SUN-448 - Temporal Trends and Divergent Incidence-Prevalence Trajectories of Glucocorticoid-Induced Adrenal Insufficiency in Adults with Severe Asthma, 2005-2025

Background:
Glucocorticoid-induced adrenal insufficiency (GIAI) is a well-recognized complication of chronic systemic glucocorticoid therapy in severe asthma, yet long-term real-world relationships between incidence and prevalence remain poorly characterized. In chronic diseases, disproportionate growth in prevalence relative to incidence may reflect improved recognition of previously underdiagnosed disease rather than a true increase in new events. This question is particularly relevant in the modern era, given the expanding use of biologic and other steroid-sparing therapies that might be expected to reduce adrenal toxicity over time.

Methods:
We conducted a retrospective cohort study using TriNetX, a federated electronic health record network, identifying adults with severe asthma receiving chronic systemic corticosteroids (≥3 months oral or parenteral exposure) between 2005 and 2025. Severe asthma and GIAI were defined using diagnostic codes (ICD-10). Annual incidence proportions, incidence rates (per 100,000 person-years), and prevalence were estimated with 95% confidence intervals. Temporal trends and inflection points were assessed using Joinpoint regression to estimate average annual percent change (AAPC), and prevalent-to-incident case ratios were examined in contemporary years.

Results:
From 2005 to 2025, GIAI prevalence increased from 0.8% (~2,100 cases) to 6.0% (>17,000 cases), representing a 7.5-fold rise. Over the same period, the annual incidence proportion increased from 0.25% to 0.75% (approximately 2.5-fold), with incidence rates rising from 7.1 to 29.3 per 100,000 person-years. In 2025, approximately 2,000 incident cases were identified compared with more than 17,000 prevalent cases, yielding a prevalent-to-incident ratio of roughly 8:1. Joinpoint analysis demonstrated modest, sustained increases in incidence across the study period, while prevalence exhibited a steeper acceleration after 2017, with higher post-inflection AAPC for prevalence than for incidence.

Conclusions:
Among adults with severe asthma on chronic systemic glucocorticoids, the burden of GIAI has increased substantially over two decades, with prevalence rising far more rapidly than incidence despite the availability of steroid-sparing therapies. This divergence is most consistent with improved recognition and documentation of a long-standing, underdiagnosed complication rather than an abrupt increase in new disease events. Use of legacy cortisol thresholds with modern assays, particularly LC/MS methods that measure systematically lower cortisol concentrations than traditional immunoassays, has increased the risk of overdiagnosis of AI, underscoring the need for assay-specific cutoffs and clinical context in diagnostic evaluation. There is a quality of care gap that supports protocol-driven approaches to adrenal surveillance.

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