Clinical Information

Vitamin D is a generic designation for a group of fat-soluble, structurally similar sterols, which act as hormones. This test is the preferred initial test for assessing vitamin D status and most accurately reflects the body's vitamin D stores.

In the presence of renal disease, testing 1,25-dihydroxyvitamin D (DHVD) levels might be needed to adequately assess vitamin D status. DHVD testing alone may not clearly indicate deficiencies of vitamin D stores.

Vitamin D compounds in the body are exogenously derived by dietary means; from plants as 25-hydroxyvitamin D2 (ergocalciferol or calciferol) or from animal products as 25-hydroxyvitamin D3 (cholecalciferol or calcidiol). Vitamin D may also be endogenously derived by conversion of 7-dihydrocholesterol to 25-hydroxyvitamin D3 in the skin upon ultraviolet exposure.

25HDN is subsequently formed by hydroxylation (CYP2R1) in the liver. 25HDN is a prohormone that represents the main reservoir and transport form of vitamin D, being stored in adipose tissue and tightly bound by a transport protein while in circulation. Biological activity is expressed in the form of DHVD, the active metabolite of 25HDN. 1-Alpha-hydroxylation (CYP27B1) occurs on demand, primarily in the kidneys, under the control of parathyroid hormone (PTH) before expressing biological activity. Like other steroid hormones, DHVD binds to a nuclear receptor, influencing gene transcription patterns in target organs.

25HDN may also be converted into the inactive metabolite 24,25-dihydroxyvitamin D (24,25D) by (CYP24A1) hydroxylation. This process, regulated by PTH, might increase DHVD synthesis at the expense of the alternative hydroxylation (CYP24A1) product 24,25D. Inactivation of 25HDN and DHVD by CYP24A1 is a crucial process that prevents over production of DHVD and resultant vitamin D toxicity.

Based on these considerations circulating 25HDN is the best indicator of optimal vitamin D body stores. The exact levels of optimal circulating 25HDN concentrations remain a matter of debate. Mild-to-modest deficiency can be associated with osteoporosis or secondary hyperparathyroidism. Severe deficiency may lead to failure to mineralize newly formed osteoid in bone, resulting in rickets in children and osteomalacia in adults. The consequences of vitamin D deficiency on organs other than bone are not fully known, but might include increased susceptibility to infections, muscular discomfort, and an increased risk of colon, breast, and prostate cancer.

Modest 25HDN deficiency is common; in institutionalized elderly, its prevalence may be greater than 50%. Although much less common, severe deficiency is not rare either. Reasons for suboptimal 25HDN levels include lack of sunshine exposure, a particular problem in Northern latitudes during winter; inadequate intake; malabsorption (eg, due to celiac disease); depressed hepatic vitamin D 25-hydroxylase activity, secondary to advanced liver disease; and enzyme-inducing drugs, in particular many antiepileptic drugs, including phenytoin, phenobarbital, and carbamazepine, which increase 25HDN metabolism.