Parathyroid hormone heterogeneity and assay-dependent interpretation in practice

Parathyroid hormone (PTH) is a key biochemical marker in the diagnosis and management of disorders of calcium-phosphate metabolism. However, circulating PTH represents a heterogeneous mixture of full-length PTH(1-84) and multiple truncated fragments that differ in biological activity and clearance. These molecular forms are variably detected by commercially available immunoassays, resulting in assay-dependent differences in measured PTH concentrations. In endocrine surgery, intraoperative PTH monitoring (ioPTH) is widely used to assess the adequacy of parathyroidectomy based on the rapid decline of circulating PTH. This approach assumes that measured PTH concentrations reliably reflect biologically relevant hormone dynamics. However, accumulating evidence indicates that both assay characteristics and physiological factors may influence observed PTH kinetics. Most data on PTH immunoheterogeneity originate from studies in chronic kidney disease, where fragment accumulation is well documented. In contrast, the implications of PTH heterogeneity for intraoperative monitoring and broader clinical interpretation remain less clearly defined. This review summarizes current evidence on PTH molecular heterogeneity, assay-dependent variability, and systemic factors affecting PTH metabolism and discusses their implications for interpretation of PTH measurements in dynamic clinical settings. Recognition of these interactions may improve interpretation of laboratory results and support more accurate clinical decision-making in endocrine practice.