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Submitted on September 21, 2005
Accepted on March 10, 2006
Departments of Medicine and Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, California; University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; Department of Pediatrics, University of Ottawa, Ottawa, Canada; All Children's Hospital, University of South Florida College of Medicine; Department of Endocrinology, University Hospital of Odense, Odense C, Denmark; Beth Israel Medical Center, Albert Einstein School of Medicine; Department of Veterans Affairs, New Jersey Health Care System, Lyons, NJ; Department of Internal Medicine, University of Virginia, Charlottesville, Virginia; Internal Medicine Specialties, Milwaukee, Wisconsin; Circolo and Fondazione Macchi Hospital, Varese, Italy; Endocrine-Diabetes Center, St. Luke's Medical Center, Milwaukee, Wisconsin; Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
* To whom correspondence should be addressed. E-mail: mecons{at}iupui.edu.
Context: Tumor induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy and osteomalacia. FGF23 is a phosphaturic protein over-expressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO.
Objective: To determine the sensitivity of FGF23 measurements in TIO.
Design: FGF23 concentrations were measured on stored samples with three ELISA assays.
Setting: Subspecialty referral centers.
Patients: 22 patients with suspected TIO, 13 with confirmed tumors.
Interventions: none.
Main Outcome Measure: FGF23 concentration.
Results: Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16/22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in 5/22 (sensitivity 23%), and the Kainos intact assay in 19/22 (sensitivity 86%). In the 13 patients with confirmed tumors, the sensitivity was higher with all assays: 92% for the Immunotopics C-terminal assay, 38% for the Immunotopics Intact assay, and 100% for the Kainos assay.
Conclusion: The Kainos intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients, or that FGF23 secretion by some tumors is partially responsive to serum phosphate. "Normal" FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.
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