Increased Circulating Levels of FGF23: an Adaptive Response in Primary Hyperparathyroidism?

Introduction: Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are major players in the bone-parathyroid-kidney axis controlling phosphate homeostasis. In patients with primary hyperparathyroidism (PHPT), data on the relationship between PTH and FGF23 are scarce and not always concordant.

Objective: The aim of our study was to evaluate the relationship between PTH and FGF23 in patients with PHPT and in euparathyroid patients cured after successful parathyroidectomy (PTx).

Patients And Methods: Twenty-one patients with PHPT and 24 patients in long-term cure after successful PTx (EuPTH) were studied. All patients underwent biochemical evaluation of renal function, parathyroid status, vitamin D status, bone turnover markers, and serum intact FGF23 levels.

Results: Mean serum FGF23 concentration was significantly higher in PHPT than in EuPTH patients (50.8±6.1 vs 33.1±2.6 pg/ml, P=0.01). FGF23 levels significantly correlated with PTH levels (r=0.361, P=0.02), also after correction for 1,25(OH)(2)D levels (r=0.419, P=0.01). FGF23 levels showed a significant negative correlation with 1,25(OH)(2)D, which was more pronounced in PHPT than in EuPTH patients (r=-0.674, P=0.001, vs r=-0.509, P=0.01).

Conclusion: Our findings suggest that in PHPT, FGF23 levels are increased independent of 1,25(OH)(2)D levels. The more pronounced negative relationship between FGF23 and 1,25(OH)(2)D in the presence of high circulating PTH levels suggests that the increase in FGF23 levels may be an adaptive mechanism to counteract the PTH-induced increase in 1,25(OH)(2)D levels, although not completely overriding it.