Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review

SIMPLE SUMMARY: Graves’ disease (GD) is the most common cause of thyrotoxicosis due to autoimmune hyperthyroidism, especially in women. This umbrella review aimed to provide an evidence-based summary of epidemiological studies conducted on the association between GD and the risk of developing thyroid cancer risk and its prognosis. Strong evidence was found for thyroid cancer risk in GD patients and nodular thyroid disease and mortality risk from thyroid cancer in GD patients, particularly in Europe. However, the results of this umbrella review should be taken with caution; as the evidence comes mainly from retrospective studies, the potential concerns are selection and recall bias. ABSTRACT: Graves’ disease (GD) is an autoimmune disease considered the most common cause of hyperthyroidism. Some studies have investigated its relationship with the risk and prognosis of developing thyroid cancer. Considering that there is no consensus on the relationship between GD and thyroid cancer risk, this umbrella review aimed to summarize the epidemiologic evidence and evaluate its strength and validity on the associations of GD with thyroid cancer risk and its prognosis. This umbrella review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed and Scopus from January 2012 to December 2022. The strength of the epidemiological evidence was graded as high, moderate, or weak by the Measurement Tool to Assess Systematic Reviews (AMSTAR-2). “Strong” evidence was found for the risk of thyroid cancer in GD patients with thyroid nodular disease (OR: 5.30; 95% CI 2.43–12) and for the risk of mortality from thyroid cancer in these patients (OR 2.93, 95% CI 1.17–7.37, p = 0.02), particularly in Europe (OR 4.89; 95% CI 1.52–16). The results of this umbrella review should be interpreted with caution; as the evidence comes mostly from retrospective studies, potential concerns are selection and recall bias, and whether the empirically observed association reflects a causal relationship remains an open question.