Abstract: FR-PO0867
A Different Kind of Checkpoint Failure: Severe Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) After Pembrolizumab
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 1
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Oldford, Elaine J., VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
- Kaur, Harsimranjit, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
- Sumida, Keiichi, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
- Sharma, Shilpa, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
- Siu, Man Kit Michael, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States
Introduction
Hyponatremia during immune checkpoint inhibitor (ICI) therapy is typically attributed to immune-related adverse events (irAEs) such as adrenal insufficiency or hypophysitis. SIADH secondary to neuro-inflammatory toxicity remains poorly characterized.
Case Description
A 57-year-old man with clear cell renal cell carcinoma status post nephrectomy and left adrenalectomy received adjuvant pembrolizumab presented with abdominal pain, nausea, and vomitting, found to have sodium of 121 mmol/L. He had longstanding chronic hyponatremia with baseline sodium in the low 130s mmol/L.
He subsequently developed diplopia and bilateral facial nerve (CN VII) palsies. Additional lab work showed serum osmolality 273 mOsm/kg, urine sodium >100 mmol/L, and urine osmolality >800 mOsm/kg, suggestive of SIADH physiology. Endocrine evaluation demonstrated normal thyroid function and an adequate cortisol response to cosyntropin stimulation, making adrenal insufficiency unlikely despite prior adrenalectomy.
Neurologic evaluation demonstrated bilateral facial paresis, impaired ocular adduction, and persistent headache with nausea. Concern was raised for immune-mediated cranial neuropathy, including possible neuro-Sjögren’s syndrome or aquaporin-4–associated disease involving the area postrema. High-dose prednisone was initiated with gradual neurologic improvement.
During hospitalization, sodium acutely worsened to 112–116 mmol/L with severe headache and nausea, requiring ICU-level care and 3% hypertonic saline. Although IVIG administration raised concern for pseudohyponatremia, measured serum osmolality remained low, confirming true hypotonic hyponatremia. Despite fluid restriction and sodium chloride tablets, correction was limited. Given markedly elevated urine osmolality and low estimated free water clearance, oral urea therapy was initiated, resulting in gradual correction of sodium to 132–133 mmol/L without overcorrection.
Discussion
Pembrolizumab can precipitate severe SIADH via neuro-immune toxicity. Recognition of non-endocrine mechanisms is vital for management. Markedly elevated urine osmolality predicted poor response to fluid restriction. Urea effectively augmented osmotic free water excretion and represents an effective physiologic treatment strategy in patients with high urine osmolality and limited free water clearance.