Update on Calcitonin Screening for Medullary Thyroid Carcinoma and the Results of a Retrospective Analysis of 12,984 Patients with Thyroid Nodules

SIMPLE SUMMARY: Medullary thyroid carcinoma (MTC) is a rare disease and accounts for about 5% of thyroid carcinomas. In contrast to other thyroid cancers, MTC can be detected by calcitonin (Ctn) measurement in blood samples. However, the interpretation of Ctn values is difficult since reference values for Ctn are sex-specific, assay-dependent, and can also be elevated in benign thyroid diseases and certain extrathyroidal conditions. Here, we report on the results of Ctn screening in 12,984 adult patients with thyroid nodules from our nuclear medicine practice. The Ctn values were elevated in 207 (1.6%) patients. Further clarification was possible in 124/207 cases, of which MTC could be ruled out in 108 cases. In 16/12,984 patients, MTC was confirmed. Thus, the extrapolated MTC prevalence is 0.14% in our patients. We thus recommend Ctn screening even in patients with very small thyroid nodules. High quality standards in pre-analytics, Ctn measurement, and the interpretation of data must be ensured. ABSTRACT: Background: We provide an update on calcitonin (Ctn) screening for the early detection of medullary thyroid carcinoma (MTC) and present the results of a large single-center analysis evaluating sex-specific cut-off-levels and long-term courses. Methods: A total of 12,984 consecutive adult patients (20.1% male and 79.9% female) with thyroid nodules who had undergone routine Ctn measurement were retrospectively analyzed. Patients with confirmed suspicious Ctn values were referred for surgery. Results: Ctn measurements were elevated in 207 (1.6%) patients, with values below twice the sex-specific reference limit in 82% of these cases. Further clarification was possible in 124/207 cases, of which MTC could be ruled out in 108 cases. Histopathological assessment confirmed MTC in 16/12,984 patients. Conclusions: Our extrapolated MTC prevalence of 0.14% is significantly lower than that described in early international screening studies. The stimulation test can usually be dispensable when using a decision-making concept based on sex-specific basal Ctn cut-off values. Ctn screening is recommended even in patients with very small thyroid nodules. High quality standards in pre-analytics, laboratory measurements, and the interpretation of data must be ensured, as well as close interdisciplinary cooperation between medical disciplines.