Abstract
BACKGROUND: Delirium is common after major surgery, yet endocrine causes such as adrenal insufficiency (AI) may be underrecognized, particularly in patients previously exposed to immune checkpoint inhibitors (ICIs); recent guidance encourages systematic hormonal monitoring (e.g., morning cortisol/ACTH) during ICI therapy. CASE PRESENTATION: We present the case of a 69-year-old female who developed hyperactive delirium following total gastrectomy for previously treated gastric cancer with nivolumab. Persistent hypotension and hypoglycemia prompted endocrine testing, which revealed low morning cortisol with inappropriately low ACTH, consistent with secondary AI. Brain MRI and EEG showed no alternative etiologies. Dynamic testing could not be performed in the acute setting, and a dedicated preoperative HPA-axis screen had not been undertaken. Hydrocortisone replacement therapy resulted in rapid resolution of neuropsychiatric and systemic symptoms. CONCLUSION: This case highlights adrenal insufficiency as an underrecognized cause of delirium in ICI-treated patients during the perioperative period. Awareness, early endocrine evaluation, and timely glucocorticoid replacement are crucial; preoperative screening may be considered in ICI-exposed patients scheduled for major surgery.