SUN-456 - When Immunotherapy Strikes the Pituitary: Severe Hypophysitis with Multi-Organ Involvement

Background: Immune checkpoint inhibitor–associated hypophysitis is a recognized endocrine adverse event, usually presenting with subtle adrenal insufficiency. We report an atypical case causing severe systemic inflammation that mimicked septic shock.

Case Presentation: A 69-year-old man with metastatic melanoma presented with six days of severe headache, fever, neck stiffness, and altered mental status two weeks after receiving combination immune checkpoint inhibitor (ICI) therapy with ipilimumab and nivolumab. On admission, he was tachycardic but otherwise hemodynamically stable. Examination revealed right axillary lymphadenopathy without focal neurologic deficits.
An extensive infectious and neurologic workup was negative. Despite broad-spectrum antibiotics, the patient worsened with persistent fevers, hypoxic respiratory failure, erythroderma, and encephalopathy, requiring ICU admission for presumed septic shock; stroke and seizure were excluded.
Given recent ICI exposure, immune-related toxicity was suspected. Endocrine testing revealed secondary adrenal insufficiency (ACTH < 5 pg/mL, cortisol 2.1 µg/dL) and central hypothyroidism (free T4 0.5 ng/dL with non-elevated TSH). Pituitary MRI showed a small hypoenhancing anterior pituitary lesion consistent with ICI-associated hypophysitis.
High-dose IV corticosteroids led to rapid resolution of fevers and rash, with improvement in cortisol levels to 28.1 µg/dL. The hospital course was complicated by acute kidney injury, transaminitis, and cytopenias, and the patient was discharged on a prednisone taper.

Discussion: This case demonstrates ICI-induced hypophysitis mimicking septic shock, in which secondary adrenal insufficiency caused fever, encephalopathy, and hemodynamic instability. Cortisol deficiency led to inflammation, hypotension, and multisystem immune toxicity. Hypophysitis is a known immune-related adverse event of ICI therapy, typically occurring weeks to months after treatment. Low cortisol with suppressed ACTH confirmed adrenal insufficiency, and rapid improvement with corticosteroids was both diagnostic and life-saving. ICI-induced hypophysitis results from immune activation after checkpoint blockade, leading to pituitary damage and hormone loss. Stress-dose hydrocortisone is recommended for unstable patients and must precede thyroid hormone replacement; long-term adrenal hormone replacement is often required.

Conclusion: ICI-induced hypophysitis can mimic septic shock. Early cortisol and ACTH testing and prompt stress-dose corticosteroids are essential, and management requires multidisciplinary care.

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