MON-358 - Cardio-Renal-Metabolic Outcomes in Hyperthyroidism and Treatment-Associated Hypothyroidism: A TriNetX Cohort Study

Background: Hyperthyroidism is associated with cardiovascular morbidity and mortality, but its long-term prognosis after treatment remains poorly defined. It is unclear whether treatment-associated hypothyroidism impacts cardio-renal-metabolic outcomes.

Methods: We conducted a retrospective longitudinal cohort study using the TriNetX Global Collaborative Network, including adults with hyperthyroidism identified between 2004 and 2026. Hyperthyroidism was defined by at least 3 diagnostic records of thyrotoxicosis/hyperthyroidism (ICD-10 E05). Controls were adults with general medical examinations (ICD-10 Z00). Hyperthyroid patients were compared with matched controls, and within the hyperthyroid population, patients were stratified into those who developed treatment-associated hypothyroidism, defined as subsequent hypothyroidism (ICD-10 E03.8/E03.9) with thyroid hormone replacement therapy, and those who did not. Cohorts were balanced with 1:1 propensity score matching. Outcomes included a composite metabolic outcome (obesity, diabetes, and hypertension), liver events, cardiovascular and thromboembolic events, renal and bone outcomes, critical care utilization, and all-cause mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models.

Results: We identified 308,116 individuals with hyperthyroidism and 358,530 controls. After propensity score matching, 192,462 patients with hyperthyroidism and 192,462 controls were analyzed. Patients were followed for a median of 40.4 months. Compared with controls, hyperthyroidism was associated with increased hazards of the composite metabolic outcome (HR 1.10; 95% CI 1.07 to 1.13), major adverse liver outcomes (HR 1.58; 95% CI 1.45 to 1.73), 3-point major adverse cardiovascular events (3P-MACE; HR 1.39; 95% CI 1.33 to 1.46), major adverse kidney events (MAKE; HR 2.32; 95% CI 1.91 to 2.83), critical care utilization (HR 1.35; 95% CI 1.27 to 1.43), and all-cause mortality (HR 2.06; 95% CI 1.95 to 2.18). Among hyperthyroid patients, those who developed treatment-associated hypothyroidism had worse outcomes than those who did not, including higher hazards of 3P-MACE (HR 1.53; 95% CI 1.39 to 1.69), MAKE (HR 1.80; 95% CI 1.36 to 2.38), critical care utilization (HR 1.65; 95% CI 1.48 to 1.84), and all-cause mortality (HR 1.15; 95% CI 1.05 to 1.26). Increased risks were also observed across metabolic, renal, skeletal, and neurocognitive domains.

Conclusions: Hyperthyroidism is associated with long-term cardio-renal-metabolic morbidity and mortality. Patients who developed treatment-associated hypothyroidism had worse outcomes across multiple clinical domains. Our findings suggest that treatment-associated hypothyroidism may warrant closer long-term monitoring.

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