What tests should be done to determine the cause of vitamin D deficiency?

Diagnostic Testing for Vitamin D Deficiency

When evaluating a patient with vitamin D deficiency, no specific testing is routinely recommended to determine the underlying cause, as most cases result from inadequate sun exposure, dietary intake, or other common risk factors rather than pathological conditions.

Understanding Vitamin D Deficiency

• Vitamin D deficiency is typically defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL (50 nmol/L), while severe deficiency is considered at levels below 10-12 ng/mL (25-30 nmol/L) 1
• There is no consensus on the exact threshold defining vitamin D deficiency, with varying cut points used in different studies 2
• Testing rates for vitamin D have increased significantly in recent years despite uncertainty about the definition of deficiency 2

Risk Assessment for Vitamin D Deficiency

Several factors may increase risk for vitamin D deficiency:

• Limited sun exposure due to season, latitude, or physical sun avoidance 2
• Low dietary vitamin D intake 2
• Decreased vitamin D absorption (malabsorption syndromes) 2
• Obesity (may allow greater sequestration of vitamin D in adipose tissue) 2
• Darker skin pigmentation (reduces skin's ability to produce vitamin D in response to UVB exposure) 2
• Older age and female sex (though findings are inconsistent) 2

Diagnostic Testing Considerations

• The standard laboratory test is total serum 25-hydroxyvitamin D [25(OH)D], which should measure both 25(OH)D2 and 25(OH)D3 forms 3

• Several testing methods are available:

  • High-performance liquid chromatography (HPLC) 3
  • Combined high-performance liquid chromatography and mass spectrometry (LC-MS/MS) 3
  • Competitive protein binding assays 3
  • Immunoassays 3

• Be aware of significant variability between testing methods:

  • Variability between assay methods and laboratories may range from 10% to 20% 2
  • Classification of samples as "deficient" or "nondeficient" can vary by 4% to 32% depending on which assay is used 2

Determining Cause of Vitamin D Deficiency

For most patients with vitamin D deficiency, extensive testing for underlying causes is not recommended as the etiology is typically related to common factors like inadequate sun exposure or dietary intake 1, 4.

However, in cases of severe, persistent, or unexplained deficiency, consider:

• Detailed history focusing on:

  • Sun exposure patterns 2
  • Dietary intake of vitamin D-rich foods 4
  • Use of supplements 4
  • Medications that may affect vitamin D metabolism 1
  • Symptoms suggesting malabsorption (chronic diarrhea, steatorrhea) 4

• Physical examination findings that may suggest vitamin D deficiency:

  • Symmetric low back pain 4
  • Proximal muscle weakness 4
  • Muscle aches 4
  • Throbbing bone pain elicited with pressure over the sternum or tibia 4

Additional Testing in Selected Cases

In patients with severe or unexplained vitamin D deficiency, consider:

• Serum calcium, phosphorus, and alkaline phosphatase to assess for metabolic bone disease 1
• Parathyroid hormone (PTH) levels to evaluate for secondary hyperparathyroidism 1
• Tests for malabsorption if clinically suspected 4
• Kidney function tests, as chronic kidney disease can affect vitamin D metabolism 2, 1

Common Pitfalls in Vitamin D Testing

• Inflammation can reduce plasma vitamin D levels, complicating interpretation of results 1
• Individual response to supplementation varies due to genetic factors, weight, and other variables 1
• Seasonal variation in vitamin D levels may affect interpretation of results 5
• Testing without a clear clinical indication may lead to unnecessary treatment 2

Follow-up Testing

• After initiating treatment for vitamin D deficiency, measure follow-up vitamin D levels after 3-6 months of therapy to ensure adequate response 1, 3
• Target serum level should be at least 30 ng/mL (75 nmol/L) for optimal health benefits 1, 3