Preoperative anti-thyroid antibodies predict malignancy risk in cytologically indeterminate thyroid nodules: a prospective multicenter study.

[BACKGROUND] Cytologically indeterminate thyroid nodules (CITNs) are heterogeneous, and their assessment remains controversial. In this study, we examined the prognostic utility of anti-thyroid antibodies for predicting thyroid cancer (TC) in CITNs.

[METHODS] This prospective multicenter analysis included all patients with CITNs who were surgically treated between August 2023 and August 2024 at two hospitals in Saudi Arabia; preoperative anti-thyroid antibodies [thyroid peroxidase and thyroglobulin antibodies (TgAbs)], thyroid stimulating hormone (TSH), and a definitive histological diagnosis were required for inclusion. Multivariate analysis was used to identify independent predictors of TC.

[RESULTS] This study included 76 individuals; 70/76 (92.1%) were women. Overall, 43/76 (56.6%) nodules had a cytological diagnosis of atypia of undetermined significance (AUS) (Bethesda III), whereas 33/76 (43.4%) were follicular neoplasms (FNs) (Bethesda IV). Pathological analysis revealed that 56/76 (73.7%) patients had benign nodules and 20/76 (26.3%) had malignant tumors. The coexistence of elevated levels of both antibodies and TSH demonstrated the highest odds ratio [3.10; 95% confidence interval (CI): 1.14-5.47], signifying a significant correlation with TC (P=0.003). Furthermore, high levels of one antibody along with elevated TSH levels resulted in an odds ratio of 2.25 (95% CI: 1.02-6.44), indicating a significant association with TC (P=0.04). The multivariate analysis identified Bethesda IV cytological diagnoses, the presence of Hashimoto's thyroiditis, and TSH levels >1 mIU/L as independent predictors of TC.

[CONCLUSIONS] Elevated anti-thyroid antibody and TSH levels were effective predictors of TC in CITNs. These findings may help guide endocrine surgeons managing patients with these nodules.