Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma
Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma
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DOI：
10.1507/endocrj.ej19-0140
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发表时间：
2019-01-01
影响因子：
2
通讯作者：
Hiasa, Yoichi
中科院分区：
文献类型：
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作者：
Koizumi, Yohei;Hirooka, Masashi;Hiasa, Yoichi
乐伐替尼对晚期肝细胞癌（HCC）具有抗肿瘤活性。甲状腺功能减退也是乐伐替尼治疗患者的常见并发症。然而，关于乐伐替尼诱导的甲状腺毒性和破坏性甲状腺炎的研究有限。因此，本研究旨在阐明乐伐替尼治疗不可切除HCC时甲状腺异常的频率和时间。这项回顾性研究入组了50例接受乐伐替尼治疗的晚期HCC患者。将患者分为甲状腺功能正常、亚临床甲状腺功能减退、显性甲状腺功能减退和甲状腺毒症。评估甲状腺功能障碍的发生时间，并使用多变量模型评估甲状腺功能减退症或甲状腺毒症的危险因素。亚临床甲状腺功能减退症、显性甲状腺功能减退症和甲状腺毒症分别发生在7例（14.0%）、26例（52.0%）和5例（10.0%）患者中。在33例甲状腺功能减退症患者中，27例（84.4%）在开始乐伐替尼治疗后2周内发生。在5例甲状腺毒症患者中，3例在开始乐伐替尼给药后8周内发生。1例患者在治疗开始后仅1周内发生甲状腺毒症。未观察到抗体的存在与自身免疫机制引起的甲状腺功能障碍的发生率和严重程度之间存在相关性。甲减组的无进展生存率明显更好。乐伐替尼治疗不可切除的HCC不仅会导致甲状腺功能减退，还会导致甲状腺毒症。此外，这些甲状腺疾病在治疗的早期以较高的患病率发展。甲状腺功能异常者预后较好。基于这些结果，在接受乐伐替尼治疗的患者中，需要从治疗开始时仔细评估甲状腺功能障碍的可能性。
Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.