Elevations in Circulating 1, 25-Dihydroxyvitamin D in Three Patients with Lymphoma-Associated Hypercalcemia

Three patients with hypercalcemia associated with malignant lymphoma and elevations in plasma 1, 25-dihydroxyvitamin D [1, 25-(OH)₂D] are described. In addition to the elevation of circulating 1, 25-(OH)₂D, these three patients were characterized by suppressed immunoreactive PTH levels and urinary cAMP excretion, elevated fasting urinary excretion of calcium, and absence of adenylate cyclase-stimulating activity in the tumor extracts. Bone marrow biopsy and skeletal radionuclide scans were negative for lymphoma in two patients. Surgical excision of a solitary splenic lymphoma in one patient and medical therapy in another patient resulted in rapid normalization of the serum calcium and plasma 1, 25-(OH)₂D levels. These findings confirm an earlier observation that elevated plasma levels of 1, 25-(OH)₂D may occur in certain patients with lymphoma and suggest that this vitamin D metabolite may act as a humoral or systemic mediator of hypercalcemia. Proof that this is the case and identification of the source of 1, 25-(OH)₂D production will require further study.