Abstract
Background: Hypothyroidism is a common disease. Although most patients achieve normal biochemical parameters with standard treatment using levothyroxine (LT4), about 10% of patients still suffer from residual symptoms. Combination therapy with LT4 and liothyronine (LT3) has not shown better effects than LT4 monotherapy. Purpose: We will assess the potential benefits and drawbacks of LT3 therapy compared to standard mono-treatment with LT4. Method: A systematic literature review was conducted, primarily in PubMed and Medline. Literature searches were performed using subject headings that formed search strings, as well as MeSH terms. The relevance of the articles was assessed based on their title and abstract, and selected articles were read in full text. Results: We analyzed 17 studies, including 4 comparing LT3 with LT4, 5 studies and 2 meta-analyses assessing combination therapy. LT3 monotherapy showed significant improvement in 12 out of 13 hypothyroidism-related outcomes, including fatigue and cognitive complaints. 7 out of 8 outcomes on the SF-36 questionnaire were also improved. TSH was not suppressed but was slightly higher on LT3 versus LT4 treatment. Resting pulse and blood pressure were comparable. LT3 monotherapy increased markers of brown adipose tissue, core body temperature and improved lipid profile compared to LT4 monotherapy. Conclusion: LT3 monotherapy may have positive effects, particularly on cold intolerance and quality of life, but new randomized double-blind studies are needed to confirm this. It is still uncertain whether LT3 monotherapy may increase bone resorption and the risk of cardiovascular events. Current LT3 preparations have short half-lives, an improvement in the future would be depot preparations.