Endocrine Abstracts

Case History: A 47 year-old female was referred to the Endocrine Bone Unit with worsening back, rib and leg pain associated with significantly reduced mobility. In the preceding year, she had repeatedly presented to healthcare providers with no clear neurological deficit, no fractures identified on X-Ray and normal MRI appearances of the whole spine. Aside from well-controlled asthma and gestational diabetes, she had no significant past medical, medication, social or family history of note.

Investigations : Her bloods revealed hypophosphataemia for over three years, reaching a nadir of 0.32mmol/l (0.80-1.50), and which persisted despite oral phosphate replacement alongside Vitamin D repletion. The remainder of her routine biochemistry was unremarkable. A DEXA scan demonstrated low bone density of L2-L4 (Z score -4.1) and hips (Z score -3.5). On assessment of urinary phosphate excretion, she had significantly reduced tubular reabsorption (TRP) 38.7% (>85%) and tubular maximum reabsorption of phosphate to GFR ratio (TmP/GFR) 0.14mmol/l (0.84-1.23). Further testing detected no abnormality in retinol binding protein or urinary amino acids, and thus excluded renal tubular injury or Fanconi syndrome. A 1,25 Vitamin D level was 66pmol/l (RR 55-139), and she notably had an inappropriately raised Fibroblast Growth Factor 23 (FGF23) level of 105 RU/mL (<100).

Results and Treatment: A Ga68 DOTATATE PET CT demonstrated focal intense uptake within the right lower mandible. An MRI mandible characterised a smooth well-circumscribed nodule 11x7mm in the right buccogingival sulcus, correlating to the focus of intense DOTATATE uptake. An ultrasound delineated a submucosal nodule over the right mandibular body, also identified on oral examination. Collectively, the biochemical, radiological and clinical findings suggested an FGF23-secreting tumour and the patient proceeded to local excision of the lesion with wide margins. The histopathology was consistent with a phosphaturic mesenchymal tumour. Her bloods subsequently demonstrated biochemical cure with a normal phosphate and FGF23 level, without supplements. Her bone density improved by 89.9% in the lumbar spine (Z score +1.7) and 60.2% in the hips (Z score +0.3). She has remained normophosphatemic since with remarkable recovery in weakness, pain and mobility observed.

Conclusion : Tumour induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by an FGF23-secreting lesion in the bone or soft tissue. It is characterised by FGF23-dependent phosphate wasting and associated osteomalacia. It is vital to suspect in cases of chronic hypophosphataemia associated with bone pain, fragility fractures or muscle weakness given that tumour excision can be biochemically and clinically curative.