Tumor-induced rickets/osteomalacia (TIO): diagnostic pitfalls and therapeutic options

A 10-year-old girl developed bilateral gonalgia and waddling gait. Biochemical and imaging studies showed hypophosphatemia with impaired proximal tubular phosphate reabsorption and high intact fibroblast growth factor 23 (FGF23) level, indicating FGF23-related hypophosphatemic rickets/osteomalacia. However, genetic analyses for hereditary FGF23-related hypophosphatemic rickets were negative. 111In-pentetreotide scintigraphy and 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) which were available at that time, failed to find a tumor associated with tumor-induced rickets/osteomalacia. She was first treated with active vitamin D and phosphate salt, followed by burosumab which alleviated her symptoms. She was then referred to our hospital to find the cause of her disease, and the previous imaging results were reevaluated. There was an asymmetrical uptake in the distal portion of her right femur by PET/CT. The following magnetic resonance imaging confirmed the presence of a tumor in the lateral portion of the right femur. Wide excision of the lesion corrected hypophosphatemia. The differential diagnoses and treatment of hypophosphatemic rickets/osteomalacia are discussed.