Metabolic crosstalk between differentiated thyroid cancer and cardiovascular disease: insulin resistance as a molecular bridge—a proposed mechanism

Differentiated thyroid cancer (DTC) is generally associated with favorable survival, yet long-term survivors may experience an increased burden of cardiovascular disease (CVD). This risk has often been attributed primarily to TSH suppression therapy, although metabolic factors might also contribute. In this article, we propose a conceptual DTC–IR–CVD axis, in which insulin resistance (IR) may represent one potential molecular link between thyroid malignancy and cardiovascular vulnerability. Available evidence supports associations between IR, diabetes, thyroid tumorigenesis, and CVD; however, direct clinical evidence that DTC itself induces systemic IR remains limited. We therefore discuss a hypothesis whereby tumor-related metabolic reprogramming, inflammatory signaling, extracellular vesicle communication, and treatment-related endocrine perturbations may together contribute to endothelial dysfunction, arterial stiffness, and myocardial remodeling in selected patients. We further outline how this framework could inform future cardio-oncologic risk stratification and generate testable translational hypotheses. Overall, the proposed model should be viewed as a hypothesis-generating framework rather than an established causal pathway.