The influence of mevinolin on the adrenal cortical response to corticotropin in heterozygous familial hypercholesterolemia.

The biosynthesis of adrenal corticosteroids in humans depends on a continuous supply of cholesterol, which can be derived from both local synthesis and receptor-mediated uptake of low density lipoproteins (LDL) from plasma. Mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase [mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88] is an effective hypolipidemic agent in patients with heterozygous familial hypercholesterolemia. To determine whether mevinolin influences the adrenal production of corticosteroids, the adrenocortical response to a continuous 36-hr infusion of corticotropin (ACTH) was examined in eight patients with heterozygous familial hypercholesterolemia before, and again during, treatment with mevinolin (40-80 mg/day). The drug produced an average decrease of 28% and 34% in the plasma concentrations of total and LDL cholesterol. Serum cortisol levels showed similar increases in response to ACTH stimulation before and during mevinolin treatment, and the rates of excretion of urine-free cortisol were also similar. We conclude that clinically effective doses of mevinolin do not affect corticosteroid production by the adrenal cortex during prolonged ACTH stimulation in patients with heterozygous familial hypercholesterolemia.