This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takeuchi, Y. Articles by Fujita, T. Search for Related Content PubMed PubMed Citation Articles by Takeuchi, Y. Articles by Fujita, T.

Venous Sampling for Fibroblast Growth Factor-23 Confirms Preoperative Diagnosis of Tumor-Induced Osteomalacia

Division of Endocrinology and Nephrology, Department of Medicine, University of Tokyo School of Medicine (Y.T., H.S., S.O., T.F.); Pharmaceutical Research Laboratories, KIRIN Brewery Co. Ltd. (R.I., Y.Y., T.Y.); Department of Orthopedics, University of Tokyo School of Medicine (Y.M., H.O., Ko.N.); and Department of Laboratory Medicine, University of Tokyo (Ka.N., S.F.), Tokyo 113-8655, Japan

Address all correspondence and requests for reprints to: Dr. Yasuhiro Takeuchi, Division of Endocrinology and Metabolism, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo 105-8470, Japan. E-mail: takeuchi-tky{at}umin.ac.jp. Or to: Dr. Seiji Fukumoto, Department of Laboratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: fukumoto-tky{at}umin.ac.jp.

Tumor-induced osteomalacia (TIO) is a paraneoplastic disorder characterized by hypophosphatemia, phosphaturia, inappropriately low serum levels of 1,25-dihydroxyvitamin D for hypophosphatemia, and skeletal undermineralization. Patients with TIO suffer from severe muscle weakness and pain. Because surgical removal of the responsible tumors is the only satisfactory treatment for TIO, identification of the tumors is clinically essential. However, because they are predominantly slow-growing neoplasms of benign mesenchymal origin, localization of the responsible tumors is often very difficult. Moreover, even if a tumor is found in a patient with hypophosphatemic osteomalacia, we have had no way to know that the tumor is actually causing the disease. Fibroblast growth factor-23 (FGF-23) was recently identified as a causative factor for TIO and was shown to induce renal phosphate wasting. We have recently shown that the circulatory FGF-23 level was high in a patient with TIO and rapidly decreased after removal of the responsible tumor. For the first time, we describe a patient with adult-onset hypophosphatemic osteomalacia in whom a clinical diagnosis of TIO was confirmed before surgical removal of the tumor by localizing the responsible tumor using venous sampling for FGF-23 together with magnetic resonance imaging. This combinatorial procedure would be clinically useful for sporadic cases of hypophosphatemic rickets/osteomalacia.

This work was supported in part by grants from Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; the National Dairy Promotion; the Research Society for Metabolic Bone Diseases, and the Yamaguchi Endocrine Research Association.

Abbreviations: FGF-23, Fibroblast growth factor-23; 1,25(OH)₂D, 1,25-dihydroxyvitamin D; MRI, magnetic resonance imaging; TIO, tumor-induced osteomalacia; TmP/GFR, maximum transport of phosphate in renal proximal tubules; XLH, X-linked hypophosphatemic rickets/osteomalacia.

This article has been cited by other articles:

				G. van Boekel, J. Ruinemans-Koerts, F. Joosten, P. Dijkhuizen, A. van Sorge, and H. de Boer Tumor producing fibroblast growth factor 23 localized by two-staged venous sampling Eur. J. Endocrinol., March 1, 2008; 158(3): 431 - 437. [Abstract] [Full Text] [PDF]

				A. Khosravi, C. M. Cutler, M. H. Kelly, R. Chang, R. E. Royal, R. M. Sherry, F. M. Wodajo, N. S. Fedarko, and M. T. Collins Determination of the Elimination Half-Life of Fibroblast Growth Factor-23 J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2374 - 2377. [Abstract] [Full Text] [PDF]

				E. A. Imel, M. Peacock, P. Pitukcheewanont, H. J. Heller, L. M. Ward, D. Shulman, M. Kassem, P. Rackoff, M. Zimering, A. Dalkin, et al. Sensitivity of Fibroblast Growth Factor 23 Measurements in Tumor-Induced Osteomalacia J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2055 - 2061. [Abstract] [Full Text] [PDF]

				T. J. Berndt, S. Schiavi, and R. Kumar "Phosphatonins" and the regulation of phosphorus homeostasis Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1170 - F1182. [Abstract] [Full Text] [PDF]

				K. Araya, S. Fukumoto, R. Backenroth, Y. Takeuchi, K. Nakayama, N. Ito, N. Yoshii, Y. Yamazaki, T. Yamashita, J. Silver, et al. A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5523 - 5527. [Abstract] [Full Text] [PDF]

				S. M. Jan de Beur Tumor-Induced Osteomalacia JAMA, September 14, 2005; 294(10): 1260 - 1267. [Abstract] [Full Text] [PDF]

				E. A. Imel and M. J. Econs Fibroblast Growth Factor 23: Roles in Health and Disease J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2565 - 2575. [Full Text] [PDF]

				T. Berndt and R. Kumar The Phosphatonins and the Regulation of Phosphorus Homeostasis IBMS BoneKEy, June 1, 2005; 2(6): 5 - 16. [Full Text] [PDF]

				S. Liu, T. A. Brown, J. Zhou, Z.-S. Xiao, H. Awad, F. Guilak, and L. D. Quarles Role of Matrix Extracellular Phosphoglycoprotein in the Pathogenesis of X-Linked Hypophosphatemia J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1645 - 1653. [Abstract] [Full Text] [PDF]