Abstract：
Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.
摘要：
中枢甲状腺功能减退和血脂异常是贝沙罗汀治疗的众所周知的不良事件（AE）。尽管已知甲状腺功能减退会导致血脂异常，在接受贝沙罗汀治疗的患者中,尚无研究检查甲状腺功能减退与血脂异常之间的关系.这项研究的目的是研究这种关联。在日本开始使用贝沙罗汀治疗的294名患者中进行了回顾性观察研究（全国上市后完全监测）。进行Jonckheere-Terpstra（单侧）测试以评估贝沙罗汀剂量对脂质代谢的影响，进行回归分析以评估贝沙罗汀剂量的关联，游离甲状腺素（FT4），体重指数（BMI），和脂质代谢。大多数患者出现甲状腺功能减退症。三分之二的患者在1周时显示FT4值低于下限。甘油三酯（TG）以贝沙罗汀剂量依赖性方式增加，在39%的患者中观察到高甘油三酯血症的≥3级AE。此外,高甘油三酯血症≥3级AE的1/3发生在1周内.delta_FT4（FT4与基线的差异）与1周时的TG升高呈负相关（p=0.012），但与任何一周的低密度脂蛋白胆固醇（LDL-C）升高均不相关。贝沙罗汀引起的甲状腺功能减退症几乎是不可避免的，并且很快发生。贝沙罗汀诱导的高甘油三酯血症表现出贝沙罗汀剂量依赖性阳性和δ_FT4依赖性阴性。预防性和适当的甲状腺激素补偿治疗以及在低剂量下开始贝沙罗汀并随后滴定，同时管理血脂异常可能对成功继续贝沙罗汀治疗而没有严重的内分泌和代谢AE具有有益作用。
