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抗程序性死亡蛋白1免疫检查点抑制剂诱发晚期肺癌患者内分泌毒性:一例报告及文献综述

Anti‑PD‑1 immune checkpoint inhibitor inducing endocrine toxicity in a patient with advanced lung cancer: A case report and literature review.

作者信息

Bao Suqing, Jiang Xia

机构信息

Department of Endocrinology and Metabolism, Tianjin First Central Hospital, Tianjin 300192, P.R. China.

出版信息

Exp Ther Med. 2022 Sep 21;24(5):681. doi: 10.3892/etm.2022.11617. eCollection 2022 Nov.

Abstract

The anti-programmed cell death protein 1 (anti-PD-1) antibody is a breakthrough immune checkpoint inhibitor that modulates T-cell function. However, it may result in multiple immune-related adverse events (irAEs), such as endocrine toxicity. The present case report describes a 59-year-old female patient with advanced non-small cell lung cancer with a tumor proportion score of 50% for programmed death ligand 1. The patient developed dry skin, dizziness and fatigue after receiving the third infusion of the anti-PD-1 antibody pembrolizumab. Based on several clinical indicators, including low serum free T3 and free T4 titers, an elevated thyroid-stimulating hormone level and a high titer of thyroid peroxidase autoantibody, the patient was diagnosed with immune-induced autoimmune thyroiditis. The patient received continuous thyroxine replacement therapy until her thyroid function returned to normal. After the fifth infusion of pembrolizumab, the patient exhibited hyperglycemia, high serum ketone levels and low arterial blood pH, thus meeting the criteria for immune-induced autoimmune diabetes and diabetic ketoacidosis. As a result, the immunotherapy was discontinued and the patient was diagnosed with insulin-dependent diabetes mellitus. Following anti-PD-1 medication, the patient experienced autoimmune thyroid damage and autoimmune diabetes. Therefore, clinicians should regularly monitor patients undergoing immunotherapy and pay close attention to the characteristics irAEs. Patients with underlying thyroiditis should be carefully monitored due to this being a risk factor, and for patients with thyroiditis care should be taken when deciding on whether they should be treated with immunotherapy. The article also discusses the features and general mechanisms of immune-related endocrine toxicity.

摘要

抗程序性细胞死亡蛋白1(抗PD-1)抗体是一种突破性的免疫检查点抑制剂,可调节T细胞功能。然而,它可能会导致多种免疫相关不良事件(irAEs),如内分泌毒性。本病例报告描述了一名59岁的晚期非小细胞肺癌女性患者,其程序性死亡配体1的肿瘤比例评分为50%。该患者在接受第三次抗PD-1抗体帕博利珠单抗输注后出现皮肤干燥、头晕和疲劳。基于多项临床指标,包括低血清游离T3和游离T4水平、升高的促甲状腺激素水平以及高滴度的甲状腺过氧化物酶自身抗体,该患者被诊断为免疫诱导的自身免疫性甲状腺炎。患者接受持续的甲状腺素替代治疗,直到甲状腺功能恢复正常。在第五次输注帕博利珠单抗后,患者出现高血糖、高血清酮水平和低动脉血pH值,从而符合免疫诱导的自身免疫性糖尿病和糖尿病酮症酸中毒的标准。结果,免疫治疗被中断,患者被诊断为胰岛素依赖型糖尿病。抗PD-1药物治疗后,患者出现了自身免疫性甲状腺损伤和自身免疫性糖尿病。因此,临床医生应定期监测接受免疫治疗的患者,并密切关注irAEs的特征。由于潜在的甲状腺炎是一个危险因素,应仔细监测有潜在甲状腺炎的患者,对于有甲状腺炎的患者,在决定是否应接受免疫治疗时应谨慎。本文还讨论了免疫相关内分泌毒性的特征和一般机制。

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