Nonparathyroid Humoral Hypercalcemia in Patients with Neoplastic Diseases

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Abstract
Eleven patients had hypercalcemia and hypophosphatemia associated with various nonparathyroid neoplasms in the absence of bony metastases (pseudohyperparathyroidism). In nine patients surgical ablation or other antitumor therapy resulted in remission of the biochemical abnormalities. Parathyroid hormone was undetectable both in peripheral blood and in tumor tissue from all patients when assessed with multiple immunoassays that detect not only intact parathyroid hormone but proparathyroid hormone and biologically active and inactive parathyroid hormone fragments in addition. However, extracts of tissues caused active calcium resorption from bone in vitro. The chemical nature of the presumed humoral substance (or substances) is unknown. The findings suggest that in many patients with neoplasms and clinical and biochemical features typical of pseudohyperparathyroidism some humoral substance other than parathyroid hormone must be responsible for hypercalcemia and other features of their disease. (N Engl J Med 289:176–181, 1973)