Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: Effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone

Objective: To attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism. Methods: This trial attempted to replicate prior findings, which suggested that substituting 12.5 μg of liothyronine (LT₃) for 50 μg of levothyroxine (LT₄) 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. At an endocrinology and diabetes clinic, 30 adult subjects with primary hypothyroidism stabilized on LT₄ were recruited. Patients randomly assigned to treatment sequence 1 received their standard LT₄ dose in one capsule and placebo in another. Patients assigned to sequence 2 received their usual LT₄ dose minus 50 μg in one capsule and 10 μg of LT₃ in the other. At the end of the first 6 weeks, subjects were crossed over to receive the other treatment. Carryover and treatment effects were assessed by t tests. Results: Of the 30 enrolled study subjects, 27 completed the trial. The mean LT₄ 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 (P<0.001), total serum thyroxine was reduced by 3.0 μg/dL (P<0.001), and total serum tri-iodothyronine was increased by 20.5 ng/dL (P = 0.004). Conclusion: With regard to the outcomes measured, substitution of LT₃ at a 1:5 ratio for a portion of baseline LT₄ yielded no better results than did treatment with the original dose of LT₄ alone.