Endocrine Abstracts (2009) 20 ME11

The relative value of 25(OH)D and 1,25(OH)2D measurements

Paul Lips

VU University Medical Center, Amsterdam, The Netherlands.

After synthesis in the skin or intake with the diet, vitamin D3 is hydroxylated in the liver to 25-hydroxyvitamin D (25(OH)D), and subsequently in the kidney to 1,25-dihydroxyvitamin D (1,25(OH)2D). The major vitamin D store is the circulating 25(OH)D. The serum 25(OH)D concentration is the measurement of choice to assess the vitamin D status. It is relatively stable and not directly influenced by hormones or calcium in the diet. The half life of serum 25(OH)D is around 25 days. Serum 25(OH)D should be assessed in patients suspected of vitamin D deficiency or insufficiency and patients with osteoporosis. The active metabolite, 1,25(OH)2D should be measured in case of disorders of 1α-hydroxylation of 25(OH)D, existing in renal failure, vitamin D dependent rickets type 1 and hypophosphatemic rickets where 1α-hydroxylase activity is decreased or absent, and vitamin D receptor defects as in vitamin D dependent rickets type 2 where 1α-hydroxylase activity is increased. Serum 1,25(OH)2D is under negative feedback control by serum calcium and phosphate. Its formation in the kidney is stimulated by parathyroid hormone (PTH). A high calcium diet or calcium supplements will decrease serum 1,25(OH)2D and immobilisation has similar effects. The half life of serum 1,25(OH)2D is around 8 h. While the renal hydroxylation of 25(OH)D is tightly regulated, the extrarenal hydroxylation in activated macrophages is not. Extrarenal formation of 1,25(OH)2D occurs in granulomatous diseases such as sarcoidosis, tuberculosis and inflammatory bowel disease, and lymphoproliferative diseases. In these disorders, serum 1,25(OH)2D may be elevated resulting in hypercalcemia and hypercalciuria. The measurement of serum 1,25(OH)2D in case of vitamin D deficiency is not very relevant. It usually stays within the normal reference range because the increase of serum PTH stimulates the renal hydroxylation of 25(OH)D. However, serum 1,25(OH)2D may fall to subnormal levels in case of severe vitamin D deficiency, where the synthesis of 1,25(OH)2D becomes substrate-dependent. When comparing groups of severely vitamin D deficient and replete patients, mean serum 1,25(OH)2D usually is lower in the former than in the latter group, but this is more important for research than for patient care. In conclusion, the measurement of serum 25(OH)D is important to assess vitamin D status and to exclude vitamin D deficiency or insufficiency. Serum 1,25(OH)2D should be measured in selected metabolic diseases associated with decreased or increased 1α-hydroxylase activity or vitamin D receptor defects.

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