Advertisement

Nontoxic Multinodular Goiter

  • Gilberto Paz-Filho
  • Hans GrafEmail author
Chapter

Abstract

Multinodular goiter (MNG), characterized as the nodular enlargement of the thyroid gland in the absence of inflammation, autoimmune thyroid disease, and malignancy, is a frequent thyroid disorder that affects women more frequently. Iodine deficiency is the most important etiological factor, but other environmental, hormonal, and genetic elements also play a role in its pathogenesis. Patients with MNG may be asymptomatic, but those more severely affected can develop compressive symptoms such as dysphonia, dysphagia, and respiratory insufficiency. Furthermore, the thyroid gland may develop autonomy and secrete thyroid hormones independent of TSH, leading to hyperthyroidism. The diagnostic workup includes thyroid hormone tests, imaging studies, evaluation of radioactive iodine uptake, pulmonary function tests, and fine-needle aspiration biopsy to exclude malignancy. The most accepted therapeutic approaches include clinical observation, surgery, and administration of radioactive iodine, which depend on the clinical presentation and on the patient’s preference. Novel therapeutical approaches, such as the use of radioiodine after circulating TSH is raised, either via the exogenous administration of recombinant human TSH or through the induction of transient primary hypothyroidism by antithyroid drugs, are being evaluated and may become available as alternative treatments.

Keywords

Benign goiter Levothyroxine Multinodular Nodule Nontoxic Radioiodine Surgery 

References

  1. 1.
    Knobel M. Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters. J Endocrinol Investig. 2016;39(4):357–73.  https://doi.org/10.1007/s40618-015-0391-7.Google Scholar
  2. 2.
    Tonacchera M, Pinchera A, Vitti P. Assessment of nodular goitre. Best Pract Res Clin Endocrinol Metab. 2010;24(1):51–61.  https://doi.org/10.1016/j.beem.2009.08.008.PubMedGoogle Scholar
  3. 3.
    Knudsen N, Bulow I, Jorgensen T, Laurberg P, Ovesen L, Perrild H. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative epidemiological study in two regions with slightly different iodine status. Clin Endocrinol. 2000;53(4):479–85.Google Scholar
  4. 4.
    Pinchera A, Aghini-Lombardi F, Antonangeli L, Vitti P. Multinodular goiter. Epidemiology and prevention. Ann Ital Chir. 1996;67(3):317–25.PubMedGoogle Scholar
  5. 5.
    Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol. 1977;7(6):481–93.Google Scholar
  6. 6.
    Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham study. Arch Intern Med. 1985;145(8):1386–8.PubMedGoogle Scholar
  7. 7.
    Knobel M, Bisi H, de Araujo Peres C, Medeiros-Neto G. Studies on functional and morphological aspects in human multinodular simple goiter tissues. Endocr Pathol. 1993;4(4):205–14.  https://doi.org/10.1007/bf02915463.Google Scholar
  8. 8.
    Schlumberger M-J, Filetti S, Hay ID. Nontoxic diffuse and nodular goiter and thyroid Neoplasia. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Williams textbook of endocrinology. 12th ed. Philadelphia: Elsevier Saunders; 2011. p. 440–75.Google Scholar
  9. 9.
    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.  https://doi.org/10.1210/edrv-10-2-125.PubMedGoogle Scholar
  10. 10.
    Hegedus L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003;24(1):102–32.  https://doi.org/10.1210/er.2002-0016.PubMedGoogle Scholar
  11. 11.
    Zimmermann MB. Iodine deficiency. Endocr Rev. 2009;30(4):376–408.  https://doi.org/10.1210/er.2009-0011.PubMedGoogle Scholar
  12. 12.
    Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008;372(9645):1251–62.  https://doi.org/10.1016/S0140-6736(08)61005-3.PubMedGoogle Scholar
  13. 13.
    Brix TH, Hansen PS, Kyvik KO, Hegedus L. Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med. 2000;160(5):661–6.PubMedGoogle Scholar
  14. 14.
    Knudsen N, Laurberg P, Perrild H, Bulow I, Ovesen L, Jorgensen T. Risk factors for goiter and thyroid nodules. Thyroid. 2002;12(10):879–88.  https://doi.org/10.1089/105072502761016502.PubMedGoogle Scholar
  15. 15.
    Zimmermann MB, Ito Y, Hess SY, Fujieda K, Molinari L. High thyroid volume in children with excess dietary iodine intakes. Am J Clin Nutr. 2005;81(4):840–4.PubMedGoogle Scholar
  16. 16.
    Graf H. Multinodular goiter: pathogenesis and management. In: Braverman LE, Cooper DS, editors. The thyroid: a fundamental and clinica textl. 10th ed. Philadelphia: Lippincott Williams & Wilkins, Wolters Kluver; 2013. p. 635–49.Google Scholar
  17. 17.
