Familial Connections and Their Impact on Hashimoto Thyroiditis Risk

A recent study has brought to light the significant genetic and environmental influences on Hashimoto thyroiditis (HT), particularly regarding familial connections. Conducted by Melissa Bujnis, PhD, from the Department of Human Genetics at the University of Utah, the research highlights that first-, second-, and third-degree relatives of patients with HT exhibit a markedly increased risk for developing the autoimmune disorder. The study's findings, published in the Journal of Clinical Endocrinology & Metabolism on June 12, 2025, reveal that the odds ratios for developing HT are notably elevated among these relatives, with female relatives experiencing a disproportionate impact.

The methodology employed in this retrospective case-control study analyzed genealogical and medical data from a Utah-based database spanning from 1996 to 2021. The study included a substantial cohort of 92,405 adult HT probands, predominantly women (73%) and White individuals (96%), alongside 184,810 matched control individuals. The extensive dataset allowed researchers to examine the health risks faced by 2,960,650 first-, second-, and third-degree relatives of HT probands in comparison to 5,730,159 relatives of control subjects.

Key findings from the study indicate that first-degree relatives have the highest risk, with an odds ratio of 1.77 (95% Confidence Interval [CI], 1.74-1.80). Second-degree relatives showed a lower, yet significant, odds ratio of 1.23 (95% CI, 1.22-1.27), and third-degree relatives presented an odds ratio of 1.11 (95% CI, 1.10-1.12). Notably, female relatives of patients were found to have an additional 2.2- to 2.6-fold higher risk across all degrees of relatedness compared to overall estimates. Among first-degree relatives, the sons of men diagnosed with HT had a notably elevated risk (OR, 2.36; 95% CI, 2.10-2.65).

Furthermore, the study revealed that spouses of individuals with HT also face increased risk, highlighting the potential influence of shared environmental factors. This observation suggests a complex interplay between genetic predisposition and environmental exposures, reinforcing the need for healthcare providers to consider familial history when assessing patient risks for HT.

In practice, understanding the familial clustering of HT can significantly improve clinical outcomes. As the authors of the study noted, identifying individuals with affected first-degree relatives may enable healthcare providers to implement earlier monitoring and intervention strategies, ultimately enhancing disease management capabilities.

However, the study is not without limitations. Researchers acknowledged that reliance on diagnostic codes may have introduced misclassification bias, particularly concerning transient hypothyroidism or instances of misdiagnosed HT. Variations in diagnostic practices across different clinics may have further contributed to sample heterogeneity. Additionally, there exists the possibility of ascertainment bias, as individuals with a known family history of HT might be more inclined to seek medical attention or receive a diagnosis.

The research received partial support from the University of Utah, the Huntsman Cancer Institute, the National Institutes of Health (NIH), and the Utah Department of Health and Human Services. The authors reported no conflicts of interest. Overall, this comprehensive analysis of familial ties and their implications for Hashimoto thyroiditis underlines the necessity for continued research in this area, as well as the importance of integrating familial health histories into clinical practices for better patient outcomes.