Background: Solid thyroid nodules are uncommon in children, with an estimated prevalence of 1-1.7%, with rates of malignancy in these nodules estimated to be as high as 26% compared to 5-10% in the adult population. Various risk factors for thyroid malignancy have been identified across the adult literature previously. The aim of this systematic review was to synthesise studies which evaluated risk factors of malignant thyroid nodules in a paediatric population.Method: Systematic review and meta-analysis in accordance with PRISMA guidelines. Pubmed and Embase were searched in October 2023. Studies were included if they evaluated risk factors of thyroid cancer in children (< 18 years of age) with a thyroid nodule. Animal studies, letters to the editor, and case reports were excluded. We evaluated all risk factors included in the studies. A random effects meta-analysis was conducted where two or more studies evaluated an outcome.Results: Sixteen articles were included in the analysis, with 876 cases of malignancy and 1791 controls.Of the malignant carcinomas: 97.3% were papillary (of which 12% were follicular subtype), 1.5% were medullary, 0.74% were follicular and 0.37% were characterised as other subtypes. Important clinical characteristics identified were palpable lymphadenopathy (Odds Ratio (OR) 7.73, 95%CI 3.03-19.75, p<0.0001), with malignant cases being slightly older (mean difference (MD) + 0.39, 95%CI -0.27-1.04, p=0.25). Ultrasound characteristics of concern included lymphadenopathy (OR 37.79, 95%CI 6.61-215.88, p<0.0001), intranodular microcalcifications (OR 18.38, 95%CI 5.22-64.69, p<0.00001), increased vascularity (OR 3.21, 95%CI 1.95- 5.28, p<0.0001), or hypoechoic pattern (OR 3.68, 95%CI 0.96-14.1, p=0.06).Biochemically, thyroid antibodies (OR 2.81, 95%CI 1.94-4.06, P<0.00001) and increased Thyroid-stimulating hormone (MD +0.80, 95%CI 0.23-1.37, p=0.006) were associated with an increased risk of carcinoma.Learning Points: - Over 800 cases of thyroid malignancy and 1700 controls were included in this systematic review and meta-analysis.- Important clinical risk factors were palpable lymphadenopathy and increased age.- Important risk factors on ultrasound were the presence of microcalcifications, increased nodular vascularity, or a hypoechoic nodular pattern on ultrasound.- Important biochemical risk factors were the presence of thyroid antibodies or increased thyroid-stimulating hormone levels.Discussion: We have identified a number of key risk factors that are associated with malignant thyroid nodules. More data is required to assess the implications and clinical significance of the potential risk factors identified here to aid the development of robust risk stratification models.
