Interpretation

Increased fibroblast growth factor 23 (FGF23) concentrations are present in individuals with renal phosphate-wasting diseases such as autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), X-linked hypophosphatemia rickets (XLH) and tumor induced osteomalacia (TIO). Clinically, FGF23 measurement is useful in the differential diagnosis of these hypophosphatemic diseases since the patient presents with high FGF23 levels along with hypophosphatemia. In other causes of hypophosphatemia, such as vitamin D deficiency, FGF23 levels are low. In FGF23-producing tumors, a decrease in FGF23 concentrations following surgery is a reliable indication of complete tumor resection.

Intact FGF23 concentrations are elevated in patients with TIO or XLH. A study detected elevations of intact FGF23 in 19 of 22 TIO cases (86%).(1) In XLH, elevations of intact FGF23 were observed in 88% of patients (9 of10 children and 13 of 15 adults).(2) While levels of intact FGF23 in XLH are usually elevated, FGF23 concentrations within the reference interval do not exclude the disease and should be interpreted in the setting of phosphate concentrations (ie, an FGF23 concentration in the upper level of the reference interval in the context of hypophosphatemia might be indicative of XLH). In ADHR, FGF23 concentrations are not consistently elevated, and the severity of renal phosphate-wasting may wax and wane; FGF23 concentrations are normal during quiescent periods when serum phosphate levels are normal, and they are elevated during active, hypophosphatemic phases of the disease.(3) FGF23 concentrations are influenced by factors such as phosphate intake and vitamin D therapy. Therefore, intact FGF23 levels are most informative in untreated patients.