Increased circulating levels of FGF23: an adaptive response in primary hyperparathyroidism?

Abstract

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 (50.8G6.1 vs 33.1G2.6 pg/ml, PZ0.01). FGF23 levels significantly correlated with PTH levels (rZ 0.361, PZ0.02), also after correction for 1,25(OH) 2 D levels (rZ0.419, PZ0.01). FGF23 levels showed a significant negative correlation with 1,25(OH) 2 D, which was more pronounced in PHPT than in EuPTH patients (rZK0.674, PZ0.001, vs rZK0.509, PZ0.01). 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.

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers

“…As far as other biomarkers, our data are in line with previous studies showing that there is an elevation of FGF23 levels in patients with PHPT Our study also provided data on the FGF23 co‐receptor, Klotho, whose elevation should not be intended in correlation with kidney disease. Hence, assessing of the two molecules is not useful in the evaluation of kidney injury in PHPT.…”

“…This point opens new questions towards the elucidation of intriguing mechanisms of action of FGF23 in PHPT. Witteveen et al demonstrated that FGF23 levels are high and negatively associated with serum 1,25(OH) 2 D levels in patients with PHPT and normalize after surgery . Authors hypothesized that the increase in FGF23 represents a compensatory response to increased 1,25(OH) 2 D levels stimulated by chronic high PTH levels .…”

Primary hyperparathyroidism

“…The relevance of this observation to the pathogenesis of PHPT in humans remains uncertain. Indeed, patients with PHPT have increased levels of FGF23 in association with high serum levels of PTH, suggesting that the increased FGF23 levels might be an adaptive response to counteract increased 1,25(OH) 2 D levels as a consequence of high PTH levels 38 .…”

Correlations and time course of FGF23 and markers of bone metabolism in maintenance hemodialysis patients

“…Ln-transformed FGF23 decreased significantly in both groups but the induction of iPTH by low dialysate calcium did not immediately affect FGF23 although elevated FGF23 has been reported in primary hyperparathyroidism [7].…”