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Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine LT4 and liothyronine LT3. Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge.
After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Authors voted upon the Consensus Statements. The remaining statements are presented as potential additional considerations.
The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations. Keywords: hypothyroidism, levothyroxine, liothyronine, combination therapy, clinical trial, patient-reported outcomes.
Endocrinologists are frequently asked to consult on adult patients with hypothyroidism taking levothyroxine LT4 who are dissatisfied with their therapy. Once other nonthyroid-related causes of these symptoms have been fully excluded, the patient and their physician may wish to explore alternative therapies for optimization of health and well-being. However, the use of combination therapy with both LT4 and liothyronine LT3 remains highly controversial with conflicting results from published clinical trials 1 , with two studies showing benefit in most measures and two showing benefit in some measures.
