Thyroid carcinoma in Graves’ disease: a retrospective analysis of prevalence, histological subtypes, and clinical predictors

Graves’ disease (GD) is an autoimmune cause of hyperthyroidism frequently associated with thyroid nodularity. However, whether GD confers an increased risk of differentiated thyroid carcinoma (DTC) compared with euthyroid populations remains uncertain, and reliable clinical predictors of DTC in patients with GD are not well defined. This retrospective cohort study included 134 adults with GD who underwent total thyroidectomy between 2015 and 2022. Clinical, biochemical, ultrasonographic, and pathological variables were systematically evaluated. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of thyroid carcinoma. DTC was identified in 47 patients (35.1%). Classic papillary thyroid carcinoma was the most common subtype (80.9%). Seven patients had incidental tumors despite no preoperative nodule detection. In univariable analysis, older age (OR 1.05, 95% CI 1.02–1.09; p < 0.001) and a family history of thyroid cancer (OR 5.53, 95% CI 1.39–21.98; p = 0.015) were significantly associated with malignancy. Multivariable modeling confirmed age (OR 1.06, p < 0.001) and family history (OR 5.75, p = 0.019) as independent predictors, whereas sex, BMI, smoking status, TRAb levels, thyroid function tests, thyroid volume, and disease duration were not significantly associated with cancer risk. More than one-third of surgically treated patients with GD harbored DTC, predominantly low-grade papillary carcinoma, with a substantial proportion detected incidentally. Older age and a positive family history of thyroid cancer emerged as independent predictors of malignancy in this surgical cohort, whereas no significant association was observed between the evaluated biochemical markers of GD activity and cancer risk. These findings may suggest that traditional clinical risk factors are more strongly associated with malignancy than biochemical disease activity parameters; however, the results should be interpreted cautiously given the retrospective study design, potential surgical selection bias, and the relatively small sample size.