Short-term kinetics of serum adrenal steroids and plasma ACTH after a single dose of metyrapone in man

Abstract

The in vivo influence of metyrapone (M) on different adrenal enzymes has been studied by simultaneous measurement of serum progesterone (P), 17-hydroxyprogesterone (17-OHP), deoxycorticosterone (DOC), corticosterone (B), deoxycortisol (S), 18-hydroxydeoxycorticosterone (18-OHDOC), aldosterone and cortisol (F) as well as by the measurement of plasma ACTH before and after oral administration of 40 mg of M/kg at 08:15 in four healthy male subjects. The well known inhibitory effect of M on adrenal 11-hydroxylase is demonstrated by a decrease of serum F and B and a synchronous increase of serum S and DOC after administration of M. The additional inhibition of 18-hydroxylase by M is documented by a decrease of serum 18-OHDOC in spite of a marked increase of serum DOC after M. The moderate increase of serum P and 17-OHP soon after drug administration, although plasma ACTH is highly elevated at this time, as well as the marked increase of these steroids in the afternoon synchronously to a rise of serum F and B suggest a further inhibitory effect of M on an enzyme prior to the total corticosteroid biosynthesis. This effect of M should be taken into account if ACTH activity is monitored in terms of adrenal steroid output in the metyrapone test.