Endocrinol Metab.  2021 Dec;36(6):1268-1276. 10.3803/EnM.2021.1227.

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

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea

Abstract

Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Keyword

Graves disease; Thyroid neoplasms; Prevalence; Aggression; Prognosis

Figure

  • Fig. 1 Flow chart of the study population. US, ultrasonography.


Reference

1. Smith TJ, Hegedus L. Graves’ disease. N Engl J Med. 2016; 375:1552–65.
Article
2. Wemeau JL, Klein M, Sadoul JL, Briet C, Velayoudom-Cephise FL. Graves’ disease: introduction, epidemiology, endogenous and environmental pathogenic factors. Ann Endocrinol (Paris). 2018; 79:599–607.
Article
3. Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013; 9:724–34.
Article
4. Staniforth JU, Erdirimanne S, Eslick GD. Thyroid carcinoma in Graves’ disease: a meta-analysis. Int J Surg. 2016; 27:118–25.
Article
5. Gabriele R, Letizia C, Borghese M, De Toma G, Celi M, Izzo L, et al. Thyroid cancer in patients with hyperthyroidism. Horm Res. 2003; 60:79–83.
Article
6. Sokal JE. Incidence of malignancy in toxic and nontoxic nodular goiter. J Am Med Assoc. 1954; 154:1321–5.
Article
7. Rieger R, Pimpl W, Money S, Rettenbacher L, Galvan G. Hyperthyroidism and concurrent thyroid malignancies. Surgery. 1989; 106:6–10.
8. Pazaitou-Panayiotou K, Michalakis K, Paschke R. Thyroid cancer in patients with hyperthyroidism. Horm Metab Res. 2012; 44:255–62.
Article
9. Keskin C, Sahin M, Hasanov R, Aydogan BI, Demir O, Emral R, et al. Frequency of thyroid nodules and thyroid cancer in thyroidectomized patients with Graves’ disease. Arch Med Sci. 2019; 16:302–7.
Article
10. Shu X, Ji J, Li X, Sundquist J, Sundquist K, Hemminki K. Cancer risk in patients hospitalised for Graves’ disease: a population-based cohort study in Sweden. Br J Cancer. 2010; 102:1397–9.
Article
11. Chen YK, Lin CL, Chang YJ, Cheng FT, Peng CL, Sung FC, et al. Cancer risk in patients with Graves’ disease: a nationwide cohort study. Thyroid. 2013; 23:879–84.
Article
12. Belfiore A, Russo D, Vigneri R, Filetti S. Graves’ disease, thyroid nodules and thyroid cancer. Clin Endocrinol (Oxf). 2001; 55:711–8.
Article
13. Papanastasiou A, Sapalidis K, Goulis DG, Michalopoulos N, Mareti E, Mantalovas S, et al. Thyroid nodules as a risk factor for thyroid cancer in patients with Graves’ disease: a systematic review and meta-analysis of observational studies in surgically treated patients. Clin Endocrinol (Oxf). 2019; 91:571–7.
Article
14. Ozaki O, Ito K, Kobayashi K, Toshima K, Iwasaki H, Yashiro T. Thyroid carcinoma in Graves’ disease. World J Surg. 1990; 14:437–41.
Article
15. Menon R, Nair CG, Babu M, Jacob P, Krishna GP. The outcome of papillary thyroid cancer associated with Graves’ disease: a case control study. J Thyroid Res. 2018; 2018:8253094.
Article
16. Cappelli C, Braga M, De Martino E, Castellano M, Gandossi E, Agosti B, et al. Outcome of patients surgically treated for various forms of hyperthyroidism with differentiated thyroid cancer: experience at an endocrine center in Italy. Surg Today. 2006; 36:125–30.
Article
17. Kasuga Y, Sugenoya A, Kobayashi S, Masuda H, Iida F. The outcome of patients with thyroid carcinoma and Graves’ disease. Surg Today. 1993; 23:9–12.
Article
18. Hales IB, McElduff A, Crummer P, Clifton-Bligh P, Delbridge L, Hoschl R, et al. Does Graves’ disease or thyrotoxicosis affect the prognosis of thyroid cancer. J Clin Endocrinol Metab. 1992; 75:886–9.
Article
19. Kikuchi S, Noguchi S, Yamashita H, Uchino S, Kawamoto H. Prognosis of small thyroid cancer in patients with Graves’ disease. Br J Surg. 2006; 93:434–9.
Article
20. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016; 26:1343–421.
Article
21. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al. 2017 AJCC Cancer Staging Manual. 8th ed. New York: Springer;2017.
22. Yano Y, Shibuya H, Kitagawa W, Nagahama M, Sugino K, Ito K, et al. Recent outcome of Graves’ disease patients with papillary thyroid cancer. Eur J Endocrinol. 2007; 157:325–9.
Article
23. Kim WB, Han SM, Kim TY, Nam-Goong IS, Gong G, Lee HK, et al. Ultrasonographic screening for detection of thyroid cancer in patients with Graves’ disease. Clin Endocrinol (Oxf). 2004; 60:719–25.
