Bexarotene‐induced hypothyroidism: characteristics and therapeutic strategies
Bexarotene‐induced hypothyroidism: characteristics and therapeutic strategies
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贝沙罗汀诱发的甲状腺功能减退症：特点和治疗策略
DOI：
10.1111/cen.13975
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发表时间：
2019
影响因子：
3.2
通讯作者：
Iiri Taroh
中科院分区：
文献类型：
--
作者：
Makita Noriko;Manaka Katsunori;Sato Junichiro;Mitani Koji;Nangaku Masaomi;Iiri Taroh
中枢性甲状腺功能减退症（CH）是贝沙罗汀治疗皮肤T细胞淋巴瘤（CTCL）的一种众所周知的不良反应。虽然在这些病例中建议合并左旋甲状腺素治疗，但尚未报告种族差异或易感性与贝沙罗汀诱导的CH之间的相关性。本研究旨在描述日本患者中贝沙罗汀诱导CH的动力学和剂量依赖性。设计和患者通过评价贝沙罗汀治疗早期甲状腺功能对66例日本CTCL患者进行了回顾性研究。然而，至少在96 - 320 mg/m2剂量下，该效应不具有贝沙罗汀剂量依赖性。大约1个月后，61例患者在相对低剂量的贝沙罗汀（平均251 mg/m2/天）下出现甲状腺功能减退症。45例研究病例在1周时显示了这种效果。简单回归分析表明，较高的治疗前TSH值（临界值为1.30：73%的灵敏度，57%的特异性）或较低的正常（参考范围的下半部分）治疗前FT 4值（84%的灵敏度，57%的特异性）可预测1周时的甲状腺功能减退症。其余21例在1周时甲状腺功能正常，TSH值可大致预测其1个月时的甲状腺功能（临界值为0.05：100%灵敏度，80%特异性）。至少，对于治疗前TSH高于1.30、治疗前FT 4正常值较低或1周时TSH低于0.05的患者，应考虑使用。
ObjectiveCentral hypothyroidism (CH) is a well‐known adverse effect of bexarotene treatment for cutaneous T‐cell lymphoma (CTCL). While concomitant levothyroxine therapy is recommended in these cases, associations between ethnic variation or susceptibility and bexarotene‐induced CH have not yet been reported. This study aimed to characterize the kinetics and dose dependency of bexarotene‐induced CH in Japanese patients.Design and patientsSixty‐six Japanese patients with CTCL were retrospectively investigated by evaluating thyroid function during the early phase of bexarotene therapy.ResultsAt one week after bexarotene initiation, TSH and FT4 values significantly declined. However, this effect was not bexarotene dose‐dependent at least at the dose of 96‐320 mg/m2. Approximately 1 month later, 61 patients exhibited hypothyroidism at a relatively low dose of bexarotene (average 251 mg/m2/day). Forty‐five study cases showed this effect at 1 week. Simple regression analyses indicated that higher pretreatment TSH values (at a cut‐off value of 1.30:73% sensitivity, 57% specificity) or lower normal (within the lower half of the reference range) pretreatment FT4 values (84% sensitivity, 57% specificity) were predictive of hypothyroidism at 1 week. The remaining 21 cases showed euthyroidism at 1 week, at which TSH values may roughly predict their thyroid function at 1 month (at a cut‐off value of 0.05:100% sensitivity, 80% specificity).ConclusionsPreventive treatment with levothyroxine is recommended for Japanese CTCL patients prior to bexarotene therapy. Minimally, it should be considered for patients with a pretreatment TSH above 1.30, a lower normal pretreatment FT4, or a TSH below 0.05 at 1 week.