BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism, where the thyroid gland becomes overactive and makes too much thyroid hormone. Graves’ disease is caused by the body making an antibody that attacks the thyroid and turns it on. The diagnosis is made by lab tests, including measuring the antibody level. Occasionally, the thyroid gland activity can be measured with a nuclear thyroid scan to diagnose Graves’ disease. Treatment options for Graves’ disease include antithyroid drugs (ATDs), radioactive iodine (RAI) ablation (where the thyroid gland is destroyed by radiation over time), or thyroid surgery (thyroidectomy where the thyroid gland is removed). The goal of treatment with ATDs is to control the thyroid activity in the hope of a remission, where the antibody decreases or goes away, and the thyroid function returns to normal. RAI and surgery are called definitive therapy as they destroy the thyroid and make the patient hypothyroid, which is treated with a thyroid hormone replacement pill.

Traditionally, RAI ablation was the most common form of therapy in the United States and was recommended if Graves’ disease does not go into remission (no longer overactive) after treatment with ATDs for 18-24 months or if there is recurrence of Graves’ disease (coming back after remission). Thyroidectomy has been less common and often reserved for patients with very large thyroid glands. In recent years, there has been more data showing the safety and higher chance of remission with long-term ATD treatments. In addition, there are some concerns about potential risk of cancer development and worsening of thyroid eye disease after RAI ablation. These may have resulted in changing trends in Graves’ disease treatment among clinicians over the years.

This study was done to evaluate current clinical practices in Graves’ disease treatment and to identify any changes in trends over the past 10 years.

THE FULL ARTICLE TITLE
Villagelin D et al. A 2023 international survey of clinical practice patterns in the management of Graves’ disease: a decade of change. J Clin Endocrinol Metab. Epub 2024 Apr 5:dgae222; doi: 10.1210/clinem/dgae222. PMID: 38577717.

SUMMARY OF THE STUDY
A total of 1252 responses to a survey of endocrinologists and specialists treating patients with Graves’ disease from 85 countries were obtained between May and August of 2023. The survey presented a case of Graves’ disease with 31 questions on the treatment options and reasons for choosing specific treatment. The questions were made similar to those in previous 2011 survey to compare and assess potential changes in treatment trends over time.

For the diagnosis of Graves’ disease, there was an increase in use of thyroid stimulating antibody test (94% vs 58% in 2011), likely related to improving assay accuracy. On the other hand, radioactive iodine scans are less frequently used (16% vs 47% in 2011). More clinicians also obtained thyroid ultrasound at initial evaluation (61% vs 26% in 2011).

For treatment options, ATDs were most frequently used as the initial treatment (92%), followed by RAI ablation (7%) and thyroidectomy (2%). In the past, RAI ablation was much more frequently used as the initial treatment. This decrease in preference of RAI ablation as the first-line therapy was most notable in the United States (11.1% compared to 69% in 1990), although also shown in other countries. The top reasons to choose long-term ATDs over RAI ablation were “to avoid hypothyroidism” and “to achieve remission.”

For patients who had persistently elevated thyroid stimulating antibody levels after treatment with ATDs for 18 months, 69% of respondents preferred continuing ATDs. Similarly, 60% of respondents chose to restart ATDs if there was a relapse of Graves’s disease rather than recommending RAI ablation or thyroidectomy.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This international survey of clinicians treating Graves’ disease showed that there was a significant decline in the use of RAI ablation and increase in the use of ATDs as the initial and long-term treatment over the last 10 years. Overall, there appear to be changing trends in how Graves’ disease is diagnosed, an increasing desire to avoid hypothyroidism, and increasing acceptance of long-term ATDs use.

The large number of responses across many different countries in this study provides unique perspective into the current global trend. The findings of this study provide important insights into the changing approaches in diagnosis and treatment of Graves’ disease by international clinicians. Understanding current clinical practices and preferences for treatment is important to provide directions for future research, practice guidelines, and allocating resources, and addressing potential barriers and disparities in care. Most notably, given increasing use of long-term ATD, further studies on potential side effects, predictors of remission, and how to monitor long-term ATD therapy would be needed with ongoing evaluation on how to best individualize therapy for Graves’ disease for each patient.

— Sun Lee, MD

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