Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Cyclophosphamide Induced Hyponatremia: ACute Cases of Hyponatremia  (#635)

Melisha Thambyaiyah 1 2 , Sue-Lynn Lau 1 2 , Rabbia Haider 1
  1. Diabetes and Endocrinology, Blacktown-Mt Druitt Hospital, Blacktown, NSW, Australia
  2. Blacktown School of Medicine, Western Sydney University, Sydney, NSW, Australia

Introduction:
Intravenous cyclophosphamide remains a cornerstone of treatment for triple-negative breast cancer (TNBC), a rare complication being severe hyponatremia (1). We present 2 case studies and review existing literature to explore mechanism, predictors and management strategies,

Case 1:
A 77- year-old female presented with generalised tonic-clonic seizure and serum sodium of 116 nmol/L, 1 day post receiving cycle 1 low-dose cyclophosphamide and doxorubicin (AC) for TNBC. Sodium was 140 mmol/L, 10 days prior. She had a history of hypertension, gastro-oesophageal reflux disease and thalassemia managed with telmisartan, amlodipine and rabeprazole. Investigations revealed serum osmolality of 250 mmol/kg, urine osmolality of 525 mmol/kg, and urine sodium of 61 mmol/L. Sodium levels normalised and symptoms resolved within 48 hours after receiving hypertonic saline. Cyclophosphamide was discontinued.

Case 2:
A 64-year-old female presented with rigors, vomiting and dyspnoea and Na of 116 mmol/L, day 2 post receiving Cycle 1 low dose AC chemotherapy for TNBC. Medical history was significant for hyperlipidemia, Na was 143 mmol/L, 1 month prior. Serum osmolality was 249 mmol/kg, urine osmolality 416 mmol/kg and urine Na 25 mmol/L. Treatment with 1 litre fluid restriction resulted in rapid sodium correction and resolution of symptoms within 24 hours. Cyclophosphamide was discontinued.

Conclusion:
Review of these 2 cases and 11 previous case-reports of cyclophosphamide-induced hyponatremia indicate that clinical and biochemical parameters are consistent with Syndrome of Inappropriate Antidiuretic Hormone. However, some cases have low plasma vasopressin levels, and two cases had known central diabetes insipidus, suggesting an alternative mechanism (2). Pre-clinical rodent studies propose a direct nephrogenic syndrome of inappropriate anti-diuresis (3). Current management typically involves close monitoring, fluid restriction, and salt tablets although tolvaptan may be a promising therapeutic option (4). Further research may identify predictive biomarkers and develop preventive strategies, potentially allowing cyclophosphamide continuation.

  1. Young-Chul Lee, Joon-Sung Park, Chang Hwa Lee, Sang-Cheol Bae, In-Soon Kim, Chong Myung Kang, Gheun-Ho Kim, Hyponatraemia induced by low-dose intravenous pulse cyclophosphamide, Nephrology Dialysis Transplantation, Volume 25, Issue 5, May 2010, Pages 1520–1524
  2. Steinman, R., Schwab, S., & Munir, K. (2015). Cyclophosphamide-Induced Hyponatremia in a Patient With Diabetes Insipidus. Journal Of Endocrinology And Metabolism, 5(6), 337-339.
  3. Kim, S., Choi, H. J., Jo, C. H., Park, J. S., Kwon, T. H., & Kim, G. H. (2015). Cyclophosphamide-induced vasopressin-independent activation of aquaporin-2 in the rat kidney. American journal of physiology. Renal physiology, 309(5), F474–F483.
  4. El-Shabrawy, M., Mishriki, A., Attia, H., Emad Aboulhoda, B., Emam, M., & Wanas, H. (2020). Protective effect of tolvaptan against cyclophosphamide-induced nephrotoxicity in rat models. Pharmacology research & perspectives, 8(5), e00659.