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Thyroid Nodule

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Thyroid Diseases

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

Benign thyroid nodules are highly prevalent in iodine-deficient areas. Histologically, benign thyroid nodules are characterized by morphologic criteria as encapsulated lesions (true adenomas) or adenomatous nodules, which lack a capsule. On functional grounds, nodules are classified as either “cold,” “normal,” or “hot,” depending on whether they show decreased, normal, or increased uptake on scintiscan. Approximately 50–85% of all nodules are “cold,” up to 40% are scintigraphically indifferent and about 10% are “hot,” although the prevalence will vary geographically with the ambient iodine supply and with the clinical setting.

Hot thyroid nodules (autonomously functioning thyroid nodules, AFTNs) are mainly due to mutations which confer a constitutive activation of the cAMP cascade (e.g., TSHR and Gsα mutations) which results in a stimulation of growth and function. In contrast, the molecular etiology of cold thyroid nodules (CTNs) is still largely unknown.

Thyroid autonomy (i.e., AFTNs) is an almost exclusively benign disease, and there is little evidence in the literature to suggest the contrary. In contrast, the differential diagnosis of scintigraphically indifferent and CTNs includes benign follicular adenoma and adenomatous nodules, as well as papillary thyroid carcinoma and its variants and follicular thyroid carcinoma. While fine-needle aspiration cytology is currently the most sensitive and specific tool to select thyroid nodules for surgery after prioritization by assessment of ultrasound malignancy criteria, it is characterized by an inherent limitation, resulting in “indeterminate” cytologies. Molecular tests in the form of “rule out” and “rule in” malignancy tests have been proposed to fill this diagnostic gap.

The most important therapeutic options for hot nodules are radioiodine therapy or surgery and surgery for scintigraphically indifferent and CTNs if symptomatic or associated with increased malignancy risk.

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References

  • Abrahamsen B, Jorgensen HL, Laulund AS, Nybo M, Brix TH, Hegedus L. Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J Bone Miner Res. 2014;29(9):2040–50.

    Article  CAS  PubMed  Google Scholar 

  • Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705–15.

    Article  PubMed  CAS  Google Scholar 

  • Alexander EK, Schorr M, Klopper J, et al. Multicenter clinical experience with the afirma gene expression classifier. J Clin Endocrinol Metab. 2014;99(1):119–25.

    Article  PubMed  CAS  Google Scholar 

  • al-Suliman NN, Ryttov NF, Qvist N, Blichert-Toft M, Graversen HP. Experience in a specialist thyroid surgery unit: a demographic study, surgical complications, and outcome. Eur J Surg. 1997;163(1):13–20.

    PubMed  CAS  Google Scholar 

  • An JH, Song KH, Kim SK, et al. RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma. Clin Endocrinol. 2015;82(5):760–6.

    Article  CAS  Google Scholar 

  • Aragon HP, Olson MT, Fazeli R, et al. The impact of molecular testing on the surgical management of patients with thyroid nodules. Ann Surg Oncol. 2014;21(6):1862–9.

    Article  Google Scholar 

  • Armstrong MJ, Yang H, Yip L, et al. PAX8/PPARgamma rearrangement in thyroid nodules predicts follicular-pattern carcinomas, in particular the encapsulated follicular variant of papillary carcinoma. Thyroid. 2014;24(9):1369–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bahre M, Hilgers R, Lindemann C, Emrich D. Thyroid autonomy: sensitive detection in vivo and estimation of its functional relevance using quantified high-resolution scintigraphy. Acta Endocrinol. 1988;117(2):145–53.

    Article  CAS  Google Scholar 

  • Baloch ZW, Seethala RR, Faquin WC et al. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a changing paradigm in thyroid surgical pathology and implications for thyroid cytopathology. Cancer Cytopathol. 2016.

    Google Scholar 

  • Basolo F, Pisaturo F, Pollina LE, et al. N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression. Thyroid. 2000;10(1):19–23.

    Article  PubMed  CAS  Google Scholar 

  • Beaudenon-Huibregtse S, Alexander EK, Guttler RB, et al. Centralized molecular testing for oncogenic gene mutations complements the local cytopathologic diagnosis of thyroid nodules. Thyroid. 2014;24(10):1479–87.

    Article  PubMed  CAS  Google Scholar 

  • Belfiore A, La Rosa GL, La Porta GA, et al. Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med. 1992;93:363–9.

    Article  PubMed  CAS  Google Scholar 

  • Bennedbaek FN, Hegedus L. Management of the solitary thyroid nodule: results of a North American survey. J Clin Endocrinol Metab. 2000;85(7):2493–8.

    Article  PubMed  CAS  Google Scholar 

  • Bennedbaek FN, Hegedus L. Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind controlled trial. J Clin Endocrinol Metab. 2003;88(12):5773–7.

    Article  PubMed  CAS  Google Scholar 

  • Bennedbaek FN, Karstrup S, Hegedus L. Percutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases. Eur J Endocrinol. 1997;136(3):240–50.

    Article  PubMed  CAS  Google Scholar 

  • Bennedbaek FN, Perrild H, Hegedus L. Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey. Clin Endocrinol. 1999;50(3):357–63.

    Article  CAS  Google Scholar 

  • Berghout A, Wiersinga WM, Smits NJ, Touber JL. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter. Am J Med. 1990;89(5):602–8.

    Article  PubMed  CAS  Google Scholar 

  • Bol S, Belge G, Thode B, Bartnitzke S, Bullerdiek J. Structural abnormalities of chromosome 2 in benign thyroid tumors. Three new cases and review of the literature. Cancer Genet Cytogenet. 1999;114(1):75–7.

