Vitamin D Testing Recommendations

Choosing Wisely and Endocrine Society guidelines recommend limiting Vitamin D testing to appropriate patients with specific risk factors for deficiency. Populations at risk for deficiency may include those with obesity, osteoporosis, and long-term treatment with corticosteroids and anti-seizure medication.

Forms of vitamin D

"Vitamin D" is a generic designation for a group of fat-soluble (pro)hormones with several forms.

In humans, the most important forms of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

• Vitamin D2 - derived from fungal and plant sources. It is available in over the counter and prescription supplements used to treat vitamin D deficiency.
• Vitamin D3 - the more common form. It is found in food and is also made in sunlight-exposed skin. It is also found in over the counter, but not prescription, supplements.

Two forms of vitamin D are measured in the blood, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

• Both vitamin D2 and vitamin D3 are converted to 25-hydroxyvitamin D [25(OH)D or calcidiol] in the liver.
• This is later hydroxylated in the kidneys and other tissues to 1,25-dihydroxyvitamin D [1,25(OH)2D or calcitriol], the most metabolically active form of vitamin D.

Vitamin D testing

Use 25-hydroxyvitamin D for routine testing

Vitamin D (25 Hydroxy) [VITDG2] is the preferred initial test for assessing vitamin D status in patients without renal disease.

• This is the main form of vitamin D circulating in the blood
• The test assesses for both vitamin D2 and vitamin D3.
• It is the best indicator of vitamin D deficiency or excess in patients not suffering from renal disease.

Additional, uncommon indications

1,25 Dihydroxy Vitamin D [VTD125] is not indicated for routine testing.

• 1,25(OH)2D measurement does not reflect vitamin D reserves and is not useful for monitoring vitamin D status of patients. Serum 1,25(OH)2D can be normal or elevated in those with vitamin D deficiency, due to secondary hyperparathyroidism.
• 1,25(OH)2D concentrations are not a reliable indicator of vitamin D toxicity.

1,25(OH)2D measurement may be used to investigate some patients with clinical evidence of vitamin D deficiency and renal impariment:

• The enzyme that activates vitamin D is produced in the kidney, so levels of 1,25(OH)2D may be of interest in patients on dialysis or with end-stage kidney disease.
• 1,25(OH)2D may also be of interest in patients with vitamin D-dependent rickets due to hereditary deficiency of renal 1-alpha hydroxylase or end-organ resistance to 1,25-vitamin D.
• 1,25(OH)2D can be high in patients with sarcoidosis or granulomatous diseases with hypercalcemia with low parathyroid hormone levels.

CYP24A1 deficiency screen and 24,25_Dihydroxy Vitamin D3

CYP24A1 Deficiency Screen [CYP24A] is a screening panel offered for CYP24A1 deficiency in patients with symptoms, signs or biochemical findings of parathyroid hormone (PTH)-independent hypercalcemia (high levels of calcium in the blood) or hypercalciuria (high levels fo calcium in the urine). Patients may also have deposits of calcium in the kidneys (nephrocalcinosis). Loss of function mutations in the CYP24A1 gene have been shown to lead to insufficient deactivation of bioactive vitamin D metabolites. This test provides a battery of vitamin D measurements, including 24,25_Dihydroxy Vitamin D3, to evaluate for CYP24A1 deficiency.

Isolated testing for 24,25_Dihydroxy Vitamin D3 is not recommended.