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

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.

The management of pediatric Graves’ disease

“…An umbrella review (reviewing meta-analyses that included both prospective and retrospective studies) was recently performed to evaluate the quality of the evidence for association between GD and thyroid cancer risk. This study found ‘strong’ evidence of cancer risk in GD patients who had thyroid nodules, compared to GD patients who did not have nodules; the odds ratio was 5.30 [95% confidence interval (CI) 2.43–12] [24]. Interestingly, there was also strong evidence of an increased mortality risk from thyroid cancer in GD patients compared to those without a GD diagnosis.…”

Autoimmune Thyroid Disease and Differentiated Thyroid Carcinoma: A Review of the Mechanisms That Explain an Intriguing and Exciting Relationship

“…The association between AITD and DTC is controversial, and although multiple mechanisms have been described that could explain this association, uncertainty and contradictory results remain. This can be explained by multiple aspects, for instance, the results of the different studies may vary according to the way in which the disease was defined (from the clinical, biochemical, and/or imaging point of view) and if confirmed by cytological (with or without subsequent surgery) or histopathological analysis [ 89 - 91 ].…”

“…could explain this association, uncertainty and contradictory results remain. This can be explained by multiple aspects, for instance, the results of the different studies may vary according to the way in which the disease was defined (from the clinical, biochemical, and/or imaging point of view) and if confirmed by cytological (with or without subsequent surgery) or histopathological analysis [89][90][91]. Additional factors could be the previous treatment received by the patients (antithyroid drugs or I-131, in GBD), use of levothyroxine (in HT), the severity of AITD (since the greater the thyroid autoimmune activity, the greater the hyperplasia, and therefore, the greater the probability of atypia and potential malignancy), the history of previous exposure to radiation and the hereditary component (especially for the development of PTC) and other environmental determinants [90][91][92].…”

Graves’ Disease in Children: A Comprehensive Review on Diagnosis, Treatment, and Long-Term Considerations

“…Pediatric otolaryngology had a significantly higher number of complications compared to pediatric surgery, although confounding factors and the low complication rate make this finding difficult to interpret. 20 Total thyroidectomy in children (≤18 years of age) was examined in a study to determine the incidence and risk factors of hypocalcemia and hypoparathyroidism. The analysis included 106 children who underwent the procedure for various indications such as Graves' disease, Multiple Endocrine Neoplasia type-2, multinodular goiter, and follicular/papillary thyroid carcinoma.…”