title: The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children.
abstract: BACKGROUND
  Normal phosphate homeostasis is essential for normal linear growth. The phosphaturic fibroblast growth factor 23 (FGF23)/Klotho axis is a major regulator of phosphate homeostasis; therefore, an intact FGF23/Klotho axis is important for normal linear growth. On the other hand, GH/IGF1 axis has opposing effects on phosphate homeostasis, but the underline mechanisms remain unclear.
  
  
  OBJECTIVE
  The main objective of this study was to investigate the possible interactions of FGF23 and its co-receptor Klotho, with growth hormone (GH)/IGF1 axis in the regulation of phosphate metabolism in GH-deficient children under GH treatment.
  
  
  METHODS
  We studied 23 GH-deficient children, before and 3 months after the onset of GH treatment. Anthropometry and assessment of biochemical parameters were performed, as well as measurement of FGF23 (intact FGF23/iFGF23 and C-terminal FGF23/cFGF23) and soluble α-Klotho (sKlotho) levels.
  
  
  RESULTS
  After 3 months on GH treatment, the elevation of serum phosphate and TmPO4/GFR (P<0.0001 and P<0.01 respectively) was accompanied by a significant increase in cFGF23 (P<0.01), iFGF23 (P<0.0001), sKlotho (P<0.0001) and IGF1 (P<0.0001). Serum phosphate and TmPO4/GFR were positively associated with iFGF23 (P<0.01 and P<0.05) and IGF1 (P<0.05 and P<0.05). iFGF23 levels were positively correlated with sKlotho (P<0.001), IGF1 (P<0.0001) and height SDS (P<0.0001), whereas sKlotho was positively associated with IGF1 (P<0.0001) and height SDS (P<0.001).
  
  
  CONCLUSIONS
  The increase in serum phosphate, which we found in GH-deficient children under GH treatment, is not associated with suppression but rather than with upregulation of the phosphaturic FGF23/Klotho axis.
authors.affiliation: Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece eythymiadou@upatras.gr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Efthymiadou
authors.affiliation: Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kritikou
authors.affiliation: Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Mantagos
authors.affiliation: Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece.
authors.forename: Dionisios
authors.initials: D
authors.lastname: Chrysis
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D001827:Body Height / Q000187:drug effects; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005966:Glucuronidase / Q000097:blood*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D010710:Phosphates / Q000097:blood; D015398:Signal Transduction
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D019382:Human Growth Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins