Graves’ disease with hyperfunctioning thyroid nodule harboring thyroid carcinoma. Case report and literature review
https://doi.org/10.17650/2222-1468-2019-9-4-62-73
Abstract
According to the American Thyroid Association’s 2015 guidelines: “Since hyperfunctioning nodules rarely harbor malignancy, if one is found that corresponds to the nodule in question, no cytologic evaluation is necessary”. These findings are based on numerous studies proving the rareness of the combination of functional autonomy and thyroid cancer, and when such casuistry is detected, the non-aggressive course of the malignant process is observed.
Rare revealing of malignant nodules functional autonomy can be attributed to several fundamental bases of non-medullary thyroid carcinoma pathogenesis. According to one of the hypotheses of carcinogenesis, dedifferentiation of thyrocytes occurs initially with the loss of the possibility of the sodium-iodine symporter synthesis, and later of the thyroid-stimulating hormone receptor synthesis by the cell, which reduces the hormone production by tumor cells. In addition, hyperthyroidism has a protective feature. It reduces the level of thyroid-stimulating hormone (which causes hypertrophy, hyperplasia of thyrocytes and has an antiapoptotic effect). This protective function is used in practice for suppressive therapy in the postoperative period, which reduces the progression, recurrence and mortality from thyroid cancer. The above circumstances prove the rareness of the clinical observation described below, which deserves additional attention and subsequent discussion.
About the Authors
A. A. Kuprin
A.K. Eramishantsev City Clinical Hospital, Moscow Healthcare Department
Russian Federation
15 Lenskaya St., Moscow 129327
Russian Federation
15 Lenskaya St., Moscow 129327
V. Y. Malyuga
Russian Clinical and Research Center of Gerontology, N. I. Pirogov Russian National Research Medical University
Russian Federation
129226, 16, 1st Leonova St., Moscow 129226
Russian Federation
129226, 16, 1st Leonova St., Moscow 129226
I. V. Makedonskaya
A.K. Eramishantsev City Clinical Hospital, Moscow Healthcare Department
Russian Federation
15 Lenskaya St., Moscow 129327
Russian Federation
15 Lenskaya St., Moscow 129327
A. A. Melnikova
A.K. Eramishantsev City Clinical Hospital, Moscow Healthcare Department
Russian Federation
15 Lenskaya St., Moscow 129327
Russian Federation
15 Lenskaya St., Moscow 129327
References
1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Thyroid Cancer. Available at: https://seer.cancer.gov/statfacts/html/thyro.html.
2. State of cancer care in Russia in 2016. Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow, 2017. 236 c.(In Russ.).
3. Kachko V.A., Semkina G.V., Platonova N.M. Diagnosis of thyroid neoplasms: state of the art on 2018. Endokrinnaya khirurgiya = Endocrine Surgery 2018;12(3):109–27. (In Russ.). DOI: 10.14341/serg9977.
4. Smirnova V.A., Semkina G.V., Platonova N.M., Vanushko V.E. Papillary thyroid microcarcinoma. Klinicheskaya i eksperimentalnaya tireoidologiya = Clinical and Experimental Thyroidology 2015;11(2):11–24. (In Russ.). DOI: 10.14341/ket2015211-24.
5. Haugen B.R., Alexander E.K., Bible K.C. 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):1–133. DOI: 10.1089/thy.2015.0020.
6. Ross D.S., Burch H.B., Cooper D.S. et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26(10): 1343–421. DOI: 10.1089/thy.2016.0229.
7. Bahn R.S., Burch H.B., Cooper D.S. et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011;21(6): 593–646. DOI: 10.1089/thy.2010.0417.
8. Pazaitou-Panayiotou K., Michalakis K., Paschke R. Thyroid cancer in patients with hyperthyroidism. Horm Metab Res 2012;44(4):255–62. DOI: 10.1055/s-0031-1299741.
9. Uludag M., Yetkin G., Citgez B. et al. Autonomously functioning thyroid nodule treated with radioactive iodine and later diagnosed as papillary thyroid cancer. Hormones(Athens) 2008;7(2):175–9. DOI: 10.1007/bf03401510.
10. Appetecchia M., Ducci M. Hyperfunctioning differentiated thyroid carcinoma. J Endocrinol Invest 1998;21(3):189–92. DOI: 10.1007/bf03347300.
11. LiVolsi V.A., Baloch Z.W. The pathology of hyperthyroidism. Front Endocrinol (Lausanne) 2018;9:737. DOI: 10.3389/fendo.2018.00737.
12. Rogova O.S., Okminyan G.F., Samsonova L.N. Papillary thyroid cancer in an adolescent with a toxic single nodular goiter. Problemy endokrinologii = Problems of Endocrinology 2017;63(2):114–6. (In Russ.). DOI: 10.14341/probl2017632114-116. (In Russ.)
13. Erdoğan M.F., Anil C., Özer D. et al. Is it useful to routinely biopsy hot nodules in iodine deficient areas? J Endocrinol Invest 2003;26(2):128–31. DOI: 10.1007/bf03345140.
14. Mirfakhraee S., Mathews D., Peng L. et al. A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature. Thyroid Res 2013;6(1):7. DOI: 10.1186/1756-6614-6-7.
15. García-Jiménez C., Santisteban P. TSH signalling and cancer. Arq Bras Endocrinol Metabol 2007;51(5):654–71. DOI: 10.1590/s0004-27302007000500003.
16. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Fundamental and clinical thyroidology. Textbook. Moscow: Meditsina, 2007. 814 p. (In Russ.).
17. Fiore E., Rago T., Provenzale M.A. et al. Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 2009;16(4):1251–60. DOI: 10.1677/erc-09-0036.
18. Tam A.A., Kaya C., Kılıç F.B. et al.Thyroid nodules and thyroid cancer in Graves’ disease. Arq Bras Endocrinol Metabol 2014;58(9):933–8.DOI: 10.1590/0004-2730000003569.
19. Bukayran F.M. Thyroid cancer combined with toxic goiter. Abstract of the dis. ... cand. of med. sciences. Saint Petersburg, 2002. 22 c. Available at: https://dlib.rsl.ru/viewer/01000246124#?page=1. (In Russ.).
20. Belfiore A., Russo D., Vigneri R., Filetti S. Graves’ disease, thyroid nodules and thyroid cancer. Clin Endocrinol (Oxf) 2001;55(6):711–8. DOI: 10.1046/j.1365-2265.2001.01415.x.
21. Staniforth J.U., Erdirimanne S., Eslick G.D. Thyroid carcinoma in Graves’ disease: a meta-analysis. Int J Surg 2016;27:118–25. DOI: 10.1016/j.ijsu.2015.11.027.
22. Bitton R.N., Sachmechi I., Tabriz M.S. et al. Papillary carcinoma of the thyroid with manifestations resembling Graves’ disease. Endocr Pract 2001;7(2):106–9. DOI: 10.4158/EP.7.2.106.
23. Can N., Ozyilmaz F., Celik M. et al. Comparison of clinicopathological features in incidental and nonincidental papillary thyroid carcinomas in 308 patients. Pol J Pathol 2017;68(3):197–209. DOI: 10.5114/pjp.2017.71527.
24. Martinez-Tello F.J., Martinez-Cabruja R., Fernandez-Martinet J. et al. Occult carcinoma of the thyroid. A systematic autopsy study from Spain of two series performed with two different methods. Cancer 1993;71(12):4022–9. DOI: 10.1002/1097-0142(19930615)71 : 12 < 4022 :: aid-cncr2820711236 > 3. 0.co ; 2-o .
25. Smith J.J., Chen X., Schneider D.F. et al. There is a high rate of incidental thyroid cancer in surgical series of toxic and nontoxic multinodular goiter.Clin Thyroidol 2013;25:168–9.
26. Lee S.L. Thyroid cancer presenting as autonomous thyroid nodule. Endocrine Today 2015 September. Available at: https://www.healio.com/endocrinology/thyroid/news/print/endocrine-today.
27. Gagliano E., Sturniolo G., Querci A. et al. Concurrent hyperthyroidism and papillary thyroid cancer. Med Rep Case Stud 2016;1(4):123. DOI: 10.4172/2572-5130.1000123.
28. Cerci C., Cerci S.S., Eroglu E. et al. Thyroid cancer in toxic and non-toxic multinodular goiter. J Postgrad Med 2007;53(3):157–60. DOI: 10.4103/0022-3859.33855.
29. Beltsevich D.G., Vanushko V.E., Melnichenko G.A. Clinic guidelines for thyroid nodules diagnostic and treatment. Moscow, 2016. 9 p. Available at: https://www.endocrincentr.ru/sites/default/files/specialists/science/clinicrecomendations/proekt_uzlovoi_zob.pdf. (In Russ.).
30. Ren M., Wu M.C., Shang C.Z. et al. Predictive factors of thyroid cancer in patients with Graves’ disease. World J Surg 2013;38(1):80–7. DOI: 10.1007/s00268-013-2287-z.
31. Kandror V.I. Pathogenesis of Graves’ disease and mechanism of action of thiroid hormones. Klinicheskaya i eksperimentalnaya tireoidologiya = Clinical and Experimental Thyroidology 2008;4(1):26–34. (In Russ.).
32. Troshina E.A., Sviridenko N.Yu., Vanushko V.E. et al. The federal clinical recommendations on diagnostics and treatment of toxic goiter. Problemi Endocrinologii = Problems of Endocrinology 2014;60(6):67–77. (In Russ.). DOI: 10.14341/probl201460667-77.
33. Yunusa G., Kotze T., Brink A. Metastatic papillary carcinoma of the thyroid in a patient previously treated for Graves’ disease. Ann Afr Med 2014;13(2):91–4. DOI: 10.4103/1596-3519.129891.
34. Tezelman S., Grossman R.F., Siperstein A.E., Clark O.H. Radioiodine-associated thyroid cancers. World J Surg 1994;18(4):522–8. DOI: 10.1007/bf00353754.
