Comparison of Calcium and Pentagastrin Tests for the Diagnosis and Follow-Up of Medullary Thyroid Cancer

Context: The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). Objective: The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. Patients: Patients with MTC in remission (n = 24) or in persistence (n = 18), RET gene mutations carriers (n = 14), patients with nodular goiter (n = 69), and healthy volunteers (n = 16) were submitted to pentagastrin and Ca (25 mg/kg) tests. Results: In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with a mean number of 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. Conclusions: High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified. (J Clin Endocrinol Metab 97: 905-913, 2012)