    Furlanetto TW, Nguyen LQ, Jameson JL. Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells. Endocrinology. 1999;140(12):5705–11.  https://doi.org/10.1210/endo.140.12.7197.PubMedGoogle Scholar
  18. 18.
    Manole D, Schildknecht B, Gosnell B, Adams E, Derwahl M. Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms. J Clin Endocrinol Metab. 2001;86(3):1072–7.  https://doi.org/10.1210/jcem.86.3.7283.PubMedGoogle Scholar
  19. 19.
    Boas M, Hegedus L, Feldt-Rasmussen U, Skakkebaek NE, Hilsted L, Main KM. Association of thyroid gland volume, serum insulin-like growth factor-I, and anthropometric variables in euthyroid prepubertal children. J Clin Endocrinol Metab. 2009;94(10):4031–5.  https://doi.org/10.1210/jc.2009-0939.PubMedGoogle Scholar
  20. 20.
    Volzke H, Friedrich N, Schipf S, Haring R, Ludemann J, Nauck M, et al. Association between serum insulin-like growth factor-I levels and thyroid disorders in a population-based study. J Clin Endocrinol Metab. 2007;92(10):4039–45.  https://doi.org/10.1210/jc.2007-0816.PubMedGoogle Scholar
  21. 21.
    von Werder K. Acromegaly and thyroid. J Endocrinol Investig. 2002;25(11):930–1.  https://doi.org/10.1007/BF03344063.Google Scholar
  22. 22.
    Clement S, Refetoff S, Robaye B, Dumont JE, Schurmans S. Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-Ir receptor in the thyroid gland. Endocrinology. 2001;142(12):5131–9.  https://doi.org/10.1210/endo.142.12.8534.PubMedGoogle Scholar
  23. 23.
    Singer J, Eszlinger M, Wicht J, Paschke R. Evidence for a more pronounced effect of genetic predisposition than environmental factors on goitrogenesis by a case control study in an area with low normal iodine supply. Horm Metab Res. 2011;43(5):349–54.  https://doi.org/10.1055/s-0031-1273699.PubMedGoogle Scholar
  24. 24.
    Hansen PS, Brix TH, Bennedbaek FN, Bonnema SJ, Iachine I, Kyvik KO, et al. The relative importance of genetic and environmental factors in the aetiology of thyroid nodularity: a study of healthy Danish twins. Clin Endocrinol. 2005;62(3):380–6.  https://doi.org/10.1111/j.1365-2265.2005.02230.x.Google Scholar
  25. 25.
    Bottcher Y, Eszlinger M, Tonjes A, Paschke R. The genetics of euthyroid familial goiter. Trends Endocrinol Metab. 2005;16(7):314–9.  https://doi.org/10.1016/j.tem.2005.07.003.PubMedGoogle Scholar
  26. 26.
    Bayer Y, Neumann S, Meyer B, Ruschendorf F, Reske A, Brix T, et al. Genome-wide linkage analysis reveals evidence for four new susceptibility loci for familial euthyroid goiter. J Clin Endocrinol Metab. 2004;89(8):4044–52.  https://doi.org/10.1210/jc.2003-032096.PubMedGoogle Scholar
  27. 27.
    Teumer A, Rawal R, Homuth G, Ernst F, Heier M, Evert M, et al. Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk. Am J Hum Genet. 2011;88(5):664–73.  https://doi.org/10.1016/j.ajhg.2011.04.015.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Yan J, Takahashi T, Ohura T, Adachi H, Takahashi I, Ogawa E, et al. Combined linkage analysis and exome sequencing identifies novel genes for familial goiter. J Hum Genet. 2013;58(6):366–77.  https://doi.org/10.1038/jhg.2013.20.PubMedGoogle Scholar
  29. 29.
    Jameson JL, Mandel SJ, Weetman AP. Disorders of the thyroid gland. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J, editors. Harrison’s principles of internal medicine. 19th ed. New York: McGraw-Hill; 2015.Google Scholar
  30. 30.
    Medeiros-Neto G. Multinodular goiter in: Endotext. MDText.com, South Dartmouth http://www.ncbi.nlm.nih.gov/books/NBK285569/. Accessed 9 Sep 2016
  31. 31.
    Bahn RS, Castro MR. Approach to the patient with nontoxic multinodular goiter. J Clin Endocrinol Metab. 2011;96(5):1202–12.PubMedGoogle Scholar
  32. 32.
    Rosenthal LH, Benninger MS, Deeb RH. Vocal fold immobility: a longitudinal analysis of etiology over 20 years. Laryngoscope. 2007;117(10):1864–70.  https://doi.org/10.1097/MLG.0b013e3180de4d49.PubMedGoogle Scholar
  33. 33.
