Tumor induced osteomalacia: associated with elevated circulating levels of fibroblast growth factor-7 in addition to fibroblast growth factor-23

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and osteomalacia. Fibroblast growth factor (FGF)-23, a phosphatonin i.e., phosphaturia-promoting hormone, is commonly implicated in the pathogenesis of TIO. However, very limited information is available about the circulating levels and clinical significance of other phosphatonins that are expressed by TIO-associated tumors. In addition, identification of the primary tumor constitutes a frequent major challenge in the management of TIO. Here, we report a patient with the clinical diagnosis of TIO with elevated blood levels of the phosphatonins FGF-23 and FGF-7; and extensive but unrewarding radiological search for the primary tumor. In selective venous sampling, both FGF-23 and FGF-7 displayed highest concentrations in the left femoral and iliac veins; although lateralization was much more pronounced for FGF-7 than FGF-23. This laboratory finding allowed us to focus on the left lower extremity as the likely location of the primary tumor. Our case is the first to show that FGF-7 can be analyzed in the circulation and used to assist in the diagnosis and localization of TIO-associated tumors.