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

Accurate measurement of parathyroid hormone (PTH) remains essential for the diagnosis and management of disorders of mineral metabolism, particularly in parathyroid disorders including in chronic kidney disease-mineral and bone disorder. Persistent inter-assay variability limits the comparability of clinical results across platforms and impedes guideline harmonization. This review focuses on recent advances in methodology, highlighting recent developments that move the field toward harmonization or even standardization of PTH assays.

Recent landmark studies have applied liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a candidate reference measurement procedure, enabling direct quantification of intact 1-84PTH with improved specificity. Novel immunocapture LC-MS/MS workflows demonstrate enhanced analytical precision and reveal substantive biases among commercial immunoassays. Recent progress in feasibility of harmonizing calibration was shown in a multicenter study where immunoassays were calibrated against LC-MS/MS reference methods, yielding reduced inter-assay bias, facilitating shared reference intervals. High-accuracy isotope-dilution mass spectrometry has been deployed to characterize reference materials, supporting future standard formulation.

Emerging LC-MS/MS methods and harmonization strategies represent significant progress toward future standardization of assays for PTH. While technical complexity and cost still remain barriers, recent developments point towards improved analytical comparability and enhanced clinical interpretation.