 ng/ml. There was a significant negative correlation between the cortisol disappearance half-time and the maximal IRHGH increment. It is suggested that the IRHGH release could be mediated through the plasma cortisol fall.