Development of a PTHrP chemiluminescent immunoassay to assess humoral hypercalcemia of malignancy.

Abstract

BACKGROUND:

Parathyroid hormone related peptide (PTHrP) measurements are helpful in the evaluation and management of individuals suspected of humoral hypercalcemia of malignancy (HHM).

AIM:

To develop a chemiluminescent assay for PTHrP quantitation, establish reference intervals, and evaluate its clinical performance.

METHOD:

PTHrP 1-86 was measured using a polyclonal rabbit antibody (capture) and an acridinium ester labeled goat polyclonal antibody for chemiluminescent detection.

RESULTS:

Assay imprecision was < 9% (intra-assay) and < 15% (inter-assay). The analytical measuring range was 0.16-50.5 pmol/L. No significant cross-reactivity was observed for PTH (1-84), PTHrP (107-139), and PTHrP (1-36); whereas PTHrP (38-94) showed 8.3% cross-reactivity. Comparison with the pre-existing Mayo assay showed a positive bias: new assay = 2.24 (pre-existing assay)-0.30 and r2 = 0.96. The reference interval was ≤ 0.7 pmol/L, however, a cut-off of ≤ 4.2 pmol/L yielded increased specificity (98%). Comparison of patients with HHM versus those without HHM resulted in an area under the ROC curve of 0.99. A significant inverse relationship between eGFR and PTHrP was observed (r = 0.738). PTHrP concentrations in patients with Chronic Kidney Disease (CKD) were ≤ 4.2 pmol/L.

CONCLUSION:

This assay is specific for PTHrP 1-86. A clinical decision limit of 4.2 pmol/L was sensitive and specific for patients with HHM.

• Authors: Susan Ashrafzadeh-Kian, Joshua Bornhorst, Alicia Algeciras-Schimnich
• Journal: Clinical biochemistry (Clin Biochem) 2022 Jul-Aug Vol. 105-106 Pg. 75-80 ISSN: 1873-2933 [Electronic] United States
• PMID: 35429486 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Chemical References

• Parathyroid Hormone
• Parathyroid Hormone-Related Protein

Topics

• Animals
• Hypercalcemia (diagnosis)
• Immunoassay
• Paraneoplastic Syndromes
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Rabbits