Endocrine Abstracts

JOINT3970

Background: Parathyroid hormone (PTH) assays lack standardization, leading to the interpretation of PTH results using manufacturer-specific reference intervals. These intervals do not account for inter-assay differences, resulting in discordant diagnoses of normocalcaemic hyperparathyroidism (NCPHPT). PTH levels increase with age independently of vitamin D, renal function, phosphate, and ionized calcium. Variations in age-nonspecific PTH reference intervals may stem from differing age distributions in reference interval studies.

Aim: This study aimed to evaluate the effect of newly derived age-specific reference intervals for Abbott and Roche PTH assays on the diagnosis of NCPHPT, focusing on diagnostic concordance when applying age- and assay-specific intervals to previously identified cases of NCPHPT.

Methods: Age- and assay-specific intact parathyroid hormone (iPTH) reference intervals from recent studies were applied to serum samples from patients previously diagnosed with NCPHPT in a prior diagnostic test assessment. The study included adult outpatients (≥18 years) with NCPHPT, whose serum samples were collected between February and June 2021. Serum samples were analysed using Abbott and Roche second-generation immunoassays. Patients with vitamin D deficiency (<50 nmol/l), impaired renal function (eGFR <60 mL/min/1. 73 m²), malignancy, pregnancy, or medications influencing calcium/PTH levels were excluded. Reference intervals from previously published studies for both Roche and Abbott iPTH derived from large population datasets using the refineR algorithm were used to assess diagnostic concordance.

Results: Among the 46 individuals initially diagnosed with NCPHPT based on elevated Abbott PTH levels, only 16 (35%) remained concordant for NCPHPT by Roche method when the results were interpreted using the manufacturer provided method-specific reference intervals. The remaining 30 (65%) had normal PTH levels. However, when method- and age-specific reference intervals were applied, diagnostic concordance improved: 31 individuals (67%) were classified with normal PTH levels by both methods, 8 (17%) remained concordant for NCPHPT, and 7 (15%) were discordant (NCPHPT diagnosed by Abbott but normal PTH by Roche). This indicates that age- and assay-specific reference intervals significantly reduced NCPHPT diagnoses and improved agreement between the assays.

Conclusion: The use of age- and assay-specific reference intervals for PTH assays enhances diagnostic accuracy, reduces unnecessary NCPHPT diagnoses, and improves concordance between different commercially available assays. This approach minimises the risk of misdiagnosis, unnecessary testing, and inappropriate management, particularly for older patients.