Elsevier

Nutrition

Volume 74, June 2020, 110754
Nutrition

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

https://doi.org/10.1016/j.nut.2020.110754Get rights and content

Highlights

  • Hypercalcemia and nephrolithiasis precipitated by vitamin D supplementation may occur with increased susceptibility in the setting of altered vitamin D catabolism involving CYP24A enzyme.

  • Serum calcium should be monitored in patients who are being supplemented with vitamin D.

Abstract

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.

Introduction

Vitamin D supplementation is common and generally regarded as safe [1,2]. Here, we report on a patient who developed hypercalcemia with nephrolithiasis in association with supplemental vitamin D intake. Further analysis suggested that the patient harbored a 25-hydroxyvitamin D-24-hydroxylase (cytochrome P450 [CYP]24A1) mutation, an enzyme responsible for inactivating 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D(1,25[OH]2D) by oxidizing the side chain to form water-soluble C23 carboxylic acid metabolites. This enzyme mutation can result in sustained or elevated serum levels of 25(OH)D and 1,25(OH)2D that can result in hypercalcemia, hyperphosphatemia, and nephrolithiasis in patients receiving vitamin D supplementation.

Section snippets

Case description

A previously healthy 58-y-old woman presented in May 2018 for recent discovery of nephrolithiasis and hypercalcemia. There was no personal or family history of similar complaints. A flulike episode in December 2017 prompted a functional medicine consultation and the initiation of various supplements, including vitamin D. Laboratory investigations before starting the supplemental vitamin D documented normal levels of calcium (9.9 mg/dL; normal 8.6–10.4) and 25(OH)D (34 ng/mL; normal 30–100).

Discussion

We described a patient who developed hypervitaminosis D, hypercalcemia, and kidney stones within a few months of starting vitamin D supplementation. The estimated vitamin D dose was 8000 IU/d at its peak but had been tapered to 2000 IU/d before presentation. A discrepancy was demonstrated between the label-reported dose and the measured content of vitamin D by high performance liquid chromatography (HPLC), with the HPLC-measured dose 30% lower than reported on the label. 24,25(OH)₂D was lower

Conclusion

This case demonstrates the effects of vitamin D supplementation in a patient harboring a vitamin D catabolic defect, leading to increased risk for hypervitaminosis D, hypercalcemia, and nephrolithiasis. Thus, high doses of vitamin D may not always be safe.

References (18)

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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.

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