Vitamin D metabolite-mediated hypercalcemia

The endogenous overproduction of active vitamin D sterols plays a central causative role in the hypercalcemic/hypercalciuric state associated with granuloma-forming diseases, most notably sarcoidosis, as well as with some human lymphomas. In sarcoidosis, the offending metabolite is most likely 1,25-(OH)2-D and the synthetic source is the disease-activated macrophage. About 50% of hypercalcemic patients with lymphoma harbor frankly elevated or inappropriately high serum 1,25-(OH)2-D concentrations. The source of the hormone in patients with lymphoma is not yet known. The endogenous synthesis of 1,25-(OH)2-D in patients with active sarcoidosis and lymphoma is not subject to regulation by those factors that normally control the production of 1,25-(OH)2-D by the renal 25-OH-D-1-hydroxylase. Treatment and prevention of vitamin D metabolite-mediated hypercalcemia/hypercalciuria consist of pharmacologic inhibition of the abnormal 1-hydroxylation reaction and limitation of substrates for the reaction. The former is best accomplished by the administration of anti-inflammatory concentrations of glucocorticoids and the latter by controlling vitamin D intake and sunlight exposure in susceptible hosts.