Clinical Information

Vitamin D is a generic designation for a group of fat-soluble, structurally similar steroids which act as hormones. Vitamin D is obtained through dietary intake as ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) and is also synthesized in the skin following ultraviolet light exposure. Both forms are converted in the liver by CYP2R1 to 25-hydroxyvitamin D (25HDN), the major circulating form and the best indicator of total body vitamin D stores.

The biologically active hormone, 1,25-dihydroxyvitamin D (DHVD), is produced primarily in the kidneys by 1alpha-hydroxylation of 25HDN through CYP27B1. Renal production is tightly regulated by parathyroid hormone (PTH), serum calcium and phosphate concentrations, and fibroblast growth factor-23. DHVD promotes intestinal calcium and phosphate absorption, as well as renal calcium and phosphate reabsorption resulting in a net positive calcium balance that supports skeletal mineralization and suppresses PTH synthesis. In addition to its effects on calcium and bone metabolism, DHVD regulates the expression of a multitude of genes in many other tissues including immune cells, muscle, vasculature, and reproductive organs.

Measurement of 25-hydroxyvitamin D is the preferred laboratory test for assessment of vitamin D status because it most accurately reflects total body vitamin D stores. Measurement of DVHD should be reserved for selected clinical situations involving disorders of calcium metabolism, chronic kidney disease, hereditary disorders of vitamin D metabolism, granulomatous disease, lymphoma, or unexplained hypercalcemia. DVHD levels are decreased in hypoparathyroidism and in chronic renal failure. DHVD levels may be high in primary hyperparathyroidism and in physiologic hyperparathyroidism secondary to low calcium or vitamin D intake or absorption. Some patients with granulomatous diseases (eg, sarcoidosis) and malignancies containing nonregulated 1-alpha hydroxylase in the lesion might have hypercalcemia that appears vitamin D mediated with normal or high serum phosphate (hyperphosphatemia) and hypercalcemia (both of which might be severe) in addition to low PTH and absent parathyroid hormone-related peptide (PTHRP). Assessment of 24,25-dihydroxyvitamin D might also be required in patients with hypercalcemia that does not appear to be driven by PTH or PTHRP and may be helpful in assessment of patients with loss of function inactivating CYP24A1 mutations.