    Ko MA, Darling GE. Acquired paralysis of the diaphragm. Thorac Surg Clin. 2009;19(4):501–10.  https://doi.org/10.1016/j.thorsurg.2009.08.011.PubMedGoogle Scholar
  34. 34.
    Leuchter I, Becker M, Mickel R, Dulguerov P. Horner’s syndrome and thyroid neoplasms. ORL J Otorhinolaryngol Relat Spec. 2002;64(1):49–52.  https://doi.org/10.1159/000049270.PubMedGoogle Scholar
  35. 35.
    Siderys H, Rowe GA. Superior vena caval syndrome caused by intrathoracic goiter. Am Surg. 1970;36(7):446–50.PubMedGoogle Scholar
  36. 36.
    Pemberton HS. Sign of submerged goitre. Lancet. 1946;248(6423):509.  https://doi.org/10.1016/S0140-6736(46)91790-4.Google Scholar
  37. 37.
    Newman E, Shaha AR. Substernal goiter. J Surg Oncol. 1995;60(3):207–12.PubMedGoogle Scholar
  38. 38.
    Huins CT, Georgalas C, Mehrzad H, Tolley NS. A new classification system for retrosternal goitre based on a systematic review of its complications and management. Int J Surg. 2008;6(1):71–6.  https://doi.org/10.1016/j.ijsu.2007.02.003.PubMedGoogle Scholar
  39. 39.
    Mercante G, Gabrielli E, Pedroni C, Formisano D, Bertolini L, Nicoli F, et al. CT cross-sectional imaging classification system for substernal goiter based on risk factors for an extracervical surgical approach. Head Neck. 2011;33(6):792–9.  https://doi.org/10.1002/hed.21539.PubMedPubMedCentralGoogle Scholar
  40. 40.
    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):1–133.  https://doi.org/10.1089/thy.2015.0020.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Brito JP, Yarur AJ, Prokop LJ, McIver B, Murad MH, Montori VM. Prevalence of thyroid cancer in multinodular goiter versus single nodule: a systematic review and meta-analysis. Thyroid. 2013;23(4):449–55.  https://doi.org/10.1089/thy.2012.0156.PubMedGoogle Scholar
  42. 42.
    Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, et al. Management of thyroid nodules detected at US: Society of Radiologists in ultrasound consensus conference statement. Radiology. 2005;237(3):794–800.  https://doi.org/10.1148/radiol.2373050220.PubMedGoogle Scholar
  43. 43.
    McCoy KL, Jabbour N, Ogilvie JB, Ohori NP, Carty SE, Yim JH. The incidence of cancer and rate of false-negative cytology in thyroid nodules greater than or equal to 4 cm in size. Surgery. 2007;142(6):837–44; discussion 44 e1–3.  https://doi.org/10.1016/j.surg.2007.08.012.PubMedGoogle Scholar
  44. 44.
    Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab. 2002;87(5):1941–6.  https://doi.org/10.1210/jcem.87.5.8504.PubMedGoogle Scholar
  45. 45.
    Biondi B, Palmieri EA, Filetti S, Lombardi G, Fazio S. Mortality in elderly patients with subclinical hyperthyroidism. Lancet. 2002;359(9308):799–800.PubMedGoogle Scholar
  46. 46.
    Hasselgren M, Hegedus L, Godballe C, Bonnema SJ. Benefit of measuring basal serum calcitonin to detect medullary thyroid carcinoma in a Danish population with a high prevalence of thyroid nodules. Head Neck. 2010;32(5):612–8.  https://doi.org/10.1002/hed.21228.PubMedGoogle Scholar
  47. 47.
    Le Moli R, Wesche MF, Tiel-Van Buul MM, Wiersinga WM. Determinants of longterm outcome of radioiodine therapy of sporadic non-toxic goitre. Clin Endocrinol. 1999;50(6):783–9.Google Scholar
  48. 48.
    Nygaard B, Knudsen JH, Hegedus L, Scient AV, Hansen JE. Thyrotropin receptor antibodies and Graves’ disease, a side-effect of 131I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab. 1997;82(9):2926–30.  https://doi.org/10.1210/jcem.82.9.4227.PubMedGoogle Scholar
  49. 49.
    Schmidt M, Gorbauch E, Dietlein M, Faust M, Stutzer H, Eschner W, et al. Incidence of postradioiodine immunogenic hyperthyroidism/Graves’ disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease. Thyroid. 2006;16(3):281–8.  https://doi.org/10.1089/thy.2006.16.281.PubMedGoogle Scholar
  50. 50.
    Belardinelli L, Gualdi G, Ceroni L, Guadalaxara A, Polettini E, Pappalardo G. Comparison between computed tomography and magnetic resonance data and pathologic findings in substernal goiters. Int Surg. 1995;80(1):65–9.PubMedGoogle Scholar
  51. 51.
