Clinical characteristics and management of nivolumab-induced hypophysitis: retrospective analysis based on case reports

Abstract

Nivolumab-associated hypophysitis is a rare endocrine immune-related adverse event with incompletely defined clinical characteristics and management. This study aimed to synthesize patient-level evidence to clarify its presentation, treatment, and clinical outcomes, thereby facilitating earlier recognition and evidence-based management. We conducted a retrospective, case-based synthesis of nivolumab-induced hypophysitis. PubMed, EMBASE, Web of Science, WanFang Data, and CNKI were systematically searched for reports published up to Jan 31, 2026, using a combination of MeSH terms: (“nivolumab” OR “PD-1 inhibitor” OR “programmed death-1 inhibitor” OR “immune checkpoint inhibitor” OR “ICI”) AND (“hypophysitis” OR “pituitary inflammation” OR “hypopituitarism”) AND (“immune-related adverse event” OR “irAE” OR “endocrinopathy”). Among 2,264 records screened, 38 case reports and case series comprising 40 patients were included in the final analysis. Median age was 62 years (range 26–84), and 72.5% were male. Hypophysitis occurred most often in melanoma (42.5%) and renal cell carcinoma (30.0%), with a median onset of 20 weeks. Fatigue (82.5%), anorexia/nausea (65.0%), and hyponatremia (42.5%) were common; pituitary MRI abnormalities were reported in 46.2%. Endocrine testing mainly showed central adrenal insufficiency with central hypothyroidism; median cortisol and ACTH were 2.9 µg/dL and 38.0 pg/mL. All patients received corticosteroids, 35.0% received levothyroxine, and nivolumab was discontinued in 80.0%. Among 16 rechallenged patients, relapse occurred in 18.8%. Clinical improvement was frequent (92.5%), whereas full hormonal recovery was uncommon. Nivolumab-induced hypophysitis primarily involves the corticotropic axis. Early hormonal evaluation and imaging are essential. Corticosteroids remain the mainstay of treatment, and long-term hormone replacement is often necessary. Rechallenge with nivolumab may be considered in selected patients, but requires careful risk-benefit assessment. Not applicable.