    Article  PubMed  CAS  Google Scholar 

  • Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012;56(4):333–9.

    Article  PubMed  Google Scholar 

  • Bonnema SJ, Hegedus L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr Rev. 2012;33(6):920–80.

    Article  PubMed  CAS  Google Scholar 

  • Bonnema SJ, Bennedbaek FN, Wiersinga WM, Hegedus L. Management of the nontoxic multinodular goitre: a European questionnaire study. Clin Endocrinol. 2000;53(1):5–12.

    Article  CAS  Google Scholar 

  • Bonnema SJ, Bennedbaek FN, Ladenson PW, Hegedus L. Management of the nontoxic multinodular goiter: a North American survey. J Clin Endocrinol Metab. 2002;87(1):112–7.

    Article  PubMed  CAS  Google Scholar 

  • Brandt F, Almind D, Christensen K, Green A, Brix TH, Hegedus L. Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding: a danish nationwide register-based cohort study of twins and singletons. J Clin Endocrinol Metab. 2012;97(11):4123–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Caillou B, Dupuy C, Lacroix L, et al. Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues. J Clin Endocrinol Metab. 2001;86(7):3351–8.

    PubMed  CAS  Google Scholar 

  • Calebiro D, Grassi ES, Eszlinger M, et al. Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas. J Clin Invest. 2016;126(9):3383–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Campenni A, Giovanella L, Siracusa M, et al. (99m)Tc-methoxy-isobutyl-isonitrile scintigraphy is a useful tool for assessing the risk of malignancy in thyroid nodules with indeterminate fine-needle cytology. Thyroid. 2016;26(8):1101–9.

    Article  PubMed  CAS  Google Scholar 

  • Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676–90.

    Article  CAS  Google Scholar 

  • Cantara S, Capezzone M, Marchisotta S, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab. 2010;95(3):1365–9.

    Article  PubMed  CAS  Google Scholar 

  • Capella G, Matias-Guiu X, Ampudia X, de Leiva A, Perucho M, Prat J. Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues. Diagn Mol Pathol. 1996;5(1):45–52.

    Article  PubMed  CAS  Google Scholar 

  • Ceccarelli C, Bencivelli W, Vitti P, Grasso L, Pinchera A. Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years’ retrospective study. Clin Endocrinol. 2005;62(3):331–5.

    Article  CAS  Google Scholar 

  • Chan JKC, Hirokawa M, et al. Tumours of the thyroid and parathyroid: follicular adenoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. WHO classification of tumours: pathology & genetics of tumours of endocrine organs. Lyon: IARC Press; 2004. p. 98–103.

    Google Scholar 

  • Cheung L, Messina M, Gill A, et al. Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2003;88(1):354–7.

    Article  PubMed  CAS  Google Scholar 

  • Chiovato L, Mariotti S, Pinchera A. Thyroid diseases in the elderly. Bailliere Clin Endocrinol Metab. 1997;11(2):251–70.

    Article  CAS  Google Scholar 

  • Chudova D, Wilde JI, Wang ET, et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab. 2010;95(12):5296–304.

    Article  PubMed  CAS  Google Scholar 

  • Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009;132(5):658–65.

    Article  PubMed  Google Scholar 

  • Cibas ES, Baloch ZW, Fellegara G, et al. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Ann Intern Med. 2013;159(5):325–32.

    Article  PubMed  Google Scholar 

  • Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905–17.

    Article  PubMed  CAS  Google Scholar 

  • Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109–42.

    Article  PubMed  Google Scholar 

  • de Vijlder JJ. Primary congenital hypothyroidism: defects in iodine pathways. Eur J Endocrinol. 2003;149(4):247–56.

    Article  PubMed  Google Scholar 

  • Deleu S, Allory Y, Radulescu A, et al. Characterization of autonomous thyroid adenoma: metabolism, gene expression, and pathology. Thyroid. 2000;10(2):131–40. 2000; 10(2):131-140.

    Article  PubMed  CAS  Google Scholar 

  • Demirel K, Kapucu O, Yucel C, Ozdemir H, Ayvaz G, Taneri F. A comparison of radionuclide thyroid angiography, (99m)Tc-MIBI scintigraphy and power Doppler ultrasonography in the differential diagnosis of solitary cold thyroid nodules. Eur J Nucl Med Mol Imaging. 2003;30(5):642–50.

    Article  PubMed  CAS  Google Scholar 

  • Depoortere F, Pirson I, Bartek J, Dumont JE, Roger PP. Transforming growth factor beta(1) selectively inhibits the cyclic AMP-dependent proliferation of primary thyroid epithelial cells by preventing the association of cyclin D3-cdk4 with nuclear p27(kip1). Mol Biol Cell. 2000;11(3):1061–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Derwahl M, Studer H. Nodular goiter and goiter nodules: Where iodine deficiency falls short of explaining the facts. Exp Clin Endocrinol Diabetes. 2001;109(5):250–60.

    Article  PubMed  CAS  Google Scholar 

  • Dohan O, Baloch Z, Banrevi Z, LiVolsi V, Carrasco N. Rapid communication: predominant intracellular overexpression of the Na(+)/I(−) symporter (NIS) in a large sampling of thyroid cancer cases. J Clin Endocrinol Metab. 2001;86(6):2697–700.

    PubMed  CAS  Google Scholar 

  • Dohan O, De la Vieja, Paroder V, et al. The sodium/iodide symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003;24(1):48–77.

