Cancer therapy-induced hyponatremia: A case-illustrated review

Abstract

Hyponatremia is the most common electrolyte disorder in patients with cancer and is associated with significant morbidity and mortality. Innovation in cancer therapies has led to substantial improvement in cancer outcomes, but also to new therapy-related toxicities, including electrolyte disturbance. Improvement in clinicians understanding of hyponatremia may mitigate adverse outcomes and improve quality of life in cancer patients. In this case-illustrated review, we discuss the mechanisms underlying drug-induced hyponatremia both in “classical” antineoplastic drugs and novel cancer therapies. Via these clinical cases, we describe hyponatremia caused by conventional chemotherapies (e.g. platinum compounds, vinca alkaloid, and alkylating agents) as well as hyponatremia related to tyrosine kinase inhibitors and other targeted therapies. We also focus on checkpoint inhibitors-induced hyponatremia, as these agents are increasingly used for a wide variety of malignancies. Lastly, we summarize therapy-related hyponatremia among recipients of newer treatments for multiple myeloma.

Severe Hyponatremia Triggered by Immune Checkpoint Inhibitor Therapy in a Patient With Mulvihill-Smith Syndrome

“…Hyponatremia is the most frequently encountered electrolyte and fluid disturbance, affecting up to 30% of hospitalized patients. 11 The first step in diagnosis begins with the categorization of the serum tonicity and the exclusion of pseudohyponatremia. Our patient was determined to have euvolemic hypotonic hyponatremia based on volume status, a low serum osmolality and an inappropriately high urine osmolality and sodium.…”

“…Between October 2019 and January 2020, the patient received nivolumab, a PD-1 inhibitor that has been associated with hyponatremia. 3 , 11 One study found that severe hyponatremia typically occurs within 1 year of ICI initiation 3 ; another reported onset as early as 9 days after initiation. 11 As the patient’s first episode of severe hyponatremia in November 2021 was noted 22 months after the discontinuation of nivolumab, we concluded that nivolumab was an unlikely trigger for the recurrent hyponatremia.…”

Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant

“…The systematic approach to the diagnosis of hyponatraemia in patients with cancer is complicated and needs awareness of pathophysiological processes related to both the tumour and the expanding compendium of anticancer therapies. SIADH is the most common underlying process in most cancer or cancer therapy-associated hyponatraemia 7…”

Hyponatremia and Fever in a Patient on Ipilimumab and Nivolumab (Immune Checkpoint Inhibitors): A Case Report

“…The risk of hyponatremia is higher with anti-CTLA-4 therapy compared with PD-1 or PD-L1 inhibitors. 14 …”

“…The risk of hyponatremia is higher with anti-CTLA-4 therapy compared with PD-1 or PD-L1 inhibitors. 14 In a retrospective observational study done on approximately 2500 patients with different cancers receiving ICIs, it was found that hyponatremia is the most common side effect occurring in 62% of patients with sodium level <134 mEq/dL, and out of those, 6% developed severe hyponatremia with sodium level <124 mEq/dL. 8 Another study shows that hypophysitis has an incidence of 10% to 17% from the anti-CTLA-4 Ipilimumab, whereas a combination of Ipilimumab and Nivolumab induced hypophysitis in 13% of patients.…”