Radioactive Iodine Considered Optimal For Graves' Disease

With Marius N. Stan, MD and Elizabeth N. Pearce, MD, MSc

In researching the relative efficacy and safety of the three usual treatment methods for Graves’ disease (GD)—antithyroid (AT) medications, radioactive iodine therapy (RAI), and thyroidectomy—RAI had the most favored efficacy and safety profile among patients.¹

"Our study provides information to physicians and patients that may be useful in selecting a treatment choice most consistent with the patient's personal values," Marius N. Stan, MD, said.

The researchers sought to provide guidance in the selection of optimal therapy for this common form of hyperthyroid disease. The study findings,¹ published in Thyroid, indicated that antithyroid (AT) medications and thyroidectomy were rejected more often by patients in this single cohort.

"“Indeed, RAI is more effective at controlling hyperthyroidism than AT drug therapy, yet for the patients who attained complete remission after AT treatment (about 50%), the value of a normally functioning thyroid without the use of any medication cannot be underestimated,” said Dr. Stan, a co-author of this study, and an endocrinologist at the Mayo Clinic in Rochester, Minnesota.

Graves’ disease, the most common cause of hyperthyroidism in the United States, is an autoimmune disorder in which thyrotropin receptor antibodies (TRAb) stimulate the TSH receptor, leading to increased thyroid hormone production.²

In this retrospective study from 2002 to 2008, 720 adults were evaluated, of which 77% were women, who were diagnosed with and treated for GD. Three-quarters of patients received RAI, 2.6% had surgery, 16% were treated with AT medications, and 5.6% were observed for worsening disease.¹ Among those in the observation group, 80% ultimately required treatment. The patients’ medical records were reviewed for an average of 3.3 years of follow-up.

Comparing Treatment Methods for Graves’ Disease

In this treatment comparison for efficacy and benefits,¹ the overall failure rate for AT medications was 48.3%, as compared to an 8% failure rate among those treated with RAI, as reported by lead author, Vishnu Sundaresh, MD, ‎assistant clinical professor at the ‎University of Utah Hospitals and Clinics, and the Mayo Clinic in Rochester, Minnesota. Surgery, as first-line therapy for 2.6% of the cohort, was successful in all cases with a low rate of complications; none of the 35 patients receiving a thyroidectomy experienced recurrence of hyperthyroidism.

Although this is the largest single-center case series on GD published to date, individuals treated at the Mayo Clinic, a tertiary referral center, may not be representative of all patients with GD, according to Elizabeth N. Pearce, MD, MSc, associate professor of medicine, Boston University School of Medicine,³ who commented on the study in Clinical Thyroidology at our request.

The surgical complication data may reflect the superior expertise of the thyroid surgeons at this site, and may not be applicable in other settings, said Dr. Pearce. In addition, the center’s preference for RAI as a first-line therapy for GD is stronger than that reported nationally,⁴she said.

In addition, Dr. Pearce speculated that differences in patient selection and/or radioactive iodine doses might account for the higher success rates for this treatment method.

A Closer Look at the Study Process

Among the 118 patients treated with long-term AT medications, 39 opted to change therapy because of patient preference, or minor side effects. Of the remaining 89 patients, 25 had either persistent hyperthyroidism at a maximum dose for AT medications, significant adverse effects requiring definitive therapy, or relapse after initial remission. RAI was chosen as second-line therapy in 101 patients whose initial treatment with either radioactive iodine or AT medications failed.¹ Among these patients, 83% experienced successful treatment.

Factors calculated to predict AT treatment failure included higher baseline TSH-receptor antibody levels, higher levels of cigarette smoking, higher free T⁴ levels, or higher radioactive iodine uptake.¹ For patients receiving RAI, only higher levels of free T⁴ were found to predict treatment failure.

In addition to the patients who were treated with long-term AT medications, another 130 patients received these drugs in preparation for other procedures. Among the total patients treated with AT medications, 17% reported adverse effects including altered taste sensation (4%), rash (3%), and nausea/gastric distress (2%). Major adverse reactions included elevated liver enzymes (2.4%), cholestasis (0.8%), and agranulocytosis (0.8%).¹

Among the RAI-treated patients, 1.2% had radiation thyroiditis and 5.9% had new ophthalmopathy after treatment.¹ Complications following surgery included hypocalcemia (29%), hematoma (2.9%), and permanent recurrent laryngeal-nerve injury (2.9%).

Applying Results to Clinical Practice

When choosing the proper treatment for Graves’ hyperthyroidism, the best course is an individualized decision that involves balancing the probability of treatment success and the likelihood of treatment complications.³ Many factors may influence patient preferences.

Therefore, while radioactive iodine as an initial treatment strategy is clearly superior to AT medications in terms of efficacy, many patients may prefer to start with AT drugs as they hold the best chance of long-term remission and avoidance of permanent hypothyroidism.

RAI and thyroidectomy almost always result in hypothyroidism, and a lifelong need for thyroid hormone replacement,¹ concluded Dr. Sundaresh.