    Article  PubMed  CAS  Google Scholar 

  • Dossing H, Bennedbaek FN, Hegedus L. Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules – a randomised study. Eur J Endocrinol. 2005;152(3):341–5.

    Article  PubMed  CAS  Google Scholar 

  • Dossing H, Bennedbaek FN, Hegedus L. Long-term outcome following interstitial laser photocoagulation of benign cold thyroid nodules. Eur J Endocrinol. 2011;165(1):123–8.

    Article  PubMed  CAS  Google Scholar 

  • Dossing H, Bennedbaek FN, Hegedus L. Interstitial laser photocoagulation (ILP) of benign cystic thyroid nodules – a prospective randomized trial. J Clin Endocrinol Metab. 2013;98(7):E1213–7.

    Article  PubMed  CAS  Google Scholar 

  • Dugrillon A, Bechtner G, Uedelhoven WM, Weber PC, Gärtner R. Evidence that an iodolactone mediates the inhibitory effect of iodide on thyroid cell proliferation but not on adenosine 3′,5′-monophosphate formation. Endocrinology. 1990;127(1):337–43.

    Article  PubMed  CAS  Google Scholar 

  • Dunn JT, Dunn AD. Update on intrathyroidal iodine metabolism. Thyroid. 2001;11(5):407–14.

    Article  PubMed  CAS  Google Scholar 

  • Eggo MC, Bachrach LK, Burrow GN. Interaction of TSH, insulin and insulin-like growth factors in regulating thyroid growth and function. Growth Factors. 1990;2(2–3):99–109.

    Article  PubMed  CAS  Google Scholar 

  • Erickson D, Gharib H, Li H, van Heerden JA. Treatment of patients with toxic multinodular goiter. Thyroid. 1998;8(4):277–82.

    Article  PubMed  CAS  Google Scholar 

  • Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Prevalence of Ras mutations in thyroid neoplasia. Clin Endocrinol. 1999;50(4):529–35.

    Article  CAS  Google Scholar 

  • Eszlinger M, Paschke R. Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol. 2010;322(1–2):29–37.

    Article  PubMed  CAS  Google Scholar 

  • Eszlinger M, Krohn K, Frenzel R, Kropf S, Tonjes A, Paschke R. Gene expression analysis reveals evidence for inactivation of the TGF-beta signaling cascade in autonomously functioning thyroid nodules. Oncogene. 2004;23(3):795–804.

    Article  PubMed  CAS  Google Scholar 

  • Eszlinger M, Krohn K, Berger K, et al. Gene expression analysis reveals evidence for increased expression of cell cycle-associated genes and Gq-protein-protein kinase C signaling in cold thyroid nodules. J Clin Endocrinol Metab. 2005;90(2):1163–70.

    Article  PubMed  CAS  Google Scholar 

  • Eszlinger M, Krogdahl A, Munz S, et al. Impact of molecular screening for point mutations and rearrangements in routine air-dried fine-needle aspiration samples of thyroid nodules. Thyroid. 2014;24(2):305–13.

    Article  PubMed  CAS  Google Scholar 

  • Eszlinger M, Piana S, Moll A, et al. Molecular testing of thyroid fine needle aspirations (FNA) improves pre-surgical diagnosis and supports the histological identification of minimally invasive follicular thyroid carcinomas. Thyroid. 2015;25(4):401–9.

    Article  PubMed  CAS  Google Scholar 

  • Eszlinger M, Lau L, Ghaznavi S, Symonds C, Chandarana SP, Khalil M, Paschke R. Molecular profiling of thyroid nodule fine-needle aspiration cytology. Nat Rev Endocrinol. 2017a. https://doi.org/10.1038/nrendo.2017.24.

  • Eszlinger M, Böhme K, Ullmann M, et al. Evaluation of a two-year routine application of molecular testing of thyroid fine needle aspirations (FNA) using a 7-gene panel in a primary refferral setting in Germany. Thyroid. 2017b. https://doi.org/10.1089/thy.2016.0445.

    Article  PubMed  Google Scholar 

  • Fagin JA. Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol Endocrinol. 2002;16(5):903–11.

    PubMed  CAS  Google Scholar 

  • Faquin WC, Wong LQ, Afrogheh AH, et al. Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology. Cancer Cytopathol. 2016;124(3):181–7.

    Article  PubMed  Google Scholar 

  • Farahati J, Demidchik EP, Biko J, Reiners C. Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus. Cancer. 2000;88(6):1470–6.

    Article  PubMed  CAS  Google Scholar 

  • Fassina AS, Montesco MC, Ninfo V, Denti P, Masarotto G. Histological evaluation of thyroid carcinomas: reproducibility of the “WHO” classification. Tumori. 1993;79(5):314–20.

    Article  PubMed  CAS  Google Scholar 

  • Fast S, Bonnema SJ, Hegedus L. The majority of Danish nontoxic goitre patients are ineligible for Levothyroxine suppressive therapy. Clin Endocrinol. 2008;69(4):653–8.

    Article  Google Scholar 

  • Ferrari C, Reschini E, Paracchi A. Treatment of the autonomous thyroid nodule: a review. Eur J Endocrinol. 1996;135(4):383–90.

    Article  PubMed  CAS  Google Scholar 

  • Ferraz C, Eszlinger M, Paschke R. Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab. 2011;96(7):2016–26.

    Article  PubMed  CAS  Google Scholar 

  • Ferraz C, Rehfeld C, Krogdahl A, et al. Detection of PAX8/PPARG and RET/PTC rearrangements is feasible in routine air-dried fine needle aspiration smears. Thyroid. 2012;22(10):1025–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Franc B, de la Salmoniere P, Lange F, et al. Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Hum Pathol. 2003;34(11):1092–100.

