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Journal of Clinical Endocrinology & Metabolism Vol. 72, No. 3 567-574
doi:10.1210/jcem-72-3-567
Copyright © 1991 by the Endocrine Society.
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The Influence of Simvastatin on Adrenal Corticosteroid Production and Urinary Mevalonate during Adrenocorticotropin Stimulation in Patients with Heterozygous Familial Hypercholesterolemia*

JAMES S. PRIHODA{dagger}, ANURADHA S. PAPPU, FANNIE E. SMITH{ddagger} and D. ROGER ILLINGWORTH

Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, Oregon Health Sciences University Portland, Oregon 97201

Address all correspondence and requests for reprints to: D. Roger Illingworth, M.D., Ph.D., Department of Medicine, L465, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201.

The adrenal gland requires a continuous supply of cholesterol for the biosynthesis of adrenal corticosteroids, which can be supplied by low density lipoprotein receptormediated uptake or local synthesis. The present study examined whether hypolipidemic therapy with a potent HMG CoA reductase inhibitor, simvastatin, compromises the adrenal response to ACTH stimulation in adult patients with heterozygous familial hypercholesterolemia. The adrenal response to a 36-h continuous ACTH infusion was determined at baseline and after 2 months of simvastatin treatment (40 mg, twice daily) in eight patients. Simvastatin reduced total and low density lipoprotein cholesterol levels by 36% and 45%, respectively. The time course of the increase in serum cortisol concentrations with continuous ACTH infusion was the same before and during simvastatin therapy, as were the rates of urinary excretion of free cortisol, 17-hydroxycorticosteroids, and 17-ketosteroids. Urinary excretion of mevalonate, which correlates with rates of whole body cholesterol synthesis, decreased from 3.8 ± 0.42 (±SEM) µ,ol/24 h at baseline to 2.75 ± 0.56 on simvastatin; no significant changes were seen in the urinary mevalonate levels before and after simvastatin therapy during ACTH stimulation. We conclude that the hypolipidemic effects of simvastatin in patients with heterozygous familial hypercholesterolemia are paralleled by a decrease in urinary mevalonate, but that the drug does not adversely affect ACTH-stimulated adrenal corticosteroid production.

* This work was supported in part by NIH Grants HL-28399 and HL-37940 and the General Clinical Research Centers program (RR-334). Presented at the 71st Annual Meeting of The Endocrine Society, Seattle, WA, June 21,1989 (Abstract 741).

{dagger} Recipient of a Clinician Scientist Award from the American Heart Association.

{ddagger} Present address: Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215.

Received April 23, 1990.







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Copyright © 1991 by The Endocrine Society