Preliminary Evidence From an Original Study Suggests Combustion, Not Nicotine, Drives Risk and Complications of Graves' Orbitopathy.

Introduction Graves' orbitopathy (GO) is a significant complication of Graves' disease (GD), often exacerbated by cigarette smoking. While smoking is a well-established risk factor, it remains unclear whether nicotine itself or toxic combustion byproducts are primarily responsible. Here, we present preliminary results from our study, which investigates the impact of different nicotine delivery systems on GO features and clinical outcomes.  Methods We retrospectively analyzed 304 adult patients with newly diagnosed GD. Patients were categorized based on nicotine exposure: combustible cigarette users (CSU), heated tobacco product users (HTPU), electronic cigarette users (ECU), and never-nicotine users (NNU). Statistical comparisons were performed to evaluate any significant difference across groups.  Results GO prevalence was highest in CSU (n=31, 50.1%) and significantly lower in HTPU (n=8, 26.7%), NNU (n=40, 21.1%), and ECU (n=2, 8.7%). No moderate-to-severe or active GO cases were found among ECUs. Logistic regression confirmed CSU as an independent risk factor for GO (OR=4.02; p<0.001).  Discussion These preliminary findings suggest how tobacco combustion byproducts, rather than nicotine itself, may be the key drivers of GO pathogenesis. The low GO prevalence in ECUs supports the hypothesis that clean nicotine delivery might carry reduced or no risk.  Conclusion Combustible tobacco use is strongly associated with GO risk, while non-combustion systems, especially ECs, might offer a safer alternative. These results will be implemented with final analyses of the study, and encourage further investigation into harm-reduction strategies in patients with GD.