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

Abstract

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.

Phosphaturic Mesenchymal Tumor with Symptoms Related to Osteomalacia that Appeared One Year after Tumorectomy

“…In most cases, bone and muscle pain are the first clinical manifestations of PMTMCT, followed by identification of the tumor because the tumor is often small and localization of the tumor is difficult (7,8 …”

Whole-body MR Imaging in Detecting Phosphaturic Mesenchymal Tumor (PMT) in Tumor-induced Hypophosphatemic Osteomalacia

“…Evidence shows that patients who undergo tumor removal-the primary treatment for TIO-enjoy complete relief from debilitating symptoms. 1,17 Various modalities, such as CT, MR imaging, 5-7 FDG-PET, 9-11 111 In-pentetreotide, octreotide scin- Magnetic Resonance in Medical Sciences tigraphy 12,13 and systemic venous sampling 1,17,18 have been used to localize the tumor of TIO. In what we believe is the largest report from a single center, Jagtap and associates analyzed 9 patients with TIO, 11 using 18 F-FDG PET to localize the tumors.…”

Mutant FGF23 Prevents the Progression of Chronic Kidney Disease but Aggravates Renal Osteodystrophy in Uremic Rats

“…Furthermore, this method is useful to examine the biological roles of longterm delivery secretory proteins in rats (25). Because the half-life of FGF23 in the circulation has been estimated to be approximately 21.5 min (26), it might be difficult to assess the efficacy of FGF23 using recombinant protein over a longer period. We used mutant FGF23 and not wild-type FGF23 because FGF23 mutants such as R176Q, R179Q and R179W, but not wild-type FGF23, induced hypophosphatemia in intact mice using the naked DNA injection method in our previous study (17).…”