Endocrine Abstracts

Objective: To review the clinical presentation, diagnosis, and management of immune checkpoint inhibitor (ICPi)-associated hypophysitis and pituitary dysfunction.

Method: A systematic review of studies published from 2005 to 2025 was conducted to evaluate pituitary immune-related adverse events (irAEs) linked to CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, and combination regimens. Eighty-four eligible studies comprising 7,259 patients were included. Extracted data included ICPi type, demographics, cancer type, treatment duration, imaging findings, type of pituitary dysfunction, clinical presentation, and management.

Results: The weighted average proportion of male patients was 68.3%, with a pooled mean age of 63.9 years. Common symptoms included fatigue, headache, hyponatraemia, nausea, anorexia, and neuropsychiatric changes. While MRI is a key diagnostic tool, it may not always detect subtle or early-stage pituitary involvement. In the CTLA-4 group, patients received ipilimumab for 2–12 cycles (mean: 3.3) before hypophysitis onset. In the PD-1/PD-L1 group, median time to onset was 28 weeks (range: 10–46 weeks). Hypophysitis induced by CTLA-4 inhibitors—particularly ipilimumab and CTLA-4-based combination therapies—is more commonly associated with hypopituitarism than that caused by other ICPi classes. In contrast, isolated ACTH deficiency, more frequently observed with PD-1 and PD-L1 inhibitors, typically presents as secondary adrenal insufficiency, often without distinct abnormalities on early MRI imaging. Reported MRI abnormalities included radiological evidence of hypophysitis, pituitary stalk abnormalities, pituitary enlargement, microadenoma, pituitary atrophy, and empty sella. Some patients showed no radiological abnormalities. The most common biochemical abnormalities in the combination group were hypopituitarism and secondary adrenal insufficiency. High-dose glucocorticoid initiation, careful tapering, and tailored long-term hormone replacement remained the mainstays of management.

Conclusion: Our systematic review demonstrates that hypopituitarism and secondary adrenal insufficiency are common and often persistent sequela of ICPi-associated hypophysitis. Prompt recognition through integrated clinical, biochemical, and radiological evaluation is crucial to minimise long-term endocrine morbidity and improve patient outcomes.