title: Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.
abstract: OBJECTIVE
  While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT).
  
  
  METHODS
  Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry.
  
  
  RESULTS
  FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23.
  
  
  CONCLUSIONS
  Serum calcium may regulate circulating FGF-23 levels in PHPT.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Onoda
authors.forename: Takehisa
authors.initials: T
authors.lastname: Kawata
authors.forename: Hideki
authors.initials: H
authors.lastname: Tahara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Goto
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
authors.forename: Eiji
authors.initials: E
authors.lastname: Ishimura
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood* / Q000601:surgery; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism; D016105:Parathyroidectomy; D010710:Phosphates / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium