lt4 and slow release t3 combination: optimum therapy for hypothyroidism?

Context: levothyroxine (lt4) is recommended as replacement therapy for thyroid hormone deficiency. however, some hypothyroid patients receiving lt4 therapy do not feel as well as healthy subjects. this article aimed to review current knowledge regarding lt4 monotherapy versus lt4+lt3 combination therapy and propose future directions regarding lt4+slow release t3 combination treatment for hypothyroidism. evidence acquisition: we searched pubmed and scopus using related keywords. results: the lt4 monotherapy causes higher serum free t4 (ft4), subnormal serum free t3 (ft3), and ft3/ft4 ratio in one-fourth of patients. the lt4+lt3 combination therapy increases serum t3 and ft3 concentrations and may normalize the ft3/ft4 ratio. however, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in lt4+lt3 combination therapy than in lt4 monotherapy. recent surveys show that combination therapy is on the rise, in particular, due to patient demand. the lt4 plus slow-release lt3 preparation has shown promising results in improving serum thyroid hormone concentrations. conclusions: the beneficial effect of lt4+lt3 combination therapy is not clear, and the safety of long-term therapy is yet under question. more scientific well-designed research projects are required in this field.