Circadian rhythm of urinary 17-hydroxycorticosteroids during metyrapone-induced ACTH release in normal subjects

The circadian rhythm of urinary 17-OHCS was studied in nine normal subjects before and after oral metyrapone administration (750 mg every 4 hrs over a period of 24 hrs). The test was carried out twice in each subject with a shift of 12 hrs in the time of first administration (0800-test and 2000-test). For data from serial measurements of steroid metabolites on urine collected at 2-h intervals, the least squares fit of a 24-h cosine curve allowed the demonstration of a rhythm both in control conditions and during the 48-h span following metyrapone administration. Circadian acrophases were substantially similar. Total urinary 17-OHCS output in the first 24-h day following metyrapone was higher in the 2000-test as compared with the 0800-test (P less than .001). Conversely, in the second 24-h day, higher values were obtained in the 0800-test (P less than .025). The combined 48-h exretion, however, was identical in the two groups. The results suggest a time-limited action of metyrapone upon the pituitary-adrenal axis, since the increased excretion of 17-OHCS seems essentially accounted for by an exaggerated impulsive phase of ACTH secretion during the early morning hours.