ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1635820
Elevated mitochondrial DNA copy number in Euthyroid Individuals with Impaired Peripheral Sensitivity to Thyroid Hormones
Provisionally accepted
- 1The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- 2The First Affiliated Hospital With Nanjing Medical University, Nanjing, China
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Background: The role of thyroid hormone sensitivity in metabolic and neoplastic diseases is well recognized, however, its association with mitochondrial DNA copy number (mtDNAcn) in euthyroid individuals remains unclear. Objective: This cross-sectional study aimed to explore the relationship between thyroid hormone sensitivity and mtDNAcn in euthyroid individuals. Methods: We recruited 350 hospitalized individuals with normal thyroid function between December 2020 and August 2022. Peripheral blood samples and clinical parameters were collected. Relative mtDNAcn levels were quantified by qPCR from peripheral blood samples. Peripheral thyroid hormone sensitivity was evaluated through the free triiodothyronine to free thyroxine (FT3/FT4) ratio, and central sensitivity was assessed using the thyrotrophic thyroxine resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and thyroid feedback quantile-based index (TFQI). Results: Significant differences in age and sex were observed between groups with lower and higher mtDNAcn. Multivariate linear regression analysis showed a negative correlation between mtDNAcn and the FT3/FT4 ratio after adjusting for confounders such as age, sex, BMI, alcohol consumption, smoking history, hypertension, diabetes, and hyperlipidemia. This negative correlation remained significant in subgroups of younger adults, females, normal-weight individuals, drinkers, non-smokers, and those with hypertension. No significant relationships were found between mtDNAcn and TSHI, TT4RI, or TFQI after adjusting for confounding factors. Conclusion: Reduced peripheral thyroid hormone sensitivity is linked to elevated mtDNAcn in euthyroid individuals, with variations based on age, sex, BMI, smoking, and hypertension.
Keywords: Euthyroid individuals, FT3/FT4 ratio, mitochondrial DNA copy number (mtDNAcn), Thyroid hormone sensitivity, thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI)
Received: 27 May 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Liu, Qin, Huang, Zhang, Li and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Juan Liu, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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