Routine Measurement of Serum Calcitonin is Useful for Early Detection of Medullary Thyroid Carcinoma in Patients with Nodular Thyroid Diseases

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Abstract
Background: Medullary thyroid carcinoma (MTC) is characterized by a high concentration of serum calcitonin. Routine measurement of serum calcitonin concentration has been advocated for detection of MTC among patients with nodular thyroid diseases. However, a minimal to moderate increase of serum calcitonin concentration has been frequently observed in diseases other than MTC. Fine-needle aspiration cytology (FNAC) is not a reliable method for detection of MTC. Therefore, we evaluated the usefulness of routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases, and studied the validity of pentagastrin stimulation test and FNAC in these patients. Subjects and Methods: We performed routine measurement of serum calcitonin concentrations in 1,448 patients (male, 285, female, 1,163) with nodular thyroid diseases. The average age was 46 years (range, 14-86 years). Initial examination included thyroid examination, thyroid scan or ultrasonography, measurements of serum free triiodothyronine) (T3), free thyroxine (T4), thyrotropin (TSH) levels, and antithyroid autoantibodies. FNAC was performed in all patients who had palpable or visible thyroid nodule by ultrasonography, and pentagastrin stimulation test was performed in 39 patients who consented. Serum calcitonin concentration was measured with a two-site immunoradiometric assay using commercial kits. We also measured the serum calcitonin concentration in 407 healthy subjects without thyroid or nonthyroid diseases. Results: Serum calcitonin concentration was 10 pg/mL or less in 403 normal subjects (99.0 percentile), and 11-13 pg/mL in the remaining 4 subjects. We found that 56 (3.87%) of 1,448 patients with nodular thyroid diseases had serum calcitonin level above 10 pg/mL. Ten patients (0.69%) with histologically confirmed MTC were detected by the routine measurement of serum calcitonin. The prevalence of MTC was 5.2% in 194 patients with thyroid carcinoma. Five of 10 patients with MTC had basal serum calcitonin level above 100 pg/mL. The remaining 5 patients had minimal or moderate elevation of basal serum calcitonin (range, 12-86 pg/mL). Serum calcitonin concentration increased to more than 100 pg/mL by pentagastrin in all patients with MTC (2.4- to 37.7-fold increase). FNAC suggested MTC in only 2 patients (22.2%), and failed to diagnose MTC in 7 patients. FNAC was not performed in 1 patient with MTC, because he had no visible mass by ultrasonography. Conclusion: These results suggested that routine measurement of serum calcitonin is useful in the early detection of MTC among patients with nodular thyroid diseases. Pentagastrin stimulation test may also be a reliable way for evaluating thyroid nodular patients with mild or moderate elevation of serum calcitonin concentrations. However, FNAC was not sensitive in detecting MTC. We recommend routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases.