Critical illness is hallmarked by neuroendocrine alterations throughout ICU stay. We investigated whether the neuroendocrine axes recover after ICU discharge and whether any residual abnormalities associate with physical functional impairments assessed 5 years after critical illness. In this preplanned secondary analysis of the EPaNIC randomized controlled trial, we compared serum concentrations of hormones and binding proteins of the thyroid axis, the somatotropic axis and the adrenal axis in 436 adult patients who participated in the prospective 5-year clinical follow-up and who provided a blood sample with those in 50 demographically matched controls. We investigated independent associations between any long-term hormonal abnormalities and physical functional impairments (handgrip strength, 6-min walk distance, and physical health-related quality-of-life) with use of multivariable linear regression analyses. At 5-year follow-up, patients and controls had comparable serum concentrations of thyroid-stimulating hormone, thyroxine (T4), triiodothyronine (T3) and thyroxine-binding globulin, whereas patients had higher reverse T3 (rT3, p = 0.0002) and lower T3/rT3 (p = 0.0012) than controls. Patients had comparable concentrations of growth hormone, insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 (IGFBP1), but higher IGFBP3 (p = 0.030) than controls. Total and free cortisol, cortisol-binding globulin and albumin concentrations were comparable for patients and controls. A lower T3/rT3 was independently associated with lower handgrip strength and shorter 6-min walk distance (p ≤ 0.036), and a higher IGFBP3 was independently associated with higher handgrip strength (p = 0.031). Five years after ICU admission, most hormones and binding proteins of the thyroid, somatotropic and adrenal axes had recovered. The residual long-term abnormality within the thyroid axis was identified as risk factor for long-term physical impairment, whereas that within the somatotropic axis may be a compensatory protective response. Whether targeting of the residual abnormality in the thyroid axis may improve long-term physical outcome of the patients remains to be investigated. Trial registration ClinicalTrials.gov: NCT00512122, registered on July 31, 2007 ( https://www.clinicaltrials.gov/ct2/show/NCT00512122 ).

中文翻译：

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危重病后 5 年持续存在神经内分泌异常及其与身体损伤的关系

危重病的特征是整个 ICU 住院期间的神经内分泌改变。我们调查了 ICU 出院后神经内分泌轴是否恢复，以及任何残留异常是否与危重病 5 年后评估的身体功能障碍相关。在这项预先计划的 EPaNIC 随机对照试验的二次分析中，我们比较了 436 名参与前瞻性 5 年临床随访和谁提供了与 50 个人口统计匹配的对照者的血样。我们调查了任何长期荷尔蒙异常与身体功能障碍（握力、6 分钟步行距离、和身体健康相关的生活质量）使用多变量线性回归分析。在 5 年的随访中，患者和对照组的促甲状腺激素、甲状腺素 (T4)、三碘甲状腺原氨酸 (T3) 和甲状腺素结合球蛋白的血清浓度相当，而患者的反向 T3 (rT3, p = 0.0002) 和T3/rT3 (p = 0.0012) 低于对照组。患者的生长激素、胰岛素样生长因子-I (IGF-I) 和 IGF 结合蛋白 1 (IGFBP1) 浓度相当，但 IGFBP3 (p = 0.030) 高于对照组。患者和对照组的总和游离皮质醇、皮质醇结合球蛋白和白蛋白浓度相当。较低的 T3/rT3 与较低的握力和较短的 6 分钟步行距离独立相关（p ≤ 0.036），较高的 IGFBP3 与较高的握力独立相关（p = 0.031）。入住 ICU 五年后，甲状腺、生长激素和肾上腺轴的大部分激素和结合蛋白已经恢复。甲状腺轴内的残余长期异常被确定为长期身体损伤的危险因素，而生长轴内的异常可能是一种代偿性保护反应。针对甲状腺轴的残余异常是否可以改善患者的长期身体结果仍有待研究。试验注册ClinicalTrials.gov：NCT00512122，2007年7月31日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。生长激素和肾上腺轴已经恢复。甲状腺轴内的残余长期异常被确定为长期身体损伤的危险因素，而生长轴内的异常可能是一种代偿性保护反应。针对甲状腺轴的残余异常是否可以改善患者的长期身体结果仍有待研究。试验注册ClinicalTrials.gov：NCT00512122，2007年7月31日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。生长激素和肾上腺轴已经恢复。甲状腺轴内的残余长期异常被确定为长期身体损伤的危险因素，而生长轴内的异常可能是一种代偿性保护反应。针对甲状腺轴的残余异常是否可以改善患者的长期身体结果仍有待研究。试验注册ClinicalTrials.gov：NCT00512122，2007年7月31日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。针对甲状腺轴的残余异常是否可以改善患者的长期身体结果仍有待研究。试验注册ClinicalTrials.gov：NCT00512122，2007年7月31日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。针对甲状腺轴的残余异常是否可以改善患者的长期身体结果仍有待研究。试验注册ClinicalTrials.gov：NCT00512122，2007年7月31日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。