Oncogenic osteomalacia Case report

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized biochemically by hypophosphatemia, excessive urinary phosphate excretion, low 1,25-dihydroxyvitamin D levels, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle weakness. TIO can occur in patients with a variety of benign mesenchimal tumors (hemangiopericitomas, fibromas, angiosarcomas, etc.) and the disease is invariably curable with the removal of the tumor, indicating that it has humoral basis. Phosphate wasting and the defect in vitamin D synthesis are caused by a humoral factor produced by tumors, initially termed phosphatonin, and recently identified as fibroblast growth factor-23 (FGF-23) although other substances as secreted frizzled-related protein 4 (SFRP4) and matrix extracellular phospho-glycoprotein (MEPE) can be involved in pathophysiology of osteomalacia. In contrast with more common forms of osteomalacia, patients with TIO have normal serum calcium, normal serum 25hydroxy-vitamin D and normal intact serum parathyroid hormone. On the other hand TIO is biochemically indistinguishable from several inherited forms of hypophosphatemic rickets as X-linked hypophosphatemia (XLH) and autosomical dominant hypophosphatemic rickets (ADHR). The definitive diagnosis of TIO is established by identification of the causative tumor and remission of the syndrome after complete tumor resection. Recently a few cases in which 111In-pentetreotide scintigraphy visualized the tumor have been reported and also positron emission tomography using F-18-fluorodeoxyglucose showed encouraging results. When the suspected tumour cannot be located, periodical follow-up with conventional imaging is indicated with special attention directed to craniofacial locations and extremities because they are the more common localization for tumour. In conclusion in patients with TIO resection of a tumour is the treatment of choice; if the tumour cannot be found or if the tumour is unresectable for its location, chronic administration of phosphate and calcitriol is indicated.