Thyroid cancer yield in patients with Graves' disease

The management of thyroid nodules in patients with Graves' disease remains an issue both of concern and controversy for those who care for these patients. At one time, thyroid cancer in patients with thyrotoxicosis was considered to be extremely rare, but this perception has proven to be incorrect. Several studies have demonstrated both an increased incidence of nodules and of thyroid cancer in patients with Graves' disease, with cancer rates varying from as low as 1% to as high as 9% of cases. These divergent estimates of malignancy rates in Graves' disease have predictably led to variability in management recommendations. Considerable controversy also exists as to whether or not thyroid cancer behaves more aggressively in patients with Graves' disease. Anecdotal experience and a number of studies have suggested an increased aggressiveness of papillary and follicular thyroid cancer in patients with Graves' disease, but these findings are not universal. Underlying both issues of the incidence and aggressiveness of thyroid cancer is the role of thyrotropin (thyroid stimulating hormone, TSH) in the development and stimulation of thyroid cancer. The association between TSH and thyroid cancer has long been known. TSH has a central role in thyroid growth and normal functioning and appears to play a similar part in the growth and development of thyroid cancer. The close relationship of TSH to the stimulating TSH-R antibodies (TSH-R AB) seen in Graves' disease has led to the perception that thyroid cancer occurring in the setting of Graves' disease may become more aggressive as a result of stimulation by these autoantibodies. This article will summarize the existing literature pertaining to thyroid cancer in Graves' disease, and suggest an evidence-based approach to the management of these patients.