When should Fibroblast Growth Factor 23 (FGF23) levels be checked?

When to Check FGF23 Levels

FGF23 levels should be checked in patients with hypophosphataemia associated with renal phosphate wasting, particularly when evaluating for X-linked hypophosphataemia (XLH) or other FGF23-mediated hypophosphataemic disorders. 1

Primary Indications for FGF23 Testing

In Children:

• Suspected rickets with:
  • Clinical or radiological signs of rickets
  • Impaired growth velocity
  • Serum phosphate below age-related reference range
  • Evidence of renal phosphate wasting
  • Absence of vitamin D or calcium deficiency 1

In Adults:

• Suspected osteomalacia with:
  • Lower limb deformities (present or history)
  • Pseudofractures
  • Early osteoarthritis
  • Enthesopathies (bone proliferation at ligament attachments)
  • Hypophosphataemia with renal phosphate wasting 1

Diagnostic Algorithm for FGF23 Testing

1. First step: Rule out other causes of hypophosphataemia

   • Exclude metabolic acidosis
   • Exclude non-selective tubular wasting (Fanconi syndrome)
   • Exclude calcipenic diseases causing secondary hyperphosphataemia 1

2. Second step: Evaluate phosphate metabolism

   • Measure serum phosphate
   • Calculate tubular maximum reabsorption of phosphate per GFR (TmP/GFR)
   • Check alkaline phosphatase (ALP) levels 1

3. Third step: Check FGF23 when:

   • Hypophosphataemia is confirmed
   • Renal phosphate wasting is documented
   • Patient is untreated (not on phosphate supplements or vitamin D) 1

Interpretation of FGF23 Results

• Elevated FGF23: Supports diagnosis of FGF23-mediated hypophosphataemia (XLH being most common, ~80% of cases) 1
• Normal FGF23: In the setting of hypophosphataemia, should be interpreted as "inappropriately normal" and still consistent with XLH 1
• Low FGF23: Suggests non-FGF23-mediated renal phosphate wasting (e.g., hereditary hypophosphataemic rickets with hypercalciuria) 1

Important Considerations and Caveats

• FGF23 levels are most informative in untreated patients as phosphate supplements and vitamin D therapy can influence results 1
• FGF23 normal ranges vary considerably depending on the assay used 1
• Even "low-normal" FGF23 levels suggest excess FGF23 in the setting of hypophosphataemia 1
• Consider family history of X-linked inheritance which strongly supports XLH diagnosis 1
• FGF23 should be measured as part of a comprehensive evaluation including calcium, phosphate, ALP, PTH, vitamin D metabolites, and urinary calcium and phosphate excretion 1

Other Clinical Scenarios for FGF23 Testing

• Suspected tumor-induced osteomalacia 1
• Following intravenous iron therapy (ferric carboxymaltose or iron isomaltoside) which can cause "6H syndrome" with elevated FGF23 1
• Evaluation of alcohol-induced FGF23 syndrome 1
• Suspected ectopic FGF23 syndrome in advanced malignancies (especially prostate and lung cancer) 1
• First-degree relatives of patients with confirmed XLH 1

By following this approach, clinicians can appropriately utilize FGF23 testing to diagnose and manage patients with phosphate metabolism disorders, particularly those with FGF23-mediated hypophosphataemia.