1,25(OH)2D Reference Ranges
Measurement of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] is done by radioimmunoassay (RIA). 1,25(OH)2D lab reference ranges are determined by statistical analysis of the people who have had 1,25(OH)2D measured. The "normal" range is where 95% of the people measured fall.
However, the current standard advises measurement of 1,25(OH)2D only in patients with, or suspected of, serious medical conditions such as hypercalcemia, renal failure, sarcoidosis, lymphoma, abnormalities of 1-alphahydroxylase, hyphophosphatic rickets, primary hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, renal osteodystrophy, vitamin D-resistant rickets or vitamin D receptor defects. This population cannot be considered normal. Thus, lab ranges do not provide an accurate assessment of a normal level of 1,25(OH)2D.
Statistics on 1,25(OH)2D in a normal population are very limited. The best data comes from a 1999 cross-sectional study of the influence of smoking on serum parathyroid hormone (PTH), serum vitamin D metabolites, serum ionized calcium, serum phosphate, and biochemical markers of bone turnover. In this study, serum 1,25(OH)2D was measured, via radioimmunoassay, in a cohort of 510 healthy Danish women aged 45 to 58 years. The average 1,25(OH)2D level of the non-smokers in this group was 29.0 pg/mL (plus or minus 9.5 pg/mL) for a range of 19.5 - 38.5 pg/mL in this healthy population. [1]
Furthermore, when measured coincidentally, the significance of elevated 1,25(OH)2D may be overlooked. For example, a 2011 study of the effect of vitamin D and calcium supplementation on patients with multiple sclerosis, revealed elevated 1,25(OH)2D at baseline and one year later (61 pg/mL � 22.6 pg/mL and 70.7 pg/mL � 18 pg/mL respectively). [2] All of these 1,25(OH)2D levels were considered normal. Calcium, phosphorus and parathyroid hormone were not measured in those whose 1,25(OH)2D exceeded the normal range.
The Merck Manual of Diagnosis and Therapy (15 Oct 2006 online) listed the range of serum 1,25(OH)2D in healthy persons as 20-45 pg/mL. The 2013 edition lists the normal range as 25-65 pg/mL. The Mayo Clinic lists 18 - 78 pg/mL as the normal range. It's disappointing to note that on March 16, 2015 Labcorp is raising their normal range of 1,25(OH)2D from 10 - 75 pg/mL to 19.9 - 79.3 pg/mL.
As the incidence of chronic illness increases and serum 1,25(OH)2D levels rise, authorities simply increase the range of 1,25(OH)2D that is considered normal. This signifies a failure to recognize elevated 1,25(OH)2D as a sign of dysregulated vitamin D metabolism and a marker of a chronic inflammatory disease process. Studies need to be done to determine the serum level of 1,25(OH))2D in healthy populations. Using reference ranges that truly represent normal will promote accurate diagnosis of vitamin D endocrine dysfunction.
References
- Brot C, Jorgensen NR, Sorensen OH The influence of smoking on vitamin D status and calcium metabolism. Eur J Clin Nutr. 1999;53:920-6.
- Kimball S, Vieth R, Dosch HM, et al. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Metab. Sep 2011(96(9)):2826-34.
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