Prevalence of Grave’s Disease Varies Widely by Race/Ethnicity

Don McLeod, MD, MPH, PhD, and Terry F. Davies, MD, Comment

Non-Hispanic blacks have a nearly 3-fold higher prevalence of thyrotoxicosis than non-Hispanic whites, according to analysis of data from National Health and Nutritional Examination Surveys (NHANES) reported in the June issue of Thyroid. Given that the study population consisted of younger patients (ages 12-49 years), for whom Graves’ disease is most likely the cause of thyrotoxicosis, the findings imply marked racial differences in the prevalence of Graves’ disease.

“This research adds to our previous work and other new data from California suggesting that there are important race differences in thyrotoxicosis and Graves’ disease occurrence,” said lead author Don McLeod, MD, MPH, PhD, NHMRC Early Career Fellow at QIMR Berghofer Medical Research Institute, Brisbane, Australia. “The clinical potential for this knowledge lies in finding the mechanism of these differences. If they are due to racial variations in immune system pathways, in the future we could use this information to design new treatments or prevention for autoimmune disease. If environmental exposures were the cause, we could educate and empower people to avoid these exposures and prevent disease,” Dr. McLeod said.

Data Analyzed From National Health and Nutritional Examination Surveys
The authors analyzed data from 17,939 participants with available thyroid function test results in 3 National Health and Nutritional Examination Surveys from 1988-1994, 1999-2002, and 2007-2010. The study population consisted of younger patients (age 12 to 49 years) from whom Graves’ disease is expected to account for most cases of thyrotoxicosis, the authors noted.

Non-Hispanic Black Subjects Had 3-Fold Higher Prevalence of Thyrotoxicosis
A total of 75 participants (0.4%) had thyrotoxicosis, which was defined as serum thyrotropin ≤0.1 mIU/L. The prevalence of thyrotoxicosis was higher in non-Hispanic black participants (0.9%) than in non-Hispanic whites or Mexican Americans (0.3% in both groups). The odds ratio (OR) for thyrotoxicosis was 2.9 among non-Hispanic black subjects compared with non-Hispanic white subjects, with no difference found between non-Hispanic whites and Mexican Americans.

Among the 27 participants with overt thyrotoxicosis (ie, high serum thyroxine and a serum TSH of ≤0.1 mIU/L), the OR were 8.7 among non-Hispanic blacks (confidence interval 0.7–112.6) compared with non-Hispanic whites.

“We can’t say whether these differences are due to heritable factors, environmental exposures, or a combination of both,” Dr. McLeod said. “Genetics are clearly an important cause of autoimmune diseases, including Graves’ disease, but race differences in Graves’ disease susceptibility genes have not yet been explored. Likewise, potential environmental exposures could differ by race, although much more work needs to be done to identify these,” Dr. McLeod said.

“Finding the mechanisms of thyroid autoimmunity has the potential to lead to prevention of Graves’ disease, and also may lead to insights into the pathways for other autoimmune disorders,” the authors concluded.

Exclusion Criteria May Limit Findings
“If the finding that the development of Graves’ disease is related to race proves reproducible, then it is a very significant observation. However, I have some concerns about the validity of the conclusions,” commented Terry F. Davies, MD, Florence and Theodore Baumritter Professor of Medicine at Icahn School of Medicine at Mount Sinai, and Director in the Division of Endocrinology and Metabolism at James J Peters Veterans Affairs Medical Center, New York, NY.

“As in all retrospective epidemiological studies, the quality of the original data extracted from the NHANES surveys is most important,” said Dr. Davies, who is also Past-President of American Thyroid Association. “In this case, everyone taking thyroid medications was excluded from the analysis. This included patients taking thyroid hormone therapy, which is usually for hypothyroidism caused by Hashimoto’s thyroiditis but may include patients [given this treatment] following radioactive iodine or thyroid surgery for Graves’ disease. The analysis also excludes everyone taking antithyroid medications for the treatment of hyperthyroidism. We are not told how many such patients were excluded, but if one hypothesizes that the non-black and non-Hispanic subjects were diagnosed and treated earlier and more often, this would skew the results to less Graves’ disease. I think there is ample evidence that the black and Hispanic population seek and obtain less medical care,” Dr. Davies told

“In addition to the inbuilt error discussed above, there is a lot of population genetic data indicating that genetic susceptibility genes may differ between populations and, therefore, also may differ between races,” Dr. Davies said. “Since Graves’ disease is a multifactorial genetic disease with many different genes providing small pieces of susceptibility, the findings may suggest a greater accumulation of such susceptibility genes in the black population. The best evidenced environmental triggers of Graves’ disease are smoking and stress, and both of these triggers also have an increased prevalence in the black population. Thus, it is more than likely that both factors are contributing to the racial differences,” Dr. Davies said.

Dr. Davies concluded that thyroid function testing should be part of every primary care assessment, and that testing is particularly important in pregnancy and in women planning pregnancy. “This care should be applied to all races,” he said.

July 9, 2015

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