Frontiers in endocrinology · 2026
Clinical characteristics, management, and prognosis of ipilimumab-induced hypophysitis: a retrospective analysis of 76 cases.
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Wu Ling, Yang Yuping, Su Qiongli
Аннотация
BACKGROUND: Ipilimumab, a cytotoxic T-lymphocyte associated antigen-4 inhibitor, is associated with immune-related endocrine adverse events, among which hypophysitis represents a distinctive but incompletely characterized toxicity. This study aimed to systematically summarize the clinical characteristics, therapeutic approaches, and prognostic outcomes of ipilimumab-induced hypophysitis.
METHODS: We conducted a retrospective, case-based synthesis of ipilimumab-induced hypophysitis. PubMed, EMBASE, Web of Science, WanFang Data, and CNKI were systematically searched from database inception to February 1, 2026, to identify eligible case reports and case series using combinations of terms related to ipilimumab, hypophysitis, and immune-related adverse events. The methodological quality of included reports was assessed using the Joanna Briggs Institute Critical Appraisal Checklist.
RESULTS: A total of 76 patients were included. The median age was 58 years (range 26-82), and 61.8% were male. The median time to onset was 9 weeks (range 1.6-37), with more than half occurring within the first 10 weeks of treatment. Headache (68.0%) and fatigue (64.0%) were the most common symptoms. Secondary adrenal insufficiency predominated, with low cortisol and ACTH levels detected in 93.4% and 89.8% of evaluated patients, respectively. Central hypothyroidism and hypogonadism were also frequent. Pituitary enlargement was observed in 71.0% of patients undergoing magnetic resonance imaging. Glucocorticoid replacement constituted the primary treatment. Clinical improvement occurred in 82.9% of patients; however, persistent endocrine dysfunction remained common, and complete hormonal recovery was rare (7.9%). Ipilimumab rechallenge was uncommon. According to the WHO-UMC system, most cases (80.3%) were classified as probable.
CONCLUSION: Ipilimumab-induced hypophysitis typically occurs early in treatment and is characterized by secondary adrenal insufficiency with frequent pituitary enlargement. Although symptoms often improve with hormone replacement, recovery of pituitary function is uncommon, warranting long-term endocrine monitoring.
METHODS: We conducted a retrospective, case-based synthesis of ipilimumab-induced hypophysitis. PubMed, EMBASE, Web of Science, WanFang Data, and CNKI were systematically searched from database inception to February 1, 2026, to identify eligible case reports and case series using combinations of terms related to ipilimumab, hypophysitis, and immune-related adverse events. The methodological quality of included reports was assessed using the Joanna Briggs Institute Critical Appraisal Checklist.
RESULTS: A total of 76 patients were included. The median age was 58 years (range 26-82), and 61.8% were male. The median time to onset was 9 weeks (range 1.6-37), with more than half occurring within the first 10 weeks of treatment. Headache (68.0%) and fatigue (64.0%) were the most common symptoms. Secondary adrenal insufficiency predominated, with low cortisol and ACTH levels detected in 93.4% and 89.8% of evaluated patients, respectively. Central hypothyroidism and hypogonadism were also frequent. Pituitary enlargement was observed in 71.0% of patients undergoing magnetic resonance imaging. Glucocorticoid replacement constituted the primary treatment. Clinical improvement occurred in 82.9% of patients; however, persistent endocrine dysfunction remained common, and complete hormonal recovery was rare (7.9%). Ipilimumab rechallenge was uncommon. According to the WHO-UMC system, most cases (80.3%) were classified as probable.
CONCLUSION: Ipilimumab-induced hypophysitis typically occurs early in treatment and is characterized by secondary adrenal insufficiency with frequent pituitary enlargement. Although symptoms often improve with hormone replacement, recovery of pituitary function is uncommon, warranting long-term endocrine monitoring.