Automated laboratory detection of hypercalcemia: Diagnostic yield, clinical pathway and outcomes in a real-world cohort

Automated laboratory detection of hypercalcemia may facilitate the recognition of previously unrecognized primary hyperparathyroidism (PHPT), but its value in routine clinical practice remains poorly defined, particularly with regard to subsequent etiological evaluation, healthcare resource utilization, and biochemical follow-up.

This retrospective cohort study evaluated an automated laboratory case-finding strategy for hypercalcemia across a healthcare area serving more than 230,000 inhabitants. Consecutive laboratory alerts generated between 2012 and 2020 were reviewed. After duplicate alerts were removed, 685 unique patients constituted the laboratory-detected cohort, of whom 258 underwent sufficient etiological evaluation and constituted the fully evaluated cohort. Clinical, biochemical, imaging, therapeutic, and longitudinal follow-up data were collected.

Among the 258 fully evaluated patients, definite PHPT was diagnosed in 229 (88.8%). Eight additional patients were retrospectively considered to have probable mild PHPT with concomitant vitamin D deficiency, while other etiologies included tertiary hyperparathyroidism associated with chronic kidney disease, malignancy-associated hypercalcemia, medication-related hypercalcemia, familial hypocalciuric hypercalcemia, sarcoidosis, and vitamin D intoxication. Patients underwent a median of seven specialist consultations. Among patients with an available date of definitive etiological diagnosis, the median interval from the initial laboratory alert to diagnosis was 432 days (IQR 94.5-1219.5). During follow-up, 219/258 patients (84.9%) had at least one documented normocalcemic measurement after biochemical confirmation of persistent hypercalcemia, and 150/258 (58.1%) fulfilled the definition of sustained normocalcemia. In Kaplan-Meier analysis, the median time to first documented normocalcemia was 595 days (95% CI 505-780).

Automated laboratory case-finding can identify patients with previously unrecognized persistent hypercalcemia and provide an entry point for subsequent etiological evaluation. PHPT was the predominant diagnosis within the fully evaluated cohort, although post-detection selection must be considered when interpreting this proportion. The prolonged diagnostic pathway and substantial healthcare use observed after the initial laboratory alert highlight the need to link automated detection strategies to structured clinical follow-up.