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Sociodemographic and clinical predictors of malignancy in thyroid nodules: a systematic review and meta-analysis
Vanessa Neto1, Catarina Leitão1, Cláudia Martins1
1iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
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.
