Multinodularity Predicts Higher Incidental Malignancy in Bethesda Categories: A 1201-Patient Analysis

Thyroid nodules (TNs) are increasingly detected with high-resolution ultrasonography, yet current risk-stratification systems may underestimate malignancy in iodine-deficient, multinodular populations. Evidence guiding surgical extent in such settings remains limited. To quantify malignancy rates across Bethesda categories in an endemic multinodular goitre cohort, identify predictors of incidental carcinoma, and propose a context-specific algorithm that minimises unnecessary total thyroidectomies while maintaining oncological safety. We retrospectively analysed 1,201 consecutive thyroidectomies performed between 2013 and 2018. Pre-operative variables (age, sex, number of nodules on ultrasound, largest-nodule diameter, Bethesda I–VI cytology) were correlated with final histopathology. Multivariable logistic regression examined the effect of ≥ 3 nodules on incidental cancer after adjustment for covariates; model performance was assessed with AUC and Hosmer–Lemeshow goodness-of-fit. Observed cancer rates by Bethesda class markedly exceeded 2017 benchmarks: I 23.7%, II 22.4%, III 34.7%, IV 52.1%, V 92.0%, VI 100% (all p < 0.001 vs upper reference limits). Incidental carcinomas constituted 34.4% micro- and 65.6% classical papillary cancers. Multivariable analysis identified ≥ 3 nodules as an independent predictor of incidental carcinoma (OR 4.13, 95% CI 2.65–6.45; p < 0.001), whereas Bethesda V status conferred a 77% lower risk relative to Bethesda III (OR 0.23, 95% CI 0.07–0.73; p = 0.014). Age and sex were non-significant. The model demonstrated good discrimination (AUC 0.79) and calibration (Hosmer–Lemeshow p = 0.46). In iodine-deficient multinodular goitre, malignancy risks in Bethesda I–IV greatly exceed global norms. Incorporating nodule burden into risk assessment improves prediction of incidental carcinoma and supports a selective, patient-centred surgical approach. Regional epidemiology should inform guideline adaptation and follow-up intervals to reduce both overtreatment and missed cancers.