Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism

Abstract

Background 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. Methods 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). Results 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. Conclusion 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.

Normocalcemic primary hyperparathyroidism is an early stage of primary hyperparathyroidism according to fibroblast growth factor 23 level

“…In our study, contrary to the study of Choi HR et al. ( 24 ) we found that patients with NPHPT had a lower prevalence of fractures compared to HPHPT although the bone densitometry scores and bone turnover markers were similar in both groups.…”

“…The most prevalent view is that NPHPT is an early form of PHPT which may progress to frank hypercalcemia. Other hypotheses related to partial PTH resistance in bone and kidney or altered parathyroid sensing ( 23 , 24 ). In a recent study, it was supposed that NPHPT could be a different disease entity, probably more severe compared to mild asymptomatic primary hyperparathyroidism ( 24 ).…”

“…Other hypotheses related to partial PTH resistance in bone and kidney or altered parathyroid sensing ( 23 , 24 ). In a recent study, it was supposed that NPHPT could be a different disease entity, probably more severe compared to mild asymptomatic primary hyperparathyroidism ( 24 ). Another hypothesis is that aging and low estrogen status (menopause) play a role in raising PTH levels through a negative calcium balance status ( 25 ).…”

“…Ionized serum calcium reflects the biologically activated calcium more accurately and directly acts on the CaSR to regulate PTH secretion. Many “normocalcemic” patients are known to have elevated ionized calcium levels ( 24 ). Second, we did not measure the level of free 25(OH) D. The value of free 25(OH) D level has been recently highlighted by Wang X et al.…”