Abstract

Parathyroid hormone (PTH) assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays). The routine assays used nowadays are immunometric “sandwich-type”. They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids) or the “intact” PTH, which includes, besides bioactive PTH, other “long” carboxyl-terminal forms, for example, 7–84-PTH. Assays for “intact” PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.

Highlights

  • Parathyroid hormone (PTH) is a linear peptide consisting of 84 amino acids and produced by the parathyroid cells

  • It plays a critical role in the calcium metabolism, and its receptor (PTH1R) is present in several tissues, with special importance in renal tubules and bone cells

  • PTH present in circulation is very heterogeneous, and this heterogeneity is the consequence of a complex metabolism that starts in the parathyroid cells and continues in other tissues, mainly in the kidneys and liver [1, 2]

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Summary

Introduction

Parathyroid hormone (PTH) is a linear peptide consisting of 84 amino acids and produced by the parathyroid cells. PTH present in circulation is very heterogeneous, and this heterogeneity is the consequence of a complex metabolism that starts in the parathyroid cells and continues in other tissues, mainly in the kidneys and liver [1, 2] The result of this complex metabolism is the presence of a circulation pool of “PTH peptides,” in pathological conditions, and in normal individuals. This phenomenon is important in patients with end-stage renal disease, where PTH fragments, with marked predominance of the carboxyl terminal ones, are present in great quantities in comparison to the intact 1–84 form (Figure 1) [3]. It is a long story, and the accumulated knowledge about physiology and metabolism of the molecule provided new tools for the development of new assays in a continuous feedback process

Evolution of PTH Assays
Immunometric Assays: A New Benchmark
65 Carboxyl terminal antibody 56
Current State
Future Prospects
Full Text
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