Fibroblast growth factor-23 is regulated by 1alpha,25-dihydroxyvitamin D.
Serum FGF-23 regulation was studied in patients with hypoparathyroidism or pseudohypoparathyroidism treated with calcitriol. Serum FGF-23 levels changed in parallel in response to changes in serum 1,25-D, suggesting that FGF-23 may be regulated by 1,25-D. In addition, the phosphaturic effect of FGF-23 may be diminished in the absence of PTH action on the kidney.


BACKGROUND
Fibroblast growth factor (FGF)-23 is a recently described hormone that has been shown to be involved in the regulation of phosphate and vitamin D metabolism. The physiologic role of FGF-23 in mineral metabolism and how serum FGF-23 levels are regulated have yet to be elucidated. Three patients with mineral metabolism defects that allowed for the investigation of the regulation of FGF-23 were studied.


METHODS
Patient 1 had postsurgical hypoparathyroidism and Munchausen's syndrome and consumed a pharmacologic dose of calcitriol. Patient 2 had postsurgical hypoparathyroidism and fibrous dysplasia of bone. She was treated with increasing doses of calcitriol followed by synthetic PTH(1-34). Patient 3 had pseudohypoparathyroidism type 1B and tertiary hyperparathyroidism. She underwent parathyroidectomy, which was followed by the development of hungry bone syndrome and hypocalcemia, requiring treatment with calcitriol. Serum FGF-23 and serum and urine levels of mineral metabolites were measured in all three patients.


RESULTS
Patient 1 had an acute and marked increase in serum FGF-23 (70 to 670 RU/ml; normal range, 18-108 RU/ml) within 24 h in response to high-dose calcitriol administration. Patient 2 showed stepwise increases in serum FGF-23 from 117 to 824 RU/ml in response to increasing serum levels of 1alpha,25-dihydroxyvitamin D (1,25-D). Finally, before parathyroidectomy, while hypercalcemic, euphosphatemic, with low levels of 1,25-D (10 pg/ml; normal range, 22-67 pg/ml), and with very high serum PTH (863.7 pg/ml; normal range, 6.0-40.0 pg/ml), patient 3 had high serum FGF-23 levels (217 RU/ml). After surgery, while hypocalcemic, euphosphatemic, and with high serum levels of serum 1,25-D (140 pg/ml), FGF-23 levels were higher than preoperative levels (305 RU/ml). It seemed that the phosphaturic effect of FGF-23 was diminished in the absence of PTH or a PTH effect.


CONCLUSIONS
Serum FGF-23 may be regulated by serum 1,25-D, and its phosphaturic effect may be less in the absence of PTH.
Collins
Michael T
MT
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4320, USA. mc247k@nih.gov
Lindsay
John R
JR
Jain
Alka
A
Kelly
Marilyn H
MH
Cutler
Carolee M
CM
Weinstein
Lee S
LS
Liu
Jie
J
Fedarko
Neal S
NS
Winer
Karen K
KK
D000328:Adult; D002117:Calcitriol / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000378:metabolism; D005359:Fibrous Dysplasia, Polyostotic / Q000097:blood / Q000628:therapy; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood / Q000652:urine; D011547:Pseudohypoparathyroidism / Q000097:blood* / Q000188:drug therapy; D019379:Teriparatide / Q000494:pharmacology / Q000627:therapeutic use
C000717427:FGF23 protein, human; D019379:Teriparatide; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium