Immune Checkpoint Inhibitor-Induced Hypophysitis Presenting as Severe Hyponatremia: A Nephrology Perspective on Avoiding the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Pitfall.

A 79-year-old woman with malignant melanoma receiving ipilimumab and nivolumab presented with headache, generalized weakness, nausea, vomiting, and severe euvolemic hyponatremia. Her sodium had declined from 136 mmol/L to 111 mmol/L over one week. Initial urine studies showed hypotonic hyponatremia with inappropriately concentrated urine and elevated urine sodium, mimicking the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Nephrology consultation identified central adrenal insufficiency, with morning cortisol at 1.6 mcg/dL and suppressed adrenocorticotropic hormone (ACTH), along with central hypothyroidism in the setting of immune checkpoint inhibitor therapy. Glucocorticoid replacement was initiated prior to levothyroxine, and tolvaptan was used as a temporizing aquaretic therapy for persistent severe hyponatremia while hormone replacement was initiated. Sodium normalized, and the patient was transitioned to outpatient endocrine management. This case highlights the importance of evaluating hypophysitis and pituitary failure in patients receiving immune checkpoint inhibitors who present with severe or refractory hyponatremia. Early recognition can prevent delayed glucocorticoid replacement and adrenal crisis.