SAT-795 - Hidden in the Brain: A Rare Intracranial Source of FGF23-Mediated Tumor-Induced Osteomalacia

A 58-year-old female with multiple sites of fractures was referred for further evaluation. Diffuse bone pain began in 2018 followed by multiple nontraumatic fractures between 2020 and 2025. She had progressive muscle weakness requiring a walker for ambulation and marked decline in quality of life. Fracture history includes right metatarsal (2020), bilateral femoral neck requiring surgical fixation (left 2021, right 2022), bilateral rib fractures (2024), bilateral sacral insufficiency fractures (2024), and left ankle fracture (2/2025).

Initial testing externally demonstrated persistent hypophosphatemia between 1.1–1.3 mg/dL (normal 2.5-4.5 mg/dL), elevated alkaline phosphatase, low-normal 25OH-Vitamin D, normal GFR, elevated PTH 99 pg/mL and slightly low corrected calcium for albumin 8.2 mg/dL. Urine phosphate was not measured. External imaging did not localize a soft tissue tumor.

Our initial testing was significant for low 25OH-Vitamin D (29 ng/ml), hypophosphatemia (1.3 mg/dL), inappropriately normal dihydroxyvitamin D (21 pg/mL), high bone alkaline phosphatase (32 mcg/L), elevated fibroblast growth factor 23 (FGF23) at 530 RU/mL (normal < 180 RU/mL), normal intact PTH and normal corrected calcium. Bone density was normal at the spine and distal third forearm (hips excluded due to hardware). Bone survey showed a trabecular pattern consistent with osteomalacia and multiple rib fractures. A PET-DOTATE relieved a right inferior frontal lobe lesion measuring 3.3 x 1.8 cm. She was referred to neurosurgery and underwent a right craniotomy for resection of the tumor. Pathology revealed a phosphaturic mesenchymal tumor (PMT) with focally positive FGF23 RNA in situ hybridization.

Immediately after surgery, she experienced hungry bone syndrome. Postoperative serum phosphorus normalized to 4.3 mg/dL without supplementation and FGF23 levels declined substantially to 204 RU/mL. Within weeks, the patient reported improvement in bone pain and mobility. No subsequent fractures reported. Repeat FGF23 is in process. Genetic testing was negative for genes associated with hypophosphatemia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excess FGF23, often associated with delayed diagnosis due to occult tumor location. The few cases of intracranial PMT reported tend to occur in the sinuses. TIO can be a clinical conundrum, but heightened awareness can lead to early diagnosis and treatment to improve patient outcomes.

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