Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?

Abstract

Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with thyroxine (T4) explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T 4/tri-iodothyronine (T3) 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 T4 (FT4) to free T3 (FT3) concentrations. Development of a sustained-release T3 preparation given as a single nighttime dose (together with levothyroxine once daily) might maintain physiological serum FT4-FT3 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 T4/T3 combination therapy than on T4 monotherapy. © 2009 European Society of Endocrinology.