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Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism

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Abstract

Introduction

Mutations and single nucleotide polymorphisms (SNPs) in the genes encoding the network of proteins involved in thyroid hormone signaling (TH) may have implications for the effectiveness of the treatment of hypothyroidism with LT4. It is conceivable that loss-of-function mutations or SNPs impair the ability of LT4 to be activated to T3, reach its targets, and ultimately resolve symptoms of hypothyroidism. Some of these patients do benefit from therapy containing LT4 and LT3.

Methods

Here, we reviewed the PubMed and examined gene mutations and SNPs in the TH cellular transporters, deiodinases, and TH receptors, along with their impact on TH signaling, and potential clinical implications.

Results

In some mechanisms, such as the Thr92Ala-DIO2 SNP, there is a compelling rationale for reduced T4 to T3 activation that limits the effectiveness of LT4 to restore euthyroidism. In other mechanisms, a potential case can be made but more studies with a larger number of individuals are needed.

Discussion/Conclusion

Understanding the clinical impact of the genetic makeup of LT4-treated patients may help in the preemptive identification of those individuals that would benefit from therapy containing LT3.

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Funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP proc. N° 2021/12746-3) (MOR); the Pró-Reitoria de Extensão (PROEX,6411133/2019-M.O. Ribeiro) (MOR); and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK – DK15070, DK58538, DK65066, DK77148) (ACB).

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  1. Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, IL, USA

    Gustavo C. Penna, Federico Salas-Lucia & Antonio C. Bianco

  2. Developmental Disorders Program, Center for Biological Sciences and Health, Mackenzie Presbyterian University, Sao Paulo, SP, Brazil

    Miriam O. Ribeiro

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  1. Gustavo C. Penna
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Correspondence to Antonio C. Bianco.

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Penna, G.C., Salas-Lucia, F., Ribeiro, M.O. et al. Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism. Endocrine (2023). https://doi.org/10.1007/s12020-023-03528-y

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