    Ioannidis O, Dalampini E, Chatzopoulos S, Kotronis A, Paraskevas G, Konstantara A, et al. Acute respiratory failure caused by neglected giant substernal nontoxic goiter. Arq Bras Endocrinol Metabol. 2011;55(3):229–32.  https://doi.org/10.1590/S0004-27302011000300009.PubMedGoogle Scholar
  52. 52.
    Nygaard B, Nygaard T, Court-Payen M, Jensen LI, Soe-Jensen P, Gerhard Nielsen K, et al. Thyroid volume measured by ultrasonography and CT. Acta Radiol. 2002;43(3):269–74.PubMedGoogle Scholar
  53. 53.
    Wesche MF, Tiel-van Buul MM, Smits NJ, Wiersinga WM. Ultrasonographic versus scintigraphic measurement of thyroid volume in patients referred for 131I therapy. Nucl Med Commun. 1998;19(4):341–6.PubMedGoogle Scholar
  54. 54.
    Uematsu H, Sadato N, Ohtsubo T, Tsuchida T, Nakamura S, Sugimoto K, et al. Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors. J Nucl Med. 1998;39(3):453–9.PubMedGoogle Scholar
  55. 55.
    Cerci C, Cerci SS, Eroglu E, Dede M, Kapucuoglu N, Yildiz M, et al. Thyroid cancer in toxic and non-toxic multinodular goiter. J Postgrad Med. 2007;53(3):157–60.PubMedGoogle Scholar
  56. 56.
    Fiore E, Rago T, Provenzale MA, Scutari M, Ugolini C, Basolo F, 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.  https://doi.org/10.1677/ERC-09-0036.PubMedGoogle Scholar
  57. 57.
    Paz-Filho G, Graf H, Ward LS. Comparative analysis of the new guidelines and consensuses for the management of hypothyroidism, thyroid nodules, and differentiated thyroid cancer. Arq Bras Endocrinol Metabol. 2013;57(4):233–9.PubMedGoogle Scholar
  58. 58.
    Can AS. Cost-effectiveness comparison between palpation- and ultrasound-guided thyroid fine-needle aspiration biopsies. BMC Endocr Disord. 2009;9:14.  https://doi.org/10.1186/1472-6823-9-14.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 2011;260(3):892–9.  https://doi.org/10.1148/radiol.11110206.PubMedGoogle Scholar
  60. 60.
    Cibas ES, Sanchez MA. The National Cancer Institute thyroid fine-needle aspiration state-of-the-science conference: inspiration for a uniform terminology linked to management guidelines. Cancer. 2008;114(2):71–3.  https://doi.org/10.1002/cncr.23343.PubMedGoogle Scholar
  61. 61.
    Pradeep PV, Tiwari P, Mishra A, Agarwal G, Agarwal A, Verma AK, et al. Pulmonary function profile in patients with benign goiters without symptoms of respiratory compromise and the early effect of thyroidectomy. J Postgrad Med. 2008;54(2):98–101.PubMedGoogle Scholar
  62. 62.
    Hegedus L, Bonnema SJ. Approach to management of the patient with primary or secondary intrathoracic goiter. J Clin Endocrinol Metab. 2010;95(12):5155–62.  https://doi.org/10.1210/jc.2010-1638.PubMedPubMedCentralGoogle Scholar
  63. 63.
    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.Google Scholar
  64. 64.
    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.PubMedGoogle Scholar
  65. 65.
    Diehl LA, Garcia V, Bonnema SJ, Hegedus L, Albino CC, Graf H. Management of the nontoxic multinodular goiter in Latin America: comparison with North America and Europe, an electronic survey. J Clin Endocrinol Metab. 2005;90(1):117–23.  https://doi.org/10.1210/jc.2004-1722.PubMedGoogle Scholar
  66. 66.
    Costante G, Crocetti U, Schifino E, Ludovico O, Capula C, Nicotera M, et al. Slow growth of benign thyroid nodules after menopause: no need for long-term thyroxine suppressive therapy in post-menopausal women. J Endocrinol Investig. 2004;27(1):31–6.  https://doi.org/10.1007/BF03350907.Google Scholar
  67. 67.
    White ML, Doherty GM, Gauger PG. Evidence-based surgical management of substernal goiter. World J Surg. 2008;32(7):1285–300.  https://doi.org/10.1007/s00268-008-9466-3.PubMedGoogle Scholar
  68. 68.
