Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe - 24/08/17
, 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, 2Abstract |
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.
Le texte complet de cet article est disponible en 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
Plan
| 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. |
Vol 188
P. 198 - septembre 2017 Retour au numéro
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