免疫检查点抑制剂相关甲状腺功能障碍研究进展

doi:10.19803/j.1672-8629.20260073

摘要/Abstract

摘要： 随着免疫检查点抑制剂（Immune Checkpoint Inhibitors, ICIs）广泛应用,其引起的免疫相关不良事件（Immune-Related Adverse Events, irAEs）已成为临床挑战。ICIs相关甲状腺功能障碍（ICIs-Associated Thyroid Dysfunction, ICIs-TD）为常见的内分泌irAEs。不同表型 ICIs-TD在发生时间及特点上存在差异,本文就ICIs-TD的流行病学特征、发生机制与标志物、风险因素、诊疗与管理等方面进行综述,旨在为后续构建ICIs-TD临床预测模型,实现早期识别和精准干预提供参考。

关键词: 免疫检查点抑制剂, 免疫治疗, 免疫相关不良事件, 甲状腺功能障碍, 药品不良反应

Abstract: With the increasing use of immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs) have become a major clinical challenge. Thyroid dysfunction associated with ICIs (ICIs-TD) is one of the most common endocrine irAEs. ICIs-TD varies in terms of both time to onset and clinical features. This review summarizes the epidemiology, underlying mechanisms, biomarkers, risk factors, diagnosis and management of ICIs-TD in the hope of providing a reference for the subsequent development of clinical prediction models for ICIs-TD and for early identification and precise interventions.

Key words: Immune Checkpoint Inhibitors (ICIs), Immunotherapy, Immune-Related Adverse Events (irAEs), Thyroid Dysfunction, Adverse Drug Reaction

中图分类号:

吕欣鸽, 潘晨, 武一, 王雨婷, 崔向丽. 免疫检查点抑制剂相关甲状腺功能障碍研究进展[J]. 中国药物警戒, 2026, 23(5): 590-594.

LYU Xinge, PAN Chen, WU Yi, WANG Yuting, CUI Xiangli. Research Progress in the Treatment of Thyroid Dysfunction Associated with Immune Checkpoint Inhibitors[J]. Chinese Journal of Pharmacovigilance, 2026, 23(5): 590-594.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://zgywjj.magtechjournal.com/CN/10.19803/j.1672-8629.20260073

