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25-hydroxyvitamin D2/D3 (calcidiol/calcifediol) in serum

Indications: - evaluation of vitamin D deficiency - evaluation of hypervitaminosis D - inflammatory bowel disease (IBD) - low serum 25-OH vitamin D is common & associated with higher morbidity & disease severity in patients with IBD [21] Normal range: - 14-60 ng/mL (35-150 nmol/L); 75-185 nmol/L [18] - considerable variability across different assays (as much as 10 ng/mL) [9] - levels >= 20 ng/mL appear to be adequate [10,22]* - levels >= 24.4 ng/mL associated with lowest rates of hip fracture & nonvertebral fractures [17] - levels 30-40 ng/mL deemed adequate for bone health [1] - serum levels lower in blacks than in whites [14] - 15.6 +/- 0.2 ng/mL vs 25.8 +/- 0.4 ng/mL * Institute of Medicine recommendations [22] Clinical significance: - circulating levels of 25-hydroxyvitamin D3 provide the best overall assessment of vitamin D status - higher levels are associated with lower risk of skin cancer (non-melanoma) in elderly men - higher levels are associated with diminished risk of colon cancer [5,27] - higher levels associated with diminished risk for any cancer (RR=0.8 for highest vs lowest quartile) [26] - low levels associated with cognitive impairment in the elderly [6] - low serum 25-OH vitamin D is associated with an increase in all cause mortality [10,13,28] - low free serum 25-OH vitamin D is the best predictor of mortality [28] - compared with the highest quintile of serum 25-OH vitamin D, the lowest quintile was associated with increased risk for - all-cause mortality (RR=1.57) - cardiovascular mortality (RR=1.41-1.65) [19] - low serum 25-OH vitamin D may be a marker of poor health rather than a cause of premature mortality [19] - women with serum 25-hydroxyvitamin D levels < 12 ng/mL with 43% higher risk of multiple sclerosis within 9 years than those with levels > 20 ng/mL [25] Specimen: 1) serum or plasma (heparin) 2) stable at room temp for 72 hours 3) store frozen; stable indefinitely at -20 degrees C Method: 1) HPLC*, RIA 2) RIA measures both 25-OH vit-D2 & 25-OH vit-D3 3) substantial variation in results by RIA methods [2] * 'gold standard' [2] Increases: 1) sunlight, tanning booths [18] 2) pharmaceutical agents: -> in vivo effects - etidronate (oral) - estrogen-containing contraceptive (20%) [24] 3) clinical disorders a) vitamin D intoxication b) excessive exposure to light c) frailty [7] d) hypercalcemia associated with lymphoma Decreases: 1) pharmaceutical agents -> in vivo effects -> aluminum hydroxide, carbamazepine, phenytoin, phenobarbital, primidone, cholestyramine, colestipol, etidronate (IV), glucocorticoids, isoniazid, mineral oil, rifampin 2) clinical disorders a) vitamin D deficiency b) malabsorption - steatorrhea - pancreatic insufficiency - celiac disease - inflammatory bowel disease - gastric bypass - bowel resection c) osteomalacia d) biliary cirrhosis & portal cirrhosis e) renal osteodystrophy (some cases) f) osteitis fibrosa cystica g) thyrotoxicosis h) rickets i) hypoparathyroidism (< 3 ng/mL, < 7.5 nmol/L) j) pseudohypoparathyroidsm k) primary hyperparathyroidism (2-11 mg/mL, 6-28 nmol/L) l) chronic renal failure (0.5-1.5 ng/mL, 1-4 nmol/L) m) frailty [7] n) hypercalcemia of malignancy (except lymphoma) o) diabetes mellitus type 2 [20] 3) suboptimal 25-OH vitamin D levels associated with increased mortality [3] 4) low 25-OH vitamin D levels may be a marker of poor health [15] * Plasma levels decrease with age & pregnancy & vary with the extent sunlight exposure. Notes: - easier to measure than calcitriol - cost is about $200 in 2008

Related

25-hydroxyvitamin D2; 25-hydroxyergocalciferol; ercalcidiol; 25-hydroxycalciferol calcifediol; 25-OH cholcalciferol; 25-OH vitamin D3 (Calderol)

Specific

25-hydroxyvitamin D2 (calcidiol) in serum 25-hydroxyvitamin D3 (calcifediol) in serum

