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Eur Thyroid J. 2018 Aug;7(4):167-186. doi: 10.1159/000490384. Epub 2018 Jul 25.

2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism.

European thyroid journal

George J Kahaly, Luigi Bartalena, Lazlo Hegedüs, Laurence Leenhardt, Kris Poppe, Simon H Pearce

Affiliations

  1. Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.
  2. Department of Medicine and Surgery, University of Insubria, Varese, Italy.
  3. Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
  4. Thyroid and Endocrine Tumors Unit, Pitié Salpêtrière Hospital, Sorbonne University, Paris, France.
  5. Endocrine Unit, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  6. Department of Endocrinology, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

PMID: 30283735 PMCID: PMC6140607 DOI: 10.1159/000490384

Abstract

Graves' disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves' hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves' hyperthyroidism are usually medically treated for 12-18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12-18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves' patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves' patients with mild/active orbitopathy receiving RAI.

Keywords: Antithyroid drugs; Graves' hyperthyroidism; Graves' orbitopathy; Management; Radioiodine therapy; Thyroidectomy

References

  1. Nat Rev Endocrinol. 2010 Aug;6(8):431-43 - PubMed
  2. Clin Endocrinol (Oxf). 2016 Jan;84(1):115-20 - PubMed
  3. Thyroid. 2013 Jun;23(6):758-65 - PubMed
  4. Endocrinol Metab Clin North Am. 2001 Jun;30(2):339-60, viii-ix - PubMed
  5. Endocrinol Metab Clin North Am. 1993 Jun;22(2):263-77 - PubMed
  6. J Clin Endocrinol Metab. 2016 May;101(5):1998-2004 - PubMed
  7. Front Endocrinol (Lausanne). 2017 Feb 15;8:28 - PubMed
  8. Eur J Endocrinol. 2006 Dec;155(6):783-6 - PubMed
  9. Int J Endocrinol. 2015;2015:678194 - PubMed
  10. Lancet Diabetes Endocrinol. 2016 Jun;4(6):507-16 - PubMed
  11. BMJ. 2007 Mar 10;334(7592):514 - PubMed
  12. J Clin Endocrinol Metab. 1990 Feb;70(2):453-60 - PubMed
  13. Autoimmun Rev. 2010 Dec;10(2):116-22 - PubMed
  14. Thyroid. 2007 Mar;17(3):223-8 - PubMed
  15. Am J Clin Pathol. 2013 Feb;139(2):192-200 - PubMed
  16. Front Endocrinol (Lausanne). 2016 Aug 23;7:120 - PubMed
  17. Clin Endocrinol (Oxf). 2003 Sep;59(3):396-401 - PubMed
  18. Thyroid. 2016 May;26(5):734-40 - PubMed
  19. Nat Commun. 2015 Jul 07;6:7633 - PubMed
  20. Eur Thyroid J. 2017 Sep;6(5):243-249 - PubMed
  21. Thyroid. 2017 Mar;27(3):315-389 - PubMed
  22. Clin Pharmacol Ther. 2017 Dec;102(6):1017-1024 - PubMed
