- Other names: 25-hydroxy D2; 25-hydroxy D3; 5-hydroxy vitamin D; 25-hydroxycholecalciferol; 25-hydroxyergocalciferol; 25-OH vitamin D; calcidiol.
Definition
- A steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus and in the mineralization of bone. The term "vitamin D " � specifically refers to two biologically inert precursors, vitamin D3 (cholecalciferol) or D2 (ergocalciferol). Neither vitamin D3 nor vitamin D2 has significant biologic activity; rather they must be metabolized within the body to the hormonally active form. Vitamin D3 is generated in the skin when light energy is absorbed (UV radiation in the UVB spectrum 290 " �320 nm) by a precursor molecule 7-dehydrocholesterol (7-DHC; provitamin D3). However, cutaneous vitamin D3 production after single prolonged UVB exposure is capped at approximately 10 " �20% of the original epidermal 7-DHC concentration, a limit achieved with suberythemogenic UV exposures. Vitamin D2 is plant derived, produced exogenously by irradiation of ergosterol, and enters the circulation through diet. Vitamin D3 from the skin and vitamin D3 and D2 from the diet enter the blood and are metabolized to their 25-hydroxy counterparts. Once formed, 25-hydroxyvitamin D (25-OHD) is metabolized in the kidney to 1,25-dihydroxyvitamin D (1,25-OHD).
- Normal range: see Table 16.84.
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TABLE 16 " �84Normal Ranges of 25-OH Vitamin DView LargeTABLE 16 " �84Normal Ranges of 25-OH Vitamin D Vitamin D Status 25-OH Vitamin D (ng/mL) Deficiency <10 Insufficiency 10 " �30 Sufficiency 30 " �100 Toxicity >100
Use
- Diagnosis of vitamin D deficiency
- Differential diagnosis of causes of rickets and osteomalacia
- Monitoring vitamin D replacement therapy
- Diagnosis of hypervitaminosis D
Interpretation
Increased In
- Vitamin D intoxication
- Excessive exposure to sunlight
Decreased In
- Malabsorption
- Steatorrhea
- Dietary osteomalacia, anticonvulsant osteomalacia
- Biliary and portal cirrhosis
- Thyrotoxicosis
- Pancreatic insufficiency
- Celiac disease
- Inflammatory bowel disease
- Rickets
- Alzheimer disease
Limitations
- More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells and that this hormone has biologic effects extending beyond the control of mineral metabolism.
- Vitamin D deficiency is not clear. Levels needed to prevent rickets and osteomalacia (15 ng/mL) are lower than those that dramatically suppress parathyroid hormone levels (20 " �30 ng/mL). In turn, those levels are lower than levels needed to optimize intestinal calcium absorption (34 ng/mL). Neuromuscular peak performance is associated with levels approximately 38 ng/mL. A recent study states that increasing mean baseline levels from 29 to 38 ng/mL was associated with a 50% lower risk for colon cancer and levels of 52 ng/mL with a 50% reduction in the incidence of breast cancer.
- Various methods for measuring circulating concentrations 25-OHD are available. Current methods include RIA, CIA, HPLC, and LCMS/MS tandem mass spectrometry. Immunoassays measure total 25-OHD, which includes levels of both 25-OHD2 and 25-OHD3. The antibodies cross-react 100% with both D2 and D3 to give the total 25-OHD. Some commercial laboratories use LCMS/MS technology and report 25-OHD2 and 25-OHD3 separately and add both values to get the total 25-OHD. The studies report reasonable correlations between methods, but with significant differences, the reasons for which are not well understood. There could be many reasons for these variations, including drifts in the reagents being manufactured, and there is an urgent need for harmonization and standardization.
- The reference ranges discussed in the preceding are related to total 25-OHD; as long as the combined total is 30 ng/mL or more, the patient has sufficient vitamin D. The Institute of Medicine 3, 4 and the Endocrine Society 5 announced that levels <20 ng/mL (50 nmol/L) are considered deficient, which is lower than in previous guidelines. Given the absence of assay standardization and lack of consensus regarding clinical cutoff values, vitamin D levels must be interpreted within the clinical context of each patient and one should not rely solely on cutoff values based on so-called normal values.