OUDE Hypoforum

In my opinion, there is a strong case for further RCTs comparing T4 monotherapy and T4/T3 combination therapy for two reasons. First, trials so far have been largely unsuccesfull in mimicking physiological serum FT4–FT3 ratios throughout 24 h. The development of sustained-release T3 preparations might be essential for reaching the goal of ‘physiological’ thyroid hormone replacement. Secondly, an increasing number of polymorphisms in deiodinases and thyroid hormone transporters are associated with psychological well-being, depression, fatigue, and preference for combination therapy. Could it be that subjects not satisfied with monotherapy are frequent carriers of these polymorphisms, and will have a better response to combination therapy? In this respect, one could envisage RCTs restricted to patients who are carriers of one or more of these polymorphisms (34). Studies should be carefully designed, with special attention to sample size calculation, T4/T3 ratio's in combination therapy, and dynamic monitoring of TSH in order to maintain a normal level by adjusting study medications if needed (35). Six years ago, three editorialists had an impossible dream: thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients (35). Hopefully, their dream will come true in the next 6 years.