E-Poster 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

FGF23-mediated hypophosphataemia following intravenous iron administration: a case series (#68)

Lucy Collins 1 , Rebecca J Foskey 1 , Paul Wraight 1 , Spiros Fourlanos 1 2
  1. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  2. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia

Background

Severe and symptomatic hypophosphataemia is an increasingly recognised complication of intravenous iron infusion, affecting up to 40% of patients (1, 2). This is likely mediated by fibroblast growth factor 23 (FGF23), a peptide hormone synthesised by osteocytes and osteoblasts. FGF23 is a key regulator of phosphate homeostasis directly through its phosphaturic actions and indirectly by reducing activation of cholecalciferol to calcitriol causing secondary hyperparathyroidism (3).

As prescription of iron infusion increases in Australia, it is important to recognise this common but underappreciated complication (4). 

Aim

To examine the clinical and biochemical characteristics of patients detected with hypophosphataemia following iron infusion, and describe its treatment and natural history.

Results

Thirteen patients were identified with hypophosphataemia following intravenous iron administration. Median age was 72.5 years (interquartile range [IQR] 66.5 to 91), three patients were male and iron preparation was ferric carboxymaltose in seven patients. Six patients had received concurrent Denosumab, a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor. The median time from iron infusion to detection of hypophosphataemia was 12 days (IQR 8 – 14.5). The median creatinine was 60 mmol/L (45-60) (IQR 52-67). The median nadir phosphate value was 0.3mmol/L (0.75-1.50) (IQR 0.27 – 0.36). The median urinary fractional excretion of phosphate was 74% (IQR 66.75 – 88) (>5% indicates renal phosphate wasting). Median PTH was 29.8 (1.7-10) (IQR 25.3-38.3). Serum FGF23 and calcitriol values continue to be acquired.  Most patients were managed with intravenous followed by oral phosphate and calcitriol. There were no severe complications. 

Conclusion

Clinicians should be aware of the potential complication of profound hypophosphataemia following iron administration. The risk may be potentiated by use of RANK ligand inhibitors, malnutrition and normal renal function. We recommend patients at risk of hypophosphataemia undergo measurement of serum phosphate at one- and two- weeks following iron infusion.  

  1. Zoller H, Schaefer B, Glodny B. Iron-induced hypophosphatemia. Current Opinion in Nephrology and Hypertension. 2017;26(4):266-275.
  2. Adkinson N, Strauss W, Macdougall I, Bernard K, Auerbach M, Kaper R et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial. American Journal of Hematology. 2018;93(5):683-690.
  3. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. Journal of Bone and Mineral Research. 2003; 19(3), 429-435.
  4. Shand A, Bell J, Henry A, Grzeskowiak L, Kidson‐Gerber G, Pearson S et al. Rapid increase in intravenous iron therapy for women of reproductive age in Australia. Medical Journal of Australia. 2020;213(2):85-86.