What labs should be checked for a patient suspected of having hypophosphatemia?

Laboratory Evaluation for Hypophosphatemia

When evaluating a patient with suspected hypophosphatemia, obtain serum phosphate, calcium, alkaline phosphatase, parathyroid hormone, 25(OH) vitamin D, 1,25(OH)₂ vitamin D, and creatinine, along with spot urine for phosphate, calcium, and creatinine to calculate TmP/GFR and urinary calcium:creatinine ratio. 1

Essential Serum Tests

The core biochemical panel should include:

• Serum phosphate - Confirms hypophosphatemia (defined as <2.5 mg/dL or 0.8 mmol/L), using age-related reference ranges 1, 2
• Serum calcium - Critical for categorizing the etiology: elevated suggests primary hyperparathyroidism, low suggests secondary hyperparathyroidism or vitamin D deficiency, and normal suggests primary renal phosphate wasting 1, 2
• Alkaline phosphatase (ALP) - Elevated levels indicate active rickets in children or osteomalacia in adults; bone-specific ALP is preferred in adults 1
• Parathyroid hormone (PTH) - Helps differentiate PTH-mediated from non-PTH-mediated causes; levels are typically at upper normal range or slightly elevated in X-linked hypophosphatemia 1
• 25(OH) vitamin D - Essential to exclude vitamin D deficiency as a cause 1
• 1,25(OH)₂ vitamin D - Typically low or inappropriately normal in the setting of hypophosphatemia due to renal phosphate wasting 1
• Creatinine - Assesses renal function and is needed for TmP/GFR calculation 1

Essential Urine Tests

A spot urine sample should be obtained for:

• Urinary phosphate, calcium, and creatinine - Required to calculate tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR) and urinary calcium:creatinine ratio 1
• TmP/GFR calculation - Fractional phosphate excretion >15% in the presence of hypophosphatemia confirms renal phosphate wasting 1, 2

Important caveat: In patients with insufficient phosphate intake or impaired intestinal absorption (suspected by low urinary phosphate levels), TmP/GFR can be falsely low until serum phosphate is restored to normal 1

Additional Tests to Exclude Fanconi Syndrome

To rule out non-selective renal tubular phosphate wasting (Fanconi syndrome), evaluate urine for:

• Bicarbonate, amino acids, glucose, and uric acid losses 1
• Low molecular mass proteinuria 1

Advanced Diagnostic Tests

When initial workup suggests hereditary hypophosphatemic disorders:

• Intact FGF23 levels - Elevated in FGF23-mediated hypophosphatemia (including X-linked hypophosphatemia and tumor-induced osteomalacia); however, normal levels do not exclude disease but should be interpreted as inappropriately normal in the setting of hypophosphatemia 1, 3
  • FGF23 is most informative in untreated patients, as levels are influenced by phosphate intake and vitamin D therapy 1
  • Normal range varies considerably by assay used 1
• Genetic testing - PHEX gene analysis confirms X-linked hypophosphatemia when feasible 1

Practical Approach Algorithm

1. Confirm hypophosphatemia with serum phosphate and calculate TmP/GFR from spot urine 1, 2
2. If TmP/GFR >15%: Renal phosphate wasting is confirmed - proceed to step 3 2
3. Check serum calcium to categorize:
   • High calcium → Primary hyperparathyroidism 2
   • Low calcium → Secondary hyperparathyroidism or vitamin D deficiency 2
   • Normal calcium → Primary renal phosphate wasting (consider FGF23 measurement) 2
4. Measure ALP and bone-specific ALP to assess for active bone disease 1, 3
5. Screen for Fanconi syndrome if multiple tubular defects suspected 1
6. Consider FGF23 and genetic testing in chronic cases with appropriate clinical features 1, 3

Common Pitfalls

• Age-related reference ranges: Serum phosphate levels in infants may be normal within the first 3-4 months of life despite underlying disease 1
• Timing of FGF23 measurement: Should be obtained before initiating phosphate or vitamin D therapy for most accurate interpretation 1
• Medication review: Always obtain thorough medication history, as glucose administration, antacids, diuretics, and steroids are common precipitants 4