Assessment of malignant risk in thyroid nodules classified as category 4 and above against a background of Hashimoto's thyroiditis.

Background: The assessment of malignancy risk in thyroid nodules classified as Thyroid Imaging, Reporting and Data System (TI-RADS) category 4 and above remains a clinical challenge. The impact of Hashimoto's thyroiditis (HT) on both the malignant risk and the predictive value of sonographic features in such nodules are not fully elucidated. This study aimed to investigate the malignant risk of TI-RADS 4+ nodules in patients with HT and to analyse the predictive value of their ultrasonic characteristics. Methods: In this retrospective study, we included 2,340 patients with TI-RADS category 4 or higher thyroid nodules treated at our hospital from January 2018 to December 2024. Based on the presence of HT, patients were divided into an HT group (n=733) and a non-HT group (n=1,607). Malignancy rates and ultrasonic features were compared between the two groups. Multivariate logistic regression was used to identify independent predictors of malignancy. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the models. Results: Among the 2,340 patients (595 males and 1,745 females), the malignancy rate was significantly higher in the HT group (86.6%, 635/733) than in the non-HT group (83.2%, 1,337/1,607; P=0.02). Univariate analysis showed that within each group, malignant nodules exhibited significantly higher proportions of several suspicious features, including solid composition, hypoechogenicity, indistinct margins, irregular shape, hyperechoic foci without acoustic shadowing, calcification, and heterogeneous internal echotexture (all P<0.05). Multivariate analysis identified hypoechogenicity [odds ratio (OR) =2.54], irregular shape (OR =1.85), and calcification (OR =2.09) as independent predictors of malignancy in the HT group (all P<0.05). For the non-HT group, independent predictors were hypoechogenicity (OR =3.182), indistinct margins (OR =2.023), irregular shape (OR =1.69), and heterogeneous internal echotexture (OR =3.65; all P<0.05). When nodules presented with "hyperechoic foci without acoustic shadowing" or "calcification", the positive predictive value (PPV) for malignancy was significantly higher in the HT group than in the non-HT group (both P<0.05). For other malignant ultrasonic features, there was no significant difference in predictive rates between the groups (P>0.05). Prediction models constructed based on the respective independent predictors showed similar discriminative performance between the two groups (P>0.05). Conclusions: HT is an independent risk factor for malignancy in thyroid nodules classified as TI-RADS category 4 and above. It reshapes the predictive value system of ultrasonic features by diminishing the diagnostic weight of features like "indistinct margins" while increasing the predictive importance of "hypoechogenicity", "irregular shape", and "calcification". Furthermore, HT exhibits a synergistic effect with the "calcification" feature, significantly amplifying the assessed malignant risk.