Thyroid hormone replacement: current status and challenges.

INTRODUCTION: Correction of hypothyroidism with synthetic levothyroxine is simple, effective and safe. In most cases levothyroxine restores well-being and normalizes serum thyrotropin (TSH) concentrations. However, up to 30 - 50% of levothyroxine users do not achieve adequate biochemical euthyroidism. Also, a small proportion of hypothyroid individuals remain dissatisfied with treatment even with normal TSH concentrations. AREAS COVERED: This review addresses strategies for achieving optimal thyroid hormone replacement based on a systematic search of the literature for controlled trials, cohort studies or systematic reviews published on the topic since 1960. EXPERT OPINION: Careful attention to factors that affect levothyroxine availability such as medication adherence, drug interactions and co-morbidities should improve the adequacy of therapy, but these factors are challenging to manage in practice. The case for combined therapy with levothyroxine and triiodothyronine (T3) is compelling but is not supported by current evidence from randomized controlled trials. Recent studies of common genetic variations in deiodinase and thyroid hormone transport proteins offer fresh insights in understanding the variable response to thyroid hormone therapy and future research may clarify whether subsets of patients will benefit from combined therapy. Despite significant challenges, opportunities abound for improving therapeutic outcomes.