Misconception About The Cause Of Vitamin D Toxicity - PMC - NCBI

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• Journal List
• CMAJ
• v.191(27); 2019 Jul 8
• PMC6739063

As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice CMAJ. 2019 Jul 8; 191(27): E769. doi: 10.1503/cmaj.72511PMCID: PMC6739063PMID: 31285383Misconception about the cause of vitamin D toxicityNipith Charoenngam, MDPostdoctoral research fellow, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass.Arash Hossein-Nezhad, MD PhDResearch assistant professor, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass.David A. Hanley, MDProfessor emeritus, Departments of Medicine, Community Health Sciences, and Oncology, Cumming School of Medicine, The University of Calgary, Calgary, Alta.Michael F. Holick, MD PhDProfessor, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass. Copyright and License information PMC DisclaimerCopyright © 2019 Joule Inc. or its licensorsSee the letter "Use of vitamin D drops leading to kidney failure in a 54-year-old man" on page E390.See the letter "The authors respond to “Misconception about the cause of vitamin D toxicity”" in volume 191 on page E770.

In the case reported by Auguste and colleagues, 1 we believe that the patient experienced vitamin D intoxication because of an underlying pathologic condition that the authors failed to recognize.

The authors incorrectly concluded that a dose of 8000–12 000 IU daily can result in vitamin D intoxication. Vitamin D toxicity generally occurs when the level of 25-hydroxyvitamin D is greater than 375 nmol/L (150 ng/mL).2 This patient had a 25-hydroxyvitamin D level of 241 nmol/L (96 ng/mL). This concentration is considered to be within the normal limit (30–100 ng/mL) according to the Endocrine Society’s clinical practice guideline.3 Daily ingestion of 10 000 IU of vitamin D3 raising blood levels of 25-hydroxyvitamin D above 100 ng/mL was not associated with hypercalcemia, as reported in a review.2 Population studies have also reported that doses of up to 20 000 IU daily were not associated with toxicity.2

Levels of 1,25-dihydroxyvitamin D3 are not increased in patients with vitamin D intoxication with hypercalcemia, because of the suppression of parathyroid hormone reducing renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.2,3 The high levels of 1,25-dihydroxyvitamin D3, and the fact that the authors observed that treatment with hydroxychloroquine resulted in a rapid decline in circulating levels of 1,25-dihydroxyvitamin D3, should have alerted the authors that the likely explanation was the unregulated extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. The renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) is not sensitive to hydroxychloroquine, ketoconazole or glucocorticoids as suggested by the authors. Only the extrarenal CYP27B1 is sensitive to these medications.4

The authors made a modest effort with imaging studies to rule out granulomatous disorders. However, they did not appreciate the patient’s previous history of urothelial carcinoma, which has been reported to be associated with vitamin D toxicity associated with unregulated extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. This was the likely cause of the patient’s vitamin D intoxication and renal failure, not the dosage of vitamin D.5

Footnotes

Competing interests: Michael Holick is a consultant for Quest Diagnostics Inc. and Ontometrics Inc., and is on the Speaker’s Bureau for Abbott Inc. David Hanley has received research funding from the Pure North S’Energy Foundation. No other competing interests were declared.

References

1. Auguste BL, Avila-Casado C, Bargman JM. Use of vitamin D drops leading to kidney failure in a 54-year-old man. CMAJ 2019;191:E390. [PMC free article] [PubMed] [Google Scholar]2. Holick MF. Vitamin D is not as toxic as was once thought: a historical and an up-to-date perspective. Mayo Clin Proc 2015;90:561–4. [PubMed] [Google Scholar]3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96: 1911–30. [PubMed] [Google Scholar]4. Adams JS, Hewison M. Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 2012;523:95–102. [PMC free article] [PubMed] [Google Scholar]5. Asao K, McHugh JB, Miller DC, et al. Hypercalcemia in upper urinary tract urothelial carcinoma: a case report and literature review. Case Rep Endocrinol 2013;2013:470890. [PMC free article] [PubMed] [Google Scholar]Articles from CMAJ : Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

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