Liothyronine Use Beyond Replacement Therapy, with Caution.
Liothyronine Use Beyond Replacement Therapy, with Caution.
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碘塞罗宁在替代治疗之外的使用需谨慎。
DOI：
10.1089/thy.2022.0196
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Celi,FrancescoSaverio
中科院分区：
文献类型：
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作者：
Celi,FrancescoSaverio
甲状腺激素的作用在肌纤维的功能和分化中起着关键作用。除了众所周知的肌球蛋白α链（1）和心肌肌浆网Ca2 + ATP酶（SERCA2a）（2）的正性转录调节外，甲状腺激素是分化的有效信号。相反，它的作用抑制胚胎转录特征，这也发生在缺血后重塑中（3），这是一种导致心脏扩张、心力衰竭和死亡率增加的适应不良事件。这一观察结果代表了Pantos等人发表在最新一期《甲状腺》杂志上的研究的前提（4）。在这项先导性双盲安慰剂对照研究中，作者在直接经皮冠状动脉介入治疗后的前48小时内使用药理学剂量的碘甲状腺原氨酸（LT 3）治疗急性心肌梗死患者，将缺血事件后6个月治疗组间左心室射血分数的差异作为主要目标。该研究在主要终点方面没有达到统计学显著性，但结果仍然很诱人，因为LT3治疗组的数据趋势是心肌功能改善。具体来说，出院时，接受LT 3治疗的患者在六个月随访时显示出更小的左心室尺寸和更小的梗死面积。这项研究的主要优势是基于动物模型中临床前观察的转化方法，该方法指导了LT3剂量和治疗窗口的选择。作者在设计中特别注意，限制招募单支血管（前降支）疾病患者，从而增加了研究的内部有效性。此外，该研究是双盲安慰剂对照研究，心肌功能通过最先进的心脏MRI进行评估，随访（6个月）是充分的。一个主要的局限性是排除了4例梗死面积最小（<左心室容积的1%）的患者，这些患者恰好都发生在安慰剂组（见文章，图2）。当
Thyroid hormone action has a pivotal role in myo-cardial function and differentiation. Aside the wellknown positive transcriptional regulation of myosin alpha chain (1) and cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2a)(2), thyroid hormone is a potent signal for differentiation. Conversely its action inhibits the embryonic transcriptional signature, which also occurs in postischemic remodeling (3), a maladaptive event leading to cardiac dilation, heart failure, and increased mortality. This observation represents the premise of the study of Pantos et al. published in the current issue of Thyroid (4). In this pilot double-blind placebo-controlled study, the authors treated patients affected by acute myocardial infarction with pharmacological doses of liothyronine (LT3) during the first 48 hours after primary percutaneous coronary intervention using as primary aim difference in left ventricle ejection fraction between the treatment arms six months after the ischemic event. The study did not reach statistical significance in the primary endpoint, but the results are nonetheless enticing since the data trend toward an improvement in myocardial function in the LT3-treated group. Specifically, at discharge LT3-treated patients showed smaller left ventricle size, and smaller infarct size at the six-month follow-up visit. A major strength of this study is the translational approach based on preclinical observations in animal models that guided the choices in LT3 dose and window of treatment. The authors posed extreme attention in the design by limiting the recruitment to patients with single vessel (anterior descending) disease, thus increasing the internal validity of the study. Moreover, the study was double blind placebo-controlled, myocardial function was assessed by state-of-the-art cardiac MRI, and the follow-up (six months) was adequate.Major caution though should be posed in the evaluation of the data in their entirety. One major limitation is the elimination of four patients with minimal infarction size (< 1% of left ventricle volume), which happened to occur all in the placebo group (see article, Fig. 2). When the