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Background  Treatment of hypothyroidism with 3,5,3′-triiodothyronine (T 3 ) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T 3 . However, the analysis included a mixture of different patient groups and dose-regimens.    Objective  To compare the effect of combination therapy with thyroxine (T 4 ) and T 3  versus T 4  monotherapy in patients with hypothyroidism on stable T 4  substitution.    Study design  Double-blind, randomised cross-over. Fifty micrograms of the usual T 4  dose was replaced with either 20 μg T 3  or 50 μg T 4  for 12 weeks, followed by cross-over for another 12 weeks. The T 4  dose was regulated if needed, intending unaltered serum TSH levels.    Evaluation  Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods.    Inclusion criteria  Serum TSH between 0.1 and 5.0 mU/l on unaltered T 4  substitution for 6 months.    Results  A total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T 4  monotherapy versus T 4 /T 3  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.    Conclusion  In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T 3  20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.

european journal of endocrinology

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