Malignancy in toxic thyroid adenoma: Revisiting risk assessment and identifying predictors

BACKGROUND: Toxic adenomas have traditionally been considered benign due to chronic TSH suppression, which is believed to inhibit thyroid tumorigenesis. However, emerging data challenge this dogma, reporting non-negligible malignancy rates even in toxic adenoma. This study aimed to assess thyroid cancer frequency and characteristics in surgically selected patients with toxic adenomas and to compare outcomes with propensity score–matched, surgically treated non-functioning nodules. METHODS: This retrospective, cross-sectional study included 204 surgically treated patients at a tertiary referral center, comprising 102 surgically selected toxic adenomas and 102 propensity score–matched, surgically treated non-functioning nodules. Clinical, biochemical, sonographic, scintigraphic, and histopathological data were analyzed. Multivariate logistic regression analysis was used to identify independent predictors of malignancy among toxic adenomas. RESULTS: In this surgically selected cohort, the malignancy rate was 16.7% for toxic adenomas and 40.2% for non-functioning nodules (p < 0.001). Papillary thyroid carcinoma comprised 82.4% of all cases, making it the leading histotype (82.4%). Among toxic nodules, higher fT4/fT3 ratio (cut-off:2.58, sensitivity:93.3%, specificity:54.2%) and European Thyroid Imaging and Reporting Data System categories 4–5 were independent predictors of malignancy. No significant differences were found between groups in terms of tumor size, invasion, American Thyroid Association risk stratification, or 5-year response rates. CONCLUSION: Among surgically treated patients, the observed malignancy rate in toxic adenomas appears to be higher than traditionally expected. Elevated fT4/fT3 ratio and suspicious ultrasound features warrant closer evaluation. These findings support using ultrasound and biochemical markers in risk assessment of all thyroid nodules, regardless of functional status.