The Identification and characterization of FGF-23 has provided an opportunity to gain new insight into
phosphorus metabolism. Circulating FGF-23 promotes renal excretion of
phosphorus, and FGF-23 is measurable in the serum of normal subjects. Serum levels of FGF-23 are elevated in patients with renal
phosphate wasting disorders such as
tumor induced osteomalacia,
X-linked hypophosphatemia and fibrous dysplasia. However, the factors that alter its serum concentration are not known. The study of serum FGF-23 is confounded by the fact that high serum
calcium, PTH, and any other putative phosphotonins, have similar effects on serum and urine
phosphorus. To circumvent the confounding effect of serum PTH and
calcium, we studied serum FGF-23 and
phosphate levels in patients with chronic
hypoparathyroidism and
hyperphosphatemia. Serum was collected in the morning after an overnight fast from three groups: 1) 9 patients with chronic
hypoparathyroidism on stable treatment with
calcium and
calcitriol, 2) 9 patients with
primary hyperparathyroidism, and 3) 77 normal controls. Patients with
hypoparathyroidism had predictably higher levels of serum
phosphorus than patients with
hyperparathyroidism or normal controls (5.6 +/- 1.1, 3.1 +/- 0.6, and 3.1 +/- 0.5 mg/dL, mean +/- 1 SD, respectively (p < 0.01 for hypoparathyroid vs. either group)). They also had higher levels of FGF-23 (150 +/- 120 vs. 70 +/- 60, or 55 +/- 20 RIU/ml, respectively (p < 0.05 vs. either group)). In conclusion, serum FGF-23 levels are elevated in patients with
hyperphosphatemia and chronic
hypoparathyroidism, suggesting a feedback system in which serum FGF-23 responds to serum
phosphorus and regulates it. However, in the setting of chronic
hypoparathyroidism, the degree of elevation of FGF-23 is insufficient to normalize serum
phosphorus.