Wiersinga Wilmar M
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Eur J Endocrinol. 2009 Dec;161(6):955-9. doi: 10.1530/EJE-09-0879. Epub 2009 Oct 6.
Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with thyroxine (T(4)) explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T(4)/tri-iodothyronine (T(3)) combination therapy over T(4) monotherapy. However, each of these trials can be criticized, and none is perfect: most of them failed to mimic the physiological ratio of serum free T(4) (FT(4)) to free T(3) (FT(3)) concentrations. Development of a sustained-release T(3) preparation given as a single nighttime dose (together with levothyroxine once daily) might maintain physiological serum FT(4)-FT(3) ratio's throughout 24 h. Genetic polymorphisms in deiodinase 2 and thyroid hormone transporters have been associated with well-being, fatigue, depression, and greater improvement on combination therapy. Future trials should target carriers of these polymorphisms to see whether they do better on T(4)/T(3) combination therapy than on T(4) monotherapy.
约10%的甲状腺功能减退患者对左甲状腺素替代治疗的效果不满意。甲状腺素（T4）治疗略有过量或不足不太可能解释患者仍存在的不适。随机临床试验的荟萃分析表明，T4/三碘甲状腺原氨酸（T3）联合治疗并不优于T4单药治疗。然而，这些试验中的每一个都可能受到批评，而且没有一个是完美的：它们中的大多数未能模拟血清游离T4（FT4）与游离T3（FT3）浓度的生理比例。开发一种夜间单次给药的缓释T3制剂（与左甲状腺素每日一次联合使用）可能会在24小时内维持生理血清FT4 - FT3比例。脱碘酶2和甲状腺激素转运体的基因多态性与健康状况、疲劳、抑郁以及联合治疗时更大程度的改善有关。未来的试验应以这些多态性的携带者为目标，看看他们接受T4/T3联合治疗是否比接受T4单药治疗效果更好。
