Department of Medicine, Washington Hospital Center, Georgetown University, Washington, District of Columbia, USA.
Curr Opin Endocrinol Diabetes Obes. 2013 Oct;20(5):460-6. doi: 10.1097/01.med.0000432611.03732.49.
Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population.
Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment.
Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.
由于长期以来一直存在关于甲状腺功能减退症患者是否可以通过单独使用左甲状腺素（L-T4）来得到最佳替代治疗的争议，因此有许多研究都探讨了三碘甲状腺原氨酸（T3）与 L-T4 联合治疗的潜在益处。这些研究的结果均未能支持联合治疗的潜在益处。直到最近的遗传研究表明，对于一小部分甲状腺功能减退症患者人群，L-T3 联合 L-T4 单药治疗具有合理依据，因此一直缺乏支持 L-T3 联合 L-T4 单药治疗的有力论据。
人们对这一问题的兴趣主要集中在脱碘酶在维持甲状腺功能正常状态中的重要性，以及脱碘酶基因中的遗传多态性在影响血液和组织中甲状腺激素浓度方面的作用。D2 基因中的一个这样的多态性，即 Thr92Ala，与骨骼肌和甲状腺中 T4 向 T3 的转化减少有关，这种转化减少与肥胖以及甲状腺-垂体反馈的改变和对甲状腺激素治疗的反应有关。
尽管我们的专业组织继续建议单独使用 L-T4 治疗甲状腺功能减退症，但对于持续抱怨尽管剂量达到血清促甲状腺激素水平正常下限仍感到疲劳的 L-T4 单药治疗患者，应考虑存在 D2 基因多态性的可能性。存在这种多态性的一个提示线索可能是游离 T4/游离 T3 比值高于正常。临床医生可以考虑在选定的患者中进行 T3 治疗试验。未来需要进行更多的对照临床试验，以更全面地解决这一争议。
