Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia

Erik A. Imel, Munro Peacock, Pisit Pitukcheewanont, Howard J. Heller, Leanne M. Ward, Dorothy Shulman, Moustapha Kassem, Paula Rackoff, Mark Zimering, Alan Dalkin, Elaine Drobny, Giacomo Colussi, Joseph L. Shaker, Elizabeth H. Hoogendoorn, Siu L. Hui, Michael J. Econs

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2055-2061
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number6
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Imel, E. A., Peacock, M., Pitukcheewanont, P., Heller, H. J., Ward, L. M., Shulman, D., Kassem, M., Rackoff, P., Zimering, M., Dalkin, A., Drobny, E., Colussi, G., Shaker, J. L., Hoogendoorn, E. H., Hui, S. L., & Econs, M. J. (2006). Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. Journal of Clinical Endocrinology and Metabolism, 91(6), 2055-2061. https://doi.org/10.1210/jc.2005-2105