Table_1_Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.docx

Background and ObjectiveNonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs.MethodsWe performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results.ResultsWe observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality.ConclusionsNTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.

背景与目标：非甲状腺疾病综合征（NTIS）在约70%的入住重症监护病房（ICU）的患者中发生，且与其死亡风险增加相关。关于NTIS患者是否应接受甲状腺激素（TH）治疗的问题仍存在争议。鉴于许多干预性随机临床试验（IRCT）未得出明确结论，当前指南不推荐对这些患者进行治疗。在本综述中，我们分析了TH治疗为何在报道的IRCT中未能提供令人信服的结果以证实潜在的有益效应的原因。方法：我们对聚焦于重症患者NTIS的荟萃分析进行了综述。经过谨慎筛选，我们从四项在不同临床状况和疾病中进行的荟萃分析中提取了数据。特别是，我们分析了TH补充的类型、给药途径、治疗剂量和持续时间以及选择的评价结果。结果：我们发现IRCTs在TH补充的类型、给药途径、剂量和持续时间等方面存在显著的异质性。我们还发现主要结局指标，如预防神经学改变、降低氧需求、恢复内分泌和临床参数以及降低死亡率等方面存在巨大差异。结论：NTIS是重症患者中常见的发现。尽管有多个IRCT，但NTIS是否应进行治疗仍然不明确。应识别新的主要结局指标，以充分验证TH治疗的有效性，并清晰回答多年前提出的疑问。