Endocrine Abstracts

Objective: Levothyroxine (LT4) is the gold standard of care for primary hypothyroidism. For most patients, it fully resolves the symptoms of hypothyroidism. However, a small proportion of treated individuals continue to experience symptoms even when euthyroid. The management of such patients has generated significant controversy and public attention throughout the years. This systematic review aims to analyse and evaluate the existing evidence for the benefits of alternative thyroid hormone replacements compared to the standard LT4 monotherapy. This includes combination therapies in the form of LT4/LT3 or Desiccated Thyroid Extracts (DTE) and LT3 monotherapy.

Method: A systematic search of the online literature was conducted on PubMed, EMBASE, Cochrane Library and Web of Science in November 2022. Out of 6,176 studies, thirteen were included and were assessed for our primary and secondary outcomes. Primary outcomes included quality-of-life scores and thyroid function tests while secondary outcomes assessed hypothyroid-related symptoms (cognitive function, cardiovascular health, body profile, psychological health) and patient preferences.

Conclusion: We observed no overall difference in clinical outcomes between combination therapies (LT4/LT3 or DTE) and LT4 monotherapy for the treatment of primary hypothyroidism in adults. Yet, consistent with previous clinical trials and meta-analyses, we observed that a higher proportion of patients preferred combination therapy over LT4 alone. Moreover, we noticed a tendency favouring combination therapies when either higher doses of LT3 or DTE were used. Our most important observation was that a significant improvement in quality of life was evident only when combination therapy was used for patients with residual symptoms or an autoimmune related pathogenesis of hypothyroidism. Regarding treatment with LT3 alone, the evidence was insufficient and definite conclusion could not be made. To resolve this controversy and validate the observations seen above future homogenous trials should be developed to address the limitations of current study designs.