Successful Medical Management of a Non-Localising Case of Tumour-Induced Osteomalacia

Introduction: TIO is a rare paraneoplastic syndrome characterised by renal phosphate wasting due to fibroblast growth factor-23 (FGF23) over-secretion from a phosphaturic mesenchymal tumour (PMT). While surgery is potentially curative, localisation is often challenging. Clinical Case: A 53 year old lady presented with recurrent fragility fractures in the spine (T10-L1, L4, S1-2), right femoral neck fracture and pelvic fractures at the bilateral superior and inferior pubic rami, associated with a 2 year onset of lower limb pain and proximal myopathy. Power was 2/5 proximally, rendering her progressively chairbound. She had no family history of fragility fractures. Biochemistry revealed hypophosphatemia of 0.48 mmol/l (NR 0.86–1.45 mmol/l), normal adjusted calcium of 2.32 mmol/l (NR 2.15–2.55 mmol/l), hyperphosphaturia (TmP/GFR 0.39 mmol/l, NR 0.88–1.42 mmol/l), mildly insufficient 25(OH)D level of 25 μg/l, inappropriately suppressed 1,25(OH)(2)D at 13 pg/ml (NR 18–78 pg/ml) and raised FGF23 at 484 RU/ml (NR<180 RU/ml). Localisation of the PMT was unsuccessful, despite multiple investigations including 68-Gallium-DOTANOC PET-CT, bilateral lower limb MRI for non-specific inguinal lymph nodes and various ultrasonographic evaluation of soft tissue lesions including biopsy of a benign breast tumour. Surgical removal of the breast papilloma did not affect FGF23 levels. In the absence of any suspicious lesion, selective venous sampling was not performed due to uncertain utility. She was treated medically, requiring 16mmol oral phosphate, 1000 IU cholecalciferol and 0.5mcg calcitriol daily, with a view to perform interval DOTA-peptide scan. Despite an increase in FGF23 to 760 RU/ml over 29 months, phosphate level was maintained in the low-normal range and alkaline phosphatase, as a marker of disease activity, normalised from 370 U/l to 92 U/l (NR 40-130U/l). Development of secondary hyperparathyroidism improved with uptitration of calcitriol. There was no hypercalciuria on monitoring of urinary calcium. Symptoms of generalised body pain resolved, and her bone mineral density (BMD) improved over 47 months of medical therapy. Power improved to 4/5, and she was able to ambulate with assistance. BMD at the femoral neck, total hip and lumbar spine increased by 68.2%, 44.6% and 65.2% respectively. Conclusion: This is a challenging case of TIO which has failed to localise despite best efforts. One must consider FGF23-independent and dependent causes of osteomalacia when patients present with severe frailty and hypophosphatemia as substantial morbidity results from delayed diagnosis and treatment. TIO-related PMTs can be difficult to localise, even with a combination of functional and anatomical imaging. With medical therapy, bone mineralisation and symptoms can improve significantly. Patients need to be monitored for complications of long-term phosphate and calcitriol replacement.