    Marqusee E, Benson CB, Frates MC, Doubilet PM, Larsen PR, Cibas ES, et al. Usefulness of ultrasonography in the management of nodular thyroid disease. Ann Intern Med. 2000;133(9):696–700.PubMedGoogle Scholar
  69. 69.
    van Roosmalen J, van Hemel B, Suurmeijer A, Groen H, Ruitenbeek T, Links TP, et al. Diagnostic value and cost considerations of routine fine-needle aspirations in the follow-up of thyroid nodules with benign readings. Thyroid. 2010;20(12):1359–65.  https://doi.org/10.1089/thy.2008.0268.PubMedGoogle Scholar
  70. 70.
    Grussendorf M, Reiners C, Paschke R, Wegscheider K, Investigators L. 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.  https://doi.org/10.1210/jc.2011-0356.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Filetti S, Durante C, Torlontano M. Nonsurgical approaches to the management of thyroid nodules. Nat Clin Pract Endocrinol Metab. 2006;2(7):384–94.  https://doi.org/10.1038/ncpendmet0215.PubMedGoogle Scholar
  72. 72.
    Berghout A, Wiersinga WM, Drexhage HA, Smits NJ, Touber JL. Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre. Lancet. 1990;336(8709):193–7.  https://doi.org/10.1016/0140-6736(90)91730-X.PubMedGoogle Scholar
  73. 73.
    Cesareo R, Iozzino M, Isgro MA, Annunziata F, Di Stasio E. Short term effects of levothyroxine treatment in thyroid multinodular disease. Endocr J. 2010;57(9):803–9.PubMedGoogle Scholar
  74. 74.
    Wesche MF, Tiel VBMM, Lips P, Smits NJ, Wiersinga WM. A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter. J Clin Endocrinol Metab. 2001;86(3):998–1005.PubMedGoogle Scholar
  75. 75.
    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.  https://doi.org/10.1111/j.1365-2265.2008.03241.x.Google Scholar
  76. 76.
    Viniol A, Hickstein L, Walker J, Donner-Banzhoff N, Baum E, Becker A. Influence of thyroid hormone therapy on the fracture rate—a claims data cohort study. Bone. 2016;86:86–90.  https://doi.org/10.1016/j.bone.2016.03.002.PubMedGoogle Scholar
  77. 77.
    Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76–131.  https://doi.org/10.1210/er.2006-0043.PubMedGoogle Scholar
  78. 78.
    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.  https://doi.org/10.1016/S0140-6736(01)06067-6.PubMedGoogle Scholar
  79. 79.
    Chen AY, Bernet VJ, Carty SE, Davies TF, Ganly I, Inabnet WB 3rd, et al. American Thyroid Association statement on optimal surgical management of goiter. Thyroid. 2014;24(2):181–9.  https://doi.org/10.1089/thy.2013.0291.PubMedGoogle Scholar
  80. 80.
    Lanitis S, Kouloura A, Zafiriadou P, Karaliotas C. Type of operation for multinodular goitre and solitary nodule. Hell J Surg. 2015;87(1):24–30.  https://doi.org/10.1007/s13126-015-0174-9.Google Scholar
  81. 81.
    Agarwal G, Aggarwal V. Is total thyroidectomy the surgical procedure of choice for benign multinodular goiter? An evidence-based review. World J Surg. 2008;32(7):1313–24.  https://doi.org/10.1007/s00268-008-9579-8.PubMedGoogle Scholar
  82. 82.
    Moalem J, Suh I, Duh QY. Treatment and prevention of recurrence of multinodular goiter: an evidence-based review of the literature. World J Surg. 2008;32(7):1301–12.  https://doi.org/10.1007/s00268-008-9477-0.PubMedGoogle Scholar
  83. 83.
    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.PubMedGoogle Scholar
  84. 84.
    Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H, Gastinger I, 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.  https://doi.org/10.1007/s002680010221.PubMedGoogle Scholar
  85. 85.
    Vaiman M, Nagibin A, Olevson J. Complications in primary and completed thyroidectomy. Surg Today. 2010;40(2):114–8.  https://doi.org/10.1007/s00595-008-4027-9.PubMedGoogle Scholar
  86. 86.
    Del Rio P, Viani L, Montana CM, Cozzani F, Sianesi M. Minimally invasive thyroidectomy: a ten years experience. Gland Surg. 2016;5(3):295–9.  https://doi.org/10.21037/gs.2016.01.04.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, 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.  https://doi.org/10.1089/thy.2010.0417.Google Scholar
  88. 88.
    Bistrup C, Nielsen JD, Gregersen G, Franch P. Preventive effect of levothyroxine in patients operated for non-toxic goitre: a randomized trial of one hundred patients with nine years follow-up. Clin Endocrinol. 1994;40(3):323–7.Google Scholar
  89. 89.
    Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2007;92(8 Suppl):S1–47.PubMedGoogle Scholar
  90. 90.
