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Determination of Plasma Calcitonin Gene-Related Peptide Concentrations by a New Immunochemiluminometric Assay in Normal Persons and Patients with Medullary Thyroid Carcinoma and Other Neuroendocrine Tumors^*

W. BRADFORD CARTER, ROBERT L. TAYLOR, PAI CHIH KAO and HUNTER HEATH, III

Endocrine Research Unit, Division of Endocrinology, Metabolism, and Internal Medicine, and the Endocrine Laboratory, Section of Clinical Chemistry, Division of Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dr. Hunter Heath, Mayo Clinic, 5–164 West Joseph Building, Rochester, Minnesota 55905.

There is doubt about concentrations of circulating calcitonin gene-related peptide (CGRP) and the value of plasma CGRP measurements in the detection and follow-up of medullary thyroid carcinoma (MTC). Thus, we developed an immunochemiluminometric sandwich assay for CGRP using antibodies purified from a polyclonal antiserum against human CGRP. The assay was sensitive (limit of detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly specific [no cross-reaction with human calcitonin (CT)]. Normal plasma CGRP values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61% having detectable levels. Values in samples from patients with MTC were elevated: unoperated patients (n = 10), 4.7–137 pmol/L (median, 7.1); and operated patients with gross persistent or recurrent tumor (n = 14), 4.7–171 pmol/L (median, 23.2). In contrast, CGRP values were normal in 78% of nine postoperative patients with elevated CT, but no detectable tumor (range, <0.4 to 6.3 pmol/L; median, 1.6). CGRP levels increased after pentagastrin injection in MTC patients, but less than did CT values. Cultured MTC cells in vitro secreted large amounts of CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial cells secreted lesser amounts. We conclude that CGRP circulates in normal plasma, but at very low levels. Plasma CGRP concentrations are frequently high in patients with MTC, but primarily in those with gross tumor or metastases. Plasma CT assay is the preferable test for MTC, but CGRP assay deserves prospective study for a possible role in predicting gross metastasis.

^* This work was supported by NIH Grant AM-32526 (to H.H.).

Present address: Thomas Jefferson University Hospital, Department of Surgery, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. Supported in part by a research training grant from the USPHS, NIH (DK-07352).

Received June 4, 1990.

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