  23. Surgery. 2012 Aug;152(2):164-72 - PubMed
  24. Thyroid. 2013 Apr;23(4):408-13 - PubMed
  25. Horm Metab Res. 2015 Sep;47(10):735-52 - PubMed
  26. J Intern Med. 1991 May;229(5):415-20 - PubMed
  27. J Clin Endocrinol Metab. 2012 Dec;97(12):4287-92 - PubMed
  28. JAMA. 2014 Apr 16;311(15):1563-5 - PubMed
  29. Ann Intern Med. 2014 Aug 5;161(3):189-99 - PubMed
  30. J Clin Endocrinol Metab. 2001 Feb;86(2):930-4 - PubMed
  31. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD003420 - PubMed
  32. Thyroid. 2018 Jan;28(1):32-40 - PubMed
  33. J Clin Endocrinol Metab. 2013 Sep;98(9):3671-7 - PubMed
  34. Thyroid. 2016 Oct;26(10):1343-1421 - PubMed
  35. Clin Endocrinol (Oxf). 1993 Apr;38(4):367-72 - PubMed
  36. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006294 - PubMed
  37. Nat Rev Endocrinol. 2011 Mar 15;7(7):396-406 - PubMed
  38. J Clin Endocrinol Metab. 2012 Jan;97(1):E49-53 - PubMed
  39. Eur J Endocrinol. 2017 Jun;176(6):669-676 - PubMed
  40. Eur J Endocrinol. 1994 May;130(5):494-7 - PubMed
  41. Clin Exp Immunol. 2017 Sep;189(3):304-309 - PubMed
  42. J Clin Endocrinol Metab. 2016 Apr;101(4):1381-9 - PubMed
  43. Thyroid. 2012 Jul;22(7):661-79 - PubMed
  44. Eur Thyroid J. 2017 Jul;6(3):152-159 - PubMed
  45. Thyroid. 2011 Nov;21(11):1191-8 - PubMed
  46. Lancet. 1985 Feb 23;1(8426):430-2 - PubMed
  47. J Clin Endocrinol Metab. 1992 Sep;75(3):738-44 - PubMed
  48. Clin Endocrinol (Oxf). 2008 Sep;69(3):479-90 - PubMed
  49. Eur Thyroid J. 2015 Sep;4(3):149-63 - PubMed
  50. J Clin Endocrinol Metab. 1994 Aug;79(2):542-6 - PubMed
  51. Thyroid. 2014 Feb;24(2):200-7 - PubMed
  52. N Engl J Med. 1998 Jan 8;338(2):73-8 - PubMed
  53. N Engl J Med. ;376(2):184 - PubMed
  54. JAMA. 2015 May 26;313(20):2055-65 - PubMed
  55. J Clin Endocrinol Metab. 2010 Jul;95(7):3260-7 - PubMed
  56. J Clin Endocrinol Metab. 2009 Sep;94(9):3381-6 - PubMed
  57. Eur J Endocrinol. 2005 Jul;153(1):15-21 - PubMed
  58. J Clin Endocrinol Metab. 2011 Mar;96(3):592-9 - PubMed
  59. Eur J Endocrinol. 2005 May;152(5):695-701 - PubMed
  60. Clin Endocrinol (Oxf). 2013 Nov;79(5):739-46 - PubMed
  61. J Autoimmun. 2015 Nov;64:82-90 - PubMed
  62. N Engl J Med. 2005 Mar 3;352(9):905-17 - PubMed
  63. Am J Med. 2012 Sep;125(9):S2 - PubMed
  64. Clin Endocrinol (Oxf). 2008 Dec;69(6):943-50 - PubMed
  65. Thyroid. 2011 Mar;21(3):279-83 - PubMed
  66. Clin Endocrinol (Oxf). 2016 Jun;84(6):912-8 - PubMed
  67. Endocr Rev. 2016 Apr;37(2):114-34 - PubMed
  68. Eur Thyroid J. 2016 Mar;5(1):9-26 - PubMed
  69. N Engl J Med. 1989 Nov 16;321(20):1349-52 - PubMed
  70. Eur J Endocrinol. 2014 Oct;171(4):451-60 - PubMed
