Abstract
We now have the ability to measure a number of different vitamin D metabolites with very accurate methods. The most abundant vitamin D metabolite, 25-hydroxyvitamin D, is currently the best marker for overall vitamin D status and is therefore most commonly measured in clinical medicine. The added value of measuring metabolites beyond 25-hydroxyvitamin D, like 1,25-, and 24,25-dihydroxyvitamin D is not broadly appreciated. Yet, in some more complicated cases, these metabolites may provide just the information needed for a legitimate diagnosis. The problem at present, is knowing when to measure, what to measure and how to measure. For 25-hydroxyvitamin D, the most frequently used automated immunoassays do not meet the requirements of today’s standards for certain patient groups and liquid chromatography-tandem mass spectrometry is the desired method of choice in these individuals. The less frequently measured 1,25-dihydroxyvitamin D metabolite enables us to identify a number of conditions, including 1α-hydroxylase deficiency, hereditary vitamin D-resistant rickets and a number of granulomatous diseases or lymphoproliferative diseases accompanied by hypercalcaemia. Furthermore, it discriminates between the FGF23-mediated and non-FGF23-mediated hypophosphatemic syndromes. The 24,25-dihydroxyvitamin D metabolite has proven its value in the diagnosis of idiopathic infantile hypercalcaemia and has the potential of having value in identifying other diseases. For both metabolites, the understanding of the origin of differences between assays is limited and requires further attention. Nonetheless, in every way, appropriate measurement of vitamin D metabolism in the clinical laboratory hinges eminently on the comprehension of the value of the different metabolites, and the importance of the choice of method.
Highlights
With the ever-growing family of measurable vitamin D metabolites and techniques to assess them, comes a predicament
Indications where measurement of 1,25(OH)2 D may contribute to diagnosis or aid in monitoring treatment include conditions where production of 1,25(OH)2 D is heavily disturbed, resulting in either a shortage of 1,25(OH)2 D, such as in 1α-hydroxylase deficiency, or an overabundance of 1,25(OH)2 D, such as in hereditary vitamin D-resistant rickets, sarcoidosis, tuberculosis, rheumatoid arthritis, inflammatory bowel disease and lymphoproliferative diseases. 1,25(OH)2 D helps to identify the hypophosphatemic syndromes mediated by Fibroblast growth factor 23 (FGF23), including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), ARHR and tumour induced osteomalacia (TIO)
Measuring 24,25(OH)2 D enables identification of CYP24A1 mutations leading to impaired catabolism of the hormone and associated hypercalcaemia, such as in infantile hypercalcaemia (IIH)
Summary
With the ever-growing family of measurable vitamin D metabolites and techniques to assess them, comes a predicament. How does a clinician decide when measurement of vitamin D metabolism benefits the diagnostic process? What metabolic product of vitamin D provides the necessary answers, and how best to measure it? The choice of method is discussed, as this is an important aspect of appropriate vitamin D metabolism measurement. Knowledge of the processes and the stimulatory and inhibitory factors involved in this ingenious metabolic pathway is a prerequisite for understanding the benefits and relevance of measuring the different metabolites. As not all available methods are suitable for every situation, knowing the flaws and pitfalls of the various measurement procedures is important to prevent a misdiagnosis or missed diagnosis.
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