Natural History of Primary Hyperparathyroidism

In the past century, the natural history of primary hyperparathyroidism has evolved. The current clinical presentation of the disease in the United States bears little resemblance to the disease described by Albright in the 1930s. 1 , 2 , 4 , 5 , 14 , 38 That disorder, now classified as “classical primary hyperparathyroidism,” was characterized by nephrolithiasis , the skeletal abnormalities of osteitis fibrosa cystica , and frequent neuromuscular complications. Since the advent of the multichannel autoanalyzer in the 1970s, the diagnosis of primary hyperparathyroidism has commonly followed the incidental finding of hypercalcemia on a laboratory examination performed for unrelated purposes. 26 , 40 , 55 Today, the vast majority of patients with primary hyperparathyroidism have no symptoms clearly referable to hypercalcemia or increased parathyroid hormone levels. The evolution of primary hyperparathyroidism into a largely asymptomatic disorder has raised many questions. First, what is the effect of the disease (if any) in these seemingly asymptomatic patients? Second, considering the change in the profile of primary hyperparathyroidism, what is appropriate therapy for the disorder? Do all patients without symptoms require surgery, which currently remains the only option for cure? The answer to this question depends, to a large extent, on the natural history of the disease in patients who do not undergo parathyroid surgery. Are these individuals at risk for the symptoms of classical primary hyperparathyroidism if not treated? The answer will also be affected by the clinical course of patients who are cured by surgery. The effects of the cure must be weighed against the effects of nonintervention in any therapeutic decision. Studies of primary hyperparathyroidism have shown that, although the disease has changed in clinical presentation, it is not without significant effects on many organ systems. This article reviews what is known about the manifestations of primary hyperparathyroidism and the natural history of treated and untreated disease.