Abstract
ObjectiveThe effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range.DesignFemale hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study.MethodsFifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods.ResultsAfter 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; P<0.0001) and cognitive complaints (mean -20 ± 20; P<0.0001). LT4 monotherapy exerted minor effects on two domains only (cognitive complaints and impaired daily life). All three dimensions’ scores in the Fatigue Questionnaire (physical, mental and total fatigue) improved after LT3 treatment compared to baseline (P<0.001), and in the SF-36 questionnaire 7 of 8 scales showed significantly better scores after LT3 treatment compared to baseline. There were no differences in blood pressure or resting heart rate between the two treatment groups. TSH in patients on LT3 was slightly higher (median 1.33 mU/L (interquartile range (IQR) 0.47-2.26)) than in patients on LT4 (median 0.61 mU/L (IQR 0.25-1.20; P<0.018). Five patients on LT3 dropped out of the study due to subjectively reported side effects, compared to only one on LT4.ConclusionsLT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy.Clinical Trial Registration ClinicalTrials.gov, identifier NCT03627611.
Highlights
Hypothyroidism remains a significant clinical conundrum for clinicians
We have previously described the primary objective of a randomized crossover study evaluating female hypothyroid patients with residual hypothyroid symptoms using LT4 and LT3 monotherapy for 12 weeks each and reported the effect of LT3 monotherapy on skin temperature and activation of brown adipose tissue as the main outcome [25]
Sixteen (34%) patients preferred LT4, 28 (60%) preferred LT3, while 3 (6%) had no preference. This is the first crossover study evaluating the effects of liothyronine versus levothyroxine on quality of life in female patients with residual hypothyroid symptoms, despite adequate hormonal substitution with LT4
Summary
Hypothyroidism remains a significant clinical conundrum for clinicians. While the majority of patients on levothyroxine (LT4) therapy are asymptomatic, 5-10% of patients present residual symptoms despite normal thyroid tests [1]. According to the available literature [2, 3], quality of life (QoL) is reduced in patients with thyroid disorders. These symptoms persist despite adequate LT4 substitution judged by free T4 (FT4), free T3 (FT3) and thyroid stimulating hormone (TSH) levels. This led to the introduction of combination therapy with LT4 and liothyronine (LT3). Clinical studies assessing the effects of LT4/LT3 combination therapy have, been disappointing, with the majority of studies showing no significant differences in psychological or quality of life (QoL) scores compared to LT4 monotherapy in several meta-analyses [5,6,7]. It has been stated that future clinical trials should include a more homogenous group of hypothyroid patients [14], and preferably patients with residual symptoms [12], in order to evaluate possible differential effects of treatment with LT4 and LT3
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
