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

Abstract

Immune checkpoint inhibitors (ICIs) are novel anticancer therapy approved in multiple tumors and their use is rapidly increasing. They are associated with various systemic side effects that are immune-mediated and clinically coined as “immune-related adverse effects” (irAE). Hyponatremia is a possible side effect in patients receiving ICIs. Fever is another side effect that is mostly non-infectious. There are different mechanisms leading to hyponatremia in patients on ICIs, which could be (1) hypovolemic hyponatremia due to hemodynamic disturbance secondary to volume depletion (eg, from irAE like colitis and enteritis) or hypervolemia due to congestive heart failure, cirrhosis, or nephrosis; (2) syndrome of inappropriate antidiuretic hormone (SIADH) secretion (especially from underlying lung cancer or neurological irAE like encephalitis and meningitis) with elevated urine sodium and urine osmolarity; and (3) irAE-related endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism leading to euvolemic hyponatremia. We describe an interesting case of hyponatremia and fever in a patient receiving Ipilimumab and Nivolumab. The possible etiology of hyponatremia, in this case, was hypovolemia and volume depletion secondary to fever.

Immune checkpoint inhibitors and acute kidney injury

“…Immune-endocrine disease is an important cause of electrolyte abnormalities, such as hypophysitis, adrenal insufficiency, primary hyperparathyroidism and hypothyroidism (144)(145)(146). In the study by Patel et al, the mechanisms of hyponatremia include hypovolemic hyponatremia due to hemodynamic disorders caused by volume depletion, hypervolemic hyponatremia due to CHF or nephrosis, syndrome of inappropriate antidiuretic hormone secretion, and endocrine diseases (147). In addition, Izzedine et al summarized the etiology of hypercalcemia, including endocrine disorders, sarcoid-like granuloma, humoral hypercalcemia due to parathyroid related hormone and pseudo-or hyperprogressive disease during ICIs therapy (148).…”