[Radioimmunoassay of the calcitonin gene-related peptide and its measurement in the plasma of patients with medullary thyroid carcinoma and in the cerebrospinal fluid of normal subjects].

Calcitonin gene-related peptide (CGRP) is a peptide recently found by recombinant DNA and molecular biological techniques in rat medullary thyroid carcinoma cells, but its physiological role(s) is unknown. We established a radioimmunoassay for this peptide using human-CGRP (1-37) as a standard, 125I-human-CGRP (1-37) as a tracer, and anti-rat-CGRP (28-37) serum as a first antibody. Aprotinin, an inhibitor of proteolytic enzymes in the plasma, was also added to the assay system, because in its absence the tracer was degraded during incubation with plasma samples. The sensitivity of the assay was 60 pg/ml and the intra- and inter-assay coefficients of variation were 6.0% and 8.5%, respectively. The recovery was 105 +/- 17%. The plasma levels of CGRP in 17 normal subjects (mean +/- S.D. age, 45 +/- 12 years) were all below 300 pg/ml, the mean level being 132 +/- 77 pg/ml. The levels were also below 300 pg/ml in 20 of 21 patients with medullary thyroid carcinoma, but one patient who had a high level of 942 pg/ml (mean value, 142 +/- 193 pg/ml). There was no significant difference between the mean plasma levels of CGRP in normal subjects and patients with medullary thyroid carcinoma. The mean plasma levels of CGRP in 5 patients with medullary thyroid carcinoma did not increase in response to infusion of either 4.3 mg/kg of calcium in 10 minutes or 4 micrograms/kg of tetragastrin in 5 minutes, although the plasma levels of calcitonin in these patients increased markedly during these provocation tests. The levels of CGRP in the cerebrospinal fluid of 16 normal volunteers were all below the detectable limit (less than 60 pg/ml). These findings suggest that fewer patients with medullary thyroid carcinoma than reported previously have high plasma levels of CGRP, either in the basal state or in response to calcium or gastrin, and that the levels of CGRP in the cerebrospinal fluid of normal subjects are very low.