免疫检查点抑制剂相关甲状腺炎的临床特点及其影响因素分析  

Clinical characters and influence factors of immune checkpoint inhibitor related thyroiditis

作　　者：杨子仲 张国庆[2] 秦博宇 张静[2] 孙琼[2] 李彬琦 焦顺昌[2] Yang Zi-Zhong;Zhang Guo-Qing;Qin Bo-Yu;Zhang Jing;Sun Qiong;Li Bin-Qi;Jiao Shun-Chang(School of Medicine,Nankai University,Tianjin 300071,China;Department of Oncologythe First Medical Center of Chinese PLA General Hospital,Beijing 100853,China;Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]南开大学医学院,天津300071 [2]解放军总医院第一医学中心肿瘤内科,北京100853 [3]解放军总医院第一医学中心内分泌科,北京100853

出　　处：《解放军医学杂志》2021年第10期989-996,共8页Medical Journal of Chinese People's Liberation Army

基　　金：国家“十三五”重大专项课题(2018ZX09201013)。

摘　　要：目的探讨在恶性肿瘤治疗中免疫检查点抑制剂(ICI)引起的免疫相关甲状腺炎(irT)的临床特点及其影响因素。方法回顾性分析2019—2020年在解放军总医院第一医学中心肿瘤内科接受ICI治疗,符合纳入标准的286例恶性肿瘤患者的临床资料。根据患者甲状腺不良反应的发生情况,将患者分为irT组(n=83)与非irT组(n=203),对比两组患者年龄、性别、肿瘤来源、既往治疗史及所用ICI药物之间的差异,并根据irT患者的临床表现及严重程度分为不同亚组,对比分析不同亚组患者甲状腺损伤的发生时间、自身抗体水平及恢复情况等。结果入组患者中83例(29.0%)出现了irT,年龄低及有放疗史的患者irT发生率高。irT患者中临床表现为甲亢28例(33.7%)、甲减48例(57.8%)、甲状腺功能正常的甲状腺炎7例(8.4%)。83例irT患者中76例(91.6%)为轻症,重症仅7例(8.4%)。28例甲亢型irT患者中7例(25%)在病程后期转化为甲减型,其演变速度较原发性甲状腺炎快。4种临床常用ICI药物(帕博利珠单抗、纳武利尤单抗、信迪利单抗、特瑞普利单抗)的irT发生率差异无统计学意义。83例irT患者中,23例(29.5%)甲状腺球蛋白抗体(TGAb)、14例(12.8%)过氧化物酶抗体(TPOAb)存在异常,重症者的TGAb、TPOAb明显高于轻症者。在患者转归方面,经过治疗后irT的症状普遍可以缓解,仅3例(3.6%)因不可耐受的症状中断了免疫治疗。结论 irT的发生率高且变化快,行免疫治疗的患者应注意监测甲状腺功能,以发现irT并及早干预。Objective To investigate the clinical characters and influence factors of immune-related thyroiditis(irT) brought by the immune checkpoint inhibitors(ICI) in treatment of malignant tumor. Methods The clinical data were retrospectively analyzed of 286 certificated patients treated with ICI in the Department of Oncology, the First Medical Center of Chinese PLA General Hospital during 2019–2020. The patients were divided into irT group(n=83) and non-irT group(n=203) according to the occurrence of thyroid dysfunction, and the differences between the two groups were compared of age, gender, tumor origin, previous treatment history and ICI types. Then the patients were divided into different subgroups according to the clinical manifestations or severity of irT, then the time of thyroid injury occurrence, auto-antibody level and recovery degree of thyroid dysfunction were compared and analyzed among different subgroups. Results Of the 286 certificated patients, 83 patients(29.0%) developed irT, those with lower age and history of radiotherapy had greater incidence rate. The clinical manifestation of irT included hyperthyroidism(n=28, 33.7%), hypothyroidism(n=48, 57.8%) and transient thyroiditis with normal thyroid function(n=7, 8.4%). All the 83 irT patients, 76 patients(91.6%) only developed mild irT, while 7 patients(8.4%) were severe. In the 28 patients initially diagnosed as immune-related hyperthyroidism, 7 patients(25%) progressed to secondary hypothyroidism in thelater course with faster evolution rate than the patients with primary thyroiditis. There was no statistical difference in irT incidence among the patients treated with 4 frequently used PD-1 inhibitors(Pembrolizumab, Nivolumab, Sintilimab and Toripalimab). Among the 83 irT patients, the serum thyroid auto-antibodies levels were often elevated in irT patients. The thyroglobulin antibody(TGAb) was elevated in 23 patients(29.5%) and the thyroid peroxidase antibody(TPOAb) were elevated in 14 patients(12.8%). The TGAb and TPOAb levels were significantly hi

关 键 词：免疫检查点抑制剂 免疫相关不良反应 桥本甲状腺炎 免疫相关甲状腺炎 

分 类 号：R730.51[医药卫生—肿瘤]