The Pathophysiological Basis of Hypercalciuria in Primary Hyperparathyroidism

When initially described in the mid-1920’s, primary hyperparathyroidism (l°HPT) was regarded as a rare and severe disorder of bone. Shortly thereafter, Albright and colleagues recognized a different clinical presentation of l°HPT in patients with renal stones who lacked evidence of overt bone disease1. It subsequently became clear that renal stones are a far more frequent complication of l°HPT than overt osteitis, being the presenting complaint in approximately 50% of patients2. Further, it was recognized that patients presenting with stones rarely display evidence of clinical bone involvement and that patients presenting with clinical bone disease only rarely gave a history of renal stones (nephrocalcinosis was variably observed in a minority of patients with both presentations). Thus, early investigators were impressed by reasonably distinctive “bone” and “stone” presentations of the disorder and offered several hypotheses in attempt to explain their observations. These included Albright’s “dietary calcium” hypothesis1. Dent’s “dual hormone” hypothesis3, and the general proposal that clinical bone involvement developed as a function of the duration of the disease. Although Albright’s general tenets concerning external calcium balance were later supported by the observation of negative balance in patients with overt bone disease and zero or even positive balance in patients with stone disease4. All three hypotheses were subsequently either disproven or could not be supported by the accumulated evidence2. Thus, the clinical “spectrum” of the disorder remained enigmatic well through the 1960’s.