Context: Despite accounting for variations in gland size and iodine kinetics the success of radioiodine therapy in patients with Graves' disease remains moderately common and unpredictable.

Objective: We hypothesized that hypoechogenic glands, with large, densely packed cells, are more radiosensitive than normoechogenic glands, where much radiation is wasted on more abundant colloid. We evaluated this hypothesis in a cohort of patients with Graves' disease.

Design: A prospective trial of patients recruited during 4 years and followed-up one year after radioiodine therapy.

Setting: University hospital-outpatient clinic.

Patients: 177 consecutive patients with first presentation of Graves' disease (28 were males), 23-76 years old, who relapsed after antithyroid therapy.

Intervention: When definitive, ablative approach was sought the patients were assigned to target absorbed dose of 200 Gy (N=78), otherwise randomly to 100 or 120 Gy (N=99).

Main outcome measures: Incidences of hyperthyroidism, euthyroidism and hypothyroidism at 12 month follow-up.

Results: At follow-up there were 25 hyperthyroid, 44 euthyroid and 108 hypothyroid patients. Compared with 96 patients with hypoechogenic gland, in 81 patients with normoechogenic gland there were more hyperthyroid (22 vs. 7%) and euthyroid (41 vs. 11%), but less hypothyroid outcomes (37 vs. 81%; p< 0.0001). The other independent predictor of increased radioresistance was the large gland volume.

Conclusion: In patients with Graves' disease normoechogenic and large glands are associated with increased radioresistance.