Stelmachowska-Banaś Maria, Czajka-Oraniec Izabella
Department of Endocrinology, The Centre of Postgraduate Medical Education, Warsaw, Polska, Poland.
Endocr Connect. 2020 Oct;9(10):R207-R228. doi: 10.1530/EC-20-0342.
Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.
免疫检查点抑制剂（ICIs）属于一类新型抗癌药物，其靶向参与对恶性肿瘤免疫反应激活的T细胞蛋白。它们被引入临床实践是现代癌症治疗的一个里程碑。然而，ICIs在治疗效果方面相对于传统化疗的显著优势伴随着与特定副作用相关的新挑战。ICI诱导的免疫系统激活可能导致自身耐受性丧失，表现为自身免疫性炎症以及各种组织和器官的功能障碍。因此，ICIs的典型副作用包括免疫相关不良事件（irAEs），其中影响众多内分泌腺的内分泌irAEs已得到普遍认可。本综述旨在从临床角度概述有关ICI诱导的内分泌紊乱的当前知识。我们提供了关于ICI诱导的内分泌病的发病率和临床进展的最新信息，包括最常见的甲状腺炎和垂体炎、罕见的胰岛素依赖型糖尿病和原发性肾上腺功能不全，以及最近描述的甲状旁腺功能减退和脂肪营养不良病例。还提供了监测、诊断和治疗ICI相关内分泌毒性的实用指南。肿瘤学家、内分泌学家和其他照顾接受ICIs治疗患者的医疗专业人员对内分泌irAEs的认识不断提高，可能有助于提高安全性和疗效。随着免疫疗法的广泛应用并被批准用于新型恶性肿瘤，预计未来内分泌irAEs的发病率会增加。
