β-CGRP, human TFA

We have established a radioimmunoassay method for calcitonin gene-related peptide (CGRP) to monitor changes in plasma CGRP levels in patients with medullary thyroid carcinoma (MTC). Preoperative plasma CGRP levels (normal level less than 12.7 pg/ml) were as high as 128 pg/ml to 2,010 pg/ml in all five patients with MTC. Ten of 17 postoperative patients with MTC were positive for CGRP. A provocation test was performed in 12 patients with MTC. Plasma CGRP changes roughly paralleled serum calcitonin levels. In particular, in three patients with poorly-differentiated MTC which progressed aggressively, plasma CGRP levels were increased to 1.4 to 2.0 times levels before the test, i.e., lower than the 2.8- to 23.3-fold increase in nine patients with the well-differentiated MTC. These results suggest that CGRP may be a humoral marker of medullary carcinoma and be related to degree of malignancy.

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.

The plasma level of calcitonin gene-related peptide (CGRP) was measured by RIA in 41 patients with endocrine tumors [22 medullary thyroid carcinomas (MTC), seven parathyroid adenomas, four benign insulinomas, five carcinoids, and three pheochromocytomas]. Of the 22 patients with MTC, all five preoperative patients had elevated CGRP levels. The correlation between CGRP and calcitonin levels was significant (P less than .001) in 22 patients with MTC. Six of 19 patients with endocrine tumors other than MTC showed elevated CGRP levels. Immunohistochemical study showed that tumor tissues from all 22 cases of MTC and seven from other endocrine tumors contained immunoreactive CGRP. CGRP reactivity was found in only small numbers of tumor cells. Thus, although CGRP appeared to be a useful additional marker for MTC, the role of CGRP in the pathophysiology of endocrine tumors was not elucidated.