Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Cancer Treat Rev. 2017 Jul;58:70-76. doi: 10.1016/j.ctrv.2017.06.002. Epub 2017 Jun 22.
Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay in cancer treatment. The clinical benefit afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events (irAE) that affect the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs associated with immune checkpoint inhibitors are generally consistent across tumor types. Immune-related endocrine events can affect the pituitary, thyroid, and adrenal glands, as well as other downstream target organs. These events are unique when compared with other irAEs because the manifestations are often irreversible. Immune-related endocrine events are typically grade 1/2 in severity and often present with non-specific symptoms, making them difficult to diagnose. The mechanisms underlying immune-related target organ damage in select individuals remain mostly undefined. Management includes close patient monitoring, appropriate laboratory testing for endocrine function, replacement of hormones, and consultation with an endocrinologist when appropriate. An awareness of the symptoms and management of immune-related endocrine events may aid in the safe and appropriate use of immune checkpoint inhibitors in clinical practice.
调节免疫检查点蛋白的药物，如细胞毒性 T 淋巴细胞抗原-4（CTLA-4）和程序性死亡受体-1（PD-1），已成为癌症治疗的主要方法。免疫检查点抑制剂带来的临床益处可能伴随着免疫相关不良反应（irAE），影响皮肤、胃肠道、肝脏和内分泌系统。与免疫检查点抑制剂相关的 irAE 类型在肿瘤类型之间通常是一致的。免疫相关的内分泌事件会影响垂体、甲状腺和肾上腺，以及其他下游靶器官。与其他 irAE 相比，这些事件是独特的，因为它们的表现往往是不可逆的。免疫相关的内分泌事件通常为 1/2 级严重程度，并且经常出现非特异性症状，因此难以诊断。在某些个体中，针对免疫相关靶器官损伤的机制在很大程度上仍未得到明确。管理包括密切监测患者、适当的内分泌功能实验室检测、激素替代以及在适当情况下咨询内分泌科医生。了解免疫相关内分泌事件的症状和管理可能有助于在临床实践中安全、适当地使用免疫检查点抑制剂。
