Tugba Matlim Ozel, Mine Yilmaz, Sezer Akbulut, Aykut Celik, Gorkem Yildiz, Nilsen Yildirim Erdogan, Serkan Sari
The Medical Bulletin of Haseki - 2026;64(2):129-137
Aim: The clinical relevance of thyroid nodules in Graves' disease (GD) remains controversial, particularly in iodine-deficient regions where both nodularity and thyroid cancer are more prevalent. This study aimed to compare clinical, biochemical, ultrasonographic, cytological, and pathological characteristics between nodular and non-nodular GD (non-NGD) to clarify the oncologic significance of nodularity. Methods: This retrospective observational cohort study included 160 patients who underwent total thyroidectomy for GD between June 2020 and July 2025 at an endocrine surgery center. Patients were classified according to preoperative ultrasonography (US) as nodular or non-NGD. Demographic features, thyroid autoimmunity markers, ophthalmopathy, fine-needle aspiration biopsy (FNAB) results, and final pathology were recorded. Multivariate logistic regression analysis was performed to identify independent predictors of nodularity. Results: Sixty-three patients (39.4%) had nodular GD (NGD), and 97 patients (60.6%) had non-NGD. Nodular patients were older and had higher body mass index (BMI) (both p<0.05), whereas thyroid-stimulating immunoglobulin and anti-thyroid peroxidase levels and ophthalmopathy were significantly higher in non-nodular patients. Fine-needle aspiration biopsy was more frequently performed in the nodular group (57.1% vs. 20.6%). Overall, papillary thyroid carcinoma (PTC) was diagnosed in 31.8% of the cohort, with a markedly higher prevalence in NGD (52.4% vs. 18.5%, p<0.001). Tumors in nodular patients were larger and more likely to exhibit lymphatic invasion. In multivariate analysis, age and BMI remained independent predictors of nodularity. Conclusion: In this surgically treated GD cohort, nodularity identifies a structural phenotype with substantially increased PTC risk, while non-NGD reflects an autoimmune-dominant phenotype. High malignancy rates across Bethesda categories and even in non-biopsied patients indicate the need for vigilant US surveillance and a low threshold for FNAB of suspicious or dominant nodules.
