Supplementary Material for: Thyroid Disease and Amyotrophic Lateral Sclerosis

Introduction: Thyroid disease has been implicated in the pathology of neurodegenerative diseases. However, its role in amyotrophic lateral sclerosis (ALS) is unclear. This study aimed to investigate the association between thyroid disease, including hypothyroidism and hyperthyroidism, and the risk of ALS. Methods: We used a matched cohort design to evaluate UK Biobank data on participants enrolled between 2006 and 2010 who were followed up until 2022. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The study cohort comprised 42,684 patients with thyroid disease (females: 80%). Thyroid disease was moderately associated with an increased risk of ALS development (HR: 1.44, 95% CI: 1.02–2.02), and this association remained similar following adjustment for comparative height at the age of 10 years (HR: 1.44, 95% CI: 1.03–2.03). Hyperthyroidism showed a potential association with an increased risk of ALS development among individuals aged ≤60 years (HR: 21.22, 95% CI: 1.64–274.46) and in females (HR: 3.02, 95% CI: 1.13–8.08). Conclusion: Our findings demonstrate that thyroid disease is associated with a moderately increased risk of ALS development. Given the multifunctional role of the thyroid gland, further in-depth studies examining the relationship between thyroid conditions and ALS are warranted.