脓毒症患者甲状腺激素敏感性与预后的关系：一项回顾性队列分析
Association between sensitivity to thyroid hormone and prognosis in septic patients: a retrospective cohort analysis.
作者信息
Wang Jia, Wang Yingbai, Xu Zihan, Chou Chuxun, Xiang Jiaofeng, Zhang Xizhi, Hou Xuefei, Yue Suru, Ye Shicai, Chen Feng, Wu Jiayuan
机构信息
Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
出版信息
Front Endocrinol (Lausanne). 2025 Aug 27;16:1611963. doi: 10.3389/fendo.2025.1611963. eCollection 2025.
PURPOSE
Sepsis is associated with significant endocrine dysfunction, particularly in thyroid hormone metabolism. This study aims to investigate the association between thyroid hormone sensitivity indices and prognosis in sepsis, exploring their potential as early prognostic markers.
METHODS
We conducted a retrospective analysis of sepsis patients admitted to the Affiliated Hospital of Guangdong Medical University. Nonlinear associations between thyroid hormones (FT3, FT4, TSH), sensitivity indices (FT3/FT4, TFQI, PTFQI, TSHI, TT4RI), and sepsis mortality were assessed using restricted cubic spline models. Kaplan-Meier curves along with Cox proportional hazards models were used to investigate the longitudinal associations. K-means clustering was applied to thyroid hormone profiles to identify distinct phenotypes.
RESULTS
Among 2,391 sepsis patients, non-survivors exhibited significantly lower levels of thyroid hormone and sensitivity indices compared to survivors. Restricted cubic spline analysis revealed a nonlinear dose-response relationship, with lower FT3, TFQI, PTFQI, TSHI, and TT4RI levels associated with increased mortality risk. Multiple Cox regression models identified FT3 (HR = 0.95, 95% CI: 0.93-0.98, = 0.001), TSH (HR = 0.89, 95% CI: 0.80-0.99, = 0.004), TFQI (HR = 0.66, 95% CI: 0.51-0.84, < 0.001), PTFQI (HR = 0.47, 95% CI: 0.37-0.61, < 0.001), TSHI (HR = 0.92, 95% CI: 0.85-0.99, = 0.040), and TT4RI (HR = 0.98, 95% CI: 0.97-0.99, = 0.001) as independent predictors of 90-day mortality. K-means clustering identified two distinct phenotypes, with Phenotype 2, characterized by profound thyroid hormone suppression and reduced sensitivity indices, was associated with a 36% higher mortality risk (HR = 1.42, 95% CI: 1.04-1.91, = 0.029).
CONCLUSION
Impaired thyroid hormone sensitivity are significantly associated with increased mortality in sepsis, emphasizing their potential as prognostic biomarkers and suggest their utility in risk stratification and personalized management of sepsis patients.
目的
脓毒症与显著的内分泌功能障碍相关，尤其是在甲状腺激素代谢方面。本研究旨在探讨甲状腺激素敏感性指标与脓毒症预后之间的关联，探索其作为早期预后标志物的潜力。
方法
我们对广东医科大学附属医院收治的脓毒症患者进行了回顾性分析。使用受限立方样条模型评估甲状腺激素（游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺激素）、敏感性指标（游离三碘甲状腺原氨酸/游离甲状腺素、甲状腺功能质量指数、蛋白结合甲状腺素功能质量指数、促甲状腺激素指数、总甲状腺素反应指数）与脓毒症死亡率之间的非线性关联。采用Kaplan-Meier曲线和Cox比例风险模型研究纵向关联。应用K均值聚类分析甲状腺激素谱以识别不同的表型。
结果
在2391例脓毒症患者中，与幸存者相比，非幸存者的甲状腺激素和敏感性指标水平显著较低。受限立方样条分析显示存在非线性剂量反应关系，游离三碘甲状腺原氨酸、甲状腺功能质量指数、蛋白结合甲状腺素功能质量指数、促甲状腺激素指数和总甲状腺素反应指数水平较低与死亡风险增加相关。多个Cox回归模型确定游离三碘甲状腺原氨酸（风险比=0.95，95%置信区间：0.93-0.98，P=0.001）、促甲状腺激素（风险比=0.89，95%置信区间：0.80-0.99，P=0.004）、甲状腺功能质量指数（风险比=0.66，95%置信区间：0.51-0.84，P<0.001）、蛋白结合甲状腺素功能质量指数（风险比=0.47，95%置信区间：0.37-0.61，P<0.001）、促甲状腺激素指数（风险比=0.92，95%置信区间：0.85-0.99，P=0.040）和总甲状腺素反应指数（风险比=0.98，95%置信区间：0.97-0.99，P=0.001）为90天死亡率的独立预测因素。K均值聚类识别出两种不同的表型，表型2的特征是甲状腺激素显著抑制和敏感性指标降低，其死亡风险高36%（风险比=1.42，95%置信区间：1.04-1.91，P=0.029）。
结论
甲状腺激素敏感性受损与脓毒症死亡率增加显著相关，强调了其作为预后生物标志物的潜力，并表明其在脓毒症患者风险分层和个性化管理中的效用。
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