ESPE Yearbook of Paediatric Endocrinology

J Bone Miner Res. 2022 Feb;37(2):179-184.Abstract: https://pubmed-ncbi-nlm-nih-gov/34464000/

In Brief: Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) both negatively regulate serum phosphate by increasing renal phosphate excretion. The clinical observation that both PTH and FGF23 are needed for adequate renal phosphate handling is confirmed in this experimental patient study.

Commentary: Serum phosphate is primarily regulated by fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) which both exert their main phosphaturic effect by actions in the proximal renal tubule, decreasing the number and activity of sodium-phosphate co-transporters and thereby decreasing renal phosphate reabsorption.

Deficiency of either PTH or FGF23 cause hyperphosphatemia, indirectly suggesting that both PTH and FGF23 are needed for adequate phosphaturic effects and renal phosphate handling.

In order to test whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, characterized by high blood phosphate despite FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (FTC), characterized by hyperphosphatemia due to FGF23 deficiency, were treated with synthetic human PTH (1–34). In patients with hypoparathyroidism, PTH treatment resulted in increased renal cAMP with phosphaturic response resulting in normalization of serum phosphate levels. In the FTC patient, PTH treatment also resulted in increased renal cAMP. Hovewer, this did not result in a phosphaturic response or decrease in serum phosphate levels indicating that both FGF23 and PTH are required for adequate renal phosphate handling.

The study provides the first direct evidence for the interdependency of PTH and FGF23 for adequate phosphaturic response of either of the two important phosphate regulating hormones.