THE USE OF REGION SPECIFIC RADIOIMMUNOASSAYS FOR CHARACTERIZATION OF CIRCULATING CALCITONIN IN PATIENTS WITH MEDULLARY CARCINOMA OF THE THYROID GLAND

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Abstract
Two antisera with known region specificities were used to characterize calcitonin immunoreactivity (iCT) in serum of patients with medullary thyroid carcinoma (MCT). Antiserum I which was raised against the synthetic hormone (1-32 amino acid residues), contained heterogeneous populations of immunoglobulins directed predominantly against carboxyterminal sequences of the hormone, but the antiserum reacted also with the amino-terminal fragment (1-10 amino acid residues). Antiserum II, which was raised against the carboxy-terminal hormone fragment (11-32 amino acid residues) reached equally well with the intact hormone and the C[carboxy]-terminal fragment, but showed negligible binding of the amino terminal fragment. Antiserum I measured amino-terminal and carboxy-terminal sequences of calcitonin while antiserum II measured only carboxy-terminal amino acid sequences. In 40 patients with MCT, antiserum I usually measured the highest concentration of serum iCT suggesting the presence of non-uniform hormone immunoreactivity. The different molecular forms of circulating iCT in 7 MCT patients were explored by using antiserum I after gel filtration on Sephadex G-100. The patients who were selected on basis of iCT measurement in serum using antiserum I and II, could be divided into 3 groups which showed characteristic iCT profiles. Group 1, where antiserum II measured a higher concentration of serum iCT, contained predominantly (60-70%) small fragments of calcitonin immunoreactivity. In the sera of group 3 in which antisera I measured an equal or the highest concentrations, the dominant form of the hormone consisted of molecular sequences equal to or larger than the intact hormone (90%). In group 2, the 2 antisera measured an equal amount of serum iCT and molecular forms mostly consisting of larger hormone fragments dominated (50%). All the patients were normocalemic despite frequently grossly elevated serum iCT, and 33 out of 36 patients had normal serum immunoreactive parathyroid hormone. Serum iCT is apparently heterogeneous and represents peptides of quite different molecular size with no or low biological activity. Most of the serum calcitonin immunoreactivity probably consists of peptides with carboxy-terminal amino acid sequences. Most if not all, of the amino-terminal calcitonin immunoreactivity is apparently due to monomeric and polymeric hormonal forms.