Blocking 3-hydroxy-3-methylglutaryl coenzyme A reductase with ML-236B enhances the plasma cortisol response to adrenocorticotropin in patients with hypercholesterolemia.

The effect of ML-236B, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipids and plasma cortisol responses to ACTH were studied in 11 hypercholesterolemic patients. Mean serum total cholesterol decreased significantly [279 +/- 57 (SD) mg/dl to 213 +/- 48 mg/dl], as did serum triglycerides (211 +/- 140 mg/dl to 166 +/- 125 mg/dl) and low density lipoprotein cholesterol (195 +/- 49 mg/dl to 139 +/- 47 mg/dl), after ML-236B treatment for 12 weeks in doses ranging from 15-60 mg/day. The mean basal plasma cortisol level was not changed after ML-236B treatment, but the mean absolute increment in plasma cortisol increased from 15.4 +/- 3.4 to 26.7 +/- 8.4 micrograms/dl (P less than 0.005) after treatment. These data demonstrate a new effect of a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human adrenal tissue.