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Abstract
This paper aims to attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism. This trial attempted to replicate prior findings, which suggested that substituting 12.5 μg of liothyronine (LT^sub 3^) for 50 μg of levothyroxine (LT^sub 4^) might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the previous findings to fatigue and to assess for differential effects in subjects with low fatigue and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. Of the 30 enrolled study subjects, 27 completed the trial. The mean LT^sub 4^ dose was 121±26 μg/day at baseline. No significant differences in fatigue and symptoms of depression were found between treatments. Measures of working memory were unchanged. During substitution treatment, the free thyroxine index was reduced by 0.7, total serum thyroxine was reduced by 3.0 μg/dL, and total serum triiodothyronine was increased by 20.5 ng/dL.