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Review

Graves’ disease: developments in first-line antithyroid drugs in the young

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Pages 59-69 | Received 09 Oct 2019, Accepted 24 Feb 2020, Published online: 05 Mar 2020

References

  • Williamson S, Greene SA. Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clin Endocrinol (Oxf). 2010;72(3):358–363.
  • Rodanaki M, Lodefalk M, Forssell K, et al. The incidence of childhood thyrotoxicosis is increasing in both girls and boys in Sweden. Horm Res Paediatr. 2019;91(3):195–202.
  • Wong GW, Cheng PS. Increasing incidence of childhood Graves’ disease in Hong Kong: a follow-up study. Clin Endocrinol (Oxf). 2001;54(4):547–550.
  • Havgaard Kjær R, Smedegård Andersen M, Hansen D. Increasing incidence of juvenile thyrotoxicosis in Denmark: a nationwide study, 1998–2012. Horm Res Paediatr. 2015;84(2):102–107.
  • Rabon S, Burton AM, White PC. Graves’ disease in children: long-term outcomes of medical therapy. Clin Endocrinol (Oxf). 2016;85(4):632–635.
  • Kaguelidou F, Carel JC, Léger J. Graves’ disease in childhood: advances in management with antithyroid drug therapy. Horm Res Paediatr. 2009;71(6):310–317.
  • Kaguelidou F, Alberti C, Castanet M, et al. Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab. 2008;93(10):3817–3826.
  • Smith J, Brown RS. Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves’ disease treated using antithyroid medication. Thyroid. 2007;17(11):1103–1107.
  • Sohal AP, Dasarathi M, Lodh R, et al. Speech and language delay in two children: an unusual presentation of hyperthyroidism. J Pediatr Endocrinol Metab. 2013;26(11–12):1171–1174.
  • Bauer AJ. Approach to the pediatric patient with Graves’ disease: when is definitive therapy warranted? J Clin Endocrinol Metab. 2011;96(3):580–588.
  • Segni M, Leonardi E, Mazzoncini B, et al. Special features of Graves’ disease in early childhood. Thyroid. 1999;9(9):871–877.
  • Rivkees SA. Controversies in the management of Graves’ disease in children. J Endocrinol Invest. 2016;39(11):1247–1257.
  • Manna D, Roy G, Mugesh G. Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action. Acc Chem Res. 2013;46(11):2706–2715.
  • Taurog A. The mechanism of action of the thioureylene antithyroid drugs. Endocrinology. 1976;98(4):1031–1046.
  • Engler H, Taurog A, Dorris ML. Preferential inhibition of thyroxine and 3,5,3ʹ-triiodothyronine formation by propylthiouracil and methylmercaptoimidazole in thyroid peroxidase-catalyzed iodination of thyroglobulin. Endocrinology. 1982;110(1):190–197.
  • Monaco F, Santolamazza C, De Ros I, et al. Effects of propylthiouracil and methylmercaptoimidazole on thyroglobulin synthesis. Acta endocrinologica. 1980;93(1):32–36.
  • Kuiper GG, Kester MH, Peeters RP, et al. Biochemical mechanisms of thyroid hormone deiodination. Thyroid. 2005;15(8):787–798.
  • Rapoport B, McLachlan SM. Graves’ hyperthyroidism is antibody-mediated but is predominantly a Th1-type cytokine disease. J Clin Endocrinol Metab. 2014 Nov;99(11):4060–4061.
  • Inukai Y, Momobayashi A, Sugawara N, et al. Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves’ disease. Eur J Endocrinol. 2007 June;156(6):623–630.
  • Weetman AP, McGregor AM, Hall R. Methimazole inhibits thyroid autoantibody production by an action on accessory cells. Clin Immunol Immunopathol. 1983;28(1):39–45.
  • Totterman TH, Karlsson FA, Bengtsson M, et al. Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves’ disease. N Engl J Med. 1987;316(1):15–22.
  • Codaccioni JL, Orgiazzi J, Blanc P, et al. Lasting remissions in patients treated for Graves’ hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease. J Clin Endocrinol Metab. 1988;67(4):656–662.
  • Marcocci C, Leo M, Altea MA. Oxidative stress in graves’ disease. Eur Thyroid J. 2012;1(2):80–87.
  • Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011;364:1920–1931.
  • Imamura M, Aoki N, Saito T, et al. Inhibitory effects of antithyroid drugs on oxygen radical formation in human neutrophils. Acta Endocrinol. 1986;112:210–216.
  • Weetman AP, Holt ME, Campbell AK, et al. Methimazole and generation of oxygen radicals by monocytes: potential role in immunosuppression. Br Med J (Clin Res Ed). 1984;288:518–520.
  • Kim H, Lee TH, Hwang YS, et al. Molecular pharmacology: methimazole as an antioxidant and immunomodulator in thyroid cells: mechanisms involving interferon-gamma signaling and H(2)O(2) scavenging. Am Soc Pharmacol Exp Ther. 2001;60:972–980.
  • Bartalena L, Burch HB, Burman KD, et al. A 2013 European survey of clinical practice patterns in the management of Graves’ disease. Clin Endocrinol (Oxf). 2016;84(1):115–120.
  • Rotondo Dottore G, Leo M, Casini G, et al. Antioxidant actions of selenium in orbital fibroblasts: a basis for the effects of selenium in Graves’ orbitopathy. Thyroid. 2017;27(2):271–278.
  • Kahaly GJ, Riedl M, Konig J, et al. Double-blind, placebo-controlled, randomized trial of selenium in Graves hyperthyroidism. J Clin Endocrinol Metab. 2017;102(11):4333–4341.
  • Winther KH, Bonnema SJ, Hegedus L. Is selenium supplementation in autoimmune thyroid diseases justified? Curr Opin Endocrinol Diabetes. 2017;24(5):348–355.
  • Ohye H, Minagawa A, Noh JY, et al. Antithyroid drug treatment for Graves’ disease in children: a long-term retrospective study at a single institution. Thyroid. 2014;24(2):200–207.
  • Lazar L, Kalter-Leibovici O, Pertzelan A, et al. Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients. J Clin Endocrinol Metab. 2000;85(10):3678–3682.
  • Sundaresh V, Brito JP, Thapa P, et al. Comparative effectiveness of treatment choices for Graves’ hyperthyroidism: a historical cohort study. Thyroid. 2017;27(4):497–505.
  • Kahaly GJ, Bartalena L, Hegedus L, et al. European thyroid association guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J. 2018;7(4):167–186.
  • Ross DS, Burch HB, Cooper DS, et al. American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–1421.
  • Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905–917.
  • Nakamura H, Miyauchi A, Miyawaki N, et al. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab. 2013;98(12):4776–4783.
  • Pearce SH. Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK. Clin Endocrinol (Oxf). 2004;61(5):589–594.
  • Mutharasan P, Oatis W, Kwaan H, et al. Delayed anithyroid drug-induced agranulocytosis. Endocr Pract. 2012;18(4):e69–72.
  • Lawrence N, Cheetham T, Elder C. How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey. Clin Endocrinol (Oxf). 2019;91:417–423.
  • Vicente N, Cardoso L, Barros L, et al. Antithyroid drug-induced agranulocytosis: state of the art on diagnosis and management. Drugs R D. 2017;17(1):91–96.
  • Andres E, Zimmer J, Mecili M, et al. Clinical presentation and management of drug-induced agranulocytosis. Expert Rev Hematol. 2011;4(2):143–151.
  • Chen PL, Shih SR, Wang PW, et al. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun. 2015;6:7633.
  • Cl C, Cw S, Cs T, et al. HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis. Clin Pharmacol Ther. 2016;99(5):555–561.
  • Hallberg P, Eriksson N, Ibanez L, et al. Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol. 2016;4(6):507–516.
  • Plantinga TS, Arts P, Knarren GH, et al. Rare NOX3 variants confer susceptibility to agranulocytosis during thyrostatic treatment of Graves’ disease. Clin Pharmacol Ther. 2017;102(6):1017–1024.
  • Rivkees SA, Mattison DR. Propylthiouracil (PTU) hepatoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol. 2009;2009:132041.
  • Rivkees SA, Szarfman A. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab. 2010;95(7):3260–3267.
  • Russo MW, Galanko JA, Shrestha R, et al. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 2004;10(8):1018–1023.