    Article  PubMed  Google Scholar 

  • Franklyn JA, Maisonneuve P, Sheppard M, Betteridge J, Boyle P. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet. 1999;353(9170):2111–5.

    Article  PubMed  CAS  Google Scholar 

  • Fuhrer D, Holzapfel HP, Wonerow P, Scherbaum WA, Paschke R. Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. J Clin Endocrinol Metab. 1997;82(11):3885–91.

    PubMed  CAS  Google Scholar 

  • Fukahori M, Yoshida A, Hayashi H, et al. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22(7):683–9.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Delgado M, Gonzalez-Navarro CJ, Napal MC, Baldonado C, Vizmanos JL, Gullon A. Higher sensitivity of denaturing gradient gel electrophoresis than sequencing in the detection of mutations in DNA from tumor samples. Biotechniques. 1998;24(1):72. 74, 76.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rostan G, Zhao H, Camp RL, et al. ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol. 2003;21(17):3226–35.

    Article  PubMed  CAS  Google Scholar 

  • Gärtner R, Schopohl D, Schaefer S, et al. Regulation of transforming growth factor beta 1 messenger ribonucleic acid expression in porcine thyroid follicles in vitro by growth factors, iodine, or delta-iodolactone. Thyroid. 1997;7(4):633–40.

    Article  PubMed  Google Scholar 

  • Gemsenjager E. The surgical treatment of autonomous nodular goiter. Prospective long-term study. Schweiz Med Wochenschr. 1992;122(18):687–92.

    PubMed  CAS  Google Scholar 

  • Georgopoulos NA, Sykiotis GP, Sgourou A, et al. Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway. Eur J Endocrinol. 2003;149(4):287–92.

    Article  PubMed  CAS  Google Scholar 

  • Gharib H, Hegedus L, Pacella CM, Baek JH, Papini E. Clinical review: nonsurgical, image-guided, minimally invasive therapy for thyroid nodules. J Clin Endocrinol Metab. 2013;98(10):3949–57.

    Article  PubMed  CAS  Google Scholar 

  • Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 2016;22(5):622–39.

    PubMed  Google Scholar 

  • Gozu HI, Bircan R, Krohn K, et al. Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey. Eur J Endocrinol. 2006;155(4):535–45.

    Article  PubMed  CAS  Google Scholar 

  • Grubeck-Loebenstein B, Buchan G, Sadeghi R, et al. Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter. J Clin Invest. 1989;83(3):764–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grussendorf M, Reiners C, Paschke R, Wegscheider K. Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: a randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2011;96(9):2786–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hall P, Boice Jr JD, Berg G, et al. Leukaemia incidence after iodine-131 exposure. Lancet. 1992;340(8810):1–4.

    Article  PubMed  CAS  Google Scholar 

  • Hamburger JI. Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab. 1980;50(6):1089–93.

    Article  PubMed  CAS  Google Scholar 

  • Haugen BR, Alexander EK, Bible KC, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hedinger C. Histological typing of thyroid tumors. Berlin: Springer Verlag; 1988.

    Book  Google Scholar 

  • Hegedus L. Thyroid ultrasound. Endocrinol Metab Clin N Am. 2001;30(2):339–ix.

    Article  CAS  Google Scholar 

  • Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med. 2004;351(17):1764–71.

    Article  PubMed  Google Scholar 

  • Hegedus L. Can elastography stretch our understanding of thyroid histomorphology? J Clin Endocrinol Metab. 2010;95(12):5213–5.

    Article  PubMed  CAS  Google Scholar 

  • Hegedus L, Nygaard B, Hansen JM. Is routine thyroxine treatment to hinder postoperative recurrence of nontoxic goiter justified? J Clin Endocrinol Metab. 1999;84(2):756–60.

    PubMed  CAS  Google Scholar 

  • Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003;24(1):102–32.

    Article  PubMed  Google Scholar 

  • Hermus AR, Huysmans DA. Treatment of benign nodular thyroid disease. N Engl J Med. 1998;338(20):1438–47.

    Article  PubMed  CAS  Google Scholar 

  • Ho AS, Sarti EE, Jain KS, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid: Off J Am Thyroid Assoc. 2014;24(5):832–9.

    Article  Google Scholar 

  • Holm LE, Hall P, Wiklund K, et al. Cancer risk after iodine-131 therapy for hyperthyroidism. J Natl Cancer Inst. 1991;83(15):1072–7.

    Article  PubMed  CAS  Google Scholar 

  • Howitt BE, Jia Y, Sholl LM, Barletta JA. Molecular alterations in partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma. Thyroid. 2013;23(10):1256–62.

    Article  PubMed  CAS  Google Scholar 

  • Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003;13(4):381–7.

    Article  PubMed  Google Scholar 

  • Jaeschke H, Mueller S, Eszlinger M, Paschke R. Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas. Clin Endocrinol. 2010;73(6):815–20.

    Article  CAS  Google Scholar 

  • Jang EK, Song DE, Sim SY, et al. NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. Thyroid. 2014;24(8):1275–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jarlov AE, Nygaard B, Hegedus L, Hartling SG, Hansen JM. Observer variation in the clinical and laboratory evaluation of patients with thyroid dysfunction and goiter. Thyroid. 1998;8(5):393–8.

    Article  PubMed  CAS  Google Scholar 

  • Kim CS, Zhu X. Lessons from mouse models of thyroid cancer. Thyroid. 2009;19(12):1317–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP. Regulation of thyroid cell proliferation by tsh and other factors: a critical evaluation of in vitro models. Endocr Rev. 2001;22(5):631–56.

    Article  PubMed  CAS  Google Scholar 

  • Knudsen N, Perrild H, Christiansen E, Rasmussen S, Dige-Petersen H, Jorgensen T. Thyroid structure and size and two-year follow-up of solitary cold thyroid nodules in an unselected population with borderline iodine deficiency. Eur J Endocrinol. 2000;142(3):224–30.

    Article  PubMed  CAS  Google Scholar 

  • Krane JF, Cibas ES, Alexander EK, Paschke R, Eszlinger M. Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity. Cancer Cytopathol. 2015;123(6):356–61.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Paschke R. Progress in understanding the etiology of thyroid autonomy. J Clin Endocrinol Metab. 2001a;86(7):3336–45.

    PubMed  CAS  Google Scholar 

  • Krohn K, Paschke R. Loss of heterozygocity at the thyroid peroxidase gene locus in solitary cold thyroid nodules. Thyroid. 2001b;11(8):741–7.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Paschke R. BRAF mutations are not an alternative explanation for the molecular etiology of ras-mutation negative cold thyroid nodules. Thyroid. 2004;14(5):359–61.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Emmrich P, Ott N, Paschke R. Increased thyroid epithelial cell proliferation in toxic thyroid nodules. Thyroid. 1999;9(3):241–6.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Wohlgemuth S, Gerber H, Paschke R. Hot microscopic areas of iodine-deficient euthyroid goitres contain constitutively activating TSH receptor mutations [In Process Citation]. J Pathol. 2000;192(1):37–42.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Reske A, Ackermann F, Muller A, Paschke R. Ras mutations are rare in solitary cold and toxic thyroid nodules. Clin Endocrinol. 2001;55(2):241–8.

    Article  CAS  Google Scholar 

  • Krohn K, Stricker I, Emmrich P, Paschke R. Cold thyroid nodules show a marked increase in proliferation markers. Thyroid. 2003;13(6):569–75.

    Article  PubMed  Google Scholar 

  • Krohn K, Fuhrer D, Bayer Y, et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev. 2005;26(4):504–24.

    Article  PubMed  CAS  Google Scholar 

  • Krohn K, Maier J, Paschke R. Mechanisms of disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nat Clin Pract Endocrinol Metab. 2007;3(10):713–20.

    Article  PubMed  CAS  Google Scholar 

  • Kuma K, Matsuzuka F, Kobayashi A, et al. Outcome of long standing solitary thyroid nodules. World J Surg. 1992;16(4):583–7.

    Article  PubMed  CAS  Google Scholar 

  • L’assurance maladie – Caisse Nationale. Pertinence des soins: une analyse de la pratique des thyroidectomies chez l’adulte. http://www.ameli.fr/fileadmin/user_upload/documents/23102013_DP_thyroidectomies.pdf. 2013. Ref Type: Online Source.

  • Labourier E, Shifrin A, Busseniers AE, et al. Molecular testing for miRNA, mRNA and DNA on fine needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab. 2015;100(7):2743–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lang W, Georgii A, Stauch G, Kienzle E. The differentiation of atypical adenomas and encapsulated follicular carcinomas in the thyroid gland. Virchows Arch A Pathol Anat Histol. 1980;385(2):125–41.

    Article  PubMed  CAS  Google Scholar 

  • Laulund AS, Nybo M, Brix TH, Abrahamsen B, Jorgensen HL, Hegedus L. Duration of thyroid dysfunction correlates with all-cause mortality. the OPENTHYRO Register Cohort. PLoS ONE. 2014;9(10):e110437.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lazar V, Bidart JM, Caillou B, et al. Expression of the Na+/I− symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab. 1999;84(9):3228–34.

    PubMed  CAS  Google Scholar 

  • Lee SR, Jung CK, Kim TE, et al. Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing. Thyroid. 2013;23(11):1416–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lewis CM, Chang KP, Pitman M, Faquin WC, Randolph GW. Thyroid fine-needle aspiration biopsy: variability in reporting. Thyroid. 2009;19(7):717–23.

    Article  PubMed  CAS  Google Scholar 

  • Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2011;96(11):E1719–26.

    Article  PubMed  CAS  Google Scholar 

  • Lim DJ, Kim JY, Baek KH, et al. Natural course of cytologically benign thyroid nodules: observation of ultrasonographic changes. Endocrinol Metab (Seoul). 2013;28(2):110–8.

    Article  Google Scholar 

  • Liu RT, Hou CY, You HL, et al. Selective occurrence of ras mutations in benign and malignant thyroid follicular neoplasms in Taiwan. Thyroid. 2004;14(8):616–21.

    Article  PubMed  CAS  Google Scholar 

  • Lodewijk L, Prins AM, Kist JW, et al. The value of miRNA in diagnosing thyroid cancer: a systematic review. Cancer Biomark. 2012;11(6):229–38.

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

    Article  PubMed  CAS  Google Scholar 

  • Marinelli LD, Quimby EH, Hine GJ. Dosage determination with radioactive isotopes; practical considerations in therapy and protection. Am J Roentgenol Radium Ther. 1948;59(2):260–81.

    PubMed  CAS  Google Scholar 

  • Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2002;87(8):3947–52.

    PubMed  CAS  Google Scholar 

  • Marti JL, Avadhani V, Donatelli LA, et al. Wide inter-institutional variation in performance of a molecular classifier for indeterminate thyroid nodules. Ann Surg Oncol. 2015;22(12):3996–4001.

