SAT-385 A Normal FGF23 Does Not Preclude Tumor Induced Osteomalacia (TIO)

Abstract

BACKGROUND: The phosphaturic, bone-derived hormone FGF23, mediates bone loss in TIO. Tumor resection typically results in skeletal healing and reversal of biochemical defects. Case: A 45-year-old Caucasian man with no past medical history presented with non-traumatic fractures of bilateral metatarsals. Over the subsequent 2 years, he sustained fragility stress fractures in bilateral femurs, eventually rendering him non-ambulatory; though he continued to work as a property manager in an office setting. History included 30 pack-years of smoking as well as osteochondrosarcoma in his mother. Labs showed a low phosphorus at 2.1 mg/dL [2.7–4.5], along with calcium 8.8 mg/dL [8.4–10.4], iPTH 48 pg/mL [12–88], and ALP of 155 [IU]/L [34–104]. 25-OH vitamin D and 1,25-(OH)2 vitamin D were 27 ng/mL [30–80] and 12 pg/mL [20–80], respectively. Free testosterone was 4.4 ng/mL [5–21] and LH 2.2 mIU/mL [3.0–10.0]. Other pituitary hormones and brain MRI were unremarkable. Vitamin D3, calcitriol, phosphate and testosterone were prescribed. Testosterone was discontinued 6 months later, after diagnosis with DVT/PE. Incidental rib fractures on CXR prompted a 3-phase 99Tc-MDP bone scan, revealing multiple sites of uptake: ribs, scapulae, sternum, thoracolumbar spine, sacrum, bilateral ankles and feet. DXA revealed T-scores of -2.8 in the spine and -1.9 in the femoral neck. Labs pointed to ongoing phosphate wasting, despite compliance with calcitriol 0.25 mcg, cholecalciferol 5000 IU and phosphorus 2250 mg in divided doses. Calculated TRP was 64% [>80%] and TmP/GFR 1.74 mg/dL [2.5–4.5], consistent with low phosphate reabsorption. Urine 24-hour calcium was 244.8 mg. Testing for causal mutations of hypophosphatemic rickets and osteogenesis imperfecta was negative. FGF23 was within the reference range at 138 RU/mL [LabCorp ELISA 44–215], interpreted as inappropriately normal given ongoing phosphate loss. This prompted a search for a suspected TIO locus. Two years after presentation, 18F-FDG-PET exhibited a hypermetabolic focus at the left suprapatellar recess. Biopsy was consistent with a mesenchymal tumor and chromogenic in situ hybridization (Mayo Clinic) was positive for FGF23 mRNA. After surgical resection of the 1.7 cm tumor, serum FGF23 declined to <50 RU/mL and was 90 RU/mL 3 weeks later [Mayo <180 RU/mL]. Calcitriol and phosphorus supplementation were discontinued. One year post-operatively phosphorus was 3.6 mg/dL [2.5–5.0], with a normal calcium, iPTH and 25-OH vitamin D. Lumbar spine T score improved to -1.0 (+46.43%). Conclusion: A high clinical index of suspicion is required for TIO in the setting of phosphaturic osteomalacia, particularly with a normal serum FGF23. Recently, similar microRNA profiles were noted in osteosarcomas and TIO1. This, along with our patient’s family history raises the question of a possible predisposition to skeletal neoplasms. 1. Green et al. Bone Reports, 2017.