• Endocrine · Aug 2020

    Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?

    • Tommaso Porcelli and Domenico Salvatore.
    • Department of Public Health, University of Naples Federico II, Naples, Italy. tommasoporcelli@gmail.com.
    • Endocrine. 2020 Aug 1; 69 (2): 244-248.

    AbstractThe universal applicability of levothyroxine (LT4) monotherapy for the treatment of hypothyroidism has been questioned in recent years. Indeed, it is now clear that about 10-15% of LT4-treated hypothyroid patients are dissatisfied with their treatment. It is plausible that this subset of hypothyroid patients may need T3 + T4 combined therapy to restore peripheral euthyroidism. To address this issue, many clinical trials have investigated the effect of T3 + T4 combinations versus standard LT4-based therapy. However, to date, results have been inconclusive, mainly due to the lack of markers that identify candidates for combination therapy. A breakthrough in this field came with the recent finding that several single-nucleotide polymorphisms in the deiodinase genes are associated with the persistence of hypothyroid symptoms in biochemically euthyroid LT4-treated patients, and are thus markers of candidates for combination therapy. In addition, whole-genome association studies are expanding our knowledge of other genes of the thyroid hormone (TH) pathway that affect serum TH levels. To target the right population for the T3 + T4 combined therapy, the next step is to translate these new findings into prospective trials. Hopefully, this will pave the way to personalized therapy for each hypothyroid patient.

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