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不同水平甲状腺自身抗体与免疫检查点抑制剂相关甲状腺功能障碍之间的相关性

Correlation between different levels of thyroid autoantibodies and immune checkpoint inhibitor-associated thyroid dysfunction.

作者信息

Jiao Yanyan, Xu Meihua, Rao Xiaopang

机构信息

Department of Nursing, People's Hospital of Chengyang District, Qingdao, Shandong, China.

Department of Endocrinology, People's Hospital of Chengyang District, Qingdao, Shandong, China.

出版信息

Front Endocrinol (Lausanne). 2025 Aug 13;16:1620718. doi: 10.3389/fendo.2025.1620718. eCollection 2025.

Abstract

BACKGROUND

To investigate the correlation between thyroid immune-related adverse events (irAEs) and thyroid autoantibodies in cancer patients treated with immune checkpoint inhibitors (ICIs).

METHODS

A retrospective analysis was conducted on 316 cancer patients (139 females, 177 males; median age 64.0 [56.0-71.0] years) treated at Qingdao Chengyang District People's Hospital from January 2018 to December 2023. Patients were divided into a euthyroid group ( = 158) and a thyroid irAEs group ( = 158) based on the occurrence of thyroid dysfunction post-ICI therapy. The researchers received at least one treatment with ICIs, and after the initial treatment, they underwent at least one or more tests for thyroid hormone levels, TPOAb, TRAb, and TgAb, with an interval of 4 weeks or more for each test. Thyroid hormone levels and autoantibodies (TPOAb, TRAb, TgAb) were measured. Clinical characteristics and baseline thyroid autoantibodies were evaluated for their association with thyroid irAEs.

RESULTS

Thyroid irAEs included subclinical thyrotoxicosis (19.94%, = 63), clinical thyrotoxicosis (2.53%, = 8), subclinical hypothyroidism (6.01%, = 19), and clinical hypothyroidism (21.52%, = 68). Baseline thyroid autoantibodies were positive in 28.48% ( = 45) of the irAEs group versus 5.70% (n = 9) in the euthyroid group ( < 0.001). Post-ICI treatment, the thyrotoxicosis group exhibited higher TRAb titers but lower TPOAb titers and TSH levels compared to the hypothyroidism group ( < 0.05). Logistic regression identified pre-treatment TRAb positivity (=6.927, 95% : 1.817-32.724, =0.002) and TPOAb positivity ( = 7.128, 95% : 1.877-37.225, = 0.001) as risk factors for thyroid irAEs.

CONCLUSION

Patients with malignant tumors who had high levels of TPOAb and/or TRAb before treatment were more likely to develop thyroid immune-related adverse events (irAEs) after treatment. The importance of screening for baseline thyroid autoantibodies in predicting thyroid irAEs needs to be clearly understood, and close monitoring and notification to patients should be carried out, along with prior intervention.

摘要

背景

探讨接受免疫检查点抑制剂(ICI)治疗的癌症患者甲状腺免疫相关不良事件(irAEs)与甲状腺自身抗体之间的相关性。

方法

对2018年1月至2023年12月在青岛市城阳区人民医院接受治疗的316例癌症患者(139例女性,177例男性;中位年龄64.0[56.0 - 71.0]岁)进行回顾性分析。根据ICI治疗后甲状腺功能障碍的发生情况,将患者分为甲状腺功能正常组(n = 158)和甲状腺irAEs组(n = 158)。研究对象接受了至少一次ICI治疗,初始治疗后,他们至少进行了一次或多次甲状腺激素水平、甲状腺过氧化物酶抗体(TPOAb)、促甲状腺素受体抗体(TRAb)和甲状腺球蛋白抗体(TgAb)检测,每次检测间隔4周或更长时间。检测甲状腺激素水平和自身抗体(TPOAb、TRAb、TgAb)。评估临床特征和基线甲状腺自身抗体与甲状腺irAEs的相关性。

结果

甲状腺irAEs包括亚临床甲状腺毒症(19.94%,n = 63)、临床甲状腺毒症(2.53%,n = 8)、亚临床甲状腺功能减退(6.01%,n = 19)和临床甲状腺功能减退(21.52%,n = 68)。irAEs组基线甲状腺自身抗体阳性率为28.48%(n = 45),而甲状腺功能正常组为5.70%(n = 9)(P < 0.001)。ICI治疗后,甲状腺毒症组的TRAb滴度高于甲状腺功能减退组,但TPOAb滴度和促甲状腺激素(TSH)水平低于甲状腺功能减退组(P < 0.05)。Logistic回归分析确定治疗前TRAb阳性(β = 6.927,95%CI:1.817 - 32.724,P = 0.002)和TPOAb阳性(β = 7.128,95%CI:1.877 - 37.225,P = 0.001)为甲状腺irAEs的危险因素。

结论

治疗前TPOAb和/或TRAb水平高的恶性肿瘤患者治疗后更易发生甲状腺免疫相关不良事件(irAEs)。需要清楚认识到筛查基线甲状腺自身抗体对预测甲状腺irAEs的重要性,并应进行密切监测、告知患者,同时进行提前干预。

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Immune Related Adverse Events of the Thyroid - A Narrative Review.甲状腺免疫相关不良反应:综述
Front Endocrinol (Lausanne). 2022 May 26;13:886930. doi: 10.3389/fendo.2022.886930. eCollection 2022.

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