https://zgywjj.magtechjournal.com/CN/Y2026/V23/I5/590

参考文献

[1] MILLER SR, SCHIPPER M, FRITSCHE LG, et al.Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System[J]. Cancer Med, 2024, 13(21):e70379.
[2] RUI R, ZHOU L, HE S.Cancer Immunotherapies:Advances and Bottlenecks[J]. Front Immunol, 2023, 14:1212476.
[3] LI Y, ZHAO J, WANG Y, et al.Common Endocrine System Adverse Events Associated with Immune Checkpoint Inhibitors[J]. Cancer Pathog Ther, 2023, 2(3):164-172.
[4] YAMAUCHI I, YABE D.Best Practices in the Management of Thyroid Dysfunction Induced by Immune Checkpoint Inhibitors[J]. Eur Thyroid J, 2025, 14(1):e240328.
[5] CHENG W, KANG K, ZHAO A, et al.Dual Blockade Immunotherapy Targeting PD-1/PD-L1 and CTLA-4 in Lung Cancer[J]. J Hematol Oncol, 2024, 17(1):54.
[6] ILLOUZ F, BRIET C, RODIEN P.Immune Checkpoint Inhibitor-Related Thyroid Dysfunction[J]. Ann Endocrinol (Paris), 2023, 84(3):346-350.
[7] GARCIA GM, VAZQUEZ GB, SANMAMED MF, et al.Thyroid Dysfunction Caused by Immune Checkpoint Inhibitors Improves Cancer Outcomes[J]. Endocr Relat Cancer, 2024, 31(10):e240064.
[8] STELMACHOWSKA-BANASM, CZAJKA-ORANIEC I.Management of Endocrine Immune-Related Adverse Events of Immune Checkpoint Inhibitors:an Updated Review[J]. Endocr Connect, 2020, 9(10):R207-R228.
[9] XU Q, YUAN Y, LI X, et al.Development and Validation of a Nomogram for Predicting Immune-Related Thyroid Dysfunction during Immunotherapy in Non-Small Cell Lung Cancer:a Prospective Cohort Study in China[J]. Front Immunol, 2025, 16:1611956.
[10] SCHONBERGER E, ŠVITEK L, GRUBISIC B, et al.Beyond Tumor Immunity:the Disruption of Endocrine and Infectious Homeostasis by Immune Checkpoint Inhibitors[J]. Int J Mol Sci, 2025, 26(23):11619.
[11] D'AIELLO A, LIN J, GUCALP R, et al. Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs):Outcomes in a Multiethnic Urban Cohort[J]. Cancers (Basel), 2021, 13(6):1464.
[12] OKADA N, IWAMA S, OKUJI T, et al.Anti-Thyroid Antibodies and Thyroid Echo Pattern at Baseline as Risk Factors for Thyroid Dysfunction Induced by Anti-Programmed Cell Death-1 Antibodies:a Prospective Study[J]. Br J Cancer, 2020, 122(6):771-777.
[13] ZHAN L, FENG HF, LIU HQ, et al.Immune Checkpoint Inhibitors-Related Thyroid Dysfunction:Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management[J]. Front Endocrinol (Lausanne), 2021, 10:649863.
[14] ZHAO P, LI J, YU L, et al.Clinical Manifestations and Risk Factors of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1 Inhibitors:a Case-Control Study[J]. Front Immunol, 2025, 16:1581057.
[15] MUIR CA, CLIFTONBLIGH RJ, LONG GV, et al.Thyroid Immune-Related Adverse Events Following Immune Checkpoint Inhibitor Treatment[J]. J Clin Endocrinol Metab, 2021, 106(9):e3704-e3713.
[16] IWAMA S, KOBAYASHI T, ARIMA H.Management, Biomarkers and Prognosis in People Developing Endocrinopathies Associated with Immune Checkpoint Inhibitors[J]. Nat Rev Endocrinol, 2025, 21(5):289-300.
[17] IWAMA S, KOBAYASHI T, YASUDA Y, et al.Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients without Thyroid Autoantibodies at Baseline[J]. J Clin Endocrinol Metab, 2022, 107(4):e1620-e1630.
[18] INABA H, ARIYASU H, IWAKURA H, et al.Distinct Clinical Features and Prognosis between Persistent and Temporary Thyroid Dysfunctions by Immune-Checkpoint Inhibitors[J]. Endocr J, 2021, 68(2):231-241.
[19] HU JH, YANG JL CHENG Q, et al. Investigation of the Mechanism and Advancements in Diagnosis and Management of Hypothyroidism Triggered by Immune Checkpoint Inhibitors[J]. China Medicine(中国医药), 2024, 19(11):1742-1746.
[20] RESCHKE R, SULLIVAN RJ, LIPSON EJ, et al.Targeting Molecular Pathways to Control Immune Checkpoint Inhibitor Toxicities[J]. Trends Immunol, 2025, 6(1):61-73.
