Tumor-induced osteomalacia (TIO) is an ultra-rare paraneoplastic syndrome caused by excessive secretion of fibroblast growth factor 23 (FGF23) from phosphaturic mesenchymal tumors, leading to renal phosphate wasting, hypophosphatemia, and osteomalacia. Diagnosis is frequently delayed due to nonspecific symptoms and the difficulty of localizing small, often indolent tumors. We report a 55-year-old male patient who presented with a 16-month history of progressive muscle weakness, chronic bone pain, and multiple bilateral metatarsal fractures. Laboratory evaluation demonstrated profound hypophosphatemia (1.6 mg/dL), markedly elevated FGF23 levels (455 RU/mL), and renal phosphate wasting (tubular reabsorption of phosphate at 35%, tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) at 1.04 mg/dL). Initial fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was non-localizing. Following referral to a tertiary center, specialized re-interpretation of imaging identified faint focal uptake in the right third metacarpal. This finding was confirmed with technetium-99m sestamibi scintigraphy and magnetic resonance imaging, which revealed a 1.9 × 1.8 × 1.2 cm soft-tissue mass within the palmar tissues. Surgical excision was performed, and histopathology confirmed a phosphaturic mesenchymal tumor with positive FGF23 in situ hybridization. Postoperatively, serum phosphorus levels normalized, confirming biochemical cure. This case underscores the diagnostic challenges associated with TIO, particularly tumor localization, and highlights the critical role of expert imaging interpretation. Complete surgical resection remains the definitive treatment, resulting in rapid biochemical normalization and clinical improvement. The unusual hand location and initially non-localizing imaging emphasize the importance of a systematic, multidisciplinary approach in the evaluation and management of this rare but highly treatable condition.
Cecil et al. (Sun,) studied this question.