Workup of Hypophosphatemia
The initial step in the workup of hypophosphatemia should include measurement of fractional phosphate excretion in urine, along with serum calcium, alkaline phosphatase, parathyroid hormone (PTH), creatinine, 25(OH) vitamin D, and 1,25(OH)2 vitamin D levels. 1
Initial Diagnostic Approach
Laboratory Assessment
- Calculate tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR) using spot urine test for phosphate and creatinine 1
- Measure serum levels of:
- Phosphate (confirm hypophosphatemia)
- Calcium
- Alkaline phosphatase (ALP) - elevated in rickets/osteomalacia
- Parathyroid hormone (PTH)
- 25(OH) vitamin D
- 1,25(OH)2 vitamin D
- Creatinine (to assess renal function)
Interpretation of Urinary Phosphate Excretion
- Fractional phosphate excretion >15% in the presence of hypophosphatemia confirms renal phosphate wasting 2
- Fractional phosphate excretion <5% suggests non-renal causes (inadequate intake, decreased intestinal absorption, or internal redistribution) 2
Differential Diagnosis Based on Mechanism
1. Renal Phosphate Wasting
- Genetic disorders: X-linked hypophosphatemic rickets (PHEX gene mutations) 1
- Acquired disorders:
- Vitamin D deficiency
- Hyperparathyroidism
- Fanconi syndrome (evaluate for urinary losses of bicarbonate, amino acids, glucose, and/or uric acid) 1
2. Non-Renal Causes
- Decreased intake/absorption:
- Malnutrition
- Alcoholism
- Vitamin D deficiency
- Internal redistribution:
- Refeeding syndrome
- Diabetic ketoacidosis
- Post-surgical states (especially hepatectomy)
- Intensive care setting 3
Severity Assessment
Classify hypophosphatemia by severity to guide treatment approach:
- Mild: 2.0-2.5 mg/dL (0.65-0.81 mmol/L)
- Moderate: 1.0-1.9 mg/dL (0.32-0.64 mmol/L)
- Severe: <1.0 mg/dL (<0.32 mmol/L) 3
Treatment Approach
Oral Supplementation
- For mild to moderate hypophosphatemia without severe symptoms:
Intravenous Replacement
- For severe hypophosphatemia (<1.0 mg/dL) or symptomatic patients:
Cautions with IV Phosphate
- Check serum potassium before administration - if ≥4 mEq/dL, consider alternative phosphate source 4
- Monitor for hyperkalemia, especially in patients with renal impairment 4
- Watch for hypocalcemia, which can occur with rapid phosphate administration 4
- Avoid in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) 4
Monitoring During Treatment
- Regular monitoring of:
- Serum phosphate, calcium, and alkaline phosphatase
- PTH levels
- Urinary calcium and phosphate
- Renal function 1
- For patients on burosumab (for X-linked hypophosphatemia):
- Monitor fasting serum phosphate levels every 2 weeks during the first month
- Then every 4 weeks for 2 months and thereafter as appropriate 1
Special Considerations
X-linked Hypophosphatemia
- Genetic testing for PHEX gene mutations may be warranted in cases of familial hypophosphatemia 1
- Consider referral to specialists in metabolic bone diseases for management 1
Severe Symptomatic Hypophosphatemia
- Watch for clinical manifestations including:
- Respiratory muscle weakness
- Cardiac dysfunction
- Rhabdomyolysis
- Altered mental status
- Hemolysis 5
Common Pitfalls to Avoid
- Failing to distinguish between acute and chronic hypophosphatemia, which have different management approaches
- Administering IV phosphate too rapidly, which can cause cardiac arrhythmias, hypotension, and death 4
- Not checking for calcium levels before phosphate replacement (risk of precipitating hypocalcemia) 4
- Overlooking refeeding syndrome as a cause in malnourished patients
- Neglecting to evaluate for underlying causes of chronic hypophosphatemia, such as genetic disorders or vitamin D deficiency
By following this systematic approach to hypophosphatemia, you can effectively diagnose the underlying cause and implement appropriate treatment while avoiding potential complications.