[21] KURIMOTO C, INABA H, ARIYASU H, et al.Predictive and Sensitive Biomarkers for Thyroid Dysfunctions During Treatment with Immune-Checkpoint Inhibitors[J]. Cancer Sci, 2020, 111(5):1468-1477.
[22] LIU J, CHEN M, LI S, et al.Biomarkers in the Early Stage of PD-1 Inhibitor Treatment have Shown Superior Predictive Capabilities for Immune-Related Thyroid Dysfunction[J]. Front Immunol, 2024, 15:1458488.
[23] ZHANG Y, GAROFANO F, WU X, et al.Integrative Analysis of Key Candidate Genes and Signaling Pathways in Autoimmune Thyroid Dysfunction Related to Anti-CTLA-4 Therapy by Bioinformatics[J]. Invest New Drugs, 2020, 38(6):1717-1729.
[24] LI W, FAN D, WEI D, et al.Causal Relationship between IgG N-Glycosylation and Autoimmune Thyroid Diseases, and the Possible Mediating Role of Immune Cells and Inflammatory Cytokines[J]. Medicine (Baltimore), 2025, 104(44):e45649.
[25] GAO J, ZHANG P, NIE X, et al.Proteomic and Metabolomic Profiling of Plasma Predicts Immune-Related Adverse Events in Older Patients with Advanced Non-Small Cell Lung Cancer[J]. iScience, 2024, 27(6):109946.
[26] SETOYAMA D, LEE HY, MOON JS, et al.Immunometabolic Signatures Predict Recovery from Thyrotoxic Myopathy in Patients with Graves’Disease[J]. J Cachexia Sarcopenia Muscle, 2022, 13(1):355-367.
[27] SHI Y, MA J, LI S, et al.Sex Difference in Human Diseases:Mechanistic Insights and Clinical Implications[J]. Signal Transduct Target Ther, 2024, 9(1):238.
[28] GONG W, ZHENG E, LIU M, et al.Risk Factors and Outcomes of Thyroid Immune-Related Adverse Events Following PD-1/PD-L1 Inhibitors Treatment in a Large Tertiary Chinese Center[J]. BMC Endocr Disord, 2025, 25(1):171.
[29] LI X, SONG Z, CHEN Y, et al.Immune Checkpoint Inhibitors-Related Thyroid Dysfunction:Influencing Factor Analysis, Prediction Model Development, and Management Strategy Proposal[J]. Cancer Immunol Immunother, 2024, 74(1):2.
[30] WANG A, HUANG H, CHEN Y, et al.Association between Platelet-to-Lymphocyte Ratio and Immune Checkpoint Inhibitor-Induced Thyroid Dysfunction[J]. Endocrine, 2025, 88(2):491-500.
[31] ZHU SY, YANG TT, ZHAO YZ, et al.Interpretable Machine Learning Model Predicting Immune Checkpoint Inhibitor-Induced Hypothyroidism:a Retrospective Cohort Study[J]. Cancer Sci, 2024, 115(11):3767-3775.
[32] KIM W, CHO YA, KIM DC, et al.Factors Associated with Thyroid-Related Adverse Events in Patients Receiving PD-1 or PD-L1 Inhibitors Using Machine Learning Models[J]. Cancers (Basel), 2021, 13(21):5465.
[33] CHRISTENSEN SK, WINTHER ML, LAURSEN IJ, et al.Frequency and Characteristics of Immune-Related Thyroid Adverse Events in Patients with Resected Stage III/IV Melanoma Treated with Adjuvant PD-1 Inhibitors:a National Cohort Study[J]. Support Care Cancer, 2024, 32(5):281.
[34] KENNEDY OJ, ALI N, LEE R, et al.Thyroid Dysfunction after Immune Checkpoint Inhibitors In a Single-Centre UK Pan-Cancer Cohort:a Retrospective Stud[J]. Eur J Cancer, 2024, 202:113949.
[35] WANG Q, WU T, ZHAO R, et al.Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients during Immuno-therapy[J]. Endocr Pract, 2024, 30(10):943-950.
[36] DOKMETAS M, MUGLU H, ÖZCAN E, et al.Endocrine Adverse Events in Patients Treated with Immune Checkpoint Inhibitors:a Comprehensive Analysis[J]. Medicina (Kaunas), 2025, 61(1):123-137.
[37] Chinese Society of Clinical Oncology Guidelines Working Committee. Guidelines of Chinese Society of Clinical Oncology (CSCO) for the Mana-gement of Immune Checkpoint Inhibitor-Related Toxicity(中国临床肿瘤学会免疫检查点抑制剂相关的毒性管理指南)[M]. Beijing:The People’s Health Press, 2023.
[38] THOMPSON JA, SCHNEIDER BJ, BRAHMER J, et al.Management of Immunotherapy-Related Toxicities, Version 1.2025, NCCN Clinical Practice Guidelines in Oncology[J]. J National Comprehensive Cancer Network, 2024, 20(4):387-405.