Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

Abstract

BackgroundTreatment of hypothyroidism with 3,5,3′-triiodothyronine (T3) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T3. However, the analysis included a mixture of different patient groups and dose-regimens.ObjectiveTo compare the effect of combination therapy with thyroxine (T4) and T3 versus T4 monotherapy in patients with hypothyroidism on stable T4 substitution.Study designDouble-blind, randomised cross-over. Fifty micrograms of the usual T4 dose was replaced with either 20 μg T3 or 50 μg T4 for 12 weeks, followed by cross-over for another 12 weeks. The T4 dose was regulated if needed, intending unaltered serum TSH levels.EvaluationTests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods.Inclusion criteriaSerum TSH between 0.1 and 5.0 mU/l on unaltered T4 substitution for 6 months.ResultsA total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T4 monotherapy versus T4/T3 combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended.ConclusionIn a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.