Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Endocr J. 2010;57(10):873-80. doi: 10.1507/endocrj.k10e-130. Epub 2010 Aug 21.
Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. (99m)Tc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of (99m)TcO(4)(-), suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.
舒尼替尼是一种多靶点酪氨酸激酶抑制剂，对晚期肾细胞癌有效。然而，舒尼替尼常引起甲状腺功能减退。在本研究中，我们报告了 8 例晚期肾细胞癌患者在舒尼替尼治疗期间发生甲状腺功能障碍的病例。7 例患者在第一个治疗周期早期出现轻度甲状腺功能减退，且可自发恢复。在第二个或第三个治疗周期期间观察到一过性甲状腺功能亢进，且在甲状腺球蛋白水平快速升高之前出现。在甲状腺功能亢进状态下的 (99m)Tc 闪烁显像显示甲状腺对 (99m)TcO(4)(-)摄取减少，提示破坏性甲状腺炎。随后发生甲状腺功能减退，需要左旋甲状腺素替代治疗。超声检查显示实质呈低回声模式，甲状腺内血流减少。甲状腺最终发生萎缩，可能进展为永久性甲状腺功能减退。这些发现提示舒尼替尼引起的甲状腺功能减退可能很常见，可能是甲状腺炎伴一过性甲状腺毒症的结果。VEGF 受体抑制引起的毛细血管血流减少导致甲状腺体积明显缩小，可能导致迟发性和/或永久性甲状腺功能减退。因此，应监测所有接受舒尼替尼治疗的患者的甲状腺功能。
