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Sensitivity of Fibroblast Growth Factor 23 Measurements in Tumor-Induced Osteomalacia

Departments of Medicine (E.A.I., M.P., S.L.H., M.J.E.), Pediatrics (E.A.I.), and Medical and Molecular Genetics (M.J.E.), Indiana University School of Medicine, Indianapolis, Indiana 46202; Childrens Hospital Los Angeles (P.P.), University of Southern California, Keck School of Medicine, Los Angeles, California 90027; University of Texas Southwestern Medical Center at Dallas (H.J.H.), Dallas, Texas 75390; Department of Pediatrics (L.M.W.), University of Ottawa, Ottawa, Ontario, Canada K1H 8L1; All Children’s Hospital (D.S.), University of South Florida College of Medicine, Tampa, Florida 33701; Department of Endocrinology (M.K.), University Hospital of Odense, DK-5000 Odense C, Denmark; Beth Israel Medical Center (P.R.), Albert Einstein School of Medicine, Bronx, New York 10003; Department of Veterans Affairs (M.Z.), New Jersey Health Care System, Lyons, New Jersey 07939; Department of Internal Medicine (A.D.), University of Virginia, Charlottesville, Virginia 22908; Internal Medicine Specialties (E.D.), Milwaukee, Wisconsin 53202; Circolo and Fondazione Macchi Hospital (G.C.), 21100 Varese, Italy; Endocrine-Diabetes Center (J.L.S.), St. Luke’s Medical Center, Milwaukee, Wisconsin 53215; and Department of Endocrinology (E.H.H.), Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Michael Econs, M.D., Indiana University School of Medicine, 541 North Clinical Drive, Clinical Building 459, Indianapolis, Indianapolis 46202. 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. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO.

Objective: The objective of this study was to determine the sensitivity of FGF23 measurements in TIO.

Design: FGF23 concentrations were measured on stored samples with three ELISAs.

Setting: This study was conducted at subspecialty referral centers.

Patients: Twenty-two patients with suspected TIO, 13 with confirmed tumors, were studied.

Interventions: There were no interventions in this study.

Main Outcome Measure: FGF23 concentration was the main outcome measure of this study.

Results: Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16 of 22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in five of 22 patients (sensitivity, 23%), and the Kainos Intact assay in 19 of 22 patients (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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