The Discrepancy Between ACTH and 11-Deoxycortisol Levels in a Single Dose Metyrapone Test

Abstract

Five healthy men were given 1.0 gr of metyrapone p.o. (MTP test) with and without 0.5 gr of 1- dopa p.o. (DOPA-MTP test) or 10 mg of metoclopramide p.o. (MTC-MTP test) and plasma 11-deoxycortisol, cortisol, ACTH and pregnenolone (only in MTP test) were determined before and hourly after the drug administrating for 6 hrs. In the MTP test, plasma 11-deoxycortisol increased significantly at 1 hr with peak at 5 hrs, whereas the significant increases of pregnenolone and ACTH were not seen until 2 hrs, although plasma cortisol levels were reduced definitely at 1 hr. Thus, the increase of 11-deoxycortisol in the MTP test should be divided into two phases; the increase in the phase II (later than 3 hrs) is due to pituitary ACTH reserve, and that in the phase I (until 2 hrs) is due to unknown mechanism other than pituitary reserve. In the DOPA-MTP test, the 11-deoxycortisol rise was significantly larger than that in the MTP test. The increases in 11-deoxycortisol at 4 hrs and 5 hrs in the MTC-MTP test were significantly smaller than those in the MTP test. The cortisol/(cortisol + 11-deoxycortisol) ratio reached its lowest point at 3 hrs in the MTP test and at 2 hrs (a 1 hr advance) in the DOPA-MTP and MTC-MTP tests. However, there were no significant differences in the responses of cortisol and ACTH to metyrapone in these tests. This provides evidence for a discrepancy between plasma 11-deoxycortisol and ACTH responses in a single dose metyrapone test, as disclosed by the simultaneous administration of dopamine agonist or antagonist with metyrapone.