Document Detail


Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status.
MedLine Citation:
PMID:  20685863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Circulating fibroblast growth factor (FGF)-23 is variably elevated in individuals with X-linked hypophosphatemia (XLH), and klotho has recently been shown to effect renal phosphate handling, yet limited data are available on circulating FGF23 and klotho in XLH.
OBJECTIVE: The objective of the study was to characterize circulating FGF23 and klotho in XLH.
DESIGN: Children and adults with XLH withheld medication for 14 d. Fasting serum FGF23, PTH, klotho, phosphate, and 1,25 dihydroxyvitamin D were obtained. Treated adults were also sampled, and circadian sampling was performed in selected individuals.
SETTING: The study was conducted at a hospital research unit at an academic medical center.
PATIENTS AND OTHER PARTICIPANTS: Participants included 23 individuals with XLH and eight controls.
INTERVENTIONS: There were no interventions.
MAIN OUTCOME MEASURES: Serum klotho and FGF23 were measured.
RESULTS: FGF23 was greater in XLH than in controls and greater in treated XLH subjects compared with XLH subjects not receiving medical therapy. Children had higher klotho levels than adults, but values in XLH were similar to controls. A strong positive correlation between FGF23 and PTH was found in XLH subjects, whereas there was no relationship between these variables in controls. Circulating klotho, but not FGF23, has a diurnal pattern.
CONCLUSIONS: Serum klotho declines with age and demonstrates circadian variation but is normal in XLH. Serum FGF23 is similar in children and adults, is elevated in XLH, further increases with therapy, and demonstrates no diurnal variation. The direct relationship between FGF23 and PTH in subjects with XLH suggests that FGF23 regulation of PTH secretion is aberrant in this disorder.
Authors:
Thomas O Carpenter; Karl L Insogna; Jane H Zhang; Bruce Ellis; Sherril Nieman; Christine Simpson; Elizabeth Olear; Caren M Gundberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-04
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-05     Completed Date:  2010-12-10     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E352-7     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Age Factors
Aged
Bone Density Conservation Agents / therapeutic use
Calcitriol / therapeutic use
Child
Circadian Rhythm / physiology*
Enzyme-Linked Immunosorbent Assay
Familial Hypophosphatemic Rickets / blood*,  drug therapy*
Female
Fibroblast Growth Factors / blood*
Genetic Diseases, X-Linked*
Glucuronidase / blood*
Humans
Male
Middle Aged
Parathyroid Hormone / blood*
Phosphates / blood,  therapeutic use
Vitamin D / analogs & derivatives,  blood
Grant Support
ID/Acronym/Agency:
P50-AR054086/AR/NIAMS NIH HHS; UL1 RR024139/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Bone Density Conservation Agents; 0/Parathyroid Hormone; 0/Phosphates; 0/fibroblast growth factor 23; 1406-16-2/Vitamin D; 62031-54-3/Fibroblast Growth Factors; 66772-14-3/1,25-dihydroxyvitamin D; EC 3.2.1.31/Glucuronidase; EC 3.2.1.31/klotho protein; FXC9231JVH/Calcitriol
Comments/Corrections

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