Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe

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.

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2017 Elsevier Inc. All rights reserved.

Figures

Figure 1

A, Serum FT3, B, FT4, C, FT3/FT4 and D, TSH levels in patients with STSL (n = 8) at 8 and 14 weeks off EZE (OFF EZE) and on EZE (ON EZE). Data are mean ± SEM. *P < .05; Wk, week.

Figure 2

A and B, Plasma and RBC sitostanol, C and D, plasma and RBC cholestanol, and E and F, plasma and RBC TC levels in patients with STSL (n = 8) throughout 14 weeks off EZE (OFF EZE) and on EZE (ON EZE). Data are mean ± SEM. *P < .05, **P < .01, ***P <.0001 vs OFF EZE. † P < .05 vs baseline; Wk, week.

Figure 3

A and B, Plasma and RBC lathosterol levels and C, serum 7α-H-C4 in patients with STSL (n = 8) throughout 14 weeks off EZE (OFF EZE) and on EZE (ON EZE). Data are mean ± SEM. *P < .05, **P < .01, ***P <.0001 vs OFF EZE. † P < .05 vs baseline; Wk, week.