  71. J Clin Endocrinol Metab. 2001 Jun;86(6):2354-9 - PubMed
  72. J Clin Endocrinol Metab. 2010 May;95(5):2123-31 - PubMed
  73. Arch Intern Med. 1989 Mar;149(3):526-32 - PubMed
  74. Ultrasonography. 2015 Oct;34(4):292-6 - PubMed
  75. JAMA. 1998 Jul 22-29;280(4):347-55 - PubMed
  76. Clin Exp Immunol. 2010 Dec;162(3):438-46 - PubMed
  77. J Clin Endocrinol Metab. 2010 Mar;95(3):1333-7 - PubMed
  78. Eur J Endocrinol. 2009 Jan;160(1):1-8 - PubMed
  79. J Clin Endocrinol Metab. 2007 Jun;92(6):2182-9 - PubMed
  80. J Endocrinol Invest. 2016 Oct;39(10):1105-14 - PubMed
  81. Eur J Endocrinol. 2002 Nov;147(5):583-9 - PubMed
  82. J Intern Med. 1995 Dec;238(6):491-7 - PubMed
  83. Eur Thyroid J. 2015 Mar;4(1):3-5 - PubMed
  84. Acta Endocrinol (Copenh). 1992 Feb;126(2):128-31 - PubMed
  85. N Engl J Med. 1992 Jun 25;326(26):1733-8 - PubMed
  86. Eur J Endocrinol. 2008 Jan;158(1):69-75 - PubMed
  87. Clin Endocrinol (Oxf). 1999 Oct;51(4):503-8 - PubMed
  88. Best Pract Res Clin Endocrinol Metab. 2012 Jun;26(3):291-302 - PubMed
  89. Eur J Endocrinol. 2006 May;154(5):623-32 - PubMed
  90. Thyroid. 1992 Summer;2(2):155-9 - PubMed
  91. J Clin Endocrinol Metab. 2012 Jan;97(1):110-9 - PubMed
  92. J Clin Endocrinol Metab. 2014 May;99(5):1648-55 - PubMed
  93. J Clin Endocrinol Metab. 2017 Jan 1;102(1):6-9 - PubMed
  94. Thyroid. 2015 Feb;25(2):169-75 - PubMed
  95. J Pediatr Endocrinol Metab. 2016 Mar;29(3):319-25 - PubMed
  96. Nat Rev Endocrinol. 2013 Dec;9(12):724-34 - PubMed
  97. Br J Clin Pharmacol. 2014 Sep;78(3):619-29 - PubMed
  98. South Med J. 1995 Sep;88(9):973-6 - PubMed
  99. Autoimmunity. 2018 Mar;51(2):62-68 - PubMed
  100. Thyroid. 2016 Aug;26(8):1144-5 - PubMed
  101. J Endocrinol Invest. 2015 Jul;38(7):769-77 - PubMed
  102. Endocr J. 2016 Dec 30;63(12):1025-1064 - PubMed
  103. J Clin Endocrinol Metab. 2015 Mar;100(3):1164-71 - PubMed
  104. Eur J Endocrinol. 2017 Aug;177(2):R59-R67 - PubMed
  105. Thyroid. 2015 Dec;25(12):1282-90 - PubMed
  106. J Clin Endocrinol Metab. 1982 Jul;55(1):108-12 - PubMed
  107. Thyroid. 2011 Jun;21(6):585-91 - PubMed
  108. Autoimmun Rev. 2012 Dec;12(2):107-13 - PubMed
  109. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62 - PubMed
  110. J Clin Endocrinol Metab. 2008 Mar;93(3):666-73 - PubMed
  111. J Clin Endocrinol Metab. 2013 Dec;98(12):4776-83 - PubMed
  112. J Clin Endocrinol Metab. 2016 Apr;101(4):1606-14 - PubMed
  113. N Engl J Med. 2016 Oct 20;375(16):1552-1565 - PubMed
  114. Arch Intern Med. 2000 Mar 13;160(5):661-6 - PubMed
  115. Am J Manag Care. 2012 Jan 01;18(1):e1-14 - PubMed
  116. Endocr Rev. 2005 Aug;26(5):704-28 - PubMed
  117. Thyroid. 2014 Oct;24(10):1515-23 - PubMed
