Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study

in European Journal of Endocrinology
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  • 1 Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
  • 2 Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
  • 3 Unit of Internal Medicine, Medical-Oncologic Department, ASST Lodi, Lodi, Italy
  • 4 PhD course in Experimental Medicine, University of Pavia, Pavia, Italy
  • 5 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  • 6 Department Advanced Medical and Surgical Science, A.O.U. Vanvitelli, University of Campania ‘Luigi Vanvitelli’, Naples, Italy
  • 7 Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
  • 8 Digestive Endoscopy Unit, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Italy
  • 9 Marienklinik, Bolzano, Italy

Correspondence should be addressed to L Chiovato; Email: luca.chiovato@icsmaugeri.it
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Objective:

The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT.

Design and methods:

A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD−; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up.

Results:

During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD− group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases.

Conclusions:

In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.

 

     European Society of Endocrinology

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  • 1

    Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. A.M.A. Archives of Surgery 1955 70 291297. (https://doi.org/10.1001/archsurg.1955.01270080137023)

    • Search Google Scholar
    • Export Citation
  • 2

    Guarino V, Castellone MD, Avilla E, Melillo RM. Thyroid cancer and inflammation. Molecular & Cellular Endocrinology 2010 321 94102. (https://doi.org/10.1016/j.mce.2009.10.003)

    • Search Google Scholar
    • Export Citation
  • 3

    French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR. Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. Journal of Clinical Endocrinology & Metabolism 2010 95 23252333. (https://doi.org/10.1210/jc.2009-2564)

    • Search Google Scholar
    • Export Citation
  • 4

    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008 454 436444. (https://doi.org/10.1038/nature07205)

  • 5

    Liotti F, Visciano C, Melillo RM. Inflammation in thyroid oncogenesis. American Journal of Cancer Research 2012 2 286297.

  • 6

    Slijepcevic N, Zivaljevic V, Marinkovic J, Sipetic S, Diklic A, Paunovic I. Retrospective evaluation of the incidental finding of 403 papillary thyroid microcarcinomas in 2466 patients undergoing thyroid surgery for presumed benign thyroid disease. BMC Cancer 2015 15 330. (https://doi.org/10.1186/s12885-015-1352-4)

    • Search Google Scholar
    • Export Citation
  • 7

    Azizi G, Keller JM, Lewis M, Piper K, Puett D, Rivenbark KM, Malchoff CD. Association of Hashimoto’s thyroiditis with thyroid cancer. Endocrine-Related Cancer 2014 21 845852. (https://doi.org/10.1530/ERC-14-0258)

    • Search Google Scholar
    • Export Citation
  • 8

    Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, Borghero A, Mariotti S. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. Journal of Endocrinological Investigation 2013 36 313320. (https://doi.org/10.3275/8579)

    • Search Google Scholar
    • Export Citation
  • 9

    Kim ES, Lim DJ, Baek KH, Lee JM, Kim MK, Kwon HS, Song KH, Kang MI, Cha BY, Lee KW, Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 2010 20 885891. (https://doi.org/10.1089/thy.2009.0384)

    • Search Google Scholar
    • Export Citation
  • 10

    Iliadou PK, Effraimidis G, Konstantinos M, Grigorios P, Mitsakis P, Patakiouta F, Pazaitou-Panayiotou K. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents. European Journal of Endocrinology 2015 173 827833. (https://doi.org/10.1530/EJE-14-1046)

    • Search Google Scholar
    • Export Citation
  • 11

    Paparodis R, Imam S, Todorova-Koteva K, Staii A, Jaume JC. Hashimoto’s thyroiditis pathology and risk for thyroid cancer. Thyroid 2014 24 11071114. (https://doi.org/10.1089/thy.2013.0588)

    • Search Google Scholar
    • Export Citation
  • 12

    Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H. Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer? Journal of Surgical Research 2008 150 4952. (https://doi.org/10.1016/j.jss.2007.09.020)

