Supplementary file 1_Role of thyroid dysfunction in long-term psychological prognosis of sepsis.docx

BackgroundAfter recovery from sepsis, approximately 10%-50% of patients develop long-term psychological complications such as anxiety, depression, and post-traumatic stress disorder, yet predictive indicators for these complications remain unclear. Emerging evidence suggests that thyroid function may hold prognostic value for sepsis itself. Building on this evidence, the present study aims to investigate the impact of baseline peripheral thyroid indicators on long-term psychological outcomes (within 28 weeks) in sepsis patients.
MethodsA consecutive sample of 814 sepsis patients was included. Baseline data including demographic characteristics, thyroid function indices, and peripheral inflammatory markers were collected, and psychological outcomes within 28 weeks of follow-up (i.e., anxiety, depression, and post-traumatic stress disorder) were evaluated. ROC analysis, Kaplan-Meier survival analysis, and multivariate COX regression were employed for analysis.
Results(1) Higher levels of peripheral TT3, FT3, TT4, and FT4 at baseline were correlated with a reduced risk of poor psychological outcomes within 28 weeks. Sepsis-induced hypothyroidism was associated with an increased risk of poor psychological outcomes within 28 weeks. (2) These associations appeared to be more pronounced in elderly patients. (3) Peripheral TSH levels showed no such predictive value; similarly, “low-normal thyroid function” (defined as relatively high peripheral TSH within the normal range) also lacked predictive value. (4) A negative monotonic relationship was observed between baseline peripheral thyroid hormones and peripheral levels of tumor necrosis factor-α, interleukin-6, and interleukin-8.
ConclusionDiminished thyroid function may be associated with relatively poor long-term psychological outcomes (within 28 weeks) in sepsis patients, possibly more so in the elderly. Given the observed association between thyroid hormones and peripheral inflammatory factors, this potential prognostic relationship may be partially mediated by inflammatory mechanisms. However, this remains a preliminary speculation and requires further validation.

背景：脓毒症（Sepsis）患者康复后，约10%~50%会出现焦虑、抑郁及创伤后应激障碍（Post-traumatic Stress Disorder, PTSD）等长期心理并发症，但此类并发症的预测指标仍不明确。新兴研究证据显示，甲状腺功能或许对脓毒症本身具有预后价值。本研究基于该证据，旨在探讨基线外周甲状腺指标对脓毒症患者28周内长期心理结局的影响。
方法：本研究纳入814例连续招募的脓毒症患者。收集人口学特征、甲状腺功能指标及外周炎症标志物等基线数据，并评估随访28周内的心理结局（即焦虑、抑郁及创伤后应激障碍）。采用受试者工作特征（Receiver Operating Characteristic, ROC）分析、Kaplan-Meier生存分析及多因素COX回归进行数据分析。
结果：(1) 基线外周总三碘甲状腺原氨酸（Total Triiodothyronine, TT3）、游离三碘甲状腺原氨酸（Free Triiodothyronine, FT3）、总甲状腺素（Total Thyroxine, TT4）及游离甲状腺素（Free Thyroxine, FT4）水平越高，患者28周内出现不良心理结局的风险越低；脓毒症诱导的甲状腺功能减退症与28周内不良心理结局风险升高相关。(2) 上述关联在老年患者中更为显著。(3) 外周促甲状腺激素（Thyroid-Stimulating Hormone, TSH）水平无此类预测价值；同理，“低正常甲状腺功能”（定义为正常范围内外周TSH相对偏高）亦无预测价值。(4) 基线外周甲状腺激素与外周肿瘤坏死因子-α（Tumor Necrosis Factor-α, TNF-α）、白细胞介素-6（Interleukin-6, IL-6）及白细胞介素-8（Interleukin-8, IL-8）水平呈负单调相关关系。
结论：甲状腺功能减低可能与脓毒症患者28周内较差的长期心理结局相关，且该关联在老年患者中可能更为明显。鉴于甲状腺激素与外周炎症因子间的关联已被观测到，这种潜在的预后关联或许部分由炎症机制介导。不过，这仍属于初步推测，尚需进一步验证。