Determinants of Quality of Life in Patients with Immune-Checkpoint-Inhibitor Induced Secondary Adrenal Insufficiency

Abstract Context Limited data are available on quality of life (QoL) and adrenal crises in patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency (ICI-SAI). Objective To 1) characterize the presentation, management, and outcomes of patients with ICI-SAI; 2) compare outcomes of ICI-SAI with other etiologies of secondary adrenal insufficiency (oSAI); and 3) identify variables associated with QoL and adrenal crisis. Methods In this single-center cross-sectional study, adults with ICI-SAI or oSAI (2018-2025) completed questionnaires assessing symptoms, management, adrenal crises, and the Addison disease-specific QoL survey (AddiQoL). Outcomes AddiQoL score and adrenal crisis events Results Patients with ICI-SAI (n=109) were older (median age 66 vs 60 years), more often women (59% vs 43%), and more frequently diagnosed within one year of symptom onset (88% vs 42%, P<0.001), compared to patients with oSAI (n=139). Patients with ICI-SAI had higher AddiQoL scores (median 87 vs 85, P=0.020). In a multivariable analysis of age, sex, glucocorticoid dose and type, insurance support and duration of SAI, ICI-SAI remained independently associated with higher AddiQoL (estimate 5.4, P=0.010). The prevalence of reported adrenal crises within the prior year was similar between groups (15% vs 14%, P=0.782). In a multivariable analysis, higher AddiQoL scores were independently associated with lower odds of adrenal crisis (OR of 0.57, 95% CI 0.42-0.76). Conclusion Patients with ICI-SAI report better QoL compared with patients with other causes of SAI, despite similar adrenal crisis rates. These differences may be related to earlier diagnosis and differing clinical contexts, underscoring the importance of timeline recognition and patient-centered management.