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Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype.

CONTEXT
Patients with elevated PTH and consistently normal serum calcium levels, in whom secondary causes of hyperparathyroidism have been excluded, may represent the earliest presentation of primary hyperparathyroidism (PHPT).


OBJECTIVE
The objective of the study was to characterize patients with normocalcemic PHPT referred to a bone disease unit.


DESIGN
This was a longitudinal cohort study.


SETTING
Ambulatory patients were referred to the metabolic bone disease unit.


PATIENTS
The study population included 37 patients [aged 58 yr, range 32-78; 95% female; serum calcium, 9.4 +/- 0.1 (sem) mg/dl (2.3 +/- 0.02 mmol/liter), reference range, 8.5-10.4 (2.1-2.6 mmol/liter); PTH, 93 +/- 5 pg/ml].


INTERVENTIONS
Interventions included yearly (median 3 yr; range 1-8 yr) physical examination, biochemical indices, and bone mineral density (BMD).


MAIN OUTCOME MEASURES
We measured the development of features of PHPT.


RESULTS
Evaluation for classical features of PHPT revealed a history of kidney stones in five (14%), fragility fractures in four (11%), and osteoporosis in 57% [spine (34%), hip (38%), and/or distal one third radius (28%)]. BMD did not show preferential bone loss at the distal one third radius (T scores: spine, -2.00 +/- 0.25; hip, -1.84 +/- 0.18; one third radius, -1.74 +/- 0.22). Further signs of PHPT developed in 40% (seven hypercalcemia; one kidney stone; one fracture; two marked hypercalciuria; six had >10% BMD loss at one or more site(s) including four patients developing World Health Organization criteria for osteoporosis). Seven patients (three hypercalcemic, four persistently normocalcemic) underwent successful parathyroidectomy.


CONCLUSIONS
Patients seen in a referral center with normocalcemic hyperparathyroidism have more substantial skeletal involvement than is typical in PHPT and develop more features and complications over time. These patients may represent the earliest form of symptomatic, rather than asymptomatic, PHPT.