General

special chemistry test

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
  2. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, DeLuca HF, Drezner MK. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab. 2004 Jul;89(7):3152-7. PMID: 15240586 - Hollis BW. Editorial: The determination of circulating 25-hydroxyvitamin D: no easy task. J Clin Endocrinol Metab. 2004 Jul;89(7):3149-51. No abstract available. PMID: 15240585
  3. Dobnig H et al, Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008 Jun 23; 168:1340. PMID: 18574092
  4. Tang JY et al Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Cancer Causes Control 2009 Nov 18 PMID: 19921445 http://dx.doi.org/10.1007/s10552-009-9470-4
  5. Jenab M et al Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: A nested case-control study. BMJ 2010 Jan 21; 340:b5500 PMID: 20093284 http://dx.doi.org/10.1136/bmj.b5500
  6. Buell JS et al. 25-hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010 Jan 5; 74:18. PMID: 19940273 - Slinin Y et al. 25-hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010 Jan 5; 74:33. PMID: 19940271 - Balion C et al. Vitamin D, cognition, and dementia: A systematic review and meta-analysis. Neurology 2012 Sep 25; 79:1397 PMID: 23008220
  7. Ensrud KE et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab 2010 Dec; 95:5266. PMID: 21131545
  8. Interpretation of Diagnostic tests, 8th edition, Wallach J, Lippincott, Williams & Wilkens, Philadelphia, 2007
  9. Barake M et al. 25-hydroxyvitamin D assay variations and impact on clinical decision making. J Clin Endocrinol Metab 2012 Mar; 97:835 PMID: 22238386
  10. de Boer IH et al. Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: A cohort study. Ann Intern Med 2012 May 1; 156:627. PMID: 22547472
  11. Vitamin D 25 OH Laboratory Test Directory ARUP: 80379
  12. Panel of 3 tests Laboratory Test Directory ARUP: 2002348
  13. Dobnig H et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008 Jun 23; 168:1340. PMID: 18574092
  14. Powe CE et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013 Nov 21; 369:1991 PMID: 24256378 http://www.nejm.org/doi/full/10.1056/NEJMoa1306357
  15. Autier P et al Vitamin D status and ill health: a systematic review. The Lancet Diabetes & Endocrinology. December 6, 2013 PMID: 24622671 http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70165-7/abstract - The Lancet Diabetes & Endocrinology Vitamin D: chasing a myth? The Lancet Diabetes & Endocrinology. December 6, 2013 PMID: 24622652 http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70164-5/fulltext
  16. Cauley JA et al Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures. Ann Intern Med. 2008 Aug 19;149(4):242-50 PMID: 18711154
  17. Bischoff-Ferrari HA, Willett WC, Orav EJ et al A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention N Engl J Med 2012; 367:40-49 PMID: 22762317 http://www.nejm.org/doi/full/10.1056/NEJMoa1109617 - Heaney RP Vitamin D - Baseline Status and Effective Dose N Engl J Med 2012; 367:77-78 PMID: 22762324 http://www.nejm.org/doi/full/10.1056/NEJMe1206858
  18. Frei B et al Enough Is Enough. Ann Intern Med. 2014;160(11):807 PMID: 24887621 http://annals.org/article.aspx?articleid=1877028
  19. Schottker B et al Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ 2014;348:g3656 PMID: 24938302 http://www.bmj.com/content/348/bmj.g3656
  20. Ye Z, Sharp SJ, Burgess S Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study. The Lancet Diabetes & Endocrinology, 1 October 2014 PMID: 25281353 http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2814%2970184-6/abstract
  21. Kabbani TA, Koutroubakis IE, Schoen RE et al Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study. Am J Gastroenterol. 2016 May;111(5):712-9. PMID: 26952579
  22. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  23. Sattar N, Welsh P, Panarelli M, Forouhi NG. Increasing requests for vitamin D measurement: costly, confusing, and without credibility. Lancet. 2012 Jan 14;379(9811):95-6. PMID: 22243814
  24. Harmon QE, Umbach DH, Baird DD Use of Estrogen-Containing Contraception Is Associated With Increased Concentrations of 25-Hydroxy Vitamin D. J Clin Endocrinol Metab 101: Aug, 2016 PMID: 27490916 http://press.endocrine.org/doi/pdf/10.1210/jc.2016-1658
  25. Munger KL, Hongell K, Aivo J et al 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. Sept 13, 2017 PMID: 28904091 http://www.neurology.org/content/early/2017/09/13/WNL.0000000000004489 - Marrie RA, Beck CA Preventing multiple sclerosis. To (take) vitamin D or not to (take) vitamin D? Neurology. Sept 13, 2017 PMID: 28904085 http://www.neurology.org/content/early/2017/09/13/WNL.0000000000004506
  26. Budhathoki S et al. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: Large case-cohort study within Japan Public Health Center- based Prospective Study cohort. BMJ 2018 Mar 7; 360:k671 PMID: 29514781 Free PMC Article
  27. McCullough ML, Zoltick ES, Weinstein SJ et al Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts. JNCI: Journal of the National Cancer Institute. June 14, 2018 PMID: 29912394 https://academic.oup.com/jnci/advance-article-abstract
  28. McCall B Low Free 25(OH)D Vitamin D Is Best Predictor of Mortality Medscape - Sep 21, 2020 https://www.medscape.com/viewarticle/937756