e24197 Background: Endocrine immune-related adverse events (irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), yet contemporary real-world data on organ-specific severity and serious outcomes are limited. We conducted a pharmacovigilance study to characterize organ-specific endocrine toxicity signals and associated serious outcomes in the current ICI era. Methods: We performed a retrospective analysis of adverse events reported to the FDA Adverse Event Reporting System (FAERS) from January 2020 through December 2024. ICI exposure was identified using drug role codes with comprehensive capture of all current PD-1, PD-L1, and CTLA-4 inhibitors, administered as monotherapy or in combination. Primary suspected (PS) ICIs were used for primary analyses, with PS plus secondary suspected (PS+SS) analyses assessing robustness and combination regimens.Endocrine adverse events were categorized into thyroid, pituitary, adrenal, and diabetes-related groups using MedDRA preferred terms. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals (CIs) relative to all other drugs. Serious outcomes were defined using FAERS outcome codes (death, hospitalization, life-threatening, disability, or other medically serious condition). Results: Among 7.47 million deduplicated FAERS cases, 104,128 PS ICI-exposed cases were identified, including 7,844 endocrine irAEs. Compared with non-ICI therapies, ICIs showed significantly increased reporting of endocrine toxicities, strongest for pituitary (ROR 41.5, 95% CI 39.0–44.2) and adrenal events (ROR 24.5, 95% CI 23.3–25.7), followed by thyroid (ROR 6.2, 95% CI 6.0–6.5) and diabetes-related toxicities (ROR 3.4, 95% CI 3.3–3.6). Findings were consistent in PS+SS analyses.Despite lower frequency, pituitary and adrenal irAEs carried the highest severity burden, with hospitalization rates of 58.1% and 58.7% versus 37.5% for thyroid events, and life-threatening outcomes in 11.8% and 10.7% versus 6.1%, respectively. Overall mortality among endocrine irAEs was 8.8%. Combination ICI therapy (21,369 PS+SS cases) showed higher endocrine toxicity burden than monotherapy (12.3% vs 6.3%) and higher hospitalization (58.9% vs 51.8%) and life-threatening event rates (12.1% vs 9.6%), with similar mortality. Conclusions: ICI-associated endocrine toxicities exhibit distinct organ-specific risk–severity profiles. Pituitary and adrenal irAEs, though less frequent than thyroid dysfunction, show disproportionately high reporting odds and serious-outcome burden, consistent with a “rare but severe” phenotype. Combination ICI therapy further increases endocrine toxicity risk and severity, underscoring the need for heightened vigilance and proactive monitoring, especially for pituitary and adrenal complications.
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