MON-481 - Pembrolizumab-Induced Hypophysitis Unmasked by Septic Shock and Persistent Hyponatremia

Introduction

Pembrolizumab, an immune checkpoint inhibitor, is associated with immune-related endocrinopathies affecting the pituitary, thyroid, and adrenal glands. Hypophysitis is a rare but potentially life-threatening complication, particularly when it results in secondary adrenal insufficiency. We describe a case of pembrolizumab-induced hypophysitis presenting with refractory shock and persistent hyponatremia during sepsis, occurring 18 months after therapy initiation.

Case Presentation
A 64-year-old Caucasian lady with squamous cell carcinoma of the lung who completed 12 cycles of pembrolizumab, presented to the emergency department with 5-days of vomiting and an episode of presyncope. She was hypotensive (MAP 60 mmHg) and hyponatremic (Na 120 mmol/L). Despite receiving 3 liters of intravenous fluids, she showed no hemodynamic improvement. Urinalysis revealed a urinary tract infection, and empiric cefepime was initiated. She was admitted to the ICU with mixed septic and hypovolemic shock, requiring norepinephrine, vasopressin, and stress-dose hydrocortisone for refractory hypotension. Vasopressors were successfully weaned by hospital day 2. Urine cultures grew Klebsiella pneumoniae sensitive to ceftriaxone, and antibiotics were de-escalated accordingly.
Serum sodium transiently improved to 127 mmol/L but subsequently declined despite euvolemia and adequate oral intake. Initial urine studies suggested SIADH, which was clinically plausible given her lung malignancy. However, sodium worsened with fluid restriction and recurrent vomiting. Repeat urine studies showed urine sodium < 10 mmol/L, arguing against SIADH. Morning cortisol was low at 3.5 μg/dL with an inadequate cosyntropin response on the next day (baseline 0.9, 5.1 at 30 minutes, and 8.8 μg/dL at 60 minutes), and ACTH was suppressed ( < 5 pg/mL), confirming central adrenal insufficiency. Given prolonged pembrolizumab exposure, immune-mediated hypophysitis was diagnosed. Hydrocortisone replacement (10 mg twice daily) led to resolution of nausea, hemodynamic stability, and normalization of sodium. At subsequent oncology clinic follow-up, sodium remained stable at 135 mmol/L.

Conclusion
Pembrolizumab-induced hypophysitis may present insidiously and exacerbate sepsis-related hypotension and hyponatremia. Central adrenal insufficiency contributed to refractory shock, persistent hyponatremia, and debilitating gastrointestinal symptoms. This case highlights the importance of maintaining a high index of suspicion for endocrine immune-related adverse events, even late in therapy, as early recognition and timely hormone replacement result in rapid clinical improvement.

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