Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism

Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients.

A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122).

NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions.

We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.