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

Keerthana Haridas, Michael F. Holick, Lynn A. Burmeister

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article number110754
StatePublished - Jun 2020

Bibliographical note

Funding Information:
KH's clerkship at the University of Minnesota was supported by St John's Medical College, affiliated to the Rajiv Gandhi University of Health Sciences, Bangalore, India. MH reports the following potentially competing interests: consultant for Quest Diagnostics Inc, speakers bureau for Abbott. LB and KH have no conflicts of interest to declare.

Publisher Copyright:
© 2020 Elsevier Inc.


  • 1,25 dihydroxyvitamin D
  • 24,25 dihydroxyvitamin D
  • 25 hydroxyvitamin D
  • CYP24A1
  • Hypercalcemia
  • Nephrolithiasis
  • Vitamin D

PubMed: MeSH publication types

  • Case Reports
  • Journal Article


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