The influence of simvastatin on adrenal corticosteroid production and urinary mevalonate during adrenocorticotropin stimulation in patients with heterozygous familial hypercholesterolemia

James S. Prihoda, Anuradha S. Pappu, Fannie E. Smith, D. Roger Illingworth

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume72
Issue number3
DOIs
StatePublished - Mar 1991

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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