SU-4885経口投与時の血漿ACTH活性の変動

抄録

The recent progress in the field of investigation of hypothalamic pituitary adrenal system is remarkable, and many reports concerning the experimental and clinical use of preparations of adrenocortical inhibitors have been published. The most widely accepted of these prreparations is SU-4885 (Metopirone, or Metyrapon.) It has the unique property of selectively inhibiting 11-β hydroxylation inthe biosynthesis of the three main corticosteroids : Cortisol, Corticosterone, & Aldosterone.
The present study was undertaken to clarify the relationship between plasma ACTH activity and Plsama 17-0HCS after oral administration of SU-4885 Materials & Methods
Eleven patients were studied. None of them had received exgenous steroid previously. Cardiovascular hepatic, and renal studies were estivated to be within normal limits in all of them. Daily 24-hour specimens of urine were collected (6 : 00 A.M. to 6 : 00 A.M.) throughout a week, analyzed for urinary 17-0HCS by the method of Peterson modified Glenn-Nelson's. SU-4885 was administered orally in a dose of 750 mg. every 4 hours 5 times. (6 A.M., 10 A.M., 2PM., 4P.M., 6P.M., 10P.M.).
No side-effects were observed during such admininistration. Blood samples were collected during every SU-4885 administration period, and Plasma 17-0HCS was measured by Rudd's method. Estimation of plasma ACTH activity was performed using the method of Arimura modified Lipscomb-Nelson's Results & Discussion
Minimum effective concentration of plasma ACTH-activity measured by Arimura's method was 0, 7 mU/d1 in human blood. Plasma ACTH-Activity at 6 : 00 A.M. starting SU-4885 administration was detectable, (0.7 to 0.9 mU/dl) in 7 patients and non-dettecable in 4 patients. Plasma 17-OHCS measured simultaneously was 8.6 to 13.7, e μg / dl. in blood. As 10 : 00 A.M., plasma ACTH activity was detectable (1.0 to 1.6 mU/dl.) in all patients and plasma 17-0HCS was slightly decreased in 8 patients, stationary in one, and slightly inereased in 2 (range 7.7 to 12.0 μg dl.). The decrease might suggest that the deppression of steroid-biosynthesis by SU-4885 had occurred transiently.
Plasma ACTH activity at 2 : 00 P.M. was 1 : 2 to 1.5 mU/dl., 1.2 to 1.7 mU/dl at 6 : 00 P.M., and 1.0 to 1.6 mU/dl. at 10 : 00 P.M.
Plasma 17-0HCS levels had gradually increased : 14.9 to 23.0 μg/dl. at 2 : 00 P.M., 20.1 to 26.6 μg/dl. at 6 : 00 P.M. and 25.1 to 32.5 μg/dl. at 10 : 00 P.M.
Pituitary ACTH discharge or secretion following the administration of SU-4885 is presumably caused through negative feedback mechanism triggered by the decrease in the level of plasma cortisol and another mechanism might exist in pitultary ACTH discharge or secretion following surgical intervention.
As corollaries to this postulate, it is inferred that SU-4885-test is useful diagnostic adjunct for estimation of pituitary reserve, but it does not necessarily demonstrate pituitary adrenocortical response following surgical intervention.