Is There a Link Between Graves’ Disease and Thyroid Cancer?

Researchers examined several studies of patients with Graves' Disease to see the prevalence of thyroid cancer in this population.

The existence of thyroid nodules is significantly linked to the prevalence of thyroid cancer in surgically treated patients with Graves’ disease, according to the results of a recent meta-analysis published in Clinical Endocrinology.

“It was previously thought that disorders characterized by hyperthyroidism, such as GD [Graves’ disease], were protective against thyroid cancer,” wrote authors, led by Anastasios Papanastasiou, 3rd Department of Surgery, “AHEPA” University Hospital, Medical School, Aristotle University of Thessaloniki, Greece.

In the study, researchers mined PubMed, Cochrane Library, Scopus, as well as “grey” literature sources, including repositories, catalogues, websites, and conference proceedings of major international congresses, for seven observational studies (n=2,582) involving the prevalence of thyroid cancer in patients with Graves’ disease.

In total, the prevalence of any type of thyroid cancer was 11.5%. Furthermore, the presence of ≥ thyroid nodules in patients with Grave disease was correlated with a heightened risk for thyroid cancer [odds ratio (OR) 5.3, 95% confidence interval (CI) 2.4 –11.6, I2 83%]. On subgroup analysis, no difference in thyroid cancer risk in patients with Graves’ disease was observed relative to to the number of nodules (solitary vs multiple) (OR 1.4, 95% CI 0.9 –2.3, I2 0%).

Although the etiopathology of Graves’ disease remains to be elucidated, it has been linked to genetic and environmental factors, with an annual incidence of 20 - 50 cases per 100,000 people. It is more common in people aged 30-50 years old, with women harboring a six-fold higher risk vs men.

The presentation of solitary or multiple thyroid nodules is a common finding in patients with thyroid disorders. Per the literature, patients with thyroid nodules are at higher risk for thyroid cancer. Of note, ultrasonography used for screening has boosted the incidence of detected thyroid nodules.

Experts once hypothesized that hyperthyroid disorders-including Graves’ disease-were protective vs thyroid cancer (0.15 - 2.5%), but recent studies have shown a higher prevalence of thyroid cancer in patients with Graves’ disease (2.6 - 15%). Moreover, the pathiogenesis of thyroid cancer in patients with Graves’ disease is debated, with some studies reporting a higher rate of lymph node metastasis and death, whereas others have reported the opposite. Of interest, although some meta-analyses have examined thyroid cancer risk in patients with Grave disease, no study has analyzed assessed thyroid nodules as a risk factor for thyroid cancer in such patients.

In addition to being retrospective, the current study had limitations.

“High heterogeneity was noticed among studies for the primary outcome, mainly because of confounding bias. More specifically, the patient characteristics and the indications for surgery varied among studies. For this reason, a sensitivity analysis was performed,” wrote the authors.

“The preoperative detection of thyroid nodules was associated with a higher prevalence of thyroid cancer in patients with GD,” they concluded. “However, the retrospective data of the selected studies had led to confounding bias and high heterogeneity. Consequently, further prospective research on cancer risk in patients with GD is required to confirm this finding.”