Thyroxine replacement: a clinical endocrinologist’s viewpoint

Background: Hypothyroidism affects 2–5% of the general population. Patients with uncorrected disease suffer significant morbidity and have an increased risk of cardiovascular disease and neurocognitive impairment. Levothyroxine, the treatment of choice, is inexpensive, easy to administer and in most cases restores well-being while normalizing thyroid function. However, 30–50% of individuals on levothyroxine are either over-treated or under-treated and others remain dissatisfied with treatment despite achieving thyroid hormone concentrations within the laboratory reference interval. 

Methods: This review is based on a systematic search of the literature for controlled trials, systematic reviews, guideline papers and cohort studies addressing best practice in thyroid hormone replacement. 

Results: Recent decades have seen improvements in patient management strategies driven by a better appreciation of levothyroxine pharmacokinetics. However, aspects of therapy such as the optimal timing of medication, strategies to overcome treatment non-adherence and target thyroid stimulating hormone concentrations in pregnancy and in patients with differentiated thyroid cancer remain challenging. Furthermore, there is now a substantial body of literature on common genetic variations in the deiodinases and thyroid hormone transporters and their role in the local regulation of thyroid hormone delivery. The benefits of combination therapy with liothyronine and levothyroxine are uncertain, and while it is theoretically probable that subsets of genetically predisposed individuals will benefit from combination therapy the existing evidence is as yet limited. 

Conclusion: Despite the availability of thyroid hormone replacement for more than a century, there are still substantial challenges in practice and opportunities to improve treatment outcomes.