    Article  PubMed  PubMed Central  Google Scholar 

  • McIver B. Evaluation of the thyroid nodule. Oral Oncol. 2013;49(7):645–53.

    Article  PubMed  Google Scholar 

  • McIver B, Castro MR, Morris JC, et al. An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2014;99(11):4069–77.

    Article  PubMed  CAS  Google Scholar 

  • Medici M, Kwong N, Angell TE, et al. The variable phenotype and low-risk nature of RAS-positive thyroid nodules. BMC Med. 2015;13:184.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mian C, Lacroix L, Alzieu L, et al. Sodium iodide symporter and pendrin expression in human thyroid tissues. Thyroid. 2001;11(9):825–30.

    Article  PubMed  CAS  Google Scholar 

  • Moses W, Weng J, Sansano I, et al. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg. 2010;34(11):2589–94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Najafzadeh M, Marra CA, Lynd LD, Wiseman SM. Cost-effectiveness of using a molecular diagnostic test to improve preoperative diagnosis of thyroid cancer. Value Health. 2012;15(8):1005–13.

    Article  PubMed  Google Scholar 

  • Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009;94(6):2092–8.

    Article  PubMed  CAS  Google Scholar 

  • Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011;96(11):3390–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nikiforov YE, Carty SE, Chiosea SI, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627–34.

    Article  PubMed  CAS  Google Scholar 

  • Nikiforov YE, Carty SE, Chiosea SI, et al. Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid. 2015;25(11):1217–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nikiforov YE, Seethala RR, Tallini G et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2016.

    Google Scholar 

  • Nikiforova MN, Biddinger PW, Caudill CM, Kroll TG, Nikiforov YE. PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am J Surg Pathol. 2002;26(8):1016–23.

    Article  PubMed  Google Scholar 

  • Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab. 2013;98(11):E1852–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nishino M. Molecular cytopathology for thyroid nodules: A review of methodology and test performance. Cancer Cytopathol. 2016;124(1):14–27.

    Article  PubMed  Google Scholar 

  • Nou E, Kwong N, Alexander LK, Cibas ES, Marqusee E, Alexander EK. Determination of the optimal time interval for repeat evaluation after a benign thyroid nodule aspiration. J Clin Endocrinol Metab. 2014;99(2):510–6.

    Article  PubMed  CAS  Google Scholar 

  • Nygaard B, Hegedus L, Nielsen KG, Ulriksen P, Hansen JM. Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules. Clin Endocrinol. 1999;50(2):197–202.

    Article  CAS  Google Scholar 

  • Oertel YC, Miyahara-Felipe L, Mendoza MG, Yu K. Value of repeated fine needle aspirations of the thyroid: an analysis of over ten thousand FNAs. Thyroid. 2007;17(11):1061–6.

    Article  PubMed  Google Scholar 

  • Ohori NP, Nikiforova MN, Schoedel KE, et al. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol. 2010;118(1):17–23.

    Article  PubMed  CAS  Google Scholar 

  • Okumura Y, Takeda Y, Sato S, et al. Comparison of differential diagnostic capabilities of 201Tl scintigraphy and fine-needle aspiration of thyroid nodules. J Nucl Med. 1999;40(12):1971–7.

    PubMed  CAS  Google Scholar 

  • Pagan M, Kloos RT, Lin CF, et al. The diagnostic application of RNA sequencing in patients with thyroid cancer: an analysis of 851 variants and 133 fusions in 524 genes. BMC Bioinformatics. 2016;17(Suppl 1):6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Panzer C, Beazley R, Braverman L. Rapid preoperative preparation for severe hyperthyroid Graves’ disease. J Clin Endocrinol Metab. 2004;89(5):2142–4.

    Article  PubMed  CAS  Google Scholar 

  • Papini E, Pacella CM, Misischi I, et al. The advent of ultrasound-guided ablation techniques in nodular thyroid disease: towards a patient-tailored approach. Best Pract Res Clin Endocrinol Metab. 2014a;28(4):601–18.

    Article  PubMed  Google Scholar 

  • Papini E, Pacella CM, Hegedus L. Diagnosis of endocrine disease: thyroid ultrasound (US) and US-assisted procedures: from the shadows into an array of applications. Eur J Endocrinol. 2014b;170(4):R133–46.

    Article  PubMed  CAS  Google Scholar 

  • Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358(9285):861–5.

    Article  PubMed  CAS  Google Scholar 

  • Parma J, Duprez L, Van Sande J, et al. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993;365(6447):649–51.

    Article  PubMed  CAS  Google Scholar 

  • Pisarev MA, Krawiec L, Juvenal GJ, et al. Studies on the goiter inhibiting action of iodolactones. Eur J Pharmacol. 1994;258(1–2):33–7.

    Article  PubMed  CAS  Google Scholar 

  • Puxeddu E, Moretti S, Elisei R, et al. BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas. J Clin Endocrinol Metab. 2004;89(5):2414–20.

    Article  PubMed  CAS  Google Scholar 

  • Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab. 2007;92(8):2917–22.

    Article  PubMed  CAS  Google Scholar 

  • Reiners C, Schneider P. Radioiodine therapy of thyroid autonomy. Eur J Nucl Med Mol Imaging. 2002;29(Suppl 2):S471–8.

    Article  PubMed  CAS  Google Scholar 

  • Reschini E, Ferrari C, Castellani M, et al. The trapping-only nodules of the thyroid gland: prevalence study. Thyroid. 2006;16(8):757–62.

