The discrepancy between plasma 11-deoxycortisol and ACTH concentrations in a single dose metyrapone test in normal...

A single dose methyrapone test (MTP test) was carried out on 6 normal men by administering 1.0 g of metyrapone at 08.00-09.00 h with and without dexamethasone (DXM-MTP test) pre-treatment. Plasma 11-deoxycortisol, pregnenolone, ACTH and cortisol were measured before administration of the drug, and at hourly intervals for 6 h. In the MTP test, 11-deoxycortisol increased significantly at 1 h with a peak at 5 h, whereas significant increases in pregnenolone and ACTH were not seen until 3 h. There was a definite decrease in the cortisol level at 1 h with the lowest level measured at 2 h. Thus, a time discrepancy between plasma 11-deoxycortisol and ACTH concentrations was observed. The increase in 11-deoxycortisol after metyrapone should be divided into two phases: the increase in phase II (after 3 h) is due to the pituitary ACTH reserve, and that in phase I (the first 2 h) is due to some mechanism other than the pituitary ACTH reserve. The increased amount of 11-dexoycortisol in phase II (218.1 nmol) occupied 60.5% of the total increased amount in phases I and II (360.6 nmol). The cortisol/(cortisol + 11-deoxycortisol) ratio reached its lowest point 3 h after metyrapone treatment. This might be due to the initiation of an additional surge in 11-deoxycortisol by the ACTH reserve at 3 h.