Laboratory comparison of diagnostic specificity of intact hormone and region-specific immunoassays of parathyroid hormone.

A 2-site immunochemiluminometric assay (ICMA) for intact parathyroid hormone (PTH) has been developed to overcome the problems of limited sensitivity and specificity associated with conventional PTH immunoassays. The present investigation assesses the relative merits of the 2-site intact PTH (ICMA) and a midmolecule PTH radioimmunoassay (RIA). Immunoassay profiles of dispersed hyperparathyroid cell supernatants and hyperparathyroid sera obtained during parathyroidectomy and from renal failure patients, fractionated by gel filtration chromatography, facilitated a direct comparison of the specificity of PTH immunoassays. Using gel filtration matrices which permitted the separation of intact hormone, large C-terminal fragment(s), and a small midmolecule fragment in adenomatous cell supernatant and peripheral sera, the intact PTH (ICMA) assay consistently yielded a single peak of immunoreactivity. In contrast, the midmolecule RIA yielded 2 and 3 broad peaks of immunoreactivity after fractionation of serum and adenomatous cell supernatant, respectively. There was no evidence for the secretion of a small midregion fragment in vitro or its peripheral derivation in vivo. These studies demonstrate the superior specificity of the 2-site intact PTH assay compared with a midmolecule RIA and, thus, confirm the potential diagnostic superiority of the ICMA.