Hyperphosphatemic tumoral calcinosis: Effects of phosphate depletion on vitamin D metabolism, and of acute hypocalcemia on parathyroid hormone secretion and action

In hyperphosphatemic tumoral calcinosis, plasma 1, 25-dihydroxyvitamin D [1, 25(OH)₂D] levels are inappropriately elevated, suggesting an abnormality in vitamin D metabolism. To define this abnormality further, we measured vitamin D metabolites in two patients and four controls before and after phosphate depletion. The patients showed elevated plasma levels of 1, 25(OH)₂D in the basal state. Phosphate depletion reduced serum phosphate in patients from a mean of 6.1 to 2.6 mg/dl; this was accompanied by a rise in plasma 25-hydroxyvitamin D from 33.6 to 41.9 ng/dl, and in 1, 25(OH)₂D from 67.7 to 93.2 pg/ml. The absolute rise in 1, 25(OH)₂D was similar to that of controls. EDTA infusion produced a normal increase of serum immunoreactive PTH levels and urinary cAMP excretion. In this form of tumoral calcinosis, 1, 25(OH)₂D levels are elevated despite hyperphosphatemia, normal immunoreactive PTH, and normal serum calcium concentrations, suggesting an abnormality in the regulation of 1, 25(OH)₂D synthesis or metabolism, or alternatively, another undefined stimulus for 1, 25(OH)₂D synthesis. These patients appear to have concurrent abnormalities of renal tubular phosphate transport and vitamin D metabolism.