This study aimed to evaluate the diagnostic performance of several thyroid ultrasound risk-stratification systems in nodules with indeterminate or suspicious cytology, within a population with a history of iodine deficiency. The systems assessed included ACR-TIRADS (American College of Radiology), EU-TIRADS (European Thyroid Association), Korean-TIRADS, Kwak-TIRADS, AACE/ACE-AME guidelines (American Association of Clinical Endocrinologists/American College of Endocrinology–Associazione Medici Endocrinologi), and ATA guidelines (American Thyroid Association). A total of 1,000 nodules with confirmed histopathology were analyzed: 329 FLUS/AUS (10.6% malignant), 167 SFN/SHT (11.6% malignant), 44 SM (77.3% malignant), 298 benign lesions, and 162 malignant neoplasms. The proportion of papillary thyroid carcinoma (PTC) was highest in Bethesda MN (86.4%) and SM (91.2%) nodules compared to FLUS/AUS (57.1%, p < 0.005) and SFN/SHT (36.8%, p < 0.001). Diagnostic performance of TIRADS was superior for MN (AUC: 0.827–0.874) and SM nodules (AUC: 0.775–0.851), while lower for FLUS/AUS (AUC: 0.655–0.701) and SFN/SHT nodules (AUC: 0.593–0.621). Among FLUS/AUS nodules classified as high-risk by TIRADS, malignancy risk was 25%, whereas TIRADS categories did not alter malignancy risk in the SFN/SHT group. EU-TIRADS and AACE/ACE-AME guidelines identified the highest number of PTC, FTC, HTC, and MTC cases, while Kwak-TIRADS (OR = 12.6) and Korean-TIRADS (OR = 12.0) showed the strongest predictive value. In conclusion, TIRADS effectiveness is influenced by the prevalence of PTC. All systems aid in selecting FLUS/AUS nodules for surgical intervention but are less useful in guiding management of SFN/SHT nodules.
