Vitamin D metabolite-mediated hypercalcemia and hypercalciuria patients with AIDS- and non-AIDS-associated lymphoma

Abstract

Fifteen patients with lymphoma and hypercalcemia (greater than or equal to 11.0 mg/dL) were identified by screening the serum chemistry profile obtained from patients upon admission to the Los Angeles County/USC Medical Center. Seven of the 15 (47%) possessed a frankly elevated serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. An additional patient with severe hypercalcemia (16.2 mg/dL) had a serum 1,25-(OH)2-D concentration in the midnormal range, not a suppressed value. To examine the potential existence of hypercalciuria in absence of overt hypercalcemia, prospective screening of 23 normocalcemic patients with lymphoma was undertaken. Four of the 23 patients (17%) had increased fractional urinary calcium excretion rates (0.35 +/- 0.3 mg calcium/100 mL glomerular filtrate [GF], mean +/- SE; normal, less than 0.16 mg/100 mL GF); two of the hypercalciuric patients had a frankly elevated serum 1,25-(OH)2-D concentration. Of the 19 hypercalcemic/hypercalciuric lymphoma patients identified, none had an elevated serum immunoreactive parathyroid hormone concentration. Fourteen of the 19 hypercalcemic/hypercalciuric patients (74%) suffered from B-cell neoplasms, three had Hodgkin's lymphoma, and two had adult T-cell leukemia/lymphoma. All hypercalcemic/hypercalciuric patients had widespread disease (stage III or IV). Six patients, four with hypercalcemia and two with hypercalciuria, had acquired immunodeficiency syndrome (AIDS). These data suggest that the deregulated synthesis of a 1,25-(OH)2-D-like metabolite is a common cause of hypercalcemia and hypercalciuria in patients with lymphoma including patients with AIDS-associated tumors.

Bone and Mineral Metabolism in Human Immunodeficiency Virus Infection

“…Hypercalcemia in protozoal, fungal, and mycobacterial infection may result from extrarenal 1α‐hydroxylation of 25‐hydroxyvitamin D 3 [25(OH)D 3 ] by macrophages, monocytes, epithelioid cells, and multinucleated giant cells (37–41) . A similar mechanism has also been suggested in patients who present with AIDS‐associated lymphoma and hypercalcemia (43,44) …”

Metabolic profiling of major vitamin D metabolites using Diels–Alder derivatization and ultra-performance liquid chromatography–tandem mass spectrometry

“…The literature data on 1α,25(OH) 2 D 3 status in patients with HIV infections are controversial. While some studies found suppressed levels of 1α,25(OH) 2 D 3 , presumably caused by antiretroviral treatment [32,33], there are many cases of reported increases in 1α, 25(OH) 2 D 3 [34][35][36][37]. The increase in 1α,25(OH) 2 D 3 in HIV-positive subjects can be caused by extrarenal production of 1α,25(OH) 2 D 3 in macrophages activated by chronic inflammation or in tumors in the final stages of the disease.…”

Rapid onset of hypercalcemia from high-grade lymphoma in the setting of HIV-related immune reconstitution inflammatory syndrome

“…In the remaining 60-70% of cases of non-Hodgkin lymphoma, hypercalcemia is mediated by PTHrP. In an older case series of 15 patients with lymphoma and hypercalcemia, seven of these patients presented with elevated 1,25-(OH) 2 vitamin D levels ( Adams et al, 1989 ). The types of lymphoma varied (B-cell, small noncleaved and immunoblastic sarcoma 40%, follicular center cell 27%, Hodgkin 20%, T-cell 13%).…”

“…This study also included 4 patients with AIDS-associated lymphoma. That series was reported in 1989, a time when highly effective ART was not available and included one patient with HIV-related lymphoma with a high 1,25-(OH) 2 vitamin D level ( Adams et al, 1989 ). Further laboratory studies using lymphoma cells cultured from the HIV-infected host showed that these cells had the capacity to metabolize 25-(OH) vitamin D into a compound similar to 1,25-(OH) 2 vitamin D by chromatography.…”