Graves' Disease Incidence Differs by Race

Veronica Hackethal, MD

April 15, 2014

The incidence rate of Graves' disease is higher among black and Asian/Pacific Islander active-duty US military personnel than whites, according to a large study. The findings could potentially open the door to new treatment or prevention strategies, authors say.

Researchers at the QIMR Research Institute in Brisbane, Australia, the US Army, and Johns Hopkins University say their study is the first to report this racial difference in the incidence of the thyroid autoimmune disease. Previously, the relationship between race and Graves' disease had been poorly characterized in the research literature.

Don McLeod, FRACP, MPH, first author of the study and an endocrinologist at the Royal Brisbane & Women's Hospital in Australia, and colleagues published their findings in the April 16, 2014 issue of the Journal of the American Medical Association.

The authors extracted data from the Defense Medical Surveillance System (DMSS) database, which contains ICD-9 diagnoses for all inpatient and outpatient active-duty US military personnel. The analysis included data for personnel aged 20 to 54 years, collected between January 1, 1997 and December 31, 2011. Race/ethnicity was based on self-report. Cases of Graves' disease and Hashimoto thyroiditis were identified using ICD-9 codes.

The analysis included over 20,000,000 person-years of follow-up, with a study population that was 85.8% male. Cases of Graves' disease occurred in 1378 women and 1388 men. Hashimoto's thyroiditis occurred in 758 women and 548 men. Incident rates of Graves' disease were significantly higher in black women (incidence rate ratio [IRR], 1.92; 95% confidence interval [CI], 1.56–2.37), and black men (IRR, 2.53; 95% CI, 2.01–3.18), as well as Asian/Pacific Islander women (IRR, 1.78; 95% CI, 1.20–2.66) and men (IRR, 3.36; 95% CI, 2.57–4.40) compared with whites. Conversely, incidence rates of Hashimoto's thyroiditis were higher in whites, compared with black women, black men, and Asian/Pacific Islander women and men.

Smoking is one of the strongest known environmental factors that raises the risk for Graves' disease, according to the authors, while decreasing the risk for Hashimoto's thyroiditis. Since whites have the highest smoking rates in the military, the authors pointed out, the results of this study run contrary to expectations. Thus, environmental risk factors alone might not easily explain this study's results. Other possible explanations include genetic influences or factors related to military-specific exposures, the latter of which could limit generalizability of the study to other populations.

"Our study identifies an important new risk factor for Graves' disease. The next key question is whether these racial differences are due to heritable factors, environmental exposures, or a combination of both," commented McLeod.

If racial variation in immune-system pathways confer differential risk, according to McLeod, this information could be used to design new treatments or prevention strategies for autoimmune thyroid disease. On the other hand, if environmental exposures substantially contribute to elevated risk, clinicians could use this information to educate and empower patients about disease exposure and prevention.

"Recognizing racial differences in autoimmune thyroid disease is key to understanding why it occurs," McLeod emphasized, "Finding the mechanisms of thyroid autoimmunity has the potential to lead to prevention of Graves' disease and may also lead to crucial insights into other autoimmune disorders."

The study has a number of limitations that the authors identify, including the potential for coding inaccuracies, which could have underestimated rates of Hashimoto's thyroiditis. Similarly, misclassification of prevalent vs incident cases could have overestimated the incidence of new cases of thyroid disease. In addition, rates of Hashimoto's thyroiditis could be lower in the military compared with the general population, they note, since military personnel tend to be younger and have higher smoking rates.

Dr. Cooper reports receiving editorial royalties from Up-to-Date. The other authors have reported no relevant financial relationships.

JAMA. 2014;311:1563-1565.

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