Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Endocrinology, Alexandra Hospital, Athens, Greece.
Endocrine. 2024 Jul;85(1):67-79. doi: 10.1007/s12020-024-03718-2. Epub 2024 Feb 12.
Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction's severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.
免疫检查点抑制剂 (ICIs) 是一类革命性的药物,通过利用免疫系统来对抗恶性肿瘤,为癌症治疗做出了重要贡献。然而,它们作为抗癌药物的成功应用伴随着广泛的免疫相关不良反应 (irAEs),包括内分泌疾病。其中,甲状腺功能障碍是 ICI 治疗引起的最常见内分泌疾病之一,也是一个突出的关注点。破坏性甲状腺炎是最常见的甲状腺毒症、甲状腺功能减退症和单纯性甲状腺功能减退症的共同病理生理基础。诊断方法以临床表现、实验室评估和影像学方式为指导。治疗方法根据甲状腺功能障碍的严重程度从左甲状腺素替代治疗到β受体阻滞剂的应用不等。随着医学界对免疫治疗的演变和复杂性的认识,识别和有效管理 ICI 诱导的甲状腺功能障碍对于提高患者安全性和改善治疗效果至关重要。本综述的目的是探讨 ICI 诱导的甲状腺功能障碍的重要性,揭示其各种模式、潜在机制、诊断方法和治疗策略。还强调了癌症亚型、ICI 剂量、年龄和遗传易感性等各种因素对发生功能障碍的风险的影响。