  118. Thyroid. 2016 May;26(5):627-33 - PubMed
  119. N Engl J Med. 1984 Aug 16;311(7):426-32 - PubMed
  120. Endocr Rev. 1998 Dec;19(6):673-716 - PubMed
  121. Eur J Endocrinol. 2003 Dec;149(6):485-92 - PubMed
  122. Circulation. 2012 Aug 28;126(9):1040-9 - PubMed
  123. J Am Coll Surg. 2009 Aug;209(2):170-179.e1-2 - PubMed
  124. J Clin Endocrinol Metab. 2013 Nov;98(11):4373-81 - PubMed
  125. J Clin Endocrinol Metab. 2002 Mar;87(3):1073-7 - PubMed
  126. Eur Thyroid J. 2015 Mar;4(1):14-9 - PubMed
  127. Thyroid. 2011 Sep;21(9):951-6 - PubMed
  128. N Engl J Med. 2009 Apr 9;360(15):1574-5 - PubMed
  129. Clin Endocrinol (Oxf). 2004 Nov;61(5):589-94 - PubMed
  130. J Clin Endocrinol Metab. 2003 Aug;88(8):3474-81 - PubMed
  131. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2301-2309 - PubMed
  132. Ann Surg. 1998 Sep;228(3):320-30 - PubMed
  133. Eur J Endocrinol. 2017 Jan;176(1):87-97 - PubMed
  134. Ophthalmology. 2011 Nov;118(11):2279-85 - PubMed
  135. J Clin Endocrinol Metab. 2010 May;95(5):2227-33 - PubMed
  136. Clin Endocrinol (Oxf). 2014 May;80(5):629-32 - PubMed
  137. Thyroid. 2006 Jun;16(6):593-8 - PubMed
  138. Br J Surg. 2014 Mar;101(4):307-20 - PubMed
  139. J Clin Endocrinol Metab. 2004 Sep;89(9):4439-44 - PubMed
  140. Lancet. 1999 Nov 13;354(9191):1691-5 - PubMed
  141. J Clin Endocrinol Metab. 2012 Jul;97(7):E1080-7 - PubMed
  142. J Clin Endocrinol Metab. 2012 Dec;97(12):4549-58 - PubMed
  143. J Endocrinol Invest. 2016 Oct;39(10):1159-65 - PubMed
  144. AJR Am J Roentgenol. 1988 Apr;150(4):781-4 - PubMed
  145. N Engl J Med. 2009 Mar 5;360(10):994-1001 - PubMed
  146. Thyroid. 2016 Jun;26(6):765-9 - PubMed
  147. Endocr Pract. 2011 May-Jun;17(3):456-520 - PubMed
  148. N Engl J Med. 1981 Nov 26;305(22):1323-6 - PubMed
  149. Arch Intern Med. 2012 May 28;172(10):799-809 - PubMed
  150. Endocr Rev. 2010 Oct;31(5):702-55 - PubMed
  151. Eur J Endocrinol. 2014 Jul;171(1):R13-20 - PubMed
  152. N Engl J Med. 2011 May 19;364(20):1920-31 - PubMed
  153. Clin Endocrinol (Oxf). 2013 May;78(5):768-76 - PubMed
  154. J Clin Endocrinol Metab. 2009 Oct;94(10):3700-7 - PubMed
  155. Eur J Endocrinol. 2016 Dec;175(6):595-603 - PubMed
  156. Medicine (Baltimore). 2005 Mar;84(2):98-106 - PubMed
  157. Clin Exp Immunol. 2013 Sep;173(3):390-7 - PubMed
  158. J Clin Endocrinol Metab. 1996 Aug;81(8):2986-93 - PubMed
  159. Endocr Rev. 2012 Dec;33(6):920-80 - PubMed
  160. Ann Surg Oncol. 2013 Feb;20(2):660-7 - PubMed
  161. J Clin Endocrinol Metab. 2005 Sep;90(9):5321-3 - PubMed
  162. J Endocrinol Invest. 2015 Apr;38(4):481-7 - PubMed

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