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 (Ͼ6 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 pentagastrinstimulation 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. (J Clin Endocrinol Metab 82: 1589 -1593, 1997

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