LAUSR

Abstract Disclosure: A. Ahmed: None. M. Ali: None. H. Ahmad: None. S. abid: None. S. Joshi: None. N.U. saleem: None. F. Ahmed: None. R. Patel: None. S. Eltawansy: None. Background: Hypothyroidism and metabolic syndrome (MetS) are major contributors to cardiovascular and all-cause mortality. Hypothyroidism exacerbates cardiovascular risk via dyslipidemia, endothelial dysfunction, and glucose metabolism disturbances, while MetS accelerates atherosclerosis and insulin resistance. This study assesses the impact of hypothyroidism in MetS on U.S. mortality trends over the past 25 years. Methods: We analyzed CDC multiple cause of death data (1999-2023) to examine hypothyroidism and MetS-related mortality in U.S. adults (25+). Age-adjusted mortality rates (AAMRs) per million were calculated, and Joinpoint regression was used to assess annual percentage change (APC), average annual percentage change (AAPC), and statistical significance (p-value). Results: Over the past 25 years, hypothyroidism and MetS contributed to 332,751 deaths. From 1999 to 2023, the overall AAMR increased by 148.5% (30.57 to 75.96; AAPC: 3.47, 95% CI: 2.89-4.24, p < 0.000001), with the most rapid rise occurring from 1999 to 2002 (APC: 16.02). Females consistently exhibited higher AAMRs (71.12) than males (37.82); however, males experienced a more pronounced increase (AAPC: 4.004, 95% CI: 3.45-4.77, p < 0.000001) compared to females (AAPC: 3.41, 95% CI: 2.86-4.17, p < 0.000001). The most striking increase among females was observed from 1999 to 2001 (APC: 21.46), whereas for males, it occurred from 2018 to 2021 (APC: 14.43). Among racial groups, American Indian or Alaska Native individuals had the highest AAMR (63.72), followed by Whites (62.37), Hispanics or Latinos (45.95), and Blacks (39.47). The fastest increase in AAMR was observed in Whites (AAPC: 3.93, 95% CI: 3.44-4.59, p < 0.000001), while Hispanics or Latinos exhibited the slowest rise (AAPC: 2.32, 95% CI: 1.50-3.26, p = 0.0008). Regionally, the Midwest reported the highest AAMR (65.34), followed by the West (58.34) and South (56.03). However, the South exhibited the steepest increase in mortality (AAPC: 4.79, 95% CI: 4.25-5.51, p < 0.000001), followed by the West (AAPC: 3.49, 95% CI: 2.82-4.49, p < 0.000001), while the Midwest had the slowest rise (AAPC: 1.38, 95% CI: 0.83-1.98, p < 0.000001). At the state level, Wyoming (325.22) had the highest AAMR, followed by Nebraska (195.75) and South Dakota (192.19). Rural areas had a higher AAMR than urban areas (68.98 vs. 52.22). Among age groups, the fastest rise in mortality was observed among individuals aged 25-54 (AAPC: 3.89, 95% CI: 3.34-4.71, p < 0.000001). Conclusion: Hypothyroidism and MetS-related mortality has surged over the past 25 years, with the most pronounced increases seen in males, Whites, rural populations, and the South. Urgent public health strategies are needed to curb these trends and reduce associated mortality risks. Presentation: Sunday, July 13, 2025