Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, VA, United States.
Front Endocrinol (Lausanne). 2020 Jul 8;11:371. doi: 10.3389/fendo.2020.00371. eCollection 2020.
Hypothyroidism is a common condition with a wide spectrum of etiologies and clinical manifestations. While the majority of patients affected by hypothyroidism respond well to levothyroxine, some patients do not and complain of symptoms despite adequate replacement. There is evidence in experimental models of hypothyroidism that levothyroxine alone may not be able to deliver an adequate amount of T3 to all the tissues targeted by the hormonal action, while liothyronine/levothyroxine combination therapy can. The results of clinical studies directed to assess the effectiveness of liothyronine/levothyroxine combination therapy on the amelioration of hypothyroid symptoms have been disappointing. Most of the trials have been short and underpowered, with several shortcomings in the study design. There is consensus that an adequately powered clinical trial should be developed to prove or disprove the efficacy and effectiveness of therapies other than LT4 alone for the treatment of hypothyroidism, and to assess which group of patients would benefit from them. Here we present some considerations on the technical aspects and necessary tradeoffs in designing such a study with a particular focus on study population selection, choice of endpoints, and study drugs formulation and regimen.
甲状腺功能减退症是一种常见病症，具有广泛的病因和临床表现。虽然大多数甲状腺功能减退症患者对左甲状腺素的反应良好，但有些患者尽管接受了充分的替代治疗仍会抱怨症状。甲状腺功能减退症的实验模型中有证据表明，左甲状腺素单独使用可能无法将足够数量的 T3 输送到激素作用所针对的所有组织，而三碘甲状腺原氨酸/左甲状腺素联合治疗则可以。针对三碘甲状腺原氨酸/左甲状腺素联合治疗改善甲状腺功能减退症症状的有效性进行评估的临床研究结果令人失望。大多数试验时间短且效力不足，研究设计存在几个缺陷。人们普遍认为，应该开发一项充分有力的临床试验，以证明或驳斥除左甲状腺素单独治疗以外的疗法治疗甲状腺功能减退症的疗效和有效性，并评估哪些患者群体将从中受益。在这里，我们提出了一些关于设计此类研究的技术方面和必要权衡的考虑因素，特别关注研究人群的选择、终点的选择以及研究药物的配方和方案。
