Approach to the Patient: Normocalcemic Primary Hyperparathyroidism

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Abstract

Normocalcemic primary hyperparathyroidism (NPHPT), a phenotype of primary hyperparathyroidism, is characterized by elevated parathyroid hormone levels in the setting of persistently normal serum calcium. Diagnosis of NPHPT can be challenging and requires that secondary causes of hyperparathyroidism be excluded. The natural history of NPHPT remains inconclusive. Although biochemically less severe, the skeletal and renal complications of NPHPT vary across studies, primarily due to underlying selection bias. Due to limited data, there is currently no consensus regarding medical and surgical treatment. Recent studies on parathyroidectomy have indicated that normocalcemic patients present more often with negative preoperative localization studies and multiglandular disease, which complicates successful surgical management. In addition, postoperative improvements in bone mineral density and nephrolithiasis vary, raising questions about the optimal treatment approach. Further studies are needed to provide better evidence-based guidance for normocalcemic patients.

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Liu, Y., Sinha Gregory, N., Andreopoulou, P., Kashyap, S., & Cusano, N. (2025). Approach to the Patient: Normocalcemic Primary Hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism, 110(3), e868–e877. https://doi.org/10.1210/clinem/dgae659

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