EPID-01. Sex-Based Disparities in Brain Cancer Mortality Among Hypothyroid Patients: A National Ecological Analysis (1999–2020)

Abstract BACKGROUND Thyroid hormones influence neuroglial development, cellular proliferation, and cerebral metabolism—mechanisms relevant to brain tumor biology. While observational studies have proposed associations between thyroid dysfunction and malignancy risk, trends in brain cancer mortality among hypothyroid patients remain unexplored at a population level. This study investigates whether such patterns exist and whether sex-based disparities are evident. OBJECTIVE To evaluate sex-specific trends in brain cancer mortality among U.S. patients with hypothyroidism over a 22-year period using CDC mortality data. METHODS Data were obtained from the CDC WONDER Multiple Cause of Death database (1999–2020). We included all deaths with hypothyroidism (ICD-10 E02–E03) listed as a contributing cause and brain cancer (ICD-10 C71) as the underlying cause. Age-adjusted mortality rates (AAMRs) were calculated per 1,000,000 population for males and females separately. Values flagged as statistically unreliable due to low counts were retained for visual transparency but excluded from interpretation. RESULTS Between 1999 and 2020, AAMRs for brain cancer among hypothyroid decedents approximately doubled in both sexes. Female mortality rates rose from ~40 to over 80 per 1,000,000, while male rates increased from ~15 to ~33 per 1,000,000. The upward trajectory was more pronounced in females, particularly post-2014, indicating possible sex-modulated differences in vulnerability or treatment response. While individual medication data were not available, the findings raise the hypothesis that long-term levothyroxine therapy may play a contributing role. CONCLUSION This ecological analysis reveals a rising burden of brain cancer mortality among hypothyroid patients, particularly in females. While causality cannot be inferred, the sex-specific divergence underscores the need to investigate thyroid dysfunction and possibly its treatment as modifiable risk factors in neuro-oncology. These hypothesis-generating findings warrant validation through mechanistic and patient-level studies.