Endocrine Abstracts

Tumour-Induced Osteomalacia (TIO) is a rare paraneoplastic syndrome that is often underdiagnosed given its non-specific manifestations. A 64-year-old Chinese male presented with chest discomfort and generalized weakness. He was treated for symptomatic iron deficiency anaemia, with two units of blood transfusion given his low haemoglobin of 6.1 g/dl; no intravenous iron replacement was given. Concurrently, laboratory results revealed a low phosphate level of 0.4 mmol/l [reference range: 0.94-1.50 mmol/l], requiring aggressive intravenous and oral phosphate replacements. Past medical history was significant for atrial fibrillation, dilated cardiomyopathy with an ejection fraction of 37%, myositis on mycophenolate mofetil, and glucocorticoid-induced osteoporosis – presently on drug holiday after three years of alendronate. There was no previous history of hypophosphataemia. On subsequent follow-up, he remained persistently hypophosphataemic (0.34-0.4 mmol/l). He had no symptoms to suggest gastrointestinal losses. His calcium and renal function were normal at 2.15 mmol/l [reference range 2.09-2.46 mmol/l] and 32 pmol/l [reference range 37-75 pmol/l] respectively. iPTH was mildly elevated 9.6 mmol/l [reference range 1.30 – 7.60 pmol/l], possibly contributed by Vitamin D insufficiency (21 ng/ml). In light of persistent hypophosphataemia, 24-hour urinary phosphate studies were pursued. The fractional excretion of phosphate of 32.9%, and the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) of 0.43 mmol/l for a corresponding low phosphate reading of 0.76 nmol/l suggested renal phosphate loss. He had no syndromic features and has no family history of abnormal phosphate metabolism or skeletal disorders. Examination did not reveal palpable lymph nodes or masses, and was otherwise systemically unremarkable. Fibroblast growth factor 23 (FGF-23) was elevated at 102 pg/ml [reference range ≤59 pg/ml]. 1,25-Dihydroxyvitamin D was normal. Following the suspicion for TIO; ⁶⁸Ga-DOTATATE PET/CT was performed with tracer-avidity localising to the left big toe. This was confirmed subsequently on magnetic resonance imaging as an ill-defined 1.2 x 0.5 x 1.2 cm³ T1 w/T2w hypointense, heterogeneously enhancing lesion at the lateral aspect of the hallux proximal phalanx. He was given phosphate, colecalciferol and calcitriol replacements and eventually underwent excision of the left big toe soft tissue tumour. Histology yielded monomorphic ovoid tumour cells, consistent with a phosphaturic mesenchymal tumour. Post-operatively, serum phosphate normalized as did FGF-23 to 24 pg/ml. This patient’s insidious presentation of muscle weakness was initially perceived to be from symptomatic anaemia. His persistent hypophosphataemia led to an eventual diagnosis of TIO, with no overt clinical findings, highlighting the challenges in the diagnosis of TIO.