Fibroblast growth factor 23 (FGF23)-mediated hypophosphataemia is a potentially under-recognised complication following intravenous iron infusion. We present a case of a 53-year-old woman with relapsing remitting multiple sclerosis who developed symptomatic severe hypophosphataemia following an iron infusion. At presentation, biochemistry revealed: serum phosphate 0.32 mmol/L (0.75-1.50 mmol/L), corrected calcium 2.33 mmol/L (2.10-2.60 mmol/L), creatinine 67 umol/L (45-90 umol/L), albumin 37 g/L (35-50 g/L), 25-hydroxyvitamin D 124 nmol/L (sufficiency > 50 nmol/L), 1,25-dihydroxyvitamin D 48 pmol/L (50-190 pmol/L) and parathyroid hormone 17.1 pmol/L (1.7-10.0 pmol/L). The patient was treated with intravenous and oral phosphate replacement. Urinary phosphate fractional excretion was calculated to be 88% (a value of > 5% indicates renal phosphate wasting). In this case serum FGF23, assayed externally using a Diasorian Liaison XL (Vercelli, Italy), was significantly elevated at 136 pg/mL (23.2-95.4 pg/mL). Following a re-admission to hospital for nausea and vomiting, presumed secondary to high dose oral phosphate, our patient was commenced on calcitriol and cholecalciferol replacement. We found this approach to be well tolerated and efficacious. Cholecalciferol and calcitriol were weaned over 18 weeks with maintenance of serum phosphate.
Intravenous iron is administered to patients across a range of medical specialities. There is limited awareness of the effect of iron infusions on serum phosphate, and no guidelines regarding the management of consequent hypophopsphataemia. We hope our case raises awareness amongst health professionals of the potential deleterious outcome of symptomatic hypophosphataemia following iron administration; likely mediated by a transient elevation of FGF23. The risk of hypophosphataemia may be further potentiated by risk factors such as malnutrition, use of Receptor activator of nuclear factor kappa-B (RANK) ligand inhibitors and possibly, multiple sclerosis given their higher basal FGF23 (1). We recommend patients at risk of hypophosphataemia receiving iron infusions undergo measurement of serum phosphate at one- and three-weeks post treatment.