Spyridoula Maraka, MD, Mayo Clinic, Rochester, Minnesota, USA, reported on results from an interim safety analysis, which found that initiating low-dose levothyroxine at 4 weeks after patients received radioactive iodine (RAI) for Graves’ disease (GD) appears safe and shows no increased incidence of hyperthyroidism.

Most patients with GD are treated with RAI and reevaluated 2 to 3 months later; the majority are hypothyroid by that time, and some have related troublesome symptoms and possible development or worsening of Graves’ orbitopathy.

This randomized double-blind controlled trial [NCT01950260] was designed to determine whether early treatment with levothyroxine after RAI therapy for GD would prevent overt hypothyroidism. This interim analysis for safety was performed after the first 17 patients were enrolled, with 11 patients receiving levothyroxine, 25 mg QD, and 6 receiving placebo in a single tablet at 4 weeks after RAI therapy. At 6 weeks after RAI therapy, the levothyroxine dose was increased to 50 mg QD and the placebo to 2 tablets per day. At 8 weeks after RAI therapy, the treating physician evaluated the patients and treated them as clinically indicated for reaching euthyroidism.

Exclusion criteria included a clinical manifestation of Graves’ orbitopathy, recent history of arrhythmias or any history of ventricular arrhythmias, preexistent cardiomyopathy, malnutrition, or psychiatric history. Researchers also considered the likelihood of whether patients would return for follow-up visits.

The enrolled patients were a median of 52.7 years of age in the levothyroxine arm and 55.3 years in the placebo arm. The levothyroxine arm was 72.7% women, and the placebo arm was 66.7% women. Median thyroid size was 30 g in both arms. Median free thyroxine was 2.7 ng/dL in the levothyroxine arm and 1.9 ng/dL in the placebo arm.

Patient history was taken at weeks 0, 8, and 24. Physical examinations and goiter size measurements occurred at weeks 0 and 8. Quality-of-life questionnaires were used at weeks 4, 6, 8, and 24.

Only 1 adverse event was reported: a patient in the levothyroxine arm had heart palpitations that led to the decision to discontinue the study drug. This patient had a history of chronic atrial fibrillation and discontinued beta-blocker therapy during the study.

At 8 weeks, overt hypothyroidism occurred in 54.5% of patients who received levothyroxine and in 66.7% of patients who received the placebo (Table 1). The rate of hyperthyroidism was lower in the levothyroxine group (18.2%) than in the placebo group (33.3%).

The thyroid symptom questionnaire scores were similar between the levothyroxine and placebo groups. The health-related quality-of-life questionnaire found that the levothyroxine group was more symptomatic than the placebo group (median score, 46 vs 36).

Initiating low-dose levothyroxine at 4 weeks after RAI appears safe and does not increase the risk of hyperthyroidism. The data, though statistically insignificant, suggest that this strategy might prevent overt hypothyroidism. The research team plans to continue the trial to completion without modifying the protocol.