Endocrine Abstracts

JOINT940

Tumour induced osteomalacia (TIO) is rare and difficult to diagnose and treat in children. We report an adolescent with TIO, his diagnostic pathway, and recovery after surgery. A 14-year-old male presented with a one-year history of generalised bone pain with a prior distal radius/ulna fracture. He had normal growth, development and unremarkable family history. Examination was normal with no leg bowing. Investigations revealed severe hypophosphataemia (0. 48 mmol/l), renal phosphate loss (TMP/GFR 0. 26 mmol/l), mild hypocalcaemia (2. 15 mmol/l), high ALP (791U/l), high-normal PTH (6. 5pmol/l), undetectable urine calcium, elevated FGF23 [177RU/mL(<100)] and low 1, 25 vitamin D3 [38nmol/l(108-246)]. He had normal knee X-rays, renal ultrasound and urine aminoacids, and low bone mineral density (L1-4 BMD -2. 5 SD). TIO was diagnosed. He was started on oral phosphate, alfacalcidol and vitamin D. Genetic testing [hypophosphatemia panel (PHEX/renal phosphate wasting) and whole-genome sequencing] was normal, as expected. Imaging to identify the tumour was initiated. X-ray skeletal survey was normal. Whole body MRI suggested a 33mm ovoid lesion in the distal left femur. Ga-68 DOTATATE PET-CT was chosen for further imaging and confirmed the juxtacortical soft tissue lesion. A dedicated MRI showed the lesion was 35x14x9mm. Peripheral venous sampling from legs and arm showed very high FGF23 (898–1019mU/mL) but was unable to localise the FGF23 production. The lesion was surgically excised. Histopathology showed osteoclast-like cells and calcification, in line with a phosphaturic mesenchymal tumour. Tumour RNA analysis (TruSight RNA Pan Cancer panel) showed a FN1-FGFR1 fusion gene. Postoperatively, phosphate supplementation was discontinued, and alfacalcidol tapered. FGF23 decreased rapidly (24RU/mL after 14 days), phosphate concentration improved, but with concomitant increase in PTH (14. 9pmol/l), 1, 25 vitamin D (919pmol/l), ALP (415 mmol/l), undetectable calciuria, and worsening bone pain suggestive of hungry bone syndrome. His symptoms improved after 2-3 months, and all medications were stopped. Three months after surgery, 1, 25 vitamin D was still high but other biochemical indices had normalised.

Conclusion: Localisation of the tumour in TIO is often unsuccessful. Whole body MRI, peripheral venous FGF23 sampling, octreotide scan and octreotide SPECT-CT are commonly used. Recently, Ga-68 DOTATATE PET-CT has shown better sensitivity in adults, although it has high radiation dose. Ga-68-DOTATATE PET-CT performed best in identifying our patient’s tumour, whereas peripheral sampling for FGF23 was unsuccessful. Tumour RNA sequencing can reveal the underlying mechanism of TIO. Post-operatively, FGF23 drops rapidly, 1, 25 vitamin D rises, and hungry bone syndrome and bone pain can occur.