PENTAGASTRIN STIMULATION TEST AND EARLY DIAGNOSIS OF MEDULLARY-THYROID CARCINOMA USING AN IMMUNORADIOMETRIC ASSAY OF CALCITONIN - COMPARISON WITH GENETIC SCREENING IN HEREDITARY MEDULLARY-THYROID CARCINOMA

A pentagastrin stimulation test using a calcitonin (CT) immunoradiomet ric assay was performed in 38 healthy subjects and in the following 50 patients: 25 subjects from families with at least 2 known cases of me dullary thyroid carcinoma (MTC), 11 subjects from families with appare ntly sporadic MTC, 2 pheochromocytoma carriers, 1 primary hyperparathy roidism, 8 patients with thyroid nodules, and 3 others with various di seases. In healthy volunteers, basal CT values were always less than 1 0 ng/L; the response to pentagastrin was below 30 ng/L for 36, and for the remaining 2, the peaks reached 30 for 1 subject and 48 ng/L for t he other. The pentagastrin-stimulated CT peak was above 30 ng/L in eac h of the patients presented here, and all were thyroidectomized. In sc reening the 25 relatives of patients with familial MTC, a CT peak leve l over 30 ng/L was constantly associated with C-cell disease (23 cases of MTC and 2 of C-cell hyperplasia). A response to pentagastrin above 100 ng/L was observed in 15 patients among the 23 with MTC. In 8 of t he 10 patients with a peak CT level between 30-100 ng/L, pathological examination showed a MTC; the other 2 had C-cell hyperplasia and a neg ative linkage study analysis. In the 25 other patients in the study wi thout familial MTC, the pentagastrin-stimulated CT level was over 100 ng/L in 11 of the 14 subjects with MTC. The abnormal CT response to pe ntagastrin, which has been used as a criterion for surgical treatment, is currently determined by an immunoradiometric assay. Our study conf irms that subjects with a peak CT level above 100 ng/L should undergo surgery whatever the reason for the test. In the context of inherited MTC, our results suggest that for patients with a CT peak level betwee n 30-100 ng/L, surgery may actually be postponed when their probabilit y of being gene carriers is low. Recent progress with the characteriza tion of specific mutations in affected individuals will make familial screening much easier in the next few months.