1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium.
2 Intensive Care, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
Thyroid. 2019 Apr;29(4):480-492. doi: 10.1089/thy.2018.0420. Epub 2019 Mar 11.
Non-thyroidal illness (NTI), which occurs with fasting and in response to illness, is characterized by thyroid hormone inactivation with low triiodothyronine (T3) and high reverse T3 (rT3), followed by suppressed thyrotropin (TSH). Withholding supplemental parenteral nutrition early in pediatric critical illness (late-PN), thus accepting low/no macronutrient intake up to day 8 in the pediatric intensive care unit (PICU), accelerated recovery compared to initiating supplemental parenteral nutrition early (early-PN). Whether NTI is harmful or beneficial in pediatric critical illness and how it is affected by a macronutrient deficit remains unclear. This study investigated the prognostic value of NTI, the impact of late-PN on NTI, and whether such impact explains or counteracts the outcome benefit of late-PN in critically ill children.
This preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial quantified serum TSH, total thyroxine (T4), T3, and rT3 concentrations in 982 patients upon PICU admission versus 64 matched healthy children and in 772 propensity score-matched early-PN and late-PN patients upon admission and at day 3 or last PICU day for shorter PICU stay. Associations between thyroid hormone concentrations upon admission and outcome, as well as impact of late-PN on NTI in relation with outcome, were assessed with univariable analyses and multivariable logistic regression, linear regression, or Cox proportional hazard analysis, adjusted for baseline risk factors.
Upon PICU admission, critically ill children revealed lower TSH, T4, T3, and T3/rT3 and higher rT3 than healthy children (p < 0.0001). A more pronounced NTI upon admission, with low T4, T3, and T3/rT3 and high rT3 was associated with higher mortality and morbidity. Late-PN further reduced T4, T3, and T3/rT3 and increased rT3 (p ≤ 0.001). Statistically, the further lowering of T4 by late-PN reduced the outcome benefit (p < 0.0001), whereas the further lowering of T3/rT3 explained part of the outcome benefit of late-PN (p ≤ 0.004). This effect was greater for infants than for older children.
In critically ill children, the peripheral inactivation of thyroid hormone, characterized by a decrease in T3/rT3, which is further accentuated by low/no macronutrient intake, appears beneficial. In contrast, the central component of NTI attributable to suppressed TSH, evidenced by the decrease in T4, seems to be a harmful response to critical illness. Whether treating the central component with TSH releasing hormone infusion in the PICU is beneficial requires further investigation.
非甲状腺疾病（NTI）在禁食和疾病反应时发生，其特征是甲状腺激素失活，三碘甲状腺原氨酸（T3）降低和反向 T3（rT3）升高，随后促甲状腺激素（TSH）受抑制。在儿科重症监护病房（PICU）早期限制补充肠外营养（晚 PN），从而接受低/无宏量营养素摄入，直到 PICU 第 8 天，与早期开始补充肠外营养（早 PN）相比，恢复速度更快。在儿科危重病中，NTI 是否有害或有益，以及它如何受到宏量营养素缺乏的影响尚不清楚。本研究调查了 NTI 的预后价值、晚 PN 对 NTI 的影响，以及这种影响是否解释或抵消了晚 PN 在危重病儿童中的结局获益。
本研究对早期与晚期肠外营养在儿科重症监护病房中的随机对照试验进行了预先计划的二次分析，在 PICU 入院时和 772 名接受早期 PN 和晚期 PN 的患者入院时和第 3 天或 PICU 最后一天测量了 982 名患者和 64 名匹配的健康儿童的血清 TSH、总甲状腺素（T4）、T3 和 rT3 浓度。入院时甲状腺激素浓度与结局之间的关系，以及晚 PN 对 NTI 的影响与结局之间的关系，通过单变量分析和多变量逻辑回归、线性回归或 Cox 比例风险分析进行评估，调整了基线风险因素。
在 PICU 入院时，危重病儿童的 TSH、T4、T3 和 T3/rT3 降低，rT3 升高（p < 0.0001）。入院时更明显的 NTI，表现为 T4、T3 和 T3/rT3 降低和 rT3 升高，与死亡率和发病率升高相关。晚 PN 进一步降低了 T4、T3 和 T3/rT3，并增加了 rT3（p ≤ 0.001）。统计学上，晚 PN 进一步降低 T4 降低了结局获益（p < 0.0001），而 T3/rT3 的进一步降低解释了晚 PN 结局获益的一部分（p ≤ 0.004）。这种影响在婴儿中比在较大儿童中更大。
在危重病儿童中，外周甲状腺激素失活，表现为 T3/rT3 降低，而低/无宏量营养素摄入进一步加重，这似乎是有益的。相反，由 TSH 抑制引起的 NTI 的中枢成分，表现为 T4 降低，似乎是对危重病的有害反应。在 PICU 中使用 TSH 释放激素输注治疗中枢成分是否有益，需要进一步研究。