    Article  PubMed  Google Scholar 

  • Rippe V, Drieschner N, Meiboom M, et al. Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas. Oncogene. 2003;22(38):6111–4.

    Article  PubMed  CAS  Google Scholar 

  • Rivera M, Ricarte-Filho J, Knauf J, et al. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol. 2010;23(9):1191–200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rochefort P, Caillou B, Michiels FM, et al. Thyroid pathologies in transgenic mice expressing a human activated Ras gene driven by a thyroglobulin promoter. Oncogene. 1996;12(1):111–8.

    PubMed  CAS  Google Scholar 

  • Roger PP, Servais P, Dumont JE. Stimulation by thyrotropin and cyclic AMP of the proliferation of quiescent canine thyroid cells cultured in a defined medium containing insulin. FEBS Lett. 1983;157(2):323–9.

    Article  PubMed  CAS  Google Scholar 

  • Rossing M. Classification of follicular cell-derived thyroid cancer by global RNA profiling. J Mol Endocrinol. 2013;50(2):R39–51.

    Article  PubMed  CAS  Google Scholar 

  • Russ G, Royer B, Bigorgne C, Rouxel A, Bienvenu-Perrard M, Leenhardt L. Prospective evaluation of thyroid imaging reporting and data system on 4550 nodules with and without elastography. Eur J Endocrinol. 2013;168(5):649–55.

    Article  CAS  PubMed  Google Scholar 

  • Ryo UY, Vaidya PV, Schneider AB, Bekerman C, Pinsky SM. Thyroid imaging agents: a comparison of I-123 and Tc-99m pertechnetate. Radiology. 1983;148(3):819–22.

    Article  PubMed  CAS  Google Scholar 

  • Saavedra HI, Knauf JA, Shirokawa JM, et al. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene. 2000;19(34):3948–54.

    Article  PubMed  CAS  Google Scholar 

  • Sandrock D, Olbricht T, Emrich D, Benker G, Reinwein D. Long-term follow-up in patients with autonomous thyroid adenoma. Acta Endocrinol. 1993;128(1):51–5.

    Article  CAS  Google Scholar 

  • Sapio MR, Guerra A, Marotta V, et al. High growth rate of benign thyroid nodules bearing RET/PTC rearrangements. J Clin Endocrinol Metab. 2011;96(6):E916–9.

    Article  PubMed  CAS  Google Scholar 

  • Schroder S, Marthaler B. Autonomy and malignancy of thyroid glad tumors. A critical analysis of the literature on the existence of hyperfunctioning follicular and papillary thyroid gland carcinomas. Pathologe. 1996;17(5):349–57.

    Article  PubMed  CAS  Google Scholar 

  • Schulten HJ, Salama S, Al-Ahmadi A, et al. Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population. Anticancer Res. 2013;33(11):4779–84.

    PubMed  CAS  Google Scholar 

  • Sebastianes FM, Cerci JJ, Zanoni PH, et al. Role of 18F-fluorodeoxyglucose positron emission tomography in preoperative assessment of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2007;92(11):4485–8.

    Article  PubMed  CAS  Google Scholar 

  • Smith TJ, Hegedus L. Graves’ disease. N Engl J Med. 2016;375(16):1552–65.

    Article  PubMed  Google Scholar 

  • Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578–80.

    Article  PubMed  CAS  Google Scholar 

  • Soelberg KK, Bonnema SJ, Brix TH, Hegedus L. Risk of malignancy in thyroid incidentalomas detected by 18F-fluorodeoxyglucose positron emission tomography: a systematic review. Thyroid. 2012;22(9):918–25.

    Article  PubMed  CAS  Google Scholar 

  • Stokowy T, Wojtas B, Fujarewicz K, Jarzab B, Eszlinger M, Paschke R. miRNAs with the potential to distinguish follicular thyroid carcinomas from benign follicular thyroid tumors – results of a meta-analysis. Horm Metab Res. 2013;46(3):171–80.

    Google Scholar 

  • Stokowy T, Wojtas B, Krajewska J, et al. A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas. Mol Cell Endocrinol. 2015;399:43–9.

    Article  PubMed  CAS  Google Scholar 

  • Stokowy T, Wojtas B, Jarzab B, et al. Two-miRNA-classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in Fine Needle Aspirations with high specificity. Endocrine. 2016;54(2):440–7.

    Article  PubMed  CAS  Google Scholar 

  • Strickland KC, Howitt BE, Marqusee E, et al. The impact of noninvasive follicular variant of papillary thyroid carcinoma on rates of malignancy for fine-needle aspiration diagnostic categories. Thyroid. 2015;25(9):987–92.

    Article  PubMed  Google Scholar 

  • Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: the basis for understanding thyroid function and nodular goiter growth. Endocr Rev. 1989;10(2):125–35.

    Article  PubMed  CAS  Google Scholar 

  • Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228–38.

    Article  PubMed  CAS  Google Scholar 

  • Taton M, Lamy F, Roger PP, Dumont JE. General inhibition by transforming growth factor beta 1 of thyrotropin and cAMP responses in human thyroid cells in primary culture. Mol Cell Endocrinol. 1993;95(1–2):13–21.

    Article  PubMed  CAS  Google Scholar 

  • Thomusch O, Machens A, Sekulla C, et al. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000;24(11):1335–41.

    Article  PubMed  CAS  Google Scholar 

  • Toft AD. Clinical practice. Subclinical hyperthyroidism. N Engl J Med. 2001;345(7):512–6.

