Hypercalcemia, nephrolithiasis, and hypervitaminosis D precipitated by supplementation in a susceptible individual

Vitamin D supplementation is common among the general public. Although generally considered safe, vitamin D supplement–induced toxicity has been reported, often in association with manufacturing or labeling errors. Additionally, selected patient populations may have a hypersensitivity to vitamin D supplementation, leading to consequences due to supraphysiologic serum 25-hydroxyvitamin D levels. A 58-y-old woman developed hypercalcemia and its sequelae while on vitamin D supplementation. Despite being vitamin D replete, a functional medicine practitioner prescribed vitamin D starting at 8000 IU/d, tapering to 2000 IU/d over 3 mo. Nephrolithiasis was diagnosed after 3 mo of vitamin D treatment. Laboratory testing revealed a high serum calcium, low parathyroid hormone (PTH), high 25-hydroxyvitamin D [25(OH)D] and high 1,25 dihydroxyvitamin D [1,25(OH)2D]. Further investigation demonstrated low serum 24,25 dihydroxyvitamin D [24,25(OH)2D] and a very high ratio of 25(OH)D to 24,25(OH)2D, leading to the consideration of loss of function mutation in cytochrome P450 (CYP)24A1, a key enzyme involved in the degradation of 25(OH)D and 1,25(OH)2D into inactive metabolites. This leads to the persistence of high levels of bioactive vitamin D metabolites, increasing the risk for development of intoxication with vitamin D supplementation. Vitamin D supplementation can precipitate hypercalcemia and nephrolithiasis in individuals with altered vitamin D catabolism. This highlights the importance of monitoring serum calcium levels in patients who are being supplemented with vitamin D.