Iwama Shintaro, Kobayashi Tomoko, Yasuda Yoshinori, Arima Hiroshi
Department of Endocrinology and Diabetes, Nagoya University Hospital, Japan.
Department of Endocrinology and Diabetes, Nagoya University Hospital, Japan.
Best Pract Res Clin Endocrinol Metab. 2022 May;36(3):101660. doi: 10.1016/j.beem.2022.101660. Epub 2022 Apr 12.
Immune-related adverse events (irAEs) are caused by immune checkpoint inhibitors in several organs including the endocrine glands. Thyroid dysfunction (thyroid irAEs) is often observed among endocrine irAEs and is induced by blockade of programmed cell death 1 (PD-1), programmed death ligand 1, or PD-1 plus cytotoxic T-lymphocyte antigen 4. Endocrinologically, destructive thyroiditis or hypothyroidism is observed in most cases, whereas hyperthyroidism (Graves' disease) is rare. Most patients who develop destructive thyroiditis or hypothyroidism subsequently require thyroid hormone replacement therapy. Thyroid irAE development is associated with prolonged survival in patients with non-small cell lung carcinoma. The incidence of thyroid irAEs is higher in patients who are positive versus negative for anti-thyroid antibodies at baseline, suggesting that these antibodies can predict thyroid irAE development. Cytotoxic T cells, especially CD4 T cells, are reportedly involved in the development of destructive thyroiditis. In this review, we describe the clinical features, potential biomarkers, and mechanism of thyroid irAEs.
免疫相关不良事件（irAEs）由免疫检查点抑制剂在包括内分泌腺在内的多个器官中引发。甲状腺功能障碍（甲状腺irAEs）在内分泌irAEs中较为常见，是由程序性细胞死亡蛋白1（PD-1）、程序性死亡配体1或PD-1加细胞毒性T淋巴细胞相关抗原4的阻断所诱导。在内分泌学方面，大多数情况下会观察到破坏性甲状腺炎或甲状腺功能减退，而甲状腺功能亢进（格雷夫斯病）则较为罕见。大多数发生破坏性甲状腺炎或甲状腺功能减退的患者随后需要甲状腺激素替代治疗。甲状腺irAE的发生与非小细胞肺癌患者的生存期延长有关。基线时抗甲状腺抗体呈阳性的患者甲状腺irAEs的发生率高于阴性患者，这表明这些抗体可以预测甲状腺irAE的发生。据报道，细胞毒性T细胞，尤其是CD4 T细胞，参与了破坏性甲状腺炎的发生。在本综述中，我们描述了甲状腺irAEs的临床特征、潜在生物标志物和发病机制。
