SUN-454 - Trends and Disparities in Adrenal Insufficiency-Associated Mortality in the United States, 1999-2020

Background
Adrenal insufficiency (AI) is a potentially life-threatening endocrine disorder that remains underrecognized despite advances in diagnosis and hormone replacement therapy. National patterns in AI-associated mortality remain poorly characterized. We examined long-term mortality trends attributable to adrenal insufficiency in the United States.

Methods
We performed a retrospective population-based analysis using the CDC WONDER Multiple Cause of Death database from 1999–2020. Deaths listing adrenal insufficiency as an underlying or contributing cause were included. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Temporal trends were assessed using segmented log-linear regression to estimate annual percent change (APC) and identify inflection points. Analyses were stratified by sex, race, and U.S. Census region.

Results
Between 1999 and 2020, deaths involving adrenal insufficiency increased from 1,013 to 1,964, while the overall AAMR rose from 0.4 to 0.5 per 100,000. Trend analysis identified a significant inflection point around 2013, followed by a marked increase from 1999–2013 (APC −2.2%/year, 95% CI −3.2 to −1.1), followed by a sharp increase from 2013–2020 (APC +6.0%/year, 95% CI +3.6 to +8.5).
Sex-specific analyses showed increasing post-2013 mortality in both sexes, with a larger relative increase among females (AAMR 0.3 to 0.5) compared with males (AAMR 0.4 to 0.5).
Regional analyses demonstrated substantial geographic heterogeneity. From 1999 to 2020, AAMRs increased in the Midwest (0.4 to 0.6, ≈50%) and South (0.3 to 0.5), with post-2015 APCs of approximately +8.7%/year and +6.2%/year, respectively. The West experienced a more moderate increase (0.4 to 0.5), while the Northeast showed the smallest rise (0.3 to 0.4), with post-2012 APCs near +2.4%/year.
Race-stratified analyses revealed increasing mortality among White individuals (AAMR 0.3 to 0.5) and Black or African American individuals (AAMR 0.4 to 0.5), particularly after 2014. In contrast, mortality among Asian or Pacific Islander individuals declined over the study period (AAMR 0.3 to 0.2). Estimates for American Indian/Alaska Native individuals were limited by small counts and incomplete early-year data.

Conclusions
Adrenal insufficiency-associated mortality in the United States has risen markedly since 2013 after a prior period of decline, revealing a concerning reversal in outcomes for a largely treatable condition. The observed disparities by sex, race, and geographic region suggest uneven access to timely diagnosis, patient education, and effective adrenal crisis prevention. These findings highlight the need for improved recognition, standardized management, and targeted public health strategies to reduce preventable mortality associated with adrenal insufficiency.

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