The Pitfalls of Calcitonin as a Tumor Marker: Real-Life Data of Patients with Elevated Basal Calcitonin Levels but Without Evidence of Medullary Thyroid Carcinoma.

Background

Calcitonin, a tumor marker primarily used to diagnose medullary thyroid carcinoma (MTC), can also be elevated in other conditions, complicating diagnosis. This study aims to provide a clinical evaluation of the real-world consequences of unexplained calcitonin elevation.

Methods

We conducted a retrospective cohort study of patients with elevated basal calcitonin levels who presented at the Department of General, Visceral, and Transplantation Surgery, University Medical Center Mainz, between January 2015 and March 2025. Additionally, we reviewed electronic health records from 2007 onward for patients with ICD codes indicating calcitonin hypersecretion. Patients with confirmed MTC or genetic syndromes were excluded.

Results

Of 345 patients with elevated calcitonin levels, 167 (48%) met the inclusion criteria, and 29 additional patients with calcitonin hypersecretion were identified via ICD, resulting in 167 patients analyzed. More than half of the patients were female (52%), had an average age of 53.9 years and a high prevalence of goiter (86%). Calcitonin levels were slightly elevated (<20 pg/mL) in 81% of cases and were above 50 pg/mL in only 10 patients. Surgery was performed in 77% of patients, mainly to exclude malignancy. Postoperatively, calcitonin normalized in 86% of patients but remained elevated in eight patients. Two of these patients were found to have false-positive results due to assay interference. Follow-up data were incomplete for a substantial proportion of patients, with a median follow-up of 4.6 months. The mortality rate was 4%, with causes unrelated to calcitonin levels.

Conclusions

Elevated basal calcitonin levels, especially slightly elevated levels (<20 pg/mL), are common in clinical practice and often do not appear to be related to malignant disease, so careful investigation is required. Persistently elevated calcitonin levels justify further examinations, especially if other explanations can be ruled out. Only a few patients attend follow-up appointments, which makes patient follow-up challenging.