Abstract
In early 2000's vitamin-D deficiency was shown to be prevalent in several countries including the United States (US). Studies exploring the role of vitamin-D metabolism in diverse disease pathways generated an increased demand for vitamin-D supplementation and an immense public interest in measurement of vitamin-D metabolite levels. In this report, we review the role of vitamin-D metabolism in disease processes, clinical utility of measuring vitamin-D metabolites including 25-hydroxyvitamin-D (25(OH)D), 1,25-dihydroxyvitamin-D and 24,25-dihydroxyvitamin-D and discuss vitamin-D assay methodologies including immunoassays and liquid chromatography mass spectrometry (LC-MS/MS) assays. We also provide examples of vitamin-D toxicity and insight into the trends in serum 25(OH)D levels in the US population based on 10 years of data from on serum 25(OH)D values from ~5,000,000 patients who were tested at the Mayo Medical Laboratories between February 2007–February 2017.
Highlights
Vitamin-D and parathyroid hormone (PTH) are the principle regulators of calcium homeostasis in all tetrapods and play an important role in bone metabolism (Lips and van Schoor, 2011; Pettifor and Prentice, 2011; Rizzoli, 2014)
It binds to a nuclear receptor (Vitamin-D receptor, VDR) that dimerizes with the retinoid X receptor (RxR) before binding to gene regulatory DNA elements
The frequency of measurements of 25(OH)D in the healthy population has significantly increased due to an increased awareness of vitamin-D deficiency and its potential association with many diseases beyond its role in maintaining bone health
Summary
In 2015, we reported a pediatric case of vitamin-D intoxication with vitamin-D3 supplements (Ketha et al, 2015). Routine chemistry blood panel revealed total calcium levels of 18.7 mg/dL indicating severe hypercalcemia. During the discussion with the mother it was discovered, that in the last two months the infant was receiving daily dosage of oral vitamin-D3 supplementation that was greater than the manufacturer's recommendation. It was estimated that the baby was receiving ~50,000 IU of vitamin-D per day while recommended dose on the label was 2,000 IU. Vitamin-D metabolites were tested in the infant's blood and were as follows: 25(OH)D3, 293 ng/mL (optimal range of total 25(OH)D:20–50 ng/mL); 1,25(OH)2D3, 138–111 pg/mL (optimal range: 24–86 pg/mL); ratio of 24,25(OH)2D3 to 25(OH)D3 was 0.11–0.14 (normal range: 0.07–0.18) and suggesting normal Cyp24A1 function. Baby was treated with fluids and calcitonin to reverse hypercalcemia and lower vitamin-D levels and both biomarkers reached the normal levels within 3 months
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