    Article  PubMed  CAS  Google Scholar 

  • Tonacchera M, Viacava P, Agretti P, et al. Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein. J Clin Endocrinol Metab. 2002;87(1):352–7.

    Article  PubMed  CAS  Google Scholar 

  • Trivalle C, Doucet J, Chassagne P, et al. Differences in the signs and symptoms of hyperthyroidism in older and younger patients. J Am Geriatr Soc. 1996;44(1):50–3.

    Article  PubMed  CAS  Google Scholar 

  • Trulzsch B, Krohn K, Wonerow P, Paschke R. DGGE is more sensitive for the detection of somatic point mutations than direct sequencing. Biotechniques. 1999;27(2):266–8.

    Article  PubMed  CAS  Google Scholar 

  • Trulzsch B, Krohn K, Wonerow P, et al. Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. J Mol Med. 2001;78(12):684–91.

    Article  PubMed  CAS  Google Scholar 

  • Tuttle RM, Ball DW, Byrd D, et al. Thyroid carcinoma. J Natl Compr Cancer Netw. 2010;8(11):1228–74.

    Article  Google Scholar 

  • Tuttle RM, Haddad RI, Ball DW, et al. Thyroid carcinoma, version 2.2014. J Natl Compr Cancer Netw. 2014;12(12):1671–80.

    Article  Google Scholar 

  • van den Bruel A, Francart J, Dubois C, et al. Regional variation in thyroid cancer incidence in Belgium is associated with variation in thyroid imaging and thyroid disease management. J Clin Endocrinol Metab. 2013;98(10):4063–71.

    Article  PubMed  CAS  Google Scholar 

  • Van Sande J, Parma J, Tonacchera M, Swillens S, Dumont J, Vassart G. Somatic and germline mutations of the TSH receptor gene in thyroid diseases. J Clin Endocrinol Metab. 1995;80(9):2577–85.

    PubMed  Google Scholar 

  • Vanderlaan PA, Krane JF, Cibas ES. The frequency of ‘atypia of undetermined significance’ interpretations for thyroid fine-needle aspirations is negatively correlated with histologically proven malignant outcomes. Acta Cytol. 2011;55(6):512–7.

    Article  PubMed  Google Scholar 

  • Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab. 2003;88(6):2745–52.

    Article  PubMed  CAS  Google Scholar 

  • Vassart G. Activating mutations of the TSH receptor. Thyroid. 2004;14(1):86–7.

    Article  PubMed  Google Scholar 

  • Vidal-Trecan GM, Stahl JE, Durand-Zaleski I. Managing toxic thyroid adenoma: a cost-effectiveness analysis. Eur J Endocrinol. 2002;146(3):283–94.

    Article  PubMed  CAS  Google Scholar 

  • Walsh PS, Wilde JI, Tom EY, et al. Analytical performance verification of a molecular diagnostic for cytology-indeterminate thyroid nodules. J Clin Endocrinol Metab. 2012;97(12):E2297–306.

    Article  PubMed  CAS  Google Scholar 

  • Walter MA, Briel M, Christ-Crain M, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011;21(3):243–51.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ward LS, Brenta G, Medvedovic M, Fagin JA. Studies of allelic loss in thyroid tumors reveal major differences in chromosomal instability between papillary and follicular carcinomas. J Clin Endocrinol Metab. 1998;83(2):525–30.

    PubMed  CAS  Google Scholar 

  • Watt T, Bjorner JB, Groenvold M, et al. Development of a short version of the thyroid-related patient-reported outcome ThyPRO. Thyroid. 2015;25(10):1069–79.

    Article  PubMed  Google Scholar 

  • Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol. 2007; 66(6):757–64.

    Article  CAS  Google Scholar 

  • Wienhold R, Scholz M, Adler JR, Nster G, Paschke R. The management of thyroid nodules: a retrospective analysis of health insurance data. Dtsch Arztebl Int. 2013;110(49):827–34.

    PubMed  PubMed Central  Google Scholar 

  • Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013; 13(3):184–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xing M, Vasko V, Tallini G, et al. BRAF T1796A transversion mutation in various thyroid neoplasms. J Clin Endocrinol Metab. 2004;89(3):1365–8.

    Article  PubMed  CAS  Google Scholar 

  • Yip L. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy. J Surg Oncol. 2015;111(1):43–50.

    Article  PubMed  CAS  Google Scholar 

  • Yoo SK, Lee S, Kim SJ, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet. 2016;12(8):e1006239.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yoon JH, Kwon HJ, Lee HS, Kim EK, Moon HJ, Kwak JY. RAS mutations in AUS/FLUS cytology: does it have an additional role in BRAFV600E mutation-negative nodules? Medicine (Baltimore). 2015;94(27):e1084.

    Article  CAS  Google Scholar 

  • Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003;120(1):71–7.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Markus Eszlinger

  2. Department of Endocrinology and Metabolism, Odense University Hospital, DK-5000, Odense, Denmark

    Laszlo Hegedüs

  3. Section of Endocrinology and Metabolism, Departments of Medicine, Oncology, Biochemistry and Molecular Biology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Ralf Paschke

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  1. Markus Eszlinger
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  2. Laszlo Hegedüs
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Correspondence to Ralf Paschke .

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  1. Department of Endocrinology, University of Pisa, Pisa, Italy

    Paolo Vitti

  2. Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

    Laszlo Hegedüs

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Eszlinger, M., Hegedüs, L., Paschke, R. (2018). Thyroid Nodule. In: Vitti, P., Hegedüs, L. (eds) Thyroid Diseases. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-45013-1_6

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