TSHR gene expression and mitochondrial-cardiac interactions as emerging predictors of cardiovascular risk in early thyroid dysfunction

Abstract Objectives To evaluate biochemical, hormonal, genetic, and mitochondrial alterations associated with cardiovascular risk in SCH, emphasizing the interplay between NT-proBNP, succinate dehydrogenase (SDH) complex activity, and thyroid-stimulating hormone receptor (TSHR) gene expression. Methods A case–control study was conducted involving SCH patients and age-matched euthyroid controls. Serum thyroid profiles, NT-proBNP, and SDH complex activity were quantified by standard assays, and TSHR gene expression was measured using RT-PCR. Receiver operating characteristic (ROC) analyses assessed diagnostic performance, and multiple linear regression identified independent predictors of TSHR expression. Results Compared with controls, SCH cases showed significantly higher TSH and NT-proBNP levels, reduced SDH complex activity, and upregulated TSHR gene expression (p<0.05). ROC analysis demonstrated excellent diagnostic accuracy for NT-proBNP, SDHA, and TSHR expression. After adjustment for confounders, SDH complex activity remained the only independent predictor of TSHR expression, whereas NT-proBNP lost independent significance, suggesting an indirect or interaction-mediated effect. Conclusions SDHA serves as a robust independent predictor of cardiovascular risk in SCH, highlighting mitochondrial dysfunction in thyroid receptor regulation. NT-proBNP showed predictive potential but not independent significance, indicating secondary modulation by hormonal or metabolic factors. Larger longitudinal studies are warranted for validation.