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阿替利珠单抗诱发的转移性肺癌患者自身免疫性糖尿病

Atezolizumab-Induced Autoimmune Diabetes in a Patient With Metastatic Lung Cancer.

作者信息

Sothornwit Jin, Phunmanee Anakapong, Pongchaiyakul Chatlert

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Division of Critical Care, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Front Endocrinol (Lausanne). 2019 Jun 11;10:352. doi: 10.3389/fendo.2019.00352. eCollection 2019.

Abstract

Immune checkpoint inhibitors (ICIs), now FDA-approved, are increasingly used as an effective treatment of various cancers. Autoimmune diabetes is a rare but life-threatening endocrine adverse event, which has been reported in patients treated with anti-programmed-cell death-1 (anti-PD-1) and anti-programmed-cell death-1 ligand (anti-PD-L1) therapies. We report a 52-year-old woman with advanced-stage non-small cell lung cancer who presented with diabetic ketoacidosis (DKA) at 24 weeks after atezolizumab initiation. She initially received oral antidiabetic medication from primary care hospital and experienced recurrent DKA 3 days later. Her plasma glucose on the day that she had recurrent DKA was 332 mg/dL (18.4 mmol/L), A1c was 7.9% (63 mmol/mol), fasting C-peptide was <0.03 nmol/L (0.1 ng/ml), fasting insulin level was <1 μIU/ml, anti-glutamic acid decarboxylase 65 (GADA) was 7.2 U/ml (normal, >5 U/ml), and human leukocyte antigen (HLA) class II typing was DR3-DQ2/DR14-DQ5. A diagnosis of autoimmune diabetes was made. After treatment for DKA, she recovered and received basal-bolus insulin treatment. Atezolizumab had been discontinued after the fifth cycle, prior to the development of DKA, due to progression of lung cancer. To date, there has been neither an effective way to detect if a patient is at high risk for autoimmune diabetes nor to prevent the complications associated with it. Regular glucose monitoring is the best method of early diabetes detection. In patients with new onset diabetes following treatment with ICIs, C-peptide levels and GADA should be screened, and insulin therapy should be prescribed to prevent hyperglycemic emergency while waiting for definite diagnosis.

摘要

免疫检查点抑制剂(ICIs)现已获得美国食品药品监督管理局(FDA)批准,越来越多地被用作各种癌症的有效治疗方法。自身免疫性糖尿病是一种罕见但危及生命的内分泌不良事件,在接受抗程序性细胞死亡蛋白1(anti-PD-1)和抗程序性细胞死亡蛋白1配体(anti-PD-L1)治疗的患者中已有报道。我们报告一名52岁晚期非小细胞肺癌女性患者,在开始使用阿替利珠单抗24周后出现糖尿病酮症酸中毒(DKA)。她最初在基层医院接受口服抗糖尿病药物治疗,3天后出现复发性DKA。她复发性DKA当天的血糖为332 mg/dL(18.4 mmol/L),糖化血红蛋白(A1c)为7.9%(63 mmol/mol),空腹C肽<0.03 nmol/L(0.1 ng/ml),空腹胰岛素水平<1 μIU/ml,抗谷氨酸脱羧酶65(GADA)为7.2 U/ml(正常,>5 U/ml),人类白细胞抗原(HLA)II类分型为DR3-DQ2/DR14-DQ5。诊断为自身免疫性糖尿病。在治疗DKA后,她康复并接受了基础-餐时胰岛素治疗。由于肺癌进展,在DKA发生前的第五个周期后停用了阿替利珠单抗。迄今为止,尚无有效的方法来检测患者是否有自身免疫性糖尿病的高风险,也无法预防与之相关的并发症。定期血糖监测是早期糖尿病检测的最佳方法。在接受ICIs治疗后新发糖尿病的患者中,应筛查C肽水平和GADA,并应开具胰岛素治疗处方,以预防高血糖急症,同时等待明确诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2003/6581023/b9635ecba86d/fendo-10-00352-g0001.jpg

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