Clinical Pathology: General Principles, Lab Management, Clinical Chemistry

• Decreased serum levels of 1,25(OH)-vitamin D are seen in renal failure, hyperphosphatemia, hypomagnesemia, hypoparathyroidism, pseudohypoparathyroidism (PHP), vitamin Ddependent rickets (type I), and hypercalcemia of malignancy.

• Increased levels of 1,25(OH)-vitamin D are seen in granulomatous diseases (e.g., sarcoidosis), primary hyperparathyroidism, lymphoma, 1,25(OH)-vitamin D intoxication, and vitamin D–dependent rickets (type II).

• 25(OH)-vitamin D has a relatively long half-life (i.e., 2 weeks), is bound tightly to vitamin D–binding protein (VDBP), and is used to determine a patient’s vitamin D status. Renal production of 1,25(OH)-vitamin D is normally tightly regulated by parathyroid hormone (PTH), serum calcium and phosphate levels, and fibroblast growth factor 23(FGF23). 1,25(OH)-vitamin D has a relatively short half-life (0.5 day) and is bound less tightly to VDBP than 25(OH)-vitamin D. 1,25(OH)-vitamin D measurements are indicated only in certain cases, such as those mentioned above.

• 1,25(OH)-vitamin D can be measured in serum and plasma by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography–tandem mass spectrometry (LC-MS/MS).

• The mechanism producing elevated 1,25(OH)-vitamin D levels in sarcoidosis is increased conversion of 25(OH)-vitamin D to 1,25(OH)-vitamin D by extrarenal 1-α-hydroxylase, which is expressed in activated macrophages.

Holick M: Vitamin D Deficiency. N Engl J Med 2007;357(3):266–281.

Zhang JTW, Chan C, Kwun SY, et al: A case of severe 1,25-dihydroxyvitamin D-mediated hypercalcemia due to a granulomatous disorder. J Clin Endocrinol Metab 2012;97(8):2579–2583.

Adams J, Hewinson M: Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 2012;523:95–102.

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