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

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Abstract

The 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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Acknowledgements

The authors thank Jean Ann Gilder (Scientific Communication srl., Naples, Italy) for writing assistance.

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  1. Department of Public Health, University of Naples Federico II, Naples, Italy

    Tommaso Porcelli & Domenico Salvatore

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  1. Tommaso Porcelli
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TP wrote the paper and DS wrote and reviewed the paper.

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Correspondence to Tommaso Porcelli.

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Porcelli, T., Salvatore, D. Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?. Endocrine 69, 244–248 (2020). https://doi.org/10.1007/s12020-020-02391-5

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