BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. It is an autoimmune disease, meaning that it is caused by the immune system that gets confused and attacks the bodies cells rather than those causing infection. In Graves’ disease, the immune system produces antibodies (thyroid stimulating antibodies) that bind to the TSH receptor on the surface of thyroid cells. When these antibodies bind to thyroid cells, they are turned on and the gland becomes enlarged and overactive (called hyperthyroidism), leading to an high levels of thyroid hormones in the blood. Graves’ disease can also cause swelling behind the eyes, a phenomenon known as thyroid eye disease (TED), which can make the eyes bulge and, in severe cases, affect vision.

Autoimmune diseases often “cluster” in patients, meaning that having one autoimmune disease increases the likelihood of developing another. Thus, patients with Graves’ disease are more likely to develop another autoimmune disease unrelated to the thyroid (called non-thyroid autoimmune disease). In general, most patients with Graves’ disease just have Graves’ disease. Until now, most research has looked at the presence of autoimmune thyroid disease in people who had other autoimmune conditions, such as systemic lupus erythematosis. However, this study looked at the opposite: it examined the risk of developing other autoimmune diseases in people who already have Graves’ disease.

THE FULL ARTICLE TITLE
Sohn SY, et al. Risk of non-thyroidal autoimmune diseases in patients with Graves’ disease: a nationwide retrospective cohort study. Rheumatology (Oxford). Epub 2024 Jan 5.

SUMMARY OF THE STUDY
The authors studied 77,401 patients in Korea who were newly diagnosed with Graves’ disease between 2008 and 2012. The average age was 48.8 years and 65% were women. These patients were compared to an equal number of age- and sex-matched controls. The study looked at how often non-thyroid autoimmune diseases were diagnosed. These diseases included lupus, Sjogren’s syndrome, vitiligo, alopecia areata, rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, and Behçet’s disease. The goal was to determine if people with Graves’ disease had a higher risk of developing these conditions compared to those without Graves’ disease.

Over an average follow-up of 9 years, 16.1% of patients with Graves’ disease (12,341 people) developed a non-thyroid autoimmune disease. On average, these conditions were diagnosed at 50.8 years of age, about 5.3 years after the initial diagnosis of Graves’ disease. Compared to the group without Graves’ disease, patients with Graves’ disease had a 15% higher risk of developing lupus, a 24% higher risk of vitiligo, and an 11% higher risk of alopecia areata. Additionally, patients with Graves’ disease who also had developed thyroid eye disease faced an even greater risk of certain autoimmune conditions. Those with eye disease were significantly more likely to develop lupus, ankylosing spondylitis, and Sjogren’s syndrome compared to Graves’ patients without eye findings.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
In this large national study, 16.1% of patients who were newly diagnosed with Graves’ disease developed another autoimmune disease within an average of 5 years. Doctors need to be aware of this connection so they can carefully monitor their patients with Graves’ disease for signs of other autoimmune disorders.

— Philip Segal, MD

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