BACKGROUND
Graves’ disease is the most common cause of an overactive thyroid gland (hyperthyroidism) and results from an antibody (Thyroid stimulating immunoglobulin) that turns on the thyroid gland. The initial treatment of Graves’ disease is usually anti-thyroid drugs (methimazole or PTU) to control the hyperthyroidism and return the thyroid levels to normal. Once the thyroid levels are normal, the treatment options include 1) continuing the antithyroid medication in the hope that the antibody will go away and the Graves’ disease will go into remission or 2) definitive treatments to destroy the thyroid gland (radioactive iodine therapy or surgery). Unfortunately, half of the patients will become hyperthyroid again once anti-thyroid drugs are stopped. For patients who have a high likelihood of becoming hyperthyroid again after stopping the anti-thyroid drugs, radioactive iodine or total thyroidectomy may be better options. If we can identify the patient characteristics that will make them more or less likely to stay in remission after completing the recommended course of anti-thyroid drugs, we will be able to offer patients more suitable treatment options and prevent recurrences of hyperthyroidism.

The goal of this study is to identify patient characteristics that will make them more likely to become hyperthyroid again after the anti-thyroid drugs are stopped.

THE FULL ARTICLE TITLE
El Kawkgi O, et al. A predictive model for Graves’ disease recurrence after antithyroid drug therapy: a retrospective multicenter cohort study. Endocr Pract. Epub 2024 Dec 16; doi:10.1016/j.eprac.2024.12.011. PMID: 39694327.

SUMMARY OF THE STUDY
Patients above the age of 18 treated at University of Arkansas for Medical Sciences (UAMS), Mayo Clinic, and University of Florida (UF) were included in the study. These patients had a first-time diagnosis of Grave’s disease and were treated initially with anti-thyroid drugs. If the patients were pregnant, treated with thyroidectomy or radioactive iodine initially, or diagnosed with other forms of hyperthyroidism, they were not included in the study. The age, sex, smoking status, family history, lab work (TSH and TSI antibodies), body mass index, presence of thyroid eye disease and goiter, imaging studies, and type of anti-thyroid drugs were studied for patients treated from 2002 to 2021 at Mayo Clinic, 2013 to 2019 at University of Florida, and 2009 to 2019 at University of Arkansas for Medical Sciences.

A recurrence of the Graves’ disease was defined as a patient needing more anti-thyroid drugs, radioactive iodine, or a thyroidectomy within a year of stopping the anti-thyroid drugs. Of the 523 patients studied, 75.66% were women, and the average age was 48.6 years. Among these, 211 patients (40.3%) discontinued anti-thyroid drugs after their hyperthyroidism was treated successfully, with 142 patients (67.3%) having ≥12 months of follow-up for reporting purposes. Unfortunately, of these 142 patients, 79 (55.6%) of them experienced a Graves’ Disease recurrence.

Elevated baseline FT4 levels (1.47 x more likely per 2.0 ng/dl increase) and early anti-thyroid drug discontinuation (if discontinued before 12 months; 2.7 x more likely) were significant predictors of recurrence. Older age (1.31 x more likely per 10 years older) and higher baseline FT4 levels (1.65 x more likely per 2.0 ng/dL increase) were independently associated with recurrence. Longer antithyroid drug therapy showed a trend toward reduced recurrence risk (15% less likely per 6 months longer use).

Using these statistics, a tool was developed to predict risk of recurrence after a certain duration of anti-thyroid drug therapy. For example, a 40-year-old female smoker with a freeT4 of 4 ng/dl and using anti-thyroid drugs for 12 months has a 70% recurrence risk of hyperthyroidism after stopping her anti-thyroid drugs. Another example is a 20-year-old nonsmoking male with a free T4 of 2 ng/dl and 24 months of anti-thyroid drug use has a 30% risk of hyperthyroidism recurrence after stopping his antithyroid drugs.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Although anti-thyroid drugs are effective, there is a chance that the patient will become hyperthyroid again after stopping the medications. If the patient has a high free T4 hormone level, is older, or has taken the anti-thyroid drug for only a short time, the chance that the patient will become hyperthyroid again after stopping the drug is higher. Only 142 of the patients studied had follow up 12 months after stopping their anti-thyroid drugs, which might limit the ability of the study to make conclusions. A tool that predicts risk of hyperthyroidism recurrence can help the physician offer patients the best option to treat their hyperthyroidism: anti-thyroid drugs, radioactive iodine, or thyroidectomy. Future research is needed to improve the accuracy of this tool. Other similar tools to predict response to hyperthyroidism treatment include “10-point GREAT+ score” that even incorporates genetic data and “Clinical Severity Score (CSS)” that incorporates goiter size, free T4 levels, and presence/ absence of thyroid eye disease

— Pinar Smith, MD

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