Abstract
Background/Objectives: Thyroid nodules exhibit substantial histopathological variability, and systemic markers that differentiate benign from malignant patterns remain poorly defined. This study evaluated clinical, biochemical, hormonal, and histopathological characteristics in patients undergoing total thyroidectomy for nodular thyroid disease. Methods: A retrospective cohort of 926 patients operated between 2017 and 2024 was analyzed. Patients were classified as: Group 1-benign lesions; Group 2-benign-malignant associations; Group 3-multiple malignant lesions. Demographic, biochemical, hormonal, and histopathological data were assessed using the Kruskal-Wallis and Mantel-Haenszel chi-square tests. Thyroid-specific tumor and autoimmunity markers (calcitonin, thyroglobulin, anti-thyroglobulin antibodies, and thyroid peroxidase antibodies) were not included in the comparative analyses due to their non-uniform availability across the retrospective cohort. Results: Most clinical and biochemical parameters showed no significant differences among the three groups, including TSH (p = 0.122), FT3 (p = 0.560), glycemia (p = 0.829), creatinine (p = 0.193), fibrinogen (p = 0.535), and thyroid dimensions (length p = 0.401, width p = 0.183, thickness p = 0.667, and total thyroid mass p = 0.109). Neutrophil count differed in the overall comparison (p = 0.021), although absolute differences were small, and lymphocyte counts were modestly lower in patients with multiple malignant lesions compared with benign disease (p = 0.009). Comorbidities and BMI were similarly distributed across groups (all p > 0.05). Overall, routinely available clinical, biochemical, and hormonal parameters demonstrated limited discriminatory value between patients with different histopathological patterns. Conclusions: Standard clinical, biochemical, and hormonal markers showed minimal ability to reflect underlying histopathological patterns in patients with thyroid nodules, underscoring their limited utility for preoperative risk stratification.