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Test Code DHVD 1,25-Dihydroxyvitamin D, Serum

Reporting Name

1,25-Dihydroxyvitamin D, S

Useful For

As a second-order test in the assessment of vitamin D status, especially in patients with renal disease

 

Investigation of some patients with clinical evidence of vitamin D deficiency (eg, vitamin D-dependent rickets due to hereditary deficiency of renal 1-alpha hydroxylase or end-organ resistance to 1,25-dihydroxyvitamin D)

 

Differential diagnosis of hypercalcemia

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum


Advisory Information


The 25-hydroxyvitamin D test (25HDN / 25-Hydroxyvitamin D2 and D3, Serum) in serum the preferred initial test for assessing vitamin D status and most accurately reflects the body's vitamin D stores. In the presence of renal disease or hypercalcemia, testing of 1,25-dihydroxy vitamin D (DHVD) might be needed to adequately assess vitamin D status.



Specimen Required


Patient Preparation: Fasting (4-hour preferred but not required)

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: At least 1.5 mL


Specimen Minimum Volume

0.7 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 7 days
  Frozen  28 days
  Ambient  7 days

Reference Values

Males:

<16 years: 24-86 pg/mL

≥16 years: 18-64 pg/mL

 

Females:

<16 years: 24-86 pg/mL

≥16 years: 18-78 pg/mL

 

For SI unit Reference Values, see https://www.mayomedicallaboratories.com/order-tests/si-unit-conversion.html.

Day(s) and Time(s) Performed

Monday through Friday; 3 p.m.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82652

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DHVD 1,25-Dihydroxyvitamin D, S 62290-2

 

Result ID Test Result Name Result LOINC Value
8822 1,25-Dihydroxyvitamin D, S 62290-2

Clinical Information

Vitamin D is a generic designation for a group of fat-soluble, structurally similar sterols, which act as hormones. In the presence of renal disease or hypercalcemia, testing of 1,25-dihydroxy vitamin D (DHVD) might be needed to adequately assess vitamin D status. The 25-hydroxyvitamin D (25HDN) test (25HDN / 25-Hydroxyvitamin D2 and D3, Serum) in serum is otherwise the preferred initial test for assessing vitamin D status and most accurately reflects the body's vitamin D stores.

 

Vitamin D compounds in the body are exogenously derived by dietary means; from plants as 25-hydroxyvitamin D2 (ergocalciferol or calciferol) or from animal products as 25-hydroxyvitamin D3 (cholecalciferol or calcidiol). Vitamin D may also be endogenously derived by conversion of 7-dihydrocholesterol to 25-hydroxyvitamin D3 in the skin upon ultraviolet exposure.

 

25HDN is subsequently formed by hydroxylation (CYP2R1) in the liver. 25HDN is a prohormone that represents the main reservoir and transport form of vitamin D, being stored in adipose tissue and tightly bound by a transport protein while in circulation. Biological activity is expressed in the form of DHVD, the active metabolite of 25HDN. 1-Alpha-hydroxylation (CYP27B1) occurs on demand, primarily in the kidneys, under the control of parathyroid hormone (PTH) before expressing biological activity. Like other steroid hormones, DHVD binds to a nuclear receptor, influencing gene transcription patterns in target organs.

 

25HDN may also be converted into the inactive metabolite 24,25-dihydroxyvitamin D (24,25D) by (CYP24A1) hydroxylation. This process, regulated by PTH, might increase DHVD synthesis at the expense of the alternative hydroxylation (CYP24A1) product 24,25D. Inactivation of 25HDN and DHVD by CYP24A1 is a crucial process that prevents over production of DHVD and resultant vitamin D toxicity.

 

DHVD stimulates calcium absorption in the intestine and its production is tightly regulated through concentrations of serum calcium, phosphorus, and PTH. DHVD promotes intestinal calcium absorption and, in concert with PTH, skeletal calcium deposition, or less commonly, calcium mobilization. Renal calcium and phosphate reabsorption are also promoted, while prepro-PTH mRNA expression in the parathyroid glands is downregulated. The net result is a positive calcium balance, increasing serum calcium and phosphate levels, and falling PTH concentrations.

 

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.

 

DHVD 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. 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 (24,25D) 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. Differential diagnostic considerations include vitamin D intoxication and CYP24A1 deficiency.

Interpretation

1,25-Dihydroxyvitamin D (DVHD) concentrations are low in chronic renal failure and hypoparathyroidism.

 

DVHD concentrations are high in sarcoidosis and other granulomatous diseases, some malignancies, primary hyperparathyroidism, and physiologic hyperparathyroidism.

 

DVHD concentrations are not a reliable indicator of vitamin D toxicity; normal (or even low) results may be seen in such cases.

Clinical Reference

1. Endres DB, Rude RK: Vitamin D and its metabolites. In Tietz Textbook of Clinical Chemisty. Third edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 1999, pp 1417-1423

2. Bringhurst FR, Demay MB, Kronenberg HM: Vitamin D (calciferols): metabolism of vitamin D. In Williams Textbook of Endocrinology. Ninth edition. Edited by JD Wilson, DW Foster, HM Kronenberg, PR Larsen. Philadelphia, WB Saunders Company, 1998, pp 1166-1169

Analytic Time

2 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

Mild OK; Gross OK

Other

NA

Method Name

Extraction/Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)