Normocalcemic Primary Hyperparathyroidism: An Evolving Understanding

Normocalcemic primary hyperparathyroidism (NPHPT) is a phenotype of classic hypercalcemic primary hyperparathyroidism characterized by elevated parathyroid hormone levels in the setting of persistently normal serum calcium. While increasingly recognized as a significant cause for endocrine referral, its pathophysiology remains poorly understood. The diagnosis of NPHPT is one of exclusion, necessitating the rigorous investigation and exclusion of all secondary causes of hyperparathyroidism. Predominantly identified in postmenopausal women during evaluation for osteoporosis or nephrolithiasis, affected patients often present with a greater burden of bone disease and renal complications than typical patients with hypercalcemic disease, likely a reflection of selection bias. The diagnosis and management of NPHPT are challenging in the setting of limited research and long-term outcome data. While parathyroidectomy has demonstrated improvements in bone density for appropriate surgical candidates, robust evidence regarding its impact on renal complications is lacking. This review synthesizes the current literature to inform clinical decision-making in the management of patients with NPHPT.