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程序性死亡-1抑制剂相关甲状腺损伤的临床特征及危险因素

[Clinical characteristics and risk factors of programmed death-1 inhibitors associated with thyroid gland injury].

作者信息

Gong W W, Zhou F Y, Guo Q H

机构信息

Department of Pharmacy, the Medical Supplies Center, Chinese PLA General Hospital, Beijing 100853, China.

Department of Endocrinology, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2023 Feb 1;62(2):176-181. doi: 10.3760/cma.j.cn112138-20220329-00220.

Abstract

To investigate the clinical characteristics and related risk factors of thyroid gland injury (TGI) in patients with a malignant tumor treated with a programmed death-1 (PD-1) inhibitor. A Retrospective case-control study. Data from 198 patients with a malignant tumor who received treatment with a PD-1 inhibitor in Chinese PLA General Hospital from October 2019 to October 2021 were collected and analyzed retrospectively. According to the TGI incurred after receiving treatment with a PD-1 inhibitor, patients were divided into a thyroid gland normal (TGN) group and TGI group. The prevalence, type, time of occurrence, and outcome of TGI were analyzed. The risk factors that may contribute to TGI were analyzed further by logistic regression. TGI prevalence was 29.8% (59/198 cases) after treatment with a PD-1 inhibitor. There were significant differences with respect to previous radiotherapy and targeted therapy between the TGN group and TGI group (<0.01 for both), but there were no significant differences with regard to sex, age, tumor type, previous surgery, previous chemotherapy, tumor metastasis, or type of PD-1 inhibitor (>0.05 for all). Patients in the TGI group included those with subclinical hypothyroidism (32.2%, =19), hypothyroidism (27.1%, =16), thyrotoxicosis (23.7%, =14), subclinical thyrotoxicosis (10.2%, =6), and thyroiditis with normal thyroid function (6.8%, =4), and the median time of occurrence (months) was 3.00, 3.00, 1.50, 1.50, and 0.80 after treatment with a PD-1 inhibitor, respectively. Among 20 patients who presented initially with thyrotoxicosis or subclinical thyrotoxicosis, 12 cases developed hypothyroidism or subclinical hypothyroidism subsequently. Logistic regression analysis suggested that previous radiotherapy (=3.737, 95% 1.390-10.046), targeted therapy (=3.763, 95% 1.553-9.117), thyroglobulin antibodies at baseline (=12.082, 95% 1.199-121.775), and thyroid-peroxidase antibodies at baseline (=10.874, 95% 1.010-117.047) were risk factors associated with the TGI caused by treatment with a PD-1 inhibitor. After treatment with a PD-1 inhibitor, TGI prevalence was high, especially in those with hypothyroidism or subclinical hypothyroidism. Some patients had a transition from thyrotoxicosis to hypothyroidism. Patients who underwent radiotherapy previously, had targeted therapy, or were thyroid autoantibody-positive at baseline may carry an increased risk of TGI following treatment with a PD-1 inhibitor.

摘要

探讨程序性死亡受体1(PD-1)抑制剂治疗的恶性肿瘤患者甲状腺损伤(TGI)的临床特征及相关危险因素。一项回顾性病例对照研究。收集并回顾性分析2019年10月至2021年10月在中国人民解放军总医院接受PD-1抑制剂治疗的198例恶性肿瘤患者的数据。根据接受PD-1抑制剂治疗后发生的TGI,将患者分为甲状腺正常(TGN)组和TGI组。分析TGI的发生率、类型、发生时间及转归。通过逻辑回归进一步分析可能导致TGI的危险因素。PD-1抑制剂治疗后TGI发生率为29.8%(59/198例)。TGN组和TGI组在既往放疗和靶向治疗方面存在显著差异(均<0.01),但在性别、年龄、肿瘤类型、既往手术、既往化疗、肿瘤转移或PD-1抑制剂类型方面无显著差异(均>0.05)。TGI组患者包括亚临床甲状腺功能减退患者(32.2%,=19)、甲状腺功能减退患者(27.1%,=16)、甲状腺毒症患者(23.7%,=14)、亚临床甲状腺毒症患者(10.2%,=6)和甲状腺功能正常的甲状腺炎患者(6.8%,=4),接受PD-1抑制剂治疗后发生的中位时间(月)分别为3.00、3.00、1.50、1.50和0.80。最初表现为甲状腺毒症或亚临床甲状腺毒症的20例患者中,12例随后发展为甲状腺功能减退或亚临床甲状腺功能减退。逻辑回归分析表明,既往放疗(=3.737,95% 1.390 - 10.046)、靶向治疗(=3.763,95% 1.553 - 9.117)、基线时甲状腺球蛋白抗体(=12.082,95% 1.199 - 121.775)和基线时甲状腺过氧化物酶抗体(=10.874,95% 1.010 - 117.047)是与PD-1抑制剂治疗引起的TGI相关的危险因素。PD-1抑制剂治疗后,TGI发生率较高,尤其是甲状腺功能减退或亚临床甲状腺功能减退患者。部分患者从甲状腺毒症转变为甲状腺功能减退。既往接受放疗、进行靶向治疗或基线时甲状腺自身抗体阳性的患者在接受PD-1抑制剂治疗后发生TGI的风险可能增加。

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