Case reportHypercalcemia, nephrolithiasis, and hypervitaminosis D precipitated by supplementation in a susceptible individual
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.
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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.
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2021, Clinics in DermatologyCitation Excerpt :Vitamin D oversupplementation may lead to some adverse effects. Vitamin D intoxication may present with nonspecific symptoms such as nausea, vomiting, constipation, weight loss, and weakness, resulting in severe hypercalcemia, nephrolithiasis hypercalciuria, cardiac arrhythmia, and neurologic manifestations.52 The major source of vitamin D is the exposure of the epidermis to solar irradiation, and patients with intensive sun exposure, which provides sufficient vitamin D stores, also have an increased risk of skin cancer.49
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2021, NutritionCitation Excerpt :There are few cases report descriptions of the acute renal crisis after 25(OH)D. Some of them have genetic alterations of critical enzymes in the vitamin D metabolism, such as loss of function mutation in cytochrome P450 (CYP)24 A1 [3]. However, most trials have shown the safety of 25(OH)D supplementation in renal stone formers [4].
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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.