Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease

J Clin Endocrinol Metab. 2013 Mar;98(3):1014-21. doi: 10.1210/jc.2012-2843. Epub 2013 Jan 24.


Context: We previously reported that differentiated thyroid cancer (DTC) has higher aggressiveness and poorer prognosis in patients with Graves' disease (GD) than DTC in euthyroid control patients. Subsequent studies on this issue reached controversial conclusions. Genetic and environmental factors, as well as the lack of appropriate control subjects and/or inadequate patient follow-up, may account for these discrepancies.

Objective: The aim of this study was to investigate the long-term disease-specific mortality of nonoccult DTCs occurring in patients with GD compared with DTCs in matched euthyroid control patients.

Patients and design: The previously described cohorts of nonoccult DTCs occurring in either patients with GD (DTC-GD, n = 21) or matched euthyroid DTC control patients (n = 70) were compared again after a longer follow-up (50-363.6 months; median, 165.6 months) to compare the major clinical endpoints of persistent/recurrent disease and overall survival. Both cohorts were recruited in 1982-1994 at a single institution. All patients had undergone total thyroidectomy and were followed up according to a standardized protocol.

Results: Persistent/recurrent disease was more frequent in DTC-GD patients than in control patients (P = .0119). Disease-specific mortality was also significantly higher in DTC-GD patients (6 of 21, 28.6%) than in euthyroid control patients (2 of 70, 2.9%) (P = .0001). At the last visit, the percentage of disease-free patients was 57.1% (12 of 21) in the DTC-GD group vs 87.1% (61 of 70) in the control group (P = .0025).

Conclusions: Nonoccult DTCs occurring in patients with GD cause increased disease-specific mortality compared with DTCs in matched euthyroid control patients. These findings emphasize the need for early diagnosis and aggressive treatment of nonoccult DTCs in patients with GD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma / mortality*
  • Carcinoma / pathology*
  • Carcinoma / surgery
  • Carcinoma, Papillary
  • Cell Differentiation
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graves Disease / mortality*
  • Graves Disease / pathology*
  • Graves Disease / surgery
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Prognosis
  • Thyroid Cancer, Papillary
  • Thyroid Gland / parasitology
  • Thyroid Gland / physiology
  • Thyroid Gland / surgery
  • Thyroid Neoplasms / mortality*
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / surgery
  • Thyroid Nodule / mortality
  • Thyroid Nodule / pathology
  • Thyroid Nodule / surgery
  • Thyroidectomy
  • Young Adult