Utility of albumin-adjusted calcium and calcium‒phosphorus difference in screening for primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism (PHPT) is often asymptomatic but increases the risk of osteoporosis, fractures, and cardiovascular mortality. We evaluated the effectiveness of albumin-adjusted calcium (aCa) formulas and the calcium–phosphorus (Ca–P) difference as prescreening tools for PHPT in health checkup populations.

METHODS

We analyzed 5550 corresponding measurements of total calcium (tCa), serum albumin (Alb), and ionized calcium (iCa) to evaluate the consistency between iCa and tCa and between iCa and three aCa formulas (Payne, KDOQI-2, and James). Receiver operating characteristic (ROC) curve analyses were performed for 64 PHPT patients and 87 controls. Cutoffs were then applied to 2562 health checkup participants.

RESULTS

The James formula demonstrated the strongest agreement with iCa (κ = 0.60), outperforming the tCa and other formulas. ROC curve analyses revealed that the James-based Ca–P difference (AUC = 0.965) surpassed all other calcium-based indices and approached the intact parathyroid hormone value (AUC = 0.983), with respective sensitivities and specificities of 0.88 and 0.94. In the health checkup cohort, the PHPT prevalence was 0.17%. Identifying all four confirmed cases required investigating 64 candidates of tCa, nine to ten of aCa, and only five to seven of the Ca–P difference.

CONCLUSIONS

Determining the albumin-adjusted calcium, particularly by the James formula, improved PHPT prescreening compared with tCa alone. The Ca–P difference demonstrated even better diagnostic performance. In populations where fasting phosphorus is routinely measured, the Ca–P difference reduces the number of candidates requiring confirmatory testing, providing a potentially resource-efficient strategy for early PHPT detection.