35. Fujikawa M., Okamura K., Sato K. et al. Anaplastic transformation of a papillary carcinoma of the thyroid in a patient with Graves’ disease with varied activity of thyrotropin receptor antibodies. Thyroid 1998;8(1):53–8. DOI: 10.1089/thy.1998.8.53.
36. Yano Y., Shibuya H., Kitagawa W. et al. Recent outcome of Graves’ disease patients with papillary thyroid cancer. Eur J Endocrinol 2007;157(3):325–9. DOI: 10.1530/eje-07-0136.
37. Boostrom S., Richards M.L. Total thyroidectomy is the preferred treatment for patients with Graves’ disease and a thyroid nodule. Otolaryngol Head Neck Surg 2007;136(2):278–81. DOI: 10.1016/j.otohns.2006.09.011.
38. Menon R., Nair C.G., Babu M. et al. The outcome of papillary thyroid cancer associated with Graves’ disease: a case control study. J Thyroid Res 2018;2018:8253094. DOI: 10.1155/2018/8253094.
39. Cross G.A., Suarez H., Pitoia F. et al. Fatal outcome of a young woman with papillary thyroid carcinoma and Graves’ disease: possible implication of “crosssignalling” mechanism. Arq Bras Endocrinol Metabol 2008;52(7):1194–200. DOI: 10.1590/s0004-27302008000700018.
40. Dumont J.E., Dremier S., Pirson I., Maenhaut C. Cross signaling, cell specificity, and physiology. Am J Physiol Cell Physiol 2002;283(1):C2–28. DOI: 10.1152/ajpcell.00581.2001.
41. Calebiro D., Persani L., Beck-Peccoz P. Clinical manifestations of mutations in RTSH: RTSH pathology. Tironet 2005;3. Available at: http:// thyronet.rusmedserv.com/spetsialistam/zhurnal/archiv/2005g/3/Patologiya_receptora_TTG.html?page=6. (In Russ.).
42. Fadeev V.V. Thyrotropin receptor antibodies assays in the management of Graves’ disease. Klinicheskaya i eksperimentalnaya tireoidologiya = Clinical and Experimental Thyroidology 2013;9(1):9–17. (In Russ.).
43. Luo Y., Yoshihara A., Oda K. et al. Excessive cytosolic DNA fragments as a potential trigger of Graves’ disease: an encrypted message sent by animal models. Front Endocrinol(Lausanne) 2016;7:144. DOI: 10.3389/fendo.2016.00144.
44. Gozu H., Avsar M., Bircan R. et al. Does a Leu 512 Arg thyrotropin receptor mutation cause an autonomously functioning papillary carcinoma? Thyroid 2004;14(11):975–80. DOI: 10.1089/thy.2004.14.975.
45. Ruggeri R.M., Campennì A., Giovinazzo S. et al. Follicular variant of papillary thyroid carcinoma presenting as toxic nodule in an adolescent: coexistent polymorphism of the TSHR and Gsα genes. Thyroid 2013;23(2):239–42. DOI: 10.1089/thy.2012.0279.
46. Spambalg D., Sharifi N., Elisei R. et al. Structural studies of the thyrotropin receptor and Gs alpha in human thyroid cancers: low prevalence of mutations predicts infrequent involvement in malignant transformation. J Clin Endocrinol Metab 1996;81(11):3898–901. DOI: 10.1210/jcem.81.11.8923835.
47. Russo D., Tumino S., Arturi F. et al. Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. J Clin Endocrinol Metab 1997;82(3):735–8. DOI: 10.1210/jcem.82.3.3838.
48. Camacho P., Gordon D., Chiefari E. et al. A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism. Thyroid 2000;10(11):1009–12. DOI: 10.1089/thy.2000.10.1009.
49. Mircescu H., Parma J., Huot C. et al. Hyperfunctioning malignant thyroid nodule in an 11-year-old girl: pathologic and molecular studies. J Pediatr 2000;137(4):585–7. DOI: 10.1067/mpd.2000.108437.
50. Führer D., Tannapfel A., Sabri O. et al. Two somatic TSH receptor mutations in a patient with toxic metastasing follicular thyroid carcinoma and nonfunctional lung metastases. Endocr Relat Cancer 2003;10(4):591–600. DOI: 10.1677/erc.0.0100591.
51. Stefan M., Faustino L.C. Genetics of thyroid-stimulating hormone receptor –relevance for autoimmune thyroid disease. Front Endocrinol (Lausanne) 2017;8:57. DOI: 10.3389/fendo.2017.00057.
52. Niedziela M., Breborowicz D., Trejster E., Korman E. Hot nodules in children and adolescents in Western Poland from 1996 to 2000: clinical analysis of 31 patients. J Pediatr Endocrinol Metab 2002;15(6):823–30. DOI: 10.1515/jpem.2002.15.6.823.
Review
For citations:
Kuprin A.A., Malyuga V.Y., Makedonskaya I.V., Melnikova A.A. Graves’ disease with hyperfunctioning thyroid nodule harboring thyroid carcinoma. Case report and literature review. Head and Neck Tumors (HNT). 2019;9(4):62-73. (In Russ.) https://doi.org/10.17650/2222-1468-2019-9-4-62-73
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