Prevalence and significance of indeterminate calcitonin values in patients with thyroid nodules: A systematic review and meta-analysis

BACKGROUND: Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally accepted for several reasons, including the lack of recommendations for managing indeterminate Ctn values (ICV); such as 10-to-100 pg/mL. This study aimed to gather data on 1) the frequency of ICV among patients undergoing Ctn test and 2) the MTC rate among patients with ICV. METHODS: This review was conducted according to the Meta-analyses Of Observational Studies in Epidemiology guidelines. PubMed and Cochrane databases were searched, with no language restrictions. The final search was completed on January 2023. Then, quality assessment and proportion meta-analyses were performed. RESULTS: The online search retrieved 233 articles and 15 were included for quantitative analysis. The risk of bias was low. The number of patients undergone Ctn testing was 29,533. The pooled percentage of those with ICV was 1.7% (95% confidence interval [CI]:1.2–2.3). The pooled proportion of MTC incidence among patients with ICV was 9.6% (95% CI:5–14.1). Heterogeneity was explained by the covariates of Ctn assay sensitivity and the resection rate. The subgroup with Ctn 10–20 pg/mL showed a significantly lower MTC rate than the subgroup with Ctn 20–100 pg/mL. CONCLUSIONS: The percentage of ICV among patients with thyroid nodules who underwent Ctn testing is negligible. The rate of MTC in patients with ICV cannot be overlooked. Among the ICV intervals, the risk of MTC increases significantly when Ctn is above 20 pg/mL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11154-023-09811-7.