Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.
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.
Kobayashi
Keisuke
K
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.
Imanishi
Yasuo
Y
Miyauchi
Akimitsu
A
Onoda
Naoyoshi
N
Kawata
Takehisa
T
Tahara
Hideki
H
Goto
Hitoshi
H
Miki
Takami
T
Ishimura
Eiji
E
Sugimoto
Toshitsugu
T
Ishikawa
Tetsuro
T
Inaba
Masaaki
M
Nishizawa
Yoshiki
Y
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
C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium