Hypercalcemia due to vitamin D toxicity

Vitamin D toxicity can be life-threatening and associated with substantial morbidity, if not identified quickly. Hypervitaminosis D with hypercalcemia may be secondary to excessive intake of parent vitamin D, its metabolites 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), or vitamin D analogs; to increased production of 25(OH)D or 1,25(OH)₂D from exogenous substrate; and even to topical applications of potent vitamin D analogs. Vitamin D toxicity is not a common cause of hypercalcemia, but it can be life threatening if not identified promptly. The major causes of hypercalcemia are primary hyperparathyroidism and malignancy. If these two etiologies are excluded, vitamin D toxicity becomes an important diagnostic consideration. Many different mechanisms have been proposed to account for vitamin D toxicity, including the vitamin D metabolite itself, vitamin D receptor (VDR) number, activity of 1α-hydroxylase, inhibition of vitamin D metabolism, and the capacity of vitamin-D-binding protein (DBP). Mounting evidence that higher levels of vitamin D may have beneficial effects on bone and cellular health may predispose to enhanced administration of vitamin D in the future and thereby increased frequency of vitamin D toxicity.