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Parathyroid Hormone (PTH) Assays and Applications to Bone Disease: Overview on Methodology

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Biomarkers in Bone Disease

Abstract

Biologically active parathyroid hormone (PTH) is an 84-amino acid-long hormone that mediates calcium homeostasis and is responsible for normal functions of bone and kidney. Accurate assessment of circulating PTH is essential for the diagnosis of hyperparathyroidism, bone diseases, and chronic kidney disease (CKD). Immunoassays have been extensively used for the measurement of PTH in biological fluids for more than 60 years. Besides several pre-analytical factors, differences in types of immunoassays influence estimation of PTH in clinical samples. First-generation PTH radioimmunoassays use a single antibody which detects fragmented PTH and does not entirely reflect levels of biologically active PTH. Second-generation assays use two antibodies directed against distinct N-terminal (12–20/26–32) and C-terminal (39–84) epitopes, respectively, to detect intact PTH (iPTH), but these antibodies also cross-react with N-terminally truncated PTH fragments. To avoid such cross-reactivity, the third-generation assays came which use an N-terminal antibody directed against the first 4 amino acids of PTH with identical C-terminal antibody, as used in second-generation assays. Both second- and third-generation assays are equally good in diagnosis of primary hyperparathyroidism (PHPT) and CKD patients. Third-generation assays are superior in performing intraoperative PTH measurement for predicting successful parathyroidectomy in PHPT patients. The ratio of PTH levels determined by the third-generation over the second-generation assay is another useful tool in detecting parathyroid carcinoma and severe PHPT. Relative measurements of PTH (1–84) and PTH (7–84) in clinical samples may provide insights in their biological roles in CKD. Recently, developed liquid chromatography-assisted mass spectrometry-based PTH assays are more accurate in quantitation of PTH, but require sophisticated instrumentation and expertise. The utility of such advanced assays to differentiate various modified forms of PTH (phosphorylation, oxidation, etc.) needs to be further explored in bone-related pathologies.

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Abbreviations

CAP:

Cyclase-activating PTH

CIP:

Cyclase-inactivating PTH

CKD:

Chronic kidney disease

CLIA:

Chemiluminescence immunoassay

C-PTHR:

C-terminal PTH receptor

ECLIA:

Electrochemiluminescence immunoassay

EDTA:

Ethylenediaminetetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

HPLC:

High-performance liquid chromatography

IFCC:

International Federation of Clinical Chemistry and Laboratory Medicine

IO-PTH:

Intraoperative PTH

IRMA:

Immunoradiometric assay

LC-MS/MS:

Liquid chromatography-assisted mass spectrometry

n-oxPTH:

Non-oxidized PTH

N-PTH:

Amino-PTH

oxPTH:

Oxidized PTH

PHP:

Pseudohypoparathyroidism

PHPT:

Primary hyperparathyroidism

PTH:

Parathyroid hormone

PTH1R:

PTH/PTHrP 1 receptor

RIA:

Radioimmunoassay

SHPT:

Secondary hyperparathyroidism

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  1. Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Room – 3024, Endocrinology Lab, Research Block-B, Chandigarh, 160012, India

    Ashutosh Kumar Arya & Naresh Sachdeva

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  2. Naresh Sachdeva
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Correspondence to Naresh Sachdeva .

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  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Arya, A.K., Sachdeva, N. (2015). Parathyroid Hormone (PTH) Assays and Applications to Bone Disease: Overview on Methodology. In: Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7745-3_6-1

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  • DOI: https://doi.org/10.1007/978-94-007-7745-3_6-1

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  • Online ISBN: 978-94-007-7745-3

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