In a prospective study, plasma concentrations of human calcitonin (hCT) were determined in 1062 consecutive patients with thyroid nodular disease. Basal plasma hCT was above the normal range (>6 pg/mL) in 55 patients and was elevated up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1 of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was found in 10 of 31 patients with basal hCT ranging from 10-100 pg/mL. Histologically, 7 of the 14 patients with either basal or stimulated plasma concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one case showed histological transition into a small (diameter, 3 mm) medullary thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12 patients. We conclude that the routine determination of hCT in all patients with thyroid nodular disease should be supplemented by pentagastrin-stimulation when the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or stimulated plasma CT concentrations of more than 100 pg/mL should be operated on because they run a substantial risk to suffer either MTC or C cell hyperplasia, a potentially precancerous condition. This will increase the chance of a timely diagnosis of MTC and provide the chance of curative surgery.
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