# Adrenal Insufficiency‐Induced Delirium Following Gastrectomy in a Patient With Gastric Cancer Treated With Nivolumab, Immune Checkpoint Inhibitors: A Case Report

## TL;DR

A patient with gastric cancer developed delirium after surgery, which was caused by adrenal insufficiency linked to prior immune therapy.

## Contribution

Highlights adrenal insufficiency as an underrecognized cause of delirium in patients treated with immune checkpoint inhibitors.

## Key findings

- Postoperative delirium was linked to secondary adrenal insufficiency in a patient previously treated with nivolumab.
- Hydrocortisone replacement resolved neuropsychiatric and systemic symptoms rapidly.
- Preoperative HPA-axis screening is recommended for ICI-exposed patients undergoing major surgery.

## Abstract

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.

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.

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.

Postoperative hyperactive delirium unmasked secondary adrenal insufficiency in a patient with prior PD‐1 inhibitor exposure. Surgical stress revealed ICI‐related hypophysitis (↓ACTH → ↓cortisol). Hypotension and hypoglycemia prompted endocrine testing (AM cortisol 1.01 μg/dL; ACTH 1.5 pg/mL). Hydrocortisone replacement led to rapid resolution and antipsychotic de‐escalation. Consider preoperative HPA‐axis screening in ICI‐exposed surgical candidates.