Parathyroid hormone assays in 2026: second versus third generation, standardization, and clinical interpretation

Area of Science:

• Clinical Chemistry
• Analytical Biochemistry
• Endocrinology

Background:

• Accurate parathyroid hormone (PTH) measurement is vital for diagnosing and managing mineral metabolism disorders, including chronic kidney disease-mineral and bone disorder.
• Inter-assay variability in current PTH testing platforms hinders clinical result comparability and guideline harmonization.

Purpose of the Study:

• To review recent methodological advances in PTH assay technology.
• To highlight developments promoting harmonization and standardization of PTH assays.

Main Methods:

• Application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference measurement procedure.
• Development of novel immunocapture LC-MS/MS workflows.
• Multicenter studies calibrating immunoassays against LC-MS/MS reference methods.
• Deployment of high-accuracy isotope-dilution mass spectrometry for reference material characterization.

Main Results:

• LC-MS/MS enables specific quantification of intact 1-84PTH with improved precision.
• Substantive biases were identified among commercial PTH immunoassays.
• Calibration against LC-MS/MS reference methods significantly reduced inter-assay bias and facilitated shared reference intervals.
• Reference materials are being characterized to support future standard formulation.

Conclusions:

• Emerging LC-MS/MS methods and harmonization strategies represent significant progress toward PTH assay standardization.
• Despite technical complexity and cost, recent developments enhance analytical comparability and clinical interpretation of PTH measurements.