Sequential development of isolated ACTH deficiency and fulminant type 1 diabetes as delayed immune-related endocrine adverse events

A man in his 70s with lung adenocarcinoma (cStage IVA) received POSEIDON-based therapy with durvalumab, tremelimumab and chemotherapy. After six cycles, progressive disease prompted a switch to carboplatin plus nab-paclitaxel. Nineteen weeks after the final immune checkpoint inhibitor (ICI) administration, he developed fatigue and anorexia. Adrenocorticotropic hormone (ACTH) and cortisol were below assay detection limits, and a corticotropin-releasing hormone stimulation test showed no ACTH response, consistent with ICI-related isolated ACTH deficiency. Symptoms improved with hydrocortisone replacement. Five weeks later, he developed diabetic ketoacidosis, with a glucose level of 30.4 mmol/L (reference range, 3.9-6.1 mmol/L) and a ketone level of 6.3 mmol/L (<0.6 mmol/L). HbA1c and urinary C-peptide excretion were 6.9% (4.6%-6.2%) and 1.8 nmol/day (7.5-51.4 nmol/day) respectively. These findings supported a diagnosis of fulminant type 1 diabetes mellitus, considered ICI-related. This case highlights the need for continued vigilance, as immune-related adverse events may develop sequentially even after ICI therapy has ended.