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.

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

“…In very early publications, only 20ß-dihydrocortisol and 20-ß-dihydrocortisone were described äs occurring in human and dog urine (l, 2). Recently, we found that both the a-and ß-isomers of cortisol and cortisone are present in human urine and that the -isomers are predominant (3,4). The origin of these urinary 20-reduced steroids obviously is multilocal.…”

Multiple-sites of inhibition by intravenous metyrapone of human adrenal steroidogenesis

“…1) document not only the absence of unspecific ACTH surges but, moreover, a fall of plasma ACTH in the intitial phase of metyrapone infusion. The molecular mechanism of this effect of metyrapone has not been elucidated so far (Schöneshöfer et al 1983). Initial step of adrenal steroidogenesis It was the primary intention of the present doseresponse experiments to monitor alterations of the 'cholesterol-cleavage enzyme' by plasma concentra¬ tions of its enzymatic product pregnenolone.…”

Pharmacological Therapy of Cushings Syndrome: Drugs and Indications

“…7), is a pyridine derivative widely used in the differential diagnosis of Cushing's syndrome and in the assessment of the integrity of the pituitary-adrenal axis [115,116]. An inhibition of ACTH secretion by high doses of metyrapone has also been reported [117]. 11 -hydroxilase blockade also inhibits aldosterone biosynthesis [116].…”