Features and outcome of differentiated thyroid carcinoma associated with Graves’ disease: results of a large, retrospective, multicenter study

Abstract

Background Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. Objective Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD−). Patients Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD−. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. Results Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD− patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. Conclusions GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD. KeywordsThyroid carcinoma • Graves' disease • Outcome • Thyroidectomy • Graves' orbitopathy • TSH-receptor antibody • Radioiodine P. Premoli and M. L. Tanda equally contributed to this study.

Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study

“…In only a few studies, US was performed in all GD patients, including non-surgically treated patients as in our study, and these studies reported lower incidences of thyroid cancer. A recent multicenter study performing preoperative US in all GD patients reported that only 38.3% of GD patients with coexisting thyroid cancer underwent thyroidectomy with suspicious FNA results and the ratio of microcarcinoma (<1 cm) was significantly higher in GD patients compared to age, sex, and tumor size-matched non-GD patients (60% vs. 37%) [37]. Our study revealed a similar ratio of microcarcinoma in GD patients, even though thyroid cancer was diagnosed by preoperative US-guided FNA in 95.8% of GD patients.…”

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

“…Cappelli et al . found a cancer rate of 6.5% in GD patients undergoing thyroidectomy compared to 4.4% of those with solitary toxic nodules ( 90 ), and some studies found that tumors in adult GD patients may behave more aggressively ( 91 , 92 , 93 ). A meta-analysis of 987 GD patients with DTC confirmed the higher prevalence of adverse prognostic features, but there was no difference in persistent disease or mortality ( 94 ).…”

Graves’ disease and papillary thyroid carcinoma: case report and literature review of a single academic center

“…The presence of nodules increases the chance of finding cancer, a metanalysis revealed that the presence of at least one nodule is associated with a fivefold increase in thyroid cancer risk [ 10 ]. The most common cancer reported in GD is PTC and microcarcinomas are particularly common [ 7 , 11 , 12 ].…”