A-075 Distinguishing Secondary Hyperparathyroidism from Early Normocalcemic Primary Hyperparathyroidism: Does Selection of Reference Change Values Change the Clinical Significance of Diagnostic Outcomes?

Abstract Background Differentiating secondary hyperparathyroidism (SHPT) from early normocalcemic primary hyperparathyroidism (PHPT) is challenging due to variability in intact parathyroid hormone (iPTH) assays and the absence of standardized reference change values (RCVs). Discrepancies in PHPT diagnoses across various iPTH assays contribute to significant diagnostic variability. The Endocrine Society*s guidelines for managing vitamin D deficiency, especially concerning SHPT, highlight the necessity of adequate calcium intake even after vitamin D normalization. A proposed diagnostic approach involves a calcium challenge test to distinguish SHPT from PHPT by observing PTH suppression following calcium supplementation. This study aims to compare the diagnostic performance of four selected RCVs and evaluate their clinical applicability in patients undergoing the calcium challenge. The data presented examined the clinical utility of one of these RCVs within the studied patient population. Methods We conducted a retrospective analysis of 97 patients with estimated glomerular filtration rate (eGFR) =45 mL/min/1.73m², normal serum calcium, normalized vitamin D (25OHD), and elevated iPTH levels, who underwent a calcium challenge test at Rush University Medical Center between 2014 and 2022. PTH levels were measured before and after calcium supplementation using Abbott Architect, Roche Cobas, and Siemens Atellica assays. Given the analytical variability among iPTH assays and the limited assay-specific within-subject coefficient of variation (CVi) data, a standardized median RCV of ±30% was calculated. This value was derived from manufacturers` reported (package inserts) analytical variability (CVa) and a CVi of 14.7% from the European Biological Variation Study (EuBIVAS) to define clinically significant changes in iPTH levels. Diagnostic metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy, were calculated to assess diagnostic performance. Results Of the 97 patients analyzed (mean age 72), 82 were diagnosed with SHPT and 15 with PHPT. The standardized RCV used in the study demonstrated an overall diagnostic accuracy of 94.8%, with a sensitivity of 94%, specificity of 100%, NPV of 75%, and PPV of 100%. The diagnostic performance of the remaining three RVCs is currently being evaluated and compared to identify the clinically optimal threshold for this patient population. Conclusion The standardized RCV demonstrated excellent overall diagnostic efficacy. The 100% PPV confirms that all SHPT patients normalized PTH levels, while NPV of 75% suggests some non-responders may still have SHPT. Standardizing the RCV across assays improves diagnostic accuracy and clinical applicability, potentially leading to improved diagnosis and management of hyperparathyroid disorders. Further prospective validation is warranted to confirm these results.