BACKGROUND
Hyperthyroidism is a condition whereby the thyroid gland becomes overactive and makes too much thyroid hormone. Graves’ disease is an autoimmune condition in which the person produces antibodies that stimulate the thyroid gland to make too much thyroid hormone and causes hyperthyroidism. Some patients with Graves’ disease develop thyroid eye disease (sometimes referred to as Graves’ eye disease or Graves’ orbitopathy). This condition is associated with inflammation of the eye and eye muscles and can cause pain, bulging of the eyes and difficulty moving the eyes which can cause double vision. Treatment of thyroid eye disease (TED) depends on severity and can include high doses of glucocorticoids such as prednisone or methylprednisolone and surgery. A newer medication, teprotumumab/Tepezza™, works differently by blocking a receptor in eye muscles (insulin-like growth factor 1 receptor), and has been markedly effective in the treatment of TED.

Treatment of Graves’ disease includes medications (antithyroid drugs), surgery to remove the thyroid and radioactive iodine, which is taken up into the thyroid and destroys it. This study examines the effects of the treatment choice for Graves’ disease affected moderate to severe TED and the response of TED to glucocorticoid treatment.

THE FULL ARTICLE TITLE
Cosentino G, et al. Ablative versus conservative approach for hyperthyroidism treatment in patients with Graves’ orbitopathy: a retrospective cohort study. Thyroid. 2025;35(3):298-306; doi: 10.1089/thy.2024.0633. PMID: 39909466

SUMMARY OF THE STUDY
The study included 49 Italian patients with Graves’ disease and moderate to severe TED. The patients were divided into 2 groups for analysis: 24 patients treated with radioactive iodine and 25 with the antithyroid medication methimazole. All patients had moderate to severe TED and received treatment with intravenous high dose glucocorticoids weekly for 12 doses starting at the baseline visit which was approximately 4 weeks after the initial screening visit. Patients that were treated with radioactive iodine received levothyroxine replacement therapy after destruction of the thyroid.

The main study endpoint for group comparisons was a composite score of TED activity at 24 weeks compared to baseline. Other outcomes measured overall TED activity and quality of life at 48 and 72 weeks of follow-up. Detailed eye exams to assess TED activity were performed at screening, baseline and every 4 weeks for a total of 72 weeks.

Results showed that the overall response of TED to glucocorticoids was greater in the radioactive iodine treatment group compared to the methimazole group at 24 weeks. However, the proportion of patient responders in the methimazole group increased over time such that at the later time points, there were no differences in eye outcomes. TED specific quality of life was improved at 24 weeks in the radioactive iodine treatment group compared to methimazole treated at 24 weeks but again, these differences were not apparent at the later time points in the study. One patient in the radioactive iodine treatment group and 4 in the methimazole group experienced worsening eye disease at week 24. These data suggest that radioactive iodine treatment for Graves’ disease seems to be associated with a faster improvement in TED activity in response to glucocorticoid treatment. However, there were no differences in TED improvements following glucocorticoid therapy when the groups were compared at 48 and 72 weeks. Thus, in the long term, TED responds equally to intravenous glucocorticoid therapy irrespective of whether the patient’s hyperthyroidism was treated with radioactive iodine or methimazole. Future studies are needed to confirm these findings.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study suggests that radioactive iodine treatment may be associated with a faster improvement in TED following glucocorticoids compared to antithyroid medications.However, there were no differences in TED response to glucocorticoids at later time points, suggesting that the chosen method of treating hyperthyroidism does not significantly impact TED response to glucocorticoids in the long term. This study shows that patients with Graves’ disease and moderate to severe TED can be treated with radioactive iodine or antithyroid drugs along with steroid without worsening the TED, increasing the options for treatment to normalize their thyroid function.

— Whitney W. Woodmansee MD

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