Antithyroid Treatment as Effective as RAI for Graves Relapse

Nancy A Melville

January 19, 2016

Low-dose antithyroid drug therapy for Graves' disease relapse is as effective as radioiodine (RAI) treatment in preventing further relapse, with Graves' ophthalmopathy showing even greater improvement with the drug therapy, according to a new study published in the journal Thyroid.

"Our findings demonstrated that for patients who relapse from the conventional use of antithyroid drugs after 12 to 18 months and do not desire a definitive treatment with RAI or surgery, the use of a prolonged low methimazole [MMI] dose is a feasible option," lead author Danilo Villagelin, MD, of the School of Medicine at Pontifical University Catholic of Campinas, Campinas, Brazil, told Medscape Medical News.

While antithyroid drug therapy is well-established as a treatment option for hyperthyroidism due to Graves' disease, research shows remission rates can range from 30% to as high as 70%, prompting some doctors to recommend RAI treatment or thyroid surgery as more definitive resolutions.

The latter approaches have their own undesirable effects, however, including the need for lifetime thyroid-hormone replacement and increased risk of hypothyroidism.

Hypothyroidism More Common in Those Treated With RAI

To evaluate the alternative of a low-dose regimen of antithyroid therapy (methimazole), Dr Villagelin and colleagues conducted a retrospective review of 238 Graves' disease patients who had relapsed 12 to 24 months after discontinuation of antithyroid therapy.

Approximately half (n=114) patients were treated with RAI treatment and L-thyroxine replacement, while the remaining 124 patients were treated with low-dose MMI (2.5 – 7 mg daily).

At a mean follow-up of 80.8 months for the RAI group and 71.3 months for the low-dose MMI group, patients in the RAI group had higher levels of thyroid dysfunction (P < .001), while those in the MMI group more commonly had normal thyroid function (P < .001).

Subclinical and overt hypothyroidism were more frequent in the RAI group at each follow-up time point, despite those patients receiving L-thyroxine replacement.

The rate of deterioration of Graves' ophthalmopathy, assessed with the clinical activity score (CAS), was also notably higher in the RAI group at all points of follow-up (P < .0005).

While there were no significant differences in quality-of-life scores reported between the two groups using the Short Form Health Survey's 36 parameters in euthyroid patients who were stable for at least 6 months, weight gain was higher in the RAI group (P < .005), particularly after a 24-month follow-up.

There were no reports of major adverse side effects relating to MMI treatment; however, five patients in the RAI group remained hyperthyroid 6 months after the treatment. Those patients were given a second dose of RAI and subsequently developed hypothyroidism.

Improved Graves' Ophthalmopathy Outcomes with MMI Surprising

The findings of improved Graves' ophthalmopathy outcomes for patients with antithyroid therapy were particularly notable — and surprising, Dr Villagelin said.

He said there are two possible explanations for these results.

"RAI treatment alters autoimmunity (for instance, it increases serum TRAb levels for a long period), while prolonged use of a low MMI dose may have immunosuppressive and anti-inflammatory effects and may influence directly, through decreases in the TRAb levels, or indirectly, in keeping the patient in euthyroidism, the recovery of Graves' ophthalmopathy."

Appropriate Treatment of Graves' Disease Still Under Debate

Despite the findings, appropriate treatment of Graves' disease remains a subject of debate, and RAI is a first option for treatment in the United States and some other countries.

Hyperthyroidism guidelines published in 2011 by the American Thyroid Association and American Association of Clinical Endocrinologists recommend any of the three approaches for treatment, with certain patient factors influencing preference of one particular approach over the others.

The guidelines note that no significant differences have been reported in long-term quality of life following treatment in patients randomly allocated to one of the three treatment options.

Ultimately, clinicians should discuss all options with patients, Dr Villagelin said.

"[Current] guidelines highlight that the patient has the final decision to choose the type of treatment," he said.

"[The decision] should be made after the treating physician and patient discuss each of the treatment options, including the benefits, expected speed of recovery, drawbacks, potential side effects, cost, and personal values and preferences of the patient."

The authors had no relevant financial relationships.

Thyroid. 2015;25:1282-1290. Abstract


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