Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods: The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Results: Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 µg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion: This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.
Eur Thyroid J

中文翻译：

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左旋甲状腺素/碘塞罗宁联合治疗甲状腺功能减退症的循证使用：共识文件

背景： 14 项临床试验未显示左甲状腺素 (LT4) 和碘塞罗宁 (LT3) 联合治疗的一致益处。尽管发表了这些试验，但联合疗法被广泛使用，报告受益的患者继续在该领域引起患者和医生的兴趣。最近的科学发展可能会提供对这种不一致的洞察力并指导未来的研究。方法：美国甲状腺协会 (ATA)、英国甲状腺协会 (BTA) 和欧洲甲状腺协会 (ETA) 于 2019 年 11 月 3 日举行了联合会议（在芝加哥和伦敦之间直播），以审查有关联合用药的新基础科学和临床证据来自 12 位内容专家的演示和意见的治疗。演讲结束后，材料被综合并用于制定当前知识状态的总结陈述。在对材料和总结陈述进行审查和修订后，大家一致认为新的联合治疗临床试验是平衡的。产生了包含讨论的材料对未来 LT4/LT3 联合治疗临床试验设计的影响的共识声明。作者对共识声明进行了投票。结果：在可供投票的 34 份共识声明中，28 份获得至少 75% 的同意，13 份获得 100% 的同意。100% 同意的研究包括旨在研究脱碘酶和甲状腺激素转运蛋白多态性对研究结果的影响的研究，纳入对目前治疗不满意且需要每天至少 1.2 µg/kg LT4 的患者，每天使用两次 LT3 或如果可用，最好使用缓释制剂，使用患者报告的结果作为主要结果（通过具有相关内容有效性和响应性的工具测量）和患者偏好作为次要结果，并使用随机安慰剂对照的充分功效双盲平行设计。其余陈述作为潜在的额外考虑因素提出。讨论：本文总结了讨论的领域并提出了共识声明，以指导未来 LT4/LT3 联合治疗临床试验的发展。预计此类重新设计的试验结果将对患者有益，并对未来的甲状腺激素替代临床实践指南治疗建议有价值。
欧洲甲状腺杂志