Endocrine Abstracts

Background: Fibroblast growth factor-23 (FGF-23) mediated chronic hypophosphataemia is rare, usually caused by genetic or acquired renal phosphate-wasting disorders. Due to their rarity, they are often under-recognised and suboptimally managed, leading to poor bone health.

Case: A 61-year-old man with hypophosphataemia, initially identified in 2014, was reviewed by renal specialists in 2016. A 24-hour urine collection demonstrated inappropriately high phosphate excretion. CT of the chest, abdomen, and pelvis was unremarkable; therefore he was discharged on oral phosphate supplementation. Seven years later, he was referred to endocrinology for further evaluation. Although he was asymptomatic and had no fracture history, his serum phosphate levels persistently fluctuated, requiring a high dose of oral phosphate (4g/day). He had osteopenia in the hip and family history was unremarkable, aside from osteoporosis. Oral phosphate was suspended for repeat assessment. Biochemistry showed low phosphate of 0.55 (N-0.80-1.50mmol/l), normal adjusted calcium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Parathyroid hormone and alkaline phosphatase were elevated, 9.7pmol/l (N-1.6-6.9pmol/l) and 131U/l (N-30-130U/l), respectively. 24-hour urine showed increased phosphate excretion of 57.1mmol/24h (N-11-33mmol/24h) and a low TmP/GFR, confirming renal phosphate wasting. FGF-23 was elevated at 165.5 (N-33-100pg/mL). Tektrotyd scintigraphy was normal; whole-body FDG-PET is pending, and genetic testing is being considered.

Discussion: FGF-23 secreted by osteocytes, is a key regulator of phosphate homeostasis. Excess FGF-23 reduces renal phosphate reabsorption, causing renal phosphate wasting. Measurement of FGF-23 and TmP/GFR is central to the diagnostic evaluation of unexplained hypophosphataemia. FGF-23–mediated hypophosphataemia is associated with genetic conditions such as X-linked hypophosphataemia (XLH) or acquired causes like tumour-induced osteomalacia (TIO). Differentiating between these is crucial, as XLH is treated with oral phosphate, activated vitamin D, or burosumab, an anti-FGF-23 monoclonal antibody, while TIO requires tumour localisation and removal. This case highlights the importance of a structured evaluation of chronic hypophosphataemia to guide appropriate management.