Normocalcemic primary hyperparathyroidism-characteristics and clinical significance of an emerging entity

The epidemiology and presentation of primary hyperparathyroidism (PHPT) is changing. Full-blown disease in its tertiary stage is rarely seen. Instead, asymptomatic hypercalcemia draws more attention because of the widespread use of screening laboratory tests. In recent years, clinicians have started ordering intact parathyroid hormone (iPTH) assays for a variety of reasons (eg, during the evaluation of fractures, nephrolithiasis, osteomalacia and low bone mass), even in individuals who have no evidence of hypercalcemia. The increased levels of iPTH without an underlying etiology may represent an early phase, or a distinct subtype, of PHPT, termed as normocalcemic primary hyperparathyroidism (NPH). The prevalence and clinical significance of NPH are unknown and are a matter of great debate. No guidelines regarding management of this entity exist. The authors describe a patient who had increased levels of iPTH, osteopenia and normal calcium and vitamin D. There was no discernible secondary cause for hyperparathyroidism (renal insufficiency, osteomalacia, vitamin D deficiency, lithium use, etc), and no intervention was offered aside from periodic monitoring of laboratory values and bone density. Analysis of data in patients with NPH should include elucidation of its natural history, temporal patterns in calcium level and prevalence of low bone mass, nephrolithiaisis and fragility fractures and could assist in devising evidence-based guidelines for management of the condition. Further characterization of NPH will be of benefit in defining its clinical impact and associated complications, to clarify the rationale behind the use of the iPTH assay as a screening test, and to assist in management of this entity.