As rightly said even though 1,25-Dihydroxy vitamin D is the most potent vitamin D metabolite, levels of the 25-OH forms of vitamin D more accurately reflect the body's vitamin D stores. Consequently, 25HDN / 25-Hydroxyvitamin D2 and D3, in serum are the preferred initial test for assessing vitamin D status.
However being a biologically active form, 1,25 (OH)2 Vitamin D stimulates calcium absorption in the intestine and its production is tightly regulated through concentrations of serum calcium, phosphorus, and parathyroid hormone.
But in the presence of renal disease, 1,25-dihydroxy vitamin D levels may be needed to adequately assess vitamin D status. The metabolite is checked for monitoring vitamin D therapy in patients with chronic kidney disease, who may have normal 25(OH)D levels. As kidney disease progresses, the ability of the kidney to produce 1,25(OH)2D decreases; supplementation with vitamin D is thus no longer effective, and patients require administration of 1,25(OH)2D.
Below is the list of conditions when decreased level of 1, 25 (OH)2 Vitamin D is seen:
1) CKD – due to impaired production of 1 alpha hydroxylase production …the test can be indicative of early kidney failure
2) Heritable disorders like D dependent rickets type by mutation in 1 alpha hydroxylase.
3) Tumor induced osteomalacia due to tumor secreted FGF23 inhibits enzyme 1 alpha hydroxylase.
4) Use of HIV protease inhibitors
5) Severe low vitamin D levels in body since the precursor is not available for conversion to 1,25 (OH)2 Vitamin D.
Furthermore, 1,25(OH)2D may even be elevated in people with secondary hyperparathyroidism because PTH enhances the conversion of 25(OH)D to 1,25(OH)2D. 1,25(OH)2D measurement is reserved for distinguishing some cases of primary hyperparathyroidism from hypocalcaemia of cancer and for the differential diagnosis of vitamin D-dependent rickets (type I vs type II).
Below is the list of conditions when increased level of 1, 25 (OH)2 Vitamin D is seen:
1. Result from extrarenal 1 alpha hydroxylation or hereditary Vitamin D resistant
2. Increased in granulomatosis diseases – due to 1 alpha hydroxylase enzyme activity from macrophages as extra renal source since this is not regulated as normal physiologic condition.
a. Lymphoproliferative disorders
Although 1,25(OH)2D may be increased or decreased in a number of other disorders too, levels are typically used for confirmation rather than diagnosis of these conditions as per table below.