Test #081091Aid in the diagnosis of primary hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, renal osteodystrophy, and vitamin D-resistant rickets.
Also Known As: 1,25(OH) Vitamin D, 1,25-Dihydroxy Vitamin D, 1,25-Dihydroxycholecalciferol, Vitamin D, 1,25-Dihydroxy
Preparation: No Fasting required.Test Type: BloodTest Results: 3-4 daysHumans get vitamin D from their normal diet, dietary supplements and from exposure to sunlight.1-5 Ultraviolet B irradiation of the skin drives the conversion of 7-dehydrocholesterol to previtamin D3, which is then rapidly converted to vitamin D3.1 Vitamin D from the skin and diet is further metabolized in the liver to 25-(OH) vitamin D (or calcidiol).1-5 Calcidiol is the principle circulating reservoir of vitamin D in plasma and is generally the best indicator of overall vitamin D status. Calcidiol is further converted by the enzyme 25-(OH) D-1?-hydroxylase (CYP27B1) in the proximal tubules of the kidney to the biologically active form of vitamin D, 1,25-(OH)2 vitamin D (or calcitriol).1-5 The renal production of calcitriol is tightly regulated by plasma parathyroid hormone (PTH)1-5 and fibroblast growth factor 23 (FGF-23). FGF-23 is a circulating hormone synthesized by osteocytes and osteoblasts.5-8 Calcitriol and phosphate intake stimulates the synthesis of FGF-23, which, in turn, suppresses calcitriol synthesis and activates calcitriol conversion to inactive metabolites.1-6 Calcitriol is a steroid-like hormone that binds to a specific cytoplasmic vitamin D receptor (VDR) in the cytoplasm of target cells. The calcitriol-VDR complex then migrates into the nucleus, where its effects are mediated at a transcriptional level.5 Renal production of calcitriol is important in the regulation of serum calcium homeostasis and in the maintenance of healthy bone.1,2,9-11 Calcitriol stimulates the absorption of calcium and phosphate by the intestine and increases calcium and phosphate resorption by the kidney.1-6,12,13 Calcitriol also suppresses PTH production and regulates osteoblast function and bone resorption.5 It has been suggested that calcitriol has roles beyond the calcium-skeletal axis.1-5,14Vitamin D deficiency can affect the production of calcitriol owing to the lack of substrate. A positive correlation between serum levels of calcidiol and calcitriol was observed during seasonal changes. Treatment with calcidiol can normalize calcitriol concentrations in patients with vitamin D deficiency.12,15,16Calcitriol assessment may be beneficial in patients with chronic kidney failure. Diminished levels of calcitriol can be seen in patients with kidney failure due to reduced 1?-hydroxylase activity and phosphate retention resulting in increased FGF-23 levels.17,18 Impaired calcitriol production plays a major role in the development of secondary hyperparathyroidism as calcitriol deficiency promotes parathyroid gland hyperplasia and increased parathyroid hormone (PTH) synthesis due to the loss of the ability to upregulate vitamin D receptor expression within parathyroid cells.19This ultimately results in elevated serum PTH and abnormal calcium and phosphorus balance.Calcitriol measurement may be of use in patients with early-onset rickets or a family history of rickets. Serum calcitriol levels can also be increased in patients with hereditary vitamin D-resistant rickets, a very rare autosomal recessive disorder in which mutations of vitamin D receptor (VDR) impair calcitriol binding to the VDR.20 Patients usually present with hypocalcemia, early-onset rickets, alopecia, and other ectodermal anomalies.20 Other heritable disorders associated with low calcitriol levels include vitamin D–dependent rickets type 1 (inactivating mutation in the 1-hydroxylase gene),21 autosomal-dominant hypophosphatemic rickets (mutation of the gene coding for FGF-23, which prevents its breakdown),22 and X-linked hypophosphatemic rickets (mutations that elevate levels of FGF-23).23 Individuals treated with glucocorticoids or anticonvulsants are at risk of hypocalcemia associated with a low concentration of calcitriol. HIV protease inhibitors have been reported to markedly suppress calcitriol synthesis24,25 In tumor-induced osteomalacia, tumor-secreted FGF-23 inhibits enzyme 1?-hydroxylase and subsequently results in decreased calcitriol synthesis.26Calcitriol may also be helpful in the diagnosis of parathyroid function disorders. A high serum level of calcitriol, for example, may suggest of primary hyperparathyroidism, whereas a normal or low serum level is more likely found in secondary hyperparathyroidism. Increased calcitriol levels can be seen in some individuals with lymphoproliferative disorders and granulomatous disease including, sarcoidosis, tuberculosis, and inflammatory bowel disease where increased macrophage activity is associated with extrarenal 1?-hydroxylase enzyme activity.27 However, unlike the kidney, the 1?-hydroxylase activity in the macrophages is not controlled by the usual physiologic regulators.14,28