Idrees Thaer, Price John D, Piccariello Thomas, Bianco Antonio C
Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, IL, United States.
Synthonics Inc., Blacksburg, VA, United States.
Front Endocrinol (Lausanne). 2019 Aug 13;10:544. doi: 10.3389/fendo.2019.00544. eCollection 2019.
The standard of care to treat hypothyroidism is daily administration of levo-thyroxine (LT4). This is based on the understanding that deiodinases can restore production of T3 and compensate for the small amounts of T3 that are normally produced by the thyroid gland. However, pre-clinical and clinical evidence indicating that deiodinases fall short of restoring T3 production is accumulating, opening the possibility that liothyronine (LT3) might have a role in the treatment of some hypothyroid patients. LT3 tablets taken orally result in a substantial peak of circulating T3 that is dissipated during the next several hours, which is markedly distinct from the relative stability of T3 levels in normal individuals. Thus, the effort to developing new delivery strategies for LT3, including slow release tablets, liquid formulations, use of T3-related/hybrid molecules such as T3 sulfate, poly-zinc-T3 and glucagon-T3, nanoparticles containing T3, subcutaneous implant of T3-containing matrices, and stem cells for de novo development of the thyroid gland. This article reviews these strategies, their applicability in animal models and translatability to humans.
治疗甲状腺功能减退症的标准护理方法是每日服用左甲状腺素（LT4）。这是基于这样的认识，即脱碘酶可以恢复T3的生成，并补偿甲状腺通常产生的少量T3。然而，越来越多的临床前和临床证据表明，脱碘酶不足以恢复T3的生成，这使得三碘甲状腺原氨酸（LT3）可能在某些甲状腺功能减退患者的治疗中发挥作用。口服LT3片剂会导致循环T3出现大幅峰值，并在接下来的几个小时内消散，这与正常个体中T3水平的相对稳定性明显不同。因此，人们致力于开发LT3的新给药策略，包括缓释片剂、液体制剂、使用T3相关/混合分子，如硫酸T3、聚锌-T3和胰高血糖素-T3、含T3的纳米颗粒、含T3基质的皮下植入物以及用于甲状腺从头发育的干细胞。本文综述了这些策略、它们在动物模型中的适用性以及向人类的转化性。
