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

J Endocrinol Invest. 2020 Jan;43(1):109-116. doi: 10.1007/s40618-019-01088-5. Epub 2019 Jul 20.


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.

Keywords: Graves’ disease; Graves’ orbitopathy; Outcome; Radioiodine; TSH-receptor antibody; Thyroid carcinoma; Thyroidectomy.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Cell Differentiation*
  • Female
  • Follow-Up Studies
  • Graves Disease / complications*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / mortality*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery
  • Thyroidectomy / mortality*