Adrenal crises and quality of life after bilateral adrenalectomy versus primary autoimmune adrenal insufficiency

Abstract Context Bilateral adrenalectomy (BLA) and autoimmune adrenal insufficiency (AAI) are two major causes of primary adrenal insufficiency (PAI). Comparative data between etiologies are limited. Objective To compare management, quality of life (QoL), and frequency of adrenal crises between participants post-BLA versus AAI. Methods We conducted a dual-center, cross-sectional study of adults with AAI or BLA, 2018-2025. All participants completed questionnaires on management, adrenal crises, and the Addison disease-specific QoL questionnaire (AddiQoL). Results Of 343 participants, 203 had AAI (median age 54 years, 72% women) and 139 had BLA (median age 57 years, 76% women). AddiQoL scores were similar between participants with AAI and BLA (median 84 vs 83, P=0.947), but better in participants post-BLA for pheochromocytoma vs hypercortisolism (median 88 vs 81, P=0.031). Participants with AAI reported a higher number of adrenal crises within the last year than those post-BLA (25% vs 13%, P=0.022). In multivariable analyses of age, sex, glucocorticoid dose and type, PAI type, AddiQoL score, and autoimmune comorbidities, only PAI type was associated with higher number of reported adrenal crisis within the last year (AAI vs BLA: Odds Ratios of 2.1-2.2, P<0.05 for all models). Conclusion QoL was comparable between participants with AAI and BLA, though patients post-BLA for pheochromocytoma reported better QoL than patients post-BLA for hypercortisolism. Adrenal crises were more common in participants with AAI than those post-BLA, a finding that was not explained by patients’ glucocorticoid management, underscoring the need for tailored crisis prevention strategies.