免疫检查点抑制剂引起肿瘤患者甲状腺功能障碍的临床分析

Clinical Studies on Thyroid Dysfunction Caused by ImmuneCheckpoint Inhibitors in Tumor Patients

目的研究恶性肿瘤患者予以免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)后发生甲状腺功能障碍(thyroiddysfunction,TD)的临床特点及相关危险因素分析。方法收集来自云南省第一人民医院2019年1月至2022年6月住院并行ICIs治疗后的157例肿瘤患者,根据是否发生TD分为甲状腺功能正常组以及甲状腺功能异常组。选取甲状腺功能正常组和异常组分别为58例患者,再随机抽取58例至云南省第一人民医院的健康成人体检者作为对照组,收集研究对象的性别、年龄、肿瘤及ICIs类型、用药前手术史、放化疗史等基线资料,分析患者肝肾功、血脂、甲状腺激素水平等相关指标,对3组病例的相关指标进行统计学分析,并将甲状腺功能正常组和异常组进行对照分析来测评使用ICIs引起TD的临床特征及相关危险因素。结果(1)在157例使用ICIs治疗的患者中,58例(36.9%)出现甲状腺功能异常,其中甲状腺功能减退症(包括亚甲减)39例,甲状腺功能亢进症(包括亚甲亢)9例,单纯相关抗体异常10例;(2)对甲状腺功能正常组、甲状腺功能异常组及对照组3组数据进行分析,结果提示3组的年龄、促甲状腺激素(thyroidstimulatinghormone,TSH)基线水平、游离三碘甲状腺原氨酸(freetriiodothyronine,FT3)基线水平和谷草转氨酶(aspartatetransaminase,AST)水平比较,差异均有统计学意义(P<0.05);甲状腺功能正常组与甲状腺功能异常组TSH基线、放疗史比较,差异均有统计学意义(P<0.05);(3)多元分析表明放疗史(OR=7.291,95%CI=1.579~33.663,P<0.05)、基线TSH水平(OR=3.917,95%CI=1.697~9.038,P<0.05)是使用ICIs治疗后肿瘤患者出现甲状腺功能异常的独立危险因素。结论甲状腺功能减退是肿瘤患者使用ICIs引起TD最常见的类型,患者基线TSH水平、既往存在放疗史是出现甲状腺功能异常的独立危险因素。

Objective To investigate the clinical characteristics and risk factors of thyroid dysfunction(TD)in malignant tumor patients treated with immune checkpoint inhibitors(ICIs).Methods A total of 157 cancer patients who were hospitalized and received ICIs treatment in the First People's Hospital of Yunnan Province from January 2019 to June 2022 were collected and divided into the normal thyroid function group and abnormal thyroid function group based on whether TD had occurred.Fifty-eight patients with the normal thyroid function and 58 patients with the abnormal thyroid function were selected,and 58 healthy adults who underwent the physical examination in our hospital were randomly selected as the control group.The baseline data on the gender,age,tumor and ICIs type,history of surgery before medication,history of radiotherapy and chemotherapy,and the related indicators of liver and kidney function,blood lipids,thyroid hormone levels and so on were collected.The relevant indicators of the three groups were statistically analyzed,and the normal thyroid function group and abnormal thyroid function group were compared to evaluate the clinical characteristics and related risk factors of TD caused by ICIs.Results 1.Among 157 patients treated with ICIs,58 cases(36.9%)had thyroid dysfunction,including 39 cases of hypothyroidism(including subclinical hypothyroidism),9 cases of hyperthyroidism(including subclinical hyperthyroidism),and 10 cases of pure related antibody abnormality.2.The analysis of the data of the normal thyroid function group,the abnormal thyroid function group and the control group showed that the age,thyroid stimulating hormone(TSH),and thyroid function of the three groups were significantly different.TSH)baseline level,free triiodothyronine(FT3)baseline level and aspartate transaminase(AST)baseline level were statistically different(P<0.05).There were significant differences in TSH baseline and radiotherapy history between the normal thyroid function group and the abnormal thyroid function group(P<0.05);Multivariate analysis showed that the radiotherapy history(OR=7.291,95%CI=1.579-33.663,P<.05),baseline TSH level(OR=3.917,95%CI=1.697-9.038,P<0.05)were the independent risk factors for thyroid dysfunction in cancer patients after ICIs treatment.Conclusion Hypothyroidism is the most common type of TD caused by ICIs in cancer patients.The baseline TSH level and the history of radiotherapy are the independent risk factors for thyroid dysfunction.