    Bonnema SJ, Hegedus L. A 30-year perspective on radioiodine therapy of benign nontoxic multinodular goiter. Curr Opin Endocrinol Diabetes Obes. 2009;16(5):379–84.  https://doi.org/10.1097/MED.0b013e32832ff2e1.PubMedGoogle Scholar
  91. 91.
    Hegedus L, Hansen BM, Knudsen N, Hansen JM. Reduction of size of thyroid with radioactive iodine in multinodular non-toxic goitre. Br Med J. 1988;297(6649):661–2.Google Scholar
  92. 92.
    Bonnema SJ, Bertelsen H, Mortensen J, Andersen PB, Knudsen DU, Bastholt L, et al. The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function. J Clin Endocrinol Metab. 1999;84(10):3636–41.PubMedGoogle Scholar
  93. 93.
    Huysmans DA, Hermus AR, Corstens FH, Barentsz JO, Kloppenborg PW. Large, compressive goiters treated with radioiodine. Ann Intern Med. 1994;121(10):757–62.PubMedGoogle Scholar
  94. 94.
    Nygaard B, Faber J, Hegedüs L, Hansen JM. 131I treatment of nodular non-toxic goitre. Eur J Endocrinol. 1996;134(1):15–20.PubMedGoogle Scholar
  95. 95.
    Nygaard B, Hegedus L, Gervil M, Hjalgrim H, Soe-Jensen P, Hansen JM. Radioiodine treatment of multinodular non-toxic goitre. Br Med J. 1993;307(6908):828–32.Google Scholar
  96. 96.
    Nygaard B, Soes-Petersen U, Hoilund-Carlsen PF, Veje A, Holst PE, Vestergaard A, et al. Improvement of upper airway obstruction after 131I-treatment of multinodular nontoxic goiter evaluated by flow volume loop curves. J Endocrinol Investig. 1996;19(2):71–5.Google Scholar
  97. 97.
    Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol. 2007;66(6):757–64.Google Scholar
  98. 98.
    Bonnema SJ, Fast S, Hegedus L. The role of radioiodine therapy in benign nodular goitre. Best Pract Res Clin Endocrinol Metab. 2014;28(4):619–31.  https://doi.org/10.1016/j.beem.2014.02.001.PubMedGoogle Scholar
  99. 99.
    Huysmans DA, Buijs WC, van de Ven MT, van den Broek WJ, Kloppenborg PW, Hermus AR, et al. Dosimetry and risk estimates of radioiodine therapy for large, multinodular goiters. J Nucl Med. 1996;37(12):2072–9.PubMedGoogle Scholar
  100. 100.
    Greenlee C, Burmeister LA, Butler RS, Edinboro CH, Morrison SM, Milas M, et al. Current safety practices relating to I-131 administration for diseases of the thyroid: a survey of physicians and allied practitioners. Thyroid. 2011;21(2):151–60.  https://doi.org/10.1089/thy.2010.0090.PubMedGoogle Scholar
  101. 101.
    Paz-Filho GJ, Graf H. Recombinant human thyrotropin in the management of thyroid disorders. Expert Opin Biol Ther. 2008;8(11):1721–32.  https://doi.org/10.1517/14712598.8.11.1721.PubMedGoogle Scholar
  102. 102.
    Ramirez L, Braverman LE, White B, Emerson CH. Recombinant human thyrotropin is a potent stimulator of thyroid function in normal subjects. J Clin Endocrinol Metab. 1997;82(9):2836–9.  https://doi.org/10.1210/jcem.82.9.4205.PubMedGoogle Scholar
  103. 103.
    Torres MST, Ramirez L, Simkin PH, Braverman LE, Emerson CH. Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects. J Clin Endocrinol Metabol. 2001;86(4):1660–4.  https://doi.org/10.1210/jcem.86.4.7405.Google Scholar
  104. 104.
    Fast S, Nielsen VE, Bonnema SJ, Hegedus L. Dose-dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function: comparison of 0.1, 0.3 and 0.9 mg of rhTSH. Clin Endocrinol (Oxf). 2010;72(3):411–6.  https://doi.org/10.1111/j.1365-2265.2009.03650.x.Google Scholar
  105. 105.
    Jarzab B, Dedecjus M, Handkiewicz-Junak D, Lange D, Lewinski A, Nasierowska-Guttmejer A, et al. Diagnostics and treatment of thyroid carcinoma. Endokrynol Pol. 2016;67(1):74–107.  https://doi.org/10.5603/EP.2016.0011.PubMedGoogle Scholar
  106. 106.
    Pacini F, Castagna MG. Diagnostic and therapeutic use of recombinant human TSH (rhTSH) in differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2008;22(6):1009–21.  https://doi.org/10.1016/j.beem.2008.09.014. PubMedGoogle Scholar
  107. 107.
    Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, et al. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012;366(18):1674–85.  https://doi.org/10.1056/NEJMoa1109589.PubMedGoogle Scholar
  108. 108.
    Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, et al. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012;366(18):1663–73.  https://doi.org/10.1056/NEJMoa1108586.PubMedGoogle Scholar
  109. 109.
    Borget I, Bonastre J, Catargi B, Deandreis D, Zerdoud S, Rusu D, et al. Quality of life and cost-effectiveness assessment of radioiodine ablation strategies in patients with thyroid cancer: results from the randomized phase III ESTIMABL trial. J Clin Oncol. 2015;33(26):2885–92.  https://doi.org/10.1200/JCO.2015.61.6722.PubMedGoogle Scholar
  110. 110.
    Huysmans DA, Nieuwlaat WA, Erdtsieck RJ, Schellekens AP, Bus JW, Bravenboer B, et al. Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter. J Clin Endocrinol Metab. 2000;85(10):3592–6.PubMedGoogle Scholar
  111. 111.
    Knobel M. Which is the ideal treatment for benign diffuse and multinodular non-toxic goiters? Front Endocrinol (Lausanne). 2016;7:48.  https://doi.org/10.3389/fendo.2016.00048.Google Scholar
  112. 112.
    Albino CC, Mesa CO, Olandoski M, Ueda CE, Woellner LC, Goedert CA, et al. Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine. J Clin Endocrinol Metab. 2005;90(5):2775–80.PubMedGoogle Scholar
  113. 113.
    Bonnema SJ, Nielsen VE, Boel-Jorgensen H, Grupe P, Andersen PB, Bastholt L, et al. Improvement of goiter volume reduction after 0.3 mg recombinant human thyrotropin-stimulated radioiodine therapy in patients with a very large goiter: a double-blinded, randomized trial. J Clin Endocrinol Metab. 2007;92(9):3424–8.PubMedGoogle Scholar
  114. 114.
    Bonnema SJ, Nielsen VE, Boel-Jorgensen H, Grupe P, Andersen PB, Bastholt L, et al. Recombinant human thyrotropin-stimulated radioiodine therapy of large nodular goiters facilitates tracheal decompression and improves inspiration. J Clin Endocrinol Metab. 2008;93(10):3981–4.PubMedGoogle Scholar
  115. 115.
    Fast S, Nielsen VE, Bonnema SJ, Hegedus L. Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre: focus on recombinant human TSH augmented radioiodine therapy. Eur J Endocrinol. 2009;160(4):517–28.PubMedGoogle Scholar
  116. 116.
    Fast S, Nielsen VE, Grupe P, Boel-Jorgensen H, Bastholt L, Andersen PB, et al. Prestimulation with recombinant human thyrotropin (rhTSH) improves the long-term outcome of radioiodine therapy for multinodular nontoxic goiter. J Clin Endocrinol Metab. 2012;97(8):2653–60.PubMedGoogle Scholar
  117. 117.
    Giusti M, Cappi C, Santaniello B, Ceresola E, Augeri C, Lagasio C, et al. Safety and efficacy of administering 0.2 mg of recombinant human TSH for two consecutive days as an adjuvant to therapy with low radioiodine doses in elderly out-patients with large nontoxic multinodular goiter. Minerva Endocrinol. 2006;31(3):191–209.PubMedGoogle Scholar
  118. 118.
    Giusti M, Caputo M, Calamia I, Bagnara M, Ceresola E, Schiavo M, et al. Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter. Thyroid Res. 2009;2(1):6.  https://doi.org/10.1186/1756-6614-2-6.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Nielsen VE, Bonnema SJ, Boel-Jorgensen H, Grupe P, Hegedus L. Stimulation with 0.3-mg recombinant human thyrotropin prior to iodine 131 therapy to improve the size reduction of benign nontoxic nodular goiter: a prospective randomized double-blind trial. Arch Intern Med. 2006;166(14):1476–82.PubMedGoogle Scholar
  120. 120.
    Nielsen VE, Bonnema SJ, Hegedus L. Transient goiter enlargement after administration of 0.3 mg of recombinant human thyrotropin in patients with benign nontoxic nodular goiter: a randomized, double-blind, crossover trial. J Clin Endocrinol Metab. 2006;91(4):1317–22.PubMedGoogle Scholar
  121. 121.
    Silva MN, Rubio IG, Romao R, Gebrin EM, Buchpiguel C, Tomimori E, et al. Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres. Clin Endocrinol. 2004;60(3):300–8.Google Scholar
  122. 122.
    Albino CC, Graf H, Paz-Filho G, Diehl LA, Olandoski M, Sabbag A, et al. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter. Braz J Med Biol Res. 2010;43(3):303–9.PubMedGoogle Scholar
  123. 123.
