Abstract

Biologically active parathyroid hormone (PTH) circulates predominantly as an 84 amino acid peptide in humans with normal renal function. However, large aminoterminally truncated PTH(1–84) fragments (ntPTH(1–84)) that are readily detectable with most first generation immunometric PTH assays may also affect bone metabolism and calcium homeostasis. Some of these ntPTH(1–84) fragments exhibit an elution profile on high performance liquid chromatography (HPLC), which is indistinguishable from that of synthetic PTH(7–84). This hormonal fragment was recently shown through in vitro experiments to be the predominant form of PTH secreted by the parathyroid glands. Furthermore, it appears to have hypocalcemic properties in vivo and to inhibit ostoclastic bone resorption and the formation of mature ostoclasts in vitro. At present, it is uncertain whether important differences in disease states can be revealed by comparing results obtained with first generation immunometric assays (detection of PTH(1–84) and ntPTH(1–84)) with those obtained with newer, second generation assays (detection of PTH(1–84) alone). While most immunometric PTH assay systems are appropriate for the diagnosis of primary hyperparathyroidism, it appears plausible that immunometric assays designed to detect only PTH(1–84) will be more useful for certain diagnostic studies, that is, for monitoring PTH concentrations intra-operatively and for assessing the pulsatility of PTH secretion. In addition, the ability to distinguish between the relative concentrations of ntPTH(1–84) and PTH(1–84) may reveal previously unsuspected biological roles of ntPTH(1–84) fragments in patients with end stage renal disease and/or other disorders involving PTH.

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