Predicting cure and hypocalcemia by intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism: A multi-institutional validation study.

Background: Normohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50-70% for normohormonal and 75-88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings.

Methods: We performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort.

Results: A total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02).

Conclusion: This multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50-65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism.