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Life sciences · Journal article
Frontiers in Oncology · September 29, 2026
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Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC) but may induce immune-related adverse events (irAEs), including hypophysitis. Although endocrine irAEs usually present with nonspecific constitutional symptoms, atypical manifestations may delay diagnosis and expose patients to unnecessary invasive procedures. We report the case of a 76-year-old man with metastatic NSCLC receiving first-line nivolumab, ipilimumab, carboplatin, and pemetrexed who developed profound asthenia, altered mental status, bilious vomiting, and severe gastrointestinal dilation suggestive of acute mechanical bowel obstruction after two treatment cycles. Computed tomography demonstrated marked gastric and intestinal distension, and surgical management was initially considered. Endocrine evaluation subsequently revealed central hypothyroidism and secondary adrenal insufficiency, consistent with ICI-induced hypophysitis. Prompt initiation of physiological hormone replacement with intravenous hydrocortisone followed by thyroid hormone supplementation resulted in rapid neurological and systemic recovery, complete restoration of gastrointestinal motility, radiological resolution of bowel dilatation, and avoidance of surgery. Follow-up imaging also demonstrated a partial tumor response, which has remained durable for more than two years without additional anticancer treatment while the patient continues long-term endocrine replacement therapy. This case expands the clinical spectrum of ICI-induced hypophysitis by describing an unusual presentation as acute paralytic ileus mimicking mechanical bowel obstruction. It underscores the importance of maintaining a high index of suspicion for endocrine irAEs in patients receiving ICIs who develop unexplained multisystem deterioration or apparent surgical abdomen. Early hormonal assessment and timely replacement therapy can be lifesaving, prevent unnecessary surgical interventions, and allow optimal multidisciplinary management without compromising oncologic outcomes.