Parathyroid hormone (PTH) and
fibroblast growth factor 23 (FGF23) both influence blood
phosphate levels by regulating urinary
phosphate reabsorption. Clinical data suggest that adequate renal
phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with
hypoparathyroidism, which features high blood
phosphate in spite of concomitant FGF23 elevation, and 1 patient with
hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting
hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Biochemical parameters, including blood
phosphate,
calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(
OH)2
vitamin D (1,25D), and tubular reabsorption of
phosphate (TRP), were measured at baseline and after
hPTH 1-34 treatment. In patients with
hypoparathyroidism, administration of
hPTH 1-34 increased nephrogenic cAMP, which resulted in serum
phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC,
hPTH 1-34 administration also increased nephrogenic cAMP, but this did not produce changes in
phosphate or TRP. No changes in
calcium were observed in any of the studied patients, although prolonged
hPTH 1-34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on
phosphate regulation are interdependent and both are required to adequately regulate renal
phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.