Suppressive effect of metyrapone on plasma corticotrophin immunoreactivity in normal man

Short term alterations of plasma corticotrophin immunoreactivity (ACTH) and cortisol were studied in healthy men under basal conditions and during intravenous administration of metyrapone. In the intravenous experiment, a low dose (1 g/5 h) and a high dose (4 g/5 h) of metyrapone ditartrate were infused. In the early phase of the metyrapone experiments, plasma ACTH fell from 9.46 +/- 0.95 (SE) pmol/l at 08.00 h to 7.7 +/- 1.1 pmol/l at 09.00 h (P greater than 0.05) in the low-dose experiment, and from 7.0 +/- 1.6 pmol/l to 4.6 +/- 0.9 pmol/l (P less than 0.05) in the high-dose experiment. A significant delayed increase of plasma ACTH secondary to the hypocortisolaemic stimulus was apparent in the high-dose experiment, in which plasma cortisol was maximally suppressed to 14 +/- 3 nmol/l at 13.00 h. No significant increase was observed in the low-dose experiment, the maximal suppression of plasma cortisol being 46 +/- 9 nmol/l at 14.00 h. The present data suggest dual effects of metyrapone on plasma ACTH: 1) a suppressive effect, the mechanism of which is not yet understood, and 2) the known increasing effect of 'feed-back' stimulation, which seems to be very sensitive to alterations of plasma cortisol only at cortisol levels lower than about 50 nmol/l. The suppressive effect of metyrapone may account for the frequently described inadequate response of plasma ACTH to metyrapone-induced hypocortisolaemia. Particularly, the diagnostic validity of the very short versions of the metyrapone test would seem to be seriously questioned.