Othman Rgia A, Myrie Semone B, Mymin David, Roullet Jean-Baptiste, DeBarber Andrea E, Steiner Robert D, Jones Peter J H
Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
J Pediatr. 2017 Sep;188:198-204.e1. doi: 10.1016/j.jpeds.2017.05.049. Epub 2017 Jun 16.
To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).
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.
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.
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.
ClinicalTrials.govNCT01584206.
评估接受依折麦布（EZE）治疗的谷甾醇血症患者甲状腺功能生物标志物与5α-甾烷醇之间的关联。
对8例谷甾醇血症患者（年龄16 - 56岁）进行研究，研究期为停用EZE治疗14周及使用EZE（10毫克/天）治疗14周。在基线、停用EZE治疗的14周及使用EZE治疗的14周期间，测量血清甲状腺生物标志物（游离三碘甲状腺原氨酸[FT3]、游离甲状腺素[FT4]、FT3/FT4比值、促甲状腺激素）、5α-甾烷醇（谷甾烷醇和胆甾烷醇）以及胆甾烷醇前体（总胆固醇及其合成标志物羊毛甾醇，以及7α-羟基-4-胆甾烯-3-酮胆甾烯醇）。
EZE使FT3/FT4升高（10% ± 4%；P = 0.02）。EZE使血浆和红细胞中的谷甾烷醇降低（分别为-38% ± 6%和-20% ± 4%；均P < 0.05）以及胆甾烷醇降低（分别为-18% ± 6%和-13% ± 3%；均P < 0.05）。使用EZE时血浆胆甾烷醇水平的变化与FT3/FT4的变化呈负相关（r = -0.86；P = 0.01）。EZE使总胆固醇降低（P < 0.0001），且不影响7α-羟基-4-胆甾烯-3-酮胆甾烯醇。EZE最初使羊毛甾醇升高（P < 0.0001），但该水平未持续，导致停用EZE治疗14周和使用EZE治疗14周时水平相似。
在谷甾醇血症患者中，5α-甾烷醇水平可能与甲状腺功能相关。EZE降低循环中的5α-甾烷醇，同时升高FT3/FT4，这意味着T4向T3的转化增加，从而可能改善甲状腺激素状态。
ClinicalTrials.govNCT01584206。
