ABNORMAL SYNTHESIS OF 1,25-DIHYDROXYVITAMIN-D IN PATIENTS WITH MALIGNANT-LYMPHOMA

High serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] can occur with hypercalcemia in malignant lymphoma. We have investigated the potential for abnormal vitamin D metabolism by giving a single oral dose of 25-hydroxyvitamin D (250HD) in 10 lymphoma patients (8 Hodgkin's and 2 T-cell) and 7 controls. Serum 250HD increased similarly in both groups (peak concentrations, 114.1 +/- 9.5 vs. 123.9 +/- 9.6 nmol/L). In controls, serum calcium and PTH did not change after treatment [calcium, 2.31 +/- 0.02 and 2.33 +/- 0.02 mmol/L (mean +/- SEM); PTH, 21.6 +/- 4.0 and 25.4 +/- 4.3 ng/L] 1,25-(OH)(2)D increased within the normal range from [median (range)] 81 (48-125) to 117 (91-156) pmol/L. In lymphoma patients, serum calcium increased from 2.29 +/- 0.04 to 2.40 +/- 0.06 mmol/L (P = 0.03), PTH decreased from 12.9 +/- 2.6 to 8.0 +/- 1.9 ng/L (P = 0.06), and one patient became hypercalcemic (2.92 mmol/L). Serum 1,25-(OH)(2)D became supranormal in 6 lymphoma patients; the group median rose from 74.5 (46-180) to 151 (120-487) pmol/L; this peak response differed from that in the controls (P = 0.019). Lymph node and spleen cells from a patient with T-cell lymphoma synthesized [H-3]1,25-(OH)(2)D-3 from [H-3] 25OHD(3) in vitro. The data suggest that abnormal production of 1,25-(OH)(2)D in lymphoma may be more common than previously recognized given an adequate supply of precursor 250HD and provide further evidence for the extrarenal synthesis of 1,25-(OH)(2)D in this condition.