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

  • Ashutosh Kumar Arya
  • Naresh SachdevaEmail author
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)

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.

Keywords

Parathyroid hormone Intact PTH Amino-PTH Immunoassay Primary hyperparathyroidism Bone Renal osteodystrophy Chronic kidney disease 

List of 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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© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Department of EndocrinologyPost Graduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia

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