    Ceccarelli C, Antonangeli L, Brozzi F, Bianchi F, Tonacchera M, Santini P, et al. Radioiodine 131I treatment for large nodular goiter: recombinant human thyrotropin allows the reduction of radioiodine 131I activity to be administered in patients with low uptake. Thyroid. 2011;21(7):759–64.PubMedGoogle Scholar
  124. 124.
    Nieuwlaat W-A, Huysmans DA, van den Bosch HC, Sweep CGF, Ross HA, Corstens FH, et al. Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter. J Clin Endocrinol Metab. 2003;88(7):3121–9.PubMedGoogle Scholar
  125. 125.
    Cubas ER, Paz-Filho GJ, Olandoski M, Goedert CA, Woellner LC, Carvalho GA, et al. Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre. Int J Clin Pract. 2009;63(4):583–90.  https://doi.org/10.1111/j.1742-1241.2008.01904.x.PubMedGoogle Scholar
  126. 126.
    Mojsak MN, Abdelrazek S, Szumowski P, Rogowski F, Sykala M, Kostecki J, et al. Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter. Nucl Med Rev Cent East Eur. 2016;19(1):3–11.  https://doi.org/10.5603/NMR.2016.0002.PubMedGoogle Scholar
  127. 127.
    Paz-Filho GJ, Mesa-Junior CO, Olandoski M, Woellner LC, Goedert CA, Boguszewski CL, et al. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone. Braz J Med Biol Res. 2007;40(12):1661–70.PubMedGoogle Scholar
  128. 128.
    Graf H, Fast S, Pacini F, Pinchera A, Leung A, Vaisman M, et al. Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study. J Clin Endocrinol Metab. 2011;96(5):1368–76.PubMedGoogle Scholar
  129. 129.
    Fast S, Hegedus L, Pacini F, Pinchera A, Leung AM, Vaisman M, et al. Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study. Thyroid. 2014;24(4):727–35.  https://doi.org/10.1089/thy.2013.0370.PubMedPubMedCentralGoogle Scholar
  130. 130.
    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.PubMedGoogle Scholar
  131. 131.
    Graf H. Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter. Eur J Endocrinol. 2015;172(2):R47–52.  https://doi.org/10.1530/EJE-14-0608.PubMedGoogle Scholar
  132. 132.
    Romao R, Rubio IG, Tomimori EK, Camargo RY, Knobel M, Medeiros-Neto G. High prevalence of side effects after recombinant human thyrotropin-stimulated radioiodine treatment with 30 mCi in patients with multinodular goiter and subclinical/clinical hyperthyroidism. Thyroid. 2009;19(9):945–51.  https://doi.org/10.1089/thy.2008.0394.PubMedGoogle Scholar
  133. 133.
    Paz-Filho GJ, Mesa CO, Carvalho GA, Goedert CA, Graf H. Recombinant human TSH associated with radioiodine does not have further effects on thyroid volume and function after 2 years. Clin Endocrinol. 2008;69(2):345–6.  https://doi.org/10.1111/j.1365-2265.2007.03165.x.Google Scholar
  134. 134.
    Lee YY, Tam KW, Lin YM, Leu WJ, Chang JC, Hsiao CL, et al. Recombinant human thyrotropin before (131)I therapy in patients with nodular goitre: a meta-analysis of randomized controlled trials. Clin Endocrinol. 2015;83(5):702–10.  https://doi.org/10.1111/cen.12654.Google Scholar
  135. 135.
    Albino CC, Graf H, Sampaio AP, Vigario A, Paz-Filho GJ. Thiamazole as an adjuvant to radioiodine for volume reduction of multinodular goiter. Expert Opin Investig Drugs. 2008;17(12):1781–6.  https://doi.org/10.1517/13543780802501325.PubMedGoogle Scholar
  136. 136.
    Flores-Rebollar A, Ruiz-Juvera A, Lopez-Carrasco G, Gonzalez-Trevino O. Effect of 1110 MBq radioiodine in reducing thyroid volume in multinodular goiter: a new protocol. J Clin Med Res. 2013;5(3):234–8.  https://doi.org/10.4021/jocmr1361w.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Kyrilli A, Tang BN, Huyge V, Blocklet D, Goldman S, Corvilain B, et al. Thiamazole pretreatment lowers the (131)I activity needed to cure hyperthyroidism in patients with nodular goiter. J Clin Endocrinol Metab. 2015;100(6):2261–7.  https://doi.org/10.1210/jc.2015-1026.PubMedGoogle Scholar
  138. 138.
    Spaulding SW. Could pretreatment with Methimazole be as effective as rhTSH in treating subclinical toxic multinodular goiter with 131I? Clin Thyroidol. 2015;27(6):144–6.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Genome Sciences DepartmentThe Australian National UniversityCanberraAustralia
  2. 2.SEMPR—Endocrinology Division, Federal University of ParanaCuritibaBrazil

Personalised recommendations