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Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe - 24/08/17

Doi : 10.1016/j.jpeds.2017.05.049 
Rgia A. Othman, PhD 1, 2, Semone B. Myrie, PhD 1, 2, * , David Mymin, MD 3, Jean-Baptiste Roullet, PhD 4, 5, Andrea E. DeBarber, PhD 6, Robert D. Steiner, MD 7, Peter J.H. Jones, PhD 1, 2
1 Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada 
2 Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada 
3 Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada 
4 College of Pharmacy, Washington State University, Spokane, WA 
5 Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 
6 Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 
7 Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 

*Reprint requests: Semone B. Myrie, PhD, Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, 196 Innovation Dr, Winnipeg, MB R3T 6C5, Canada.Richardson Center for Functional Foods and NutraceuticalsUniversity of Manitoba196 Innovation DrWinnipegMBR3T 6C5Canada

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.gov NCT01584206.

Il testo completo di questo articolo è disponibile in PDF.

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

Abbreviations : 7α-H-C4, C4-d7, CTX, CV, ddH2O, EZE, FT3, FT3/FT4, FT4, RBC, STSL, TC, TSH


Mappa


 Supported by the Canadian Institutes of Health Research (MOP12339). The Sterol and Isoprenoid Research (STAIR; U54HD061939) Consortium is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research (U54HD061939) at the National Center for Advancing Translational Science, and National Institute of Child Health and Human Development. R.O. was supported by the Libyan Scholarship Program and Research Manitoba Fellowship. The authors declare no conflicts of interest.


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