    • Search Google Scholar
    • Export Citation
  • 13

    Mukasa K, Noh JY, Kunii Y, Matsumoto M, Sato S, Yasuda S, Suzuki M, Ito K, Ito K. Prevalence of malignant tumors and adenomatous lesions detected by ultrasonographic screening in patients with autoimmune thyroid diseases. Thyroid 2011 21 3741. (https://doi.org/10.1089/thy.2010.0050)

    • Search Google Scholar
    • Export Citation
  • 14

    Zhang Y, Dai J, Wu T, Yang N, Yin Z. The study of the coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma. Journal of Cancer Research & Clinical Oncology 2014 140 10211026. (https://doi.org/10.1007/s00432-014-1629-z)

    • Search Google Scholar
    • Export Citation
  • 15

    Dvorkin S, Robenshtok E, Hirsch D, Strenov Y, Shimon I, Benbassat CA. Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimotos thyroiditis. Journal of Clinical Endocrinology & Metabolism 2013 98 24092414. (https://doi.org/10.1210/jc.2013-1309)

    • Search Google Scholar
    • Export Citation
  • 16

    Baser H, Ozdemir D, Cuhaci N, Aydin C, Ersoy R, Kilicarslan A, Cakir B. Hashimoto’s thyroiditis does not affect ultrasonographical, cytological, and histopathological features in patients with papillary thyroid carcinoma. Endocrine Pathology 2015 26 356364. (https://doi.org/10.1007/s12022-015-9401-8)

    • Search Google Scholar
    • Export Citation
  • 17

    Castagna MG, Belardini V, Memmo S, Maino F, Di Santo A, Toti P, Carli AF, Caruso G, Pacini F. Nodules in autoimmune thyroiditis are associated with increased risk of thyroid cancer in surgical series but not in cytological series: evidence for selection bias. Journal of Clinical Endocrinology & Metabolism 2014 99 31933198. (https://doi.org/10.1210/jc.2014-1302)

    • Search Google Scholar
    • Export Citation
  • 18

    Donangelo I, Walts AE, Bresee C, Braunstein GD. Lymphocytic thyroiditis is associated WITH increased number of benign cervical nodes and fewer central neck compartment metastatic lymph nodes in patients with differentiated thyroid cancer. Endocrine Practice 2016 22 11921198. (https://doi.org/10.4158/E151078.OR)

    • Search Google Scholar
    • Export Citation
  • 19

    Giagourta I, Evangelopoulou C, Papaioannou G, Kassi G, Zapanti E, Prokopiou M, Papapostolou K, Karga H. Autoimmune thyroiditis in benign and malignant thyroid nodules: 16-year results. Head & Neck 2014 36 531535. (https://doi.org/10.1002/hed.23331)

    • Search Google Scholar
    • Export Citation
  • 20

    Kim SK, Woo JW, Lee JH, Park I, Choe JH, Kim JH, Kim JS. Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma. Endocrine-Related Cancer 2016 23 2734. (https://doi.org/10.1530/ERC-15-0408)

    • Search Google Scholar
    • Export Citation
  • 21

    Qu N, Zhang L, Lin DZ, Ji QH, Zhu YX, Wang Y. The impact of coexistent Hashimoto’s thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma. Tumour Biology 2016 37 76857692. (https://doi.org/10.1007/s13277-015-4534-4)

    • Search Google Scholar
    • Export Citation
  • 22

    Radetti G, Loche S, D’Antonio V, Salerno M, Guzzetti C, Aversa T, Cassio A, Cappa M, Gastaldi R & Deluca F, Influence of Hashimoto thyroiditis on the development of thyroid nodules and cancer in children and adolescents. Journal of the Endocrine Society 2019 3 607616. (https://doi.org/10.1210/js.2018-00287)

    • Search Google Scholar
    • Export Citation
  • 23

    Jackson D, Handelsman RS, Farrá JC, Lew JI. Increased incidental thyroid cancer in patients With subclinical chronic lymphocytic thyroiditis. Journal of Surgical Research 2020 245 115118. (https://doi.org/10.1016/j.jss.2019.07.025)

    • Search Google Scholar
    • Export Citation
  • 24

    Jankovic B, Le KT, Hershman JM. Clinical review: Hashimoto’s thyroiditis and papillary thyroid carcinoma: is there a correlation? Journal of Clinical Endocrinology & Metabolism 2013 98 474482. (https://doi.org/10.1210/jc.2012-2978)

