Sociodemographic and clinical predictors of malignancy in thyroid nodules: a systematic review and meta-analysis.

BACKGROUND: Thyroid nodules (TNs) are prevalent, particularly in women and older adults, yet only a minority are malignant. Clinical decisions on biopsy and follow-up are complicated by selective use of fine-needle aspiration cytology, indeterminate results, and efforts to limit unnecessary procedures. We systematically identified and synthesized sociodemographic, laboratory, and ultrasonographic (US) factors associated with malignancy in TNs. METHODS: PubMed, Scopus, Web of Science, and EMBASE were searched (PROSPERO CRD42024557085). Two reviewers independently screened studies, extracted data, and assessed risk of bias (Joanna Briggs Institute tools). Random-effects meta-analyses were performed for predictors reported in ≥5 studies, with heterogeneity quantified using I2. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Malignancy was defined according to each study's reference standard (histology and/or cytology). Sensitivity analyses assessed robustness across diagnostic method and key study-level characteristics (e.g. geographic region and sample size). RESULTS: Of 35,359 records, 194 studies met the inclusion criteria. Of these, 47 with poolable crude ORs (predictors reported in ≥5 studies) contributed to meta-analysis, and the remainder to qualitative synthesis. Male sex, family history of thyroid cancer, higher thyroid-stimulating hormone levels, and several US features (including hypoechogenicity, solid composition, calcifications/microcalcifications, taller-than-wide shape, and irregular margins) were associated with higher odds of malignancy, whereas increasing age and larger nodule size showed inverse associations, though with substantial between-study heterogeneity. CONCLUSIONS: Malignancy in TNs reflects both patient-related and nodule-specific characteristics. Integrating these factors may support pre-biopsy risk assessment and more consistent biopsy and follow-up decisions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024557085.