信迪利单抗致自身免疫性多内分泌腺病综合征(Ⅱ型)  

Autoimmune polyendocrinopthy syndrome(type Ⅱ)due to sintilimab

作　　者：汪乐 原海燕[2] 叶溪[3] Wang Le;Yuan Haiyan;Ye Xi(Department of Pharmacy,People′s Hospital of Xiangyin County,Hunan Province,Xiangyin 414600,China;Department of Pharmacy,Second Xiangya Hospital of Central South University,Changsha 410011,China;Department of Pharmacy,the People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China)

机构地区：[1]湘阴县人民医院药剂科,湖南省湘阴县414600 [2]中南大学湘雅二医院药学部,长沙410011 [3]广西壮族自治区人民医院药学部,南宁530021

出　　处：《药物不良反应杂志》2022年第7期373-375,共3页Adverse Drug Reactions Journal

摘　　要：1例52岁男性原发性支气管肺癌患者接受信迪利单抗200 mg静脉滴注、第1天,安罗替尼胶囊12 mg口服、1次/d,服用14 d;21 d为1个周期。治疗第3个周期实验室检查示患者促甲状腺激素(TSH)0.08 mU/L,未予干预;治疗第5个周期,游离甲状腺素(FT_(4))11.45 pmol/L,TSH 8.19 mU/L,提示甲状腺功能减退,予左甲状腺素钠片50μg口服、1次/d,56 d后复查甲状腺功能恢复正常;第8个周期治疗第3天,患者出现口干、多饮、多尿、恶心、呕吐等症状,实验室检查示血pH 7.02、β-羟丁酸6.740 mmol/L,随机血糖66.0 mmol/L,提示糖尿病酮症酸中毒;停用信迪利单抗及安罗替尼并予补液、胰岛素等治疗,11 d后酮体转阴,空腹血糖5.8 mmol/L。约2周后实验室检查示糖化血红蛋白7.8%,空腹及早餐后2 h血清C肽均<0.01 nmol/L,胰岛细胞抗体、胰岛素自身抗体、谷氨酸脱羧酶抗体及蛋白酪氨酸磷酸酶自身抗体均阴性,符合暴发性1型糖尿病(T1DM)特征。停用信迪利单抗及安罗替尼第32天晨,实验室检查示皮质醇50.7 nmol/L,促肾上腺皮质激素(ACTH)2.73 pmol/L,提示肾上腺皮质功能减退,予糖皮质激素治疗。考虑患者为信迪利单抗致自身免疫性多内分泌腺病综合征(APS)Ⅱ型(甲状腺功能减退症,暴发性T1DM,肾上腺皮质功能减退症)。糖皮质激素治疗9个月后复查,皮质醇8:00、16:00和24:00分别为16.6、79.4和17.2 nmol/L,ACTH 1.12 pmol/L。患者仍需接受替代性激素维持治疗。A 52-year-old male patient with primary bronchogenic carcinoma received an IV infusion of sintilimab 200 mg on the first day,oral anlotinib capsules 12 mg once daily on day 1-14,and 3 weeks were a cycle.At the 3rd cycle of treatments,the laboratory tests showed thyroid stimulating hormone(TSH)0.08 mU/L,and no intervention was given.At the 5th cycle,his free thyroxine(FT_(4))was 11.45 pmol/L and TSH was 8.19 mU/L,indicating hypothyroidism.The patient received levothyroxine sodium tablets 50μg orally once daily.Fifty-six days later,his thyroid function returned to normal.On the 3rd day of the 8th cycle of treatments,the patient developed dry mouth,polydipsia,polyuria,nausea,and vomiting,and laboratory tests showed blood pH 7.02,β-hydroxybutyric acid 6.740 mmol/L,and random blood glucose 66.0 mmol/L,indicating diabetes ketoacidosis.Sintilimab and anlotinib were stopped and fluid replacement and insulin hypoglycemic therapy were given.Eleven days later,his ketone body turned negative,and the fasting blood glucose was 5.8 mmol/L.About 2 weeks later,the laboratory tests showed that hemoglobin A1c was 7.8%,the serum C-peptide levels on an empty stomach and 2 hours after breakfast both were less than 0.01 nmol/L,and the islet cell antibody,insulin autoantibody,glutamic acid decarboxylase antibody,and protein tyrosine phosphatase autoantibody were negative,which was consistent with the characteristics of fulminant type 1 diabetes(T1DM).On the morning of the 32nd day of sintilimab and anlotinib withdrawal,laboratory tests showed cortisol 50.7 nmol/L and adrenocorticotropic hormone(ACTH)2.73 pmol/L,indicating hypoadrenocorticism.Treatment with glucocorticoid was given.It was considered that the patient was with autoimmune polyendocrinopthy syndrome(APS)type II(hypothyroidism,fulminant T1DM,hypoadrenocorticism)caused by sintilimab.After 9 months of glucocorticoid treatment,cortisol was 16.6,79.4,and 17.2 nmol/L at 8:00,16:00,and 24:00,respectively,and ACTH was 1.12 pmol/L.The patient still needed maintenance treatment with

关 键 词：免疫检查点抑制剂 多内分泌腺疾病 自身免疫性 药物相关副作用和不良反应 信迪利单抗 

分 类 号：R969.3[医药卫生—药理学]