Article
24. Kraimps JL, Bouin-Pineau MH, Mathonnet M, De Calan L, Ronceray J, Visset J, et al. Multicentre study of thyroid nodules in patients with Graves’ disease. Br J Surg. 2000; 87:1111–3.
Article
25. Erbil Y, Barbaros U, Ozbey N, Kapran Y, Tukenmez M, Bozbora A, et al. Graves’ disease, with and without nodules, and the risk of thyroid carcinoma. J Laryngol Otol. 2008; 122:291–5.
Article
26. Ren M, Wu MC, Shang CZ, Wang XY, Zhang JL, Cheng H, et al. Predictive factors of thyroid cancer in patients with Graves’ disease. World J Surg. 2014; 38:80–7.
Article
27. Ergin AB, Saralaya S, Olansky L. Incidental papillary thyroid carcinoma: clinical characteristics and prognostic factors among patients with Graves’ disease and euthyroid goiter, Cleveland Clinic experience. Am J Otolaryngol. 2014; 35:784–90.
Article
28. Tam AA, Kaya C, Kilic FB, Ersoy R, Cakir B. Thyroid nodules and thyroid cancer in Graves’ disease. Arq Bras Endocrinol Metabol. 2014; 58:933–8.
Article
29. Alvarez AL, Mulder M, Handelsman RS, Lew JI, Farra JC. High rates of underlying thyroid cancer in patients undergoing thyroidectomy for hyperthyroidism. J Surg Res. 2020; 245:523–8.
Article
30. Casella C, Morandi R, Verrengia A, Galani A, Molfino S, Cuka D, et al. Thyroid cancer and nodules in Graves’ disease: a single center experience. Endocr Metab Immune Disord Drug Targets. 2021; 21:2028–34.
Article
31. Imam S, Dar P, Paparodis R, Almotah K, Al-Khudhair A, Hasan SA, et al. Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer. J Immunother Cancer. 2019; 7:3.
Article
32. Paparodis RD, Karvounis E, Bantouna D, Chourpiliadis C, Chourpiliadi H, Livadas S, et al. Incidentally discovered papillary thyroid microcarcinomas are more frequently found in patients with chronic lymphocytic thyroiditis than with multinodular goiter or Graves’ disease. Thyroid. 2020; 30:531–5.
Article
33. Jia Q, Li X, Liu Y, Li L, Kwong JS, Ren K, et al. Incidental thyroid carcinoma in surgery-treated hyperthyroid patients with Graves’ disease: a systematic review and meta-analysis of cohort studies. Cancer Manag Res. 2018; 10:1201–7.
34. Lee HJ, Li CW, Hammerstad SS, Stefan M, Tomer Y. Immunogenetics of autoimmune thyroid diseases: a comprehensive review. J Autoimmun. 2015; 64:82–90.
Article
35. Ferrari SM, Fallahi P, Elia G, Ragusa F, Ruffilli I, Paparo SR, et al. Thyroid autoimmune disorders and cancer. Semin Cancer Biol. 2020; 64:135–46.
Article
36. Filetti S, Belfiore A, Amir SM, Daniels GH, Ippolito O, Vigneri R, et al. The role of thyroid-stimulating antibodies of Graves’ disease in differentiated thyroid cancer. N Engl J Med. 1988; 318:753–9.
Article
37. Premoli P, Tanda ML, Piantanida E, Veronesi G, Gallo D, Masiello E, et al. Features and outcome of differentiated thyroid carcinoma associated with Graves’ disease: results of a large, retrospective, multicenter study. J Endocrinol Invest. 2020; 43:109–16.
Article
38. Vaccarella S, Franceschi S, Bray F, Wild CP, Plummer M, Dal Maso L. Worldwide thyroid-cancer epidemic?: the increasing impact of overdiagnosis. N Engl J Med. 2016; 375:614–7.
Article
39. Vaccarella S, Dal Maso L, Laversanne M, Bray F, Plummer M, Franceschi S. The impact of diagnostic changes on the rise in thyroid cancer incidence: a population-based study in selected high-resource countries. Thyroid. 2015; 25:1127–36.
Article
40. Boutzios G, Vasileiadis I, Zapanti E, Charitoudis G, Karakostas E, Ieromonachou P, et al. Higher incidence of tall cell variant of papillary thyroid carcinoma in Graves’ disease. Thyroid. 2014; 24:347–54.
Article
41. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016; 26:1–133.
Article
42. Mekraksakit P, Rattanawong P, Karnchanasorn R, Kanitsoraphan C, Leelaviwat N, Poonsombudlert K, et al. Prognosis of differentiated thyroid carcinoma in patients with Graves disease: a systematic review and meta-analysis. Endocr Pract. 2019; 25:1323–37.
Article
43. Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R, et al. Increased mortality in patients with differentiated thyroid cancer associated with Graves’ disease. J Clin Endocrinol Metab. 2013; 98:1014–21.
Article
Full Text Links
  • ENM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr