Phenotypes of primary hyperparathyroidism: Does parathyroidectomy improve clinical outcomes for all?

Background: Primary hyperparathyroidism consists of 3 biochemical phenotypes: classic, normocalcemic, and normohormonal primary hyperparathyroidism. The clinical outcomes of patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism are not well described. Method: A retrospective review of patients who underwent parathyroidectomy at a single institution was performed. A logistical regression analysis of postoperative nephrolithiasis and highest percentage change in dual-energy x-ray absorptiometry scan comparison using Kruskal-Wallis test and Cox proportional hazard analysis of recurrence-free survival were performed. Results: A total of 421 patients were included (340 classic, 39 normocalcemic primary hyperparathyroidism, 42 normohormonal primary hyperparathyroidism). Median follow-up was 8.8 months (range 0–126). Higher rates of multigland disease were seen in normocalcemic primary hyperparathyroidism (64.1%) and normohormonal primary hyperparathyroidism (56.1%) compared to the classic (25.8%), P <.001. There were no differences in postoperative complications. The largest percentage increases in bone mineral density at the first postoperative dual-energy x-ray absorptiometry scan were higher for classic (mean ± SD, 6.4 ± 9.1) and normocalcemic primary hyperparathyroidism (4.8 ± 11.9) compared to normohormonal primary hyperparathyroidism, which remained stable (0.2 ± 14.2). Normocalcemic primary hyperparathyroidism were more likely to experience nephrolithiasis postoperatively, 6/13 (46.2%) compared to 11/68 (16.2%) classic, and 2/13 (15.4%) normohormonal primary hyperparathyroidism, P =.0429. Normocalcemic primary hyperparathyroidism was the only univariate predictor of postoperative nephrolithiasis recurrence (odds ratio [95% confidence interval] 4.44 [1.25–15.77], P =.029). Normocalcemic primary hyperparathyroidism was significantly associated with persistent disease with 6/32 (18.8%) compared to 1/36 (2.8%) and 3/252 (1.2%) in normohormonal primary hyperparathyroidism and classic (P <.001). Conclusion: Three phenotypes of primary hyperparathyroidism are distinct clinical entities. Normocalcemic primary hyperparathyroidism had higher incidence of persistent disease and postoperative nephrolithiasis but demonstrated improvements in postoperative bone density. These data should inform preoperative discussions with patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism regarding postoperative expectations.