Calcitonin Radioimmunoassay

Calcitonin is a 32-amino-acid polypeptide that is secreted primarily by the parafollicular C-cells. Its main biological effect is to inhibit osteoclastic bone resorption. This property has led to Calcitonin’s use for disorders characterized by increased resorption such as Paget’s disease and for some patients with osteoporosis. The amino acid sequences of porcine, bovine, salmon, and human Calcitonin are known, and biologically active molecules have been synthesized. The structure of each is similar, whereas the immunologic activity of Calcitonin from various species differs profoundly. The most prominent clinical syndrome associated with a disordered hypersecretion of Calcitonin is medullary carcinoma of the thyroid (MTC). MTC is a tumor of the Calcitonin producing C-cells of the thyroid gland. MTC comprises 5 - 10% of all thyroid cancer. It may occur sporadically or in a familial form that is transmitted as an autosomal dominant trait. Despite its being a relatively uncommon tumor, MTC has great clinical importance because of its familial distribution. Further, it lent itself to be diagnosed early by serum Calcitonin. This is frequently associated with other clinical features and it has good potential for cure with surgery. Although a rare tumor, it can occur in a familial pattern as a Type II multiple endocrine neoplasia. These tumors usually produce diagnostically elevated serum concentrations of Calcitonin therefore, the immunoassay for Calcitonin in serum can be used to diagnose the presence of MTC with an exceptional degree of accuracy and specificity. In the small but increasing percentage of patients, however, basal hormone levels are indistinguishable from normal. Some of these subjects represent the early stages of C-cell neoplasia or hyperplasia that are most amenable to surgical cure. To diagnose these patients with early disease, provocative tests for Calcitonin secretion are necessary to preclude false negatives if only basal Calcitonin determination are performed. Most tumors respond with increased Calcitonin levels to the administration of either calcium or pentagastrin or their combination, but either agent can still give misleading results. Therefore, in cases with clinical manifestations, both agents should be considered for diagnostic testing. Further, calcitonin measurements can also be used to monitor the efficacy of therapy in patients with Calcitonin producing tumors. Neoplastic disorders of other neuroendocrine cells can also elevate Calcitonin. The best example is small cell lung cancer. Other tumors such as carcinoids and islet cell tumors of the pancreas can also result in elevated serum Calcitonin. Increases in serum Calcitonin have also been noted in both acute and chronic renal failure, hypercalciuria and hypocalcaemia.