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Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement

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Abstract

Purpose

The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment.

Methods

Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3 months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy.

Results

1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different.

Conclusion

These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, Italy

    C. Piras, M. Pibiri, V. P. Leoni, A. Balsamo, L. Tronci & L. Atzori

  2. Department of Medical Sciences and Public Health, University of Cagliari, 09042, Monserrato, Italy

    N. Arisci & S. Mariotti

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  1. C. Piras
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Contributions

LA and SM conceived the study and supervised the project. NA obtained the samples and clinical details. CP, AB. VPL and LT performed metabolomics experiments and data analysis. CP, MP, and NA wrote the first draft of the manuscript, and CP, MP, VPL, LA, SM, and NA, contributed to the final version. CP, MP, LA, and SM critically reviewed the data and the manuscript. All the authors have read and approved the whole content of this submitted manuscript.

Corresponding author

Correspondence to S. Mariotti.

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The authors declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study has been performed according to the Declaration of Helsinki and was approved by the Ethical Committee of the University Hospital of Cagliari.

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All the participants were provided written informed consent to participate and to publish data.

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Piras, C., Pibiri, M., Leoni, V.P. et al. Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement. J Endocrinol Invest 44, 1309–1319 (2021). https://doi.org/10.1007/s40618-020-01434-y

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  • DOI: https://doi.org/10.1007/s40618-020-01434-y

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