Exploring cardiovascular risk in subclinical hypothyroidism: The impact of TSHR gene expression and systemic biomarkers.

Abstract

Introduction: Subclinical hypothyroidism (SCH), defined by elevated thyroid-stimulating hormone (TSH) with normal thyroid hormone levels, affects approximately 3-8% of the population. Growing evidence indicates that thyroid-stimulating hormone receptor (TSHR) expression in cardiovascular tissues, together with systemic inflammation (IL-6) and oxidative stress (3-nitrotyrosine), may contribute to cardiovascular dysfunction in SCH. This study aimed to evaluate the association between TSHR gene expression and systemic biomarkers-hormonal, inflammatory, and oxidative-and to assess their predictive value for cardiovascular risk in SCH patients.

Methods: A case-control design was adopted involving 150 SCH subjects and 150 age- and sex-matched healthy controls. Demographic and clinical data were collected using structured interviews. Fasting blood samples were analyzed for TSH (CLIA), IL-6, and 3-nitrotyrosine (ELISA), while TSHR gene expression was quantified using real-time PCR with GAPDH as an internal control. Statistical analyses were performed using Stata version 17.0.

Results: Compared with controls, SCH patients showed significantly higher levels of TSH, IL-6, 3-nitrotyrosine, and TSHR gene expression (P<0.05). Receiver operating characteristic (ROC) analysis revealed high diagnostic accuracy for these parameters. Although univariate analysis associated TSHR dysregulation with SCH, multivariate regression identified TSH as the only independent predictor of disease status. Oxidative stress demonstrated a significant positive association with TSHR expression, whereas IL-6 showed no independent influence.

Conclusion: SCH is characterized by elevated hormonal, oxidative, and inflammatory markers, with oxidative stress contributing to TSHR upregulation. TSH remains the strongest independent predictor, underscoring the hormonal-oxidative interaction in cardiovascular risk among SCH patients.