Thyroid nodules in Graves' disease: classification, characterization, and response to treatment

Thyroid nodules in patients with Graves' disease are common and raise concern about coexistent thyroid malignancy. Alternative etiologies for such nodules are more frequent, and separation from thyroid malignancy is important for rational management. To characterize the types of thyroid nodules present in patients with Graves' disease, evaluate the response of these nodules to treatment, and stratify the risk of thyroid malignancy, we report on a retrospective single center study in an ambulatory setting of 468 Graves' patients ages (12-75) followed for 1-31 years (mean = 5.1) treated with radioiodine (n = 345), near-total thyroidectomy (n = 19), thionamide antithyroid drugs (n = 88), or observation (n = 18). Sixty patients (12.8% of the total) had nodules and were classified as: (1) Graves' disease with a solitary hypofunctional nodule (n = 27, 5.8%); (2) Graves' disease with multiple nodules (n = 21, 4.5%); (3) Graves' disease with autonomous nodule (n = 4, 1%); or (4) patchy Graves' disease (n = 8, 1.7%). Six patients (1.3% of total or 10% of nodule patients) had cancer: five in group 1 and and one in Group 4. Based on the response to therapy or surgical and fine-needle aspirate pathology, the remaining patients demonstrated pseudo-nodules of autoimmune thyroid disease, autonomous nodules of Marine-Lenhart syndrome, colloid goiter, hyperplastic adenomatous disease, and Hashitoxicosis. In conclusion, Graves, patients commonly present with or may develop nodules (12.6%) and the majority of these are benign expressions of autoimmune changes and coexistent nodular goiter. Thyroid cancer occurs in 10% of all nodules, 19% of palpable solitary cold nodules, and 1.3% of the total patients. If the fine-needle aspiration biopsy (FNAB) cytology is benign, it is reasonable to use nonsurgical therapy. Any single cold nodule that remains or develops after treatment needs careful re-examination due to the high risk of malignancy.