The Application of Assay- and Age-Specific Parathyroid Hormone (PTH) Reference Intervals Decreases the Diagnosis of Normocalcaemic Primary Hyperparathyroidism and Improves Diagnostic Concordance of PTH Assays

Parathyroid hormone (PTH) assays are not standardized and therefore PTH results are interpreted using manufacturer-provided assay-specific reference intervals. Assay-specific PTH reference intervals, however, do not account for between-assay differences and lead to discordance in the diagnosis of normocalcaemic primary hyperparathyroidism (NCPHPT). PTH increases with age independent of vitamin D, renal function, phosphate and ionized calcium. The observed variations in age-nonspecific PTH reference intervals may, in part, be attributed to the varying proportions of individuals from different age sub-sets included in the direct sampling reference interval studies. We assessed the impact of recently derived age-specific reference intervals for Abbott and Roche PTH assays on the diagnosis and diagnostic concordance of previously identified NCPHPT individuals. Of the 46 NCPHPT individuals identified using elevated Abbott PTH, only 16 (35%) were concordant for NCPHPT whereas 30 (65%) had normal PTH when samples were analysed by the Roche method and results were interpreted using the manufacturer-provided reference intervals for both methods. However, interpreting results using the method-specific age-related PTH reference intervals resulted in 31 (67%) individuals having a concordant normal PTH, eight (17%) having concordant NCPHPT and only seven (15%) remaining discordant (NCPHPT by Abbott and normal by Roche methods). Application of assay- and age-specific reference intervals decreases the diagnosis of NCPHPT and improves diagnostic concordance between PTH assays. We suggest that the diagnosis of NCPHPT should be based on assay- and age-specific PTH reference intervals. Until PTH assays are harmonized, subsequent PTH measurements for NCPHPT patients should ideally be performed using the same assay.