    • Search Google Scholar
    • Export Citation
  • 25

    Haymart MR, Banerjee M, Reyes-Gastelum D, Caoili E, Norton EC. Thyroid ultrasound and the increase in diagnosis of low-risk thyroid cancer. Journal of Clinical Endocrinology & Metabolism 2019 104 785792. (https://doi.org/10.1210/jc.2018-01933)

    • Search Google Scholar
    • Export Citation
  • 26

    Dal Maso L, Panato C, Franceschi S, Serraino D, Buzzoni C, Busco S, Ferretti S, Torrisi A, Falcini F & Zorzi M, The impact of overdiagnosis on thyroid cancer epidemic in Italy, 1998–2012. European Journal of Cancer 2018 94 615. (https://doi.org/10.1016/j.ejca.2018.01.083)

    • Search Google Scholar
    • Export Citation
  • 27

    Rotondi M, Coperchini F, Magri F, Chiovato L. Serum-negative autoimmune thyroiditis: what’s in a name? Journal of Endocrinological Investigation 2014 37 589591. (https://doi.org/10.1007/s40618-014-0083-8)

    • Search Google Scholar
    • Export Citation
  • 28

    Croce L, De Martinis L, Pinto S, Coperchini F, Dito G, Bendotti G, Pasquali D, Cappelli C, Latrofa F & Magri F, Compared with classic Hashimoto’s thyroiditis, chronic autoimmune serum-negative thyroiditis requires a lower substitution dose of L-thyroxine to correct hypothyroidism. Journal of Endocrinological Investigation 2020 [Online ahead of print]. (https://doi.org/10.1007/s40618-020-01249-x)

    • Search Google Scholar
    • Export Citation
  • 29

    Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. European thyroid association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. European Thyroid Journal 2017 6 225237. (https://doi.org/10.1159/000478927)

    • Search Google Scholar
    • Export Citation
  • 30

    Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid 2009 19 11591165. (https://doi.org/10.1089/thy.2009.0274)

    • Search Google Scholar
    • Export Citation
  • 31

    Hegedüs L. Clinical practice. The thyroid nodule. New England Journal of Medicine 2004 351 17641771. (https://doi.org/10.1056/NEJMcp031436)

    • Search Google Scholar
    • Export Citation
  • 32

    Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S & Attard M The natural history of benign thyroid nodules. JAMA 2015 313 926935. (https://doi.org/10.1001/jama.2015.0956)

    • Search Google Scholar
    • Export Citation
  • 33

    Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R & Balestrieri A, The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. Journal of Clinical Endocrinology & Metabolism 1999 84 561566. (https://doi.org/10.1210/jcem.84.2.5508)

    • Search Google Scholar
    • Export Citation
  • 34

    Fiore E, Latrofa F, Vitti P. Iodine, thyroid autoimmunity and cancer. European Thyroid Journal 2015 4 2635. (https://doi.org/10.1159/000371741)

    • Search Google Scholar
    • Export Citation
  • 35

    Fiore E, Rago T, Provenzale MA, Scutari M, Ugolini C, Basolo F, Di Coscio G, Berti P, Grasso L & Elisei R, 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. Endocrine-Related Cancer 2009 16 12511260. (https://doi.org/10.1677/ERC-09-0036)

    • Search Google Scholar
    • Export Citation
  • 36

    Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, Chen H. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. Journal of Clinical Endocrinology & Metabolism 2008 93 809814. (https://doi.org/10.1210/jc.2007-2215)

    • Search Google Scholar
    • Export Citation
  • 37

    Azizi G, Malchoff CD. Autoimmune thyroid disease: a risk factor for thyroid cancer. Endocrine Practice 2011 17 201209. (https://doi.org/10.4158/EP10123.OR)

    • Search Google Scholar
    • Export Citation
  • 38

    Holm LE, Blomgren H, Löwhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. New England Journal of Medicine 1985 312 601604. (https://doi.org/10.1056/NEJM198503073121001)

    • Search Google Scholar
    • Export Citation