Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Cetuximab induced hypocalcaemia, hypomagnesaemia and hypoparathyroidism (#254)

Shan Jiang 1 , Tang Wong 1 2 , Jeff Flack 1 3
  1. Diabetes Centre, Bankstown-Lidcombe Hospital, Bankstown, NSW, Australia
  2. Department of Medicine, University of NSW, Sydney, NSW, Australia
  3. Department of Medicine, University of Western Sydney Bankstown Campus, Bankstown, NSW, Australia

Introduction

Cetuximab is an epidermal growth factor receptor (EGFR) monoclonal antibody used in combination with chemotherapy for the management of RAS-wild-type metastatic colorectal cancer. Hypomagnesaemia is a common side effect of Cetuximab treatment.1 We present the case of a patient who developed symptomatic hypocalcaemia with hypomagnesaemia related to Cetuximab treatment for metastatic colorectal cancer.

Case History

A 58 year old male presented to Bankstown-Lidcombe hospital with acute vomiting and acral paraesthaesias. He was treated with Cetuximab and FOLFOX chemotherapy of 8 months duration for management of metastatic colorectal cancer. He was previously noted to have intermittent hypomagnesemia with nadir levels of 0.15mmol/L associated with hypocalcaemia as low as 1.77mmol/L.

On this presentation, his corrected calcium was 1.55mmol/L, in context of hypomagnesaemia of 0.10mmol/L and inappropriately low intact PTH level of 1.6pmol/L. Further investigations demonstrated replete 25-hydroxy-Vitamin-D3 level of 68nmol/L and elevated 24 hour urinary excretions of magnesium and calcium. The patient received intravenous magnesium sulphate, calcium gluconate, oral calcium carbonate and calcitriol. Cetuximab was ceased, and patient was discharged on oral magnesium aspartate, calcium carbonate and calcitriol. While hypomagnesaemia persisted for a further 2 months before spontaneous resolution, there were no further episodes of hypocalcaemia.

Discussion

Cetuximab induced hypomagnesaemia may be related to inhibition of EGFR receptors highly expressed in the ascending limb of the Loop of Henle, leading to impaired renal resorption of magnesium via the transient receptor potential melastatin subtype6 (TRPM6) ion channel.2 PTH suppression in severe hypomagnesaemia may be mediated by an increase in G-alpha subunit activation of the calcium-sensing receptor, leading to severe hypocalcaemia.3 Administration of calcitriol in this context ameliorates the effect of hypoparathyroidism until the suppressive effect of hypomagnesaemia resolves.

Conclusion

Severe hypomagnesaemia from Cetuximab use can induce hypocalcaemia via PTH suppression. Patients can benefit from calcitriol therapy in addition to calcium, magnesium replacement.

  1. 1. Mahtani, Reshma L., and John S. Macdonald. "Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract." The Oncologist 13.1 (2008): 39-50.
  2. 2. Schrag, Deborah, et al. "Cetuximab therapy and symptomatic hypomagnesemia." Journal of the National Cancer Institute 97.16 (2005): 1221-1224.
  3. 3. Quitterer, Ursula, et al. "Paradoxical block of parathormone secretion is mediated by increased activity of Gα subunits." Journal of Biological Chemistry 276.9 (2001): 6763-6769.