title: Suppressive effect of metyrapone on plasma corticotrophin immunoreactivity in normal man.
abstract: 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.
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007263:Infusions, Parenteral; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay; D013997:Time Factors
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008797:Metyrapone