Patients with normocalcemic versus hypercalcemic hyperparathyroidism: What's really the difference?

Primary hyperparathyroidism (HPT) is typically characterized by elevated parathyroid hormone (PTH) and hypercalcemia; however, some patients develop normocalcemic hyperparathyroidism. Patients with normocalcemic HPT have an elevated PTH with normal calcium levels and no other secondary causes of elevated PTH, and therefore have a unique biochemical profile. The aim of this project is to compare the demographics, presentation, and outcomes for patients with normocalcemic HPT versus patients with hypercalcemic HPT undergoing parathyroidectomy.

A single institution, retrospective review was conducted between January 2016 and June 2022. Patients were classified as either having hypercalcemic (calcium >10.4 ​mg/dL) or normocalcemic (calcium ≤10.4 ​mg/dL) HPT. Cure was defined as normal calcium for 6 months post-operatively in the hypercalcemic HPT group and normal PTH (<88 ​pg/mL) for 6 months post-operatively in the normocalcemic HPT group.

Of the 701 patients included in the study, 566 (80.7 ​%) had hypercalcemic HPT and 135 (19.3 ​%) had normocalcemic HPT. The preoperative Ca was 11 ​± ​0.7 ​mg/dL in the hypercalcemic group and 9.8 ​± ​0.4 ​mg/dL in the normocalcemic group (p ​< ​0.001). The preoperative PTH was 148.2 ​± ​180 ​pg/dL in the hypercalcemic group and 117.4 ​± ​105.3 ​pg/dL in the normocalcemic group (p ​= ​0.06). The average age of normocalcemic patients was 56 ​± ​15 years, compared to 59 ​± ​15 years in the hypercalcemic group (p ​= ​0.07). There was no significant difference in sex (p ​= ​0.42). African American patients were more likely to present with hypercalcemic HPT (19.1 ​%) than with normocalcemic HPT (9.6 ​%, p ​= ​0.01). Normocalcemic patients were more likely to report pre-operative symptoms of kidney stones compared to patients with hypercalcemia (53.3 ​% versus 30.4 ​%, p ​< ​0.001). There was no significant difference in pre-operative symptoms of fatigue, bone pain, or fractures. Patients with hypercalcemic HPT were more likely to present with adenoma (64.3 ​%); whereas patients with normocalcemic HPT were more likely to present with hyperplasia (43.3 ​%, p ​< ​0.001). More patients with normocalcemic HPT underwent thymectomy compared to patients with hypercalcemia (39.3 ​% versus 20.8 ​% respectively, p ​< ​0.001). 92.0 ​% of normocalcemic patients achieved cure post-operatively, which was significantly less than in the hypercalcemic group (97.0 ​%, p ​= ​0.02). The 8.0 ​% of normocalcemic patients that did not achieve cure had a mean PTH level of 147.9 ​± ​159 ​pg/mL at 6 months post-operative. Four patients with normocalcemic HPT had recurrence of disease (3 ​%), and three of the four patients underwent bilateral exploration.

Patients with normocalcemic HPT present with different symptoms compared to patients with hypercalcemic HPT prior to surgery. Additionally, patients with normocalcemic HPT are less likely to achieve cure after surgery, which warrants further investigation.