Determination of silica-purified plasma calcitonin for the detection and management of medullary thyroid carcinoma: comparison of two provocative tests.

Radioimmunoassays for human calcitonin in whole plasma are limited in sensitivity and specificity; basal values of calcitonin are often undetectable in normal plasma, and nonspecific increases are occasionally found in seemingly healthy persons. We avoided these problems by applying a silica-cartridge extraction-concentration technique for calcitonin assay, and the effectiveness of two calcitonin stimulation tests in healthy volunteers and patients with medullary thyroid carcinoma was compared. The radioimmunoassay was improved by using a new antiserum and a sequential incubation procedure that reduced the previously used sample-volume requirement and incubation period substantially. This method was used to measure mean basal plasma levels of calcitonin (+/-SD) in 45 normal men (8.2 +/- 5 pg/ml) and 47 normal women (4.8 +/- 4 pg/ml) (P less than 0.001). Calcium infusions (2 mg/kg over 5 minutes) in 18 normal men and 37 normal women yielded a significantly greater secretory response than did pentagastrin (0.5 micrograms/kg as a bolus). Among 12 patients with medullary thyroid carcinoma, pentagastrin seemed to be a better secretagogue than calcium (P less than 0.001). We recommend routine measurement of plasma silica-extractable calcitonin and pentagastrin injection as the provocative test of choice for the detection and management of medullary thyroid carcinoma. The short calcium-infusion test is a good alternative.