Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe

J Pediatr. 2017 Sep:188:198-204.e1. doi: 10.1016/j.jpeds.2017.05.049. Epub 2017 Jun 16.

Abstract

Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).

Study design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE.

Results: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE.

Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status.

Trial registration: ClinicalTrials.govNCT01584206.

Keywords: 7α-hydroxy-4-cholesten-3-one; cholestanol; lathosterol; phytosterolemia; sitostanol; total cholesterol.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticholesteremic Agents / therapeutic use*
  • Cholestanol / blood
  • Cholestenones / blood
  • Cholesterol / blood
  • Ezetimibe / therapeutic use*
  • Female
  • Humans
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / drug therapy*
  • Intestinal Diseases / blood*
  • Intestinal Diseases / drug therapy*
  • Lipid Metabolism, Inborn Errors / blood*
  • Lipid Metabolism, Inborn Errors / drug therapy*
  • Male
  • Middle Aged
  • Phytosterols / adverse effects*
  • Phytosterols / blood
  • Sitosterols / blood
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Cholestenones
  • Phytosterols
  • Sitosterols
  • Triiodothyronine
  • 7 alpha-hydroxy-4-cholesten-3-one
  • lathosterol
  • Cholestanol
  • Thyrotropin
  • Cholesterol
  • stigmastanol
  • Ezetimibe
  • Thyroxine

Supplementary concepts

  • Sitosterolemia

Associated data

  • ClinicalTrials.gov/NCT01584206