Endocrine Abstracts

Background: Chronic hypophosphataemia due to renal phosphorus wasting results in bone disease (rickets and osteomalacia). The principal regulators of renal phosphorous handling are parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). X-linked hypophosphatemic (XLH) rickets is the most common genetic disorder of renal phosphorus wasting; acquired disorders include tumour-induced osteomalacia (TIO). The aims of this study were: i) to assess the clinical utility of FGF23 measurement in congenital and acquired disorders of phosphate homeostasis and ii) to assess the relative effects of PTH and FGF23 on renal phosphorus handling.

Methods: 55 subjects consented to participate in this study. They were subdivided into three groups: i) FGF23-mediated (n=15) including congenital hypophosphataemia (n=13) and TIO (n=2); ii) non-FGF23-mediated (n=38) including a variety of metabolic bone disorders; and iii) two cases of XLH with hypoparathyroidism post total parathyroidectomy for severe hyperparathyroidism. Fasting morning serum and urine samples were obtained. Tests included FGF23, TmP/GFR, ionised calcium, 25OHD, PTH, and creatinine.

Results: Subjects with FGF23-mediated disease had higher FGF23 and lower TmP/GFR than the non-FGF23-mediated disease group. In the FGF23-mediated group significant inverse correlations were noted between TmP/GFR and ionised calcium (r=−0.659, P=0.01) and FGF23 (r=−0.595, P=0.026). In the non-FGF23-mediated group significant inverse correlations were noted between TmP/GFR and ionised calcium (r=−0.514, P<0.001) and PTH (r=−0.506, P=0.001). Adjusting for ionised calcium, PTH, and creatinine the relationship between TmP/GFR and FGF23 approached significance (r=−0.581, P=0.061) in subjects with FGF23-mediated group, but not in the non-FGF23-mediated group (r=−0.063, P=0.721). In XLH patients with hypoparathyroidism post total parathyroidectomy, TmP/GFR was normal despite marked elevation in FGF23 with undetectable PTH

Conclusions: FGF23 levels are a determinant of TmP/GFR in congenital and acquired disorders of FGF23 excess, but the effect of FGF23 on renal phosphorus handling is dependent on PTH secretion, even if there is a disorder in FGF23 production.