BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. Graves’ disease is caused by an antibody that attacks and turns on the thyroid. As such, it is an autoimmune disorder. Graves’ disease calso can be associated with other conditions like thyroid eye disease (TED), and occasionally, skin issues known as dermopathy. It is also linked to various other autoimmune disorders. When treating Graves’ disease, the first priority is to normalize thyroid hormone levels using antithyroid drugs (ATD) such as methimazole or propylthiouracil. While these drugs are first-line treatment in many places, they come with some side effects, and ~50% of patients may experience a recurrence of Graves’ disease after stopping the drug. Consequently, more definitive treatments like radioactive iodine therapy or thyroidectomy may be necessary.

Patients frequently ask their physician how long they will need to take anti-thyroid medications or whether they will have Graves’ disease forever. Unfortunately, the long-term behavior of Graves’ disease remains unknown. This study examines the clinical outcomes of individuals with Graves’ disease more than 20 years after their initial diagnosis and treatment. The researchers explore the progression of the disease, the impact on quality of life, and factors that influence the likelihood of disease remission or relapse.

THE FULL ARTICLE TITLE
Meling Stokland AE et al Outcomes of patients with Graves disease 25 years after initiating antithyroid drug therapy. 2023 J Clin Endocrinol Metab. Epub 2023 Sep 25. PMID: 37747433.

SUMMARY OF THE STUDY
The researchers examined a group from Norway who had participated in a two-year trial in the late 1990s, comparing different medical treatments for Graves’ disease. In 2021, more than two decades after their initial diagnosis, these patients were contacted again to assess their long-term outcomes. Surprisingly, the researchers successfully re-enrolled 155 of the 195 patients still alive from the original study. The records of 23 patients who had passed away during the intervening years and 4 patients who could not be reached were also included, resulting in 182 cases for analysis. Participants were asked to complete questionnaires about their medical history and quality of life. Where available, blood samples in storage from the original study were re-examined for thyroid hormone levels, TSH-receptor antibodies, as well as other inflammatory markers like gastric parietal cell antibodies (linked to autoimmune gastritis and pernicious anemia) and transglutaminase antibodies (associated with celiac disease).

Following the initial 2-year study, 82 patients (45%) had a relapse of their Graves’ disease. 20 years later only 11% of those that had relapsed were able to maintain normal thyroid function. The remaining 89% needed definitive treatment, either with radioactive iodine therapy or thyroid surgery. Some still used ATDs, while others had developed hypothyroidism. Among the 78 patients (43%) who achieved remission after the initial study, 62% had normal thyroid homone levels in the long term follow-up, with 14% having received definitive treatment. Hypothyroidism was more prevalent in this group (21%), and those with hypothyroidism experienced a reduced quality of life. Among the 22 patients (12%) who did not complete the initial study, only 18% had normal thyroid levels in the follow-up. Overall, only 34% of all patients were in remission at the 20-year follow-up.

The levels of inflammatory markers in the blood did not offer much useful information about the overall course of the disease. In the first study, 43% had TED. Over the next two decades, an additional 10 patients (7%) developed TED, with 7 of these cases occurring after radioactive iodine treatment. By the end of the follow-up, 47% of all patients had developed another autoimmune disease, including vitamin B12 deficiency (26%) and rheumatoid arthritis (5%).

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This research shows that Graves’ disease is a challenging condition with unpredictable long-term results. Many patients go through a persistent or recurring pattern and need either decisive treatment or prolonged use of antithyroid medications. Additionally, many develop other autoimmune disorders or thyroid eye disease. Given the relatively frequent rate of disease reccurrence, even in those who initially achieved remission, long term monitoring of thyroid function is necessary.

— Phillip Segal, MD

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