程序性死亡受体-1抑制剂相关内分泌腺体疾患26例临床特征分析

Clinical characteristics of 26 cases with endocrine gland diseases related to programmed death receptor-1(PD-1)inhibitors in cancer patients

目的:探讨肿瘤患者使用程序性死亡受体-1(programmed death receptor-1,PD-1)抑制剂后相关内分泌腺体疾患的临床特征。方法:回顾性总结2020年1月至12月复旦大学附属中山医院内分泌科收治的因各类癌症使用PD-1抑制剂后出现内分泌系统免疫相关不良反应(immune-related adverse events,irAEs)26例患者的临床资料,分析PD-1抑制剂与内分泌腺体损害的关系及临床特征。结果:26例患者中,男19例(73.08%),女7例(26.92%),平均年龄(61.62±9.77)岁。PD-1抑制剂相关垂体炎18例(69.23%),全部累及垂体肾上腺轴,同时累及肾上腺轴及甲状腺轴4例,未出现累及垂体后叶病例;PD-1抑制剂相关的原发性甲状腺功能障碍9例(34.62%);相关1型糖尿病5例(19.23%);相关自身免疫性多内分泌腺综合征(autoimmune polyendocrine syndrome,APS)7例(26.92%),其中累及垂体、甲状腺6例,累及垂体、胰腺1例;未发现PD-1相关的原发性肾上腺皮质功能减退。结论:癌症患者使用免疫检查点抑制剂(immune checkpoint inhibitors,ICPis)前及治疗中应评估内分泌腺体相关指标,以减少误诊漏诊,提高免疫治疗过程中的安全性,改善患者生活质量。

Objective:To explore the clinical characteristics of endocrine gland diseases related to programmed death receptor-1(PD-1)inhibitors in cancer patients.Methods:From January 2020 to December 2020,26 patients admitted by the Department of Endocrinology,Zhongshan Hospital affiliated to Fudan University were retrospected.All patients showed immune-related adverse events(irAEs)in endocrine system after the administration of PD-1 inhibitors due to cancers.The relationship and clinical features of PD-1 inhibitor induced endocrine gland damages were analyzed.Results:Of 26 patients,19 were male(73.08%)and 7 were female(26.92%).The average age was(61.62±9.77)years.PD-1 inhibitor-associated hypophysitis was found in 18 cases(69.23%),among whom,the pituitary adrenal axis involvement was found in all cases,adrenal axis and thyroid axis involvement was found in 4 cases,and posterior pituitary lobe involvement was not found.PD-1 inhibitors associated primary thyroid dysfunction was found in 9 patients(34.62%).Related type 1 diabetes was found in 5 cases(19.23%).Autoimmune polyendocrine syndrome(APS)was found in 7 cases(26.92%),including 6 cases involving pituitary and thyroid gland,and 1 case involving pituitary and pancreas.PD-1-related primary adrenal hypofunction was not observed.Conclusion:The endocrine gland related indicators should be evaluated before and during the administration of immune checkpoint inhibitors(ICPis)in cancer patients to reduce misdiagnosis and missed diagnosis,improve safety during the immunotherapy,and enhance the patients′quality of life.