Characterization of normocalcemic primary hyperparathyroidism

Abstract

The introduction of multichannel serum biochemistry testing in the early 1970s uncovered a large number of patients with primary hyperparathyroidism who were asymptomatic, turning an extremely rare and severe disease into a fairly common and benign condition (1). The diagnosis of primary hyperparathyroidism—whether symptomatic or not—still requires hypercalcemia along with an elevated intact parathyroid hormone (PTH) level (2). Recently, endocrinologists have become aware of patients with normocalcemic primary hyperparathyroidism. This entity has not been characterized systematically, and it is not yet clear whether this is a “forme fruste” of the disease or a harbinger of the hypercalcemic type (3). The purpose of the present study was to define the characteristics of patients with this diagnosis in one endocrine outpatient clinic during the last 5 years. METHODS We reviewed medical records of patients with a diagnosis of primary hyperparathyroidism (International Classification of Diseases, Ninth Revision, code 252.0) seen in the endocrine clinic at Tel Aviv Sourasky Medical Center between January 1998 and October 2003. (Institutional review board approval was not required for this study.) The diagnosis of normocalcemic primary hyperparathyroidism was confirmed if a patient had never had documented hypercalcemia, and if all apparent causes of secondary hyperparathyroidism had been ruled out. Specifically, patients with impaired renal function, and those in whom vitamin D supplementation unmasked hypercalcemia, were excluded. Patients in whom elevated PTH levels decreased following treatment (vitamin D or calcium supplementation, or thiazides) were considered to have secondary hyperparathyroidism and thus were not eligible. We identified 32 patients who met these criteria. Serum calcium levels were determined on a Hitachi 747 random-access analyzer (Roche Diagnostics Boehringer Mannheim, Mannheim, Germany) or a Bayer Advia 1650 analyzer (Leverkusen, Germany) with identical analytical performances; the normal range was 8.5 to