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    Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment and Relationship to Parathyroid Status

    J Clin Endocrinol Metab. 2010 Aug 4. [Epub ahead of print]

    The authors examined the relationships between serum levels of klotho and FGF23 in X-Linked Hypophosphatemia (XLH) patients and normal controls. They find a direct relationship between serum levels of FGF23 and PTH in subjects with XLH but not in controls. These results suggest that FGF23 regulation of PTH secretion is aberrant in this disorder.

    Authors: Carpenter TO, Insogna KL, Zhang JH, et. al

    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 lower 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.

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