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

ABSTRACT Context Vitamin D supplementation is common amongst the general public. While generally considered safe, vitamin D supplement-induced toxicity has been reported, often in association with manufacturing or labelling errors. In addition, selected patient populations may have a hypersensitivity to vitamin D supplementation leading to consequences due to supraphysiological serum 25-hydroxyvitamin D levels. Case Description A 58-year-old woman developed hypercalcemia and its sequelae while on supplementation with vitamin D. Despite being vitamin D replete, a functional medicine practitioner prescribed Vitamin D starting at 8000 IU/day, tapering to 2000 IU/day over 3 months. Nephrolithiasis was diagnosed after three months of Vitamin D treatment. Laboratory testing revealed a high serum calcium, low parathyroid hormone (PTH), high 25-hydroxyvitamin D [25(OH)D], 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 CYP24A1, 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. Conclusion 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.