  • Paediatric Formulary Committee. BNF for Children (online). London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2019 Sept 05. Available from: http://www.medicinescomplete.com
  • Nakamura H, Noh JY, Itoh K, et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab. 2007;92(6):2157–2162.
  • Andersen SL, Olsen J, Laurberg P. Antithyroid drug side effects in the population and in pregnancy. J Clin Endocrinol Metab. 2016 Apr;101(4):1606–1614.
  • Laurberg P, Andersen SL. Antithyroid drug use in pregnancy and birth defects: why some studies find clear associations, and some studies report none. Thyroid. 2015 Nov;25(11):1185–1190.
  • Song R, Lin H, Chen Y, et al. Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: a meta-analysis. PloS One. 2017;12(7):e0180108.
  • Kourime M, McGowan S, Al Towati M, et al. Long-term outcome of thyrotoxicosis in childhood and adolescence in the west of Scotland: the case for long-term antithyroid treatment and the importance of initial counselling. Arch Dis Child. 2018;103(7):637.
  • Abraham P, Avenell A, McGeoch SC, et al. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. 2010;1:Cd003420.
  • Reinwein D, Benker G, Lazarus JH, et al. A prospective randomized trial of antithyroid drug dose in Graves’ disease therapy. European multicenter study group on antithyroid drug treatment. J Clin Endocrinol Metab. 1993;76(6):1516–1521.
  • Vaidya B, Wright A, Shuttleworth J, et al. Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves’ disease: a retrospective observational study. Clin Endocrinol (Oxf). 2014;81(4):610–613.
  • Raza J, Hindmarsh PC, Brook CG. Thyrotoxicosis in children: thirty years’ experience. Acta Paediatrica. 1999;88(9):937–941.
  • Mathew RP, Moore DJ. Autoimmune alternating hypo- and hyperthyroidism in children. Clin Pediatr (Phila). 2011;50(11):1040–1044.
  • Martins LC, Coutinho AR, Jerónimo M, et al. Autoimmune alternating hyper- and hypo-thyroidism: a rare condition in pediatrics. Endocrinol Diabetes Metab Case Rep. 2016;2016:150131.
  • Razvi S, Vaidya B, Perros P, et al. What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves’ disease. Eur J Endocrinol. 2006;154(6):783–786.
  • Wang MT, Lee WJ, Huang TY, et al. Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study. Br J Clin Pharmacol. 2014;78(3):619–629.
  • Takata K, Kubota S, Fukata S, et al. Methimazole-induced agranulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid. 2009;19(6):559–563.
  • Huang MJ, Liaw YF. Clinical associations between thyroid and liver diseases. J Gastroenterol Hepatol. 1995;10(3):344–350.
  • Aggarwal N, Tee SA, Saqib W, et al. Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves’ disease. Clin Endocrinol (Oxf). 2016;85(6):949–953.
  • Leger J, Carel JC. Management of endocrine disease: arguments for the prolonged use of antithyroid drugs in children with Graves’ disease. Eur J Endocrinol. 2017;177(2):R59–r67.
  • Leger J, Gelwane G, Kaguelidou F, et al. Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves’ disease: national long-term cohort study. J Clin Endocrinol Metab. 2012;97(1):110–119.
  • Lippe BM, Landaw EM, Kaplan SA. Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years. J Clin Endocrinol Metab. 1987;64(6):1241–1245.
  • Glaser NS, Styne DM. Predictors of early remission of hyperthyroidism in children. J Clin Endocrinol Metab. 1997;82(6):1719–1726.
  • Hamburger J. Management of hyperthyroidism in children and adolescents. J Clin Endocrinol Metab. 1985;60(5):1019–1024.
  • Laurberg P. Remission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol. 2006;155(6):783–786.
  • Rotondi M, Chiovato L, Romagnani S, et al. Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 2007;28(5):492–520.
  • Mazza E, Carlini M, Flecchia D, et al. Long-term follow-up of patients with hyperthyroidism due to Graves’ disease treated with methimazole. Comparison of usual treatment schedule with drug discontinuation vs continuous treatment with low methimazole doses: a retrospective study. J Endocrinol Invest. 2008;31(10):866–872.
  • Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest. 2013;123(3):958–965.
  • Sjolin G, Holmberg M, Torring O, et al. The long-term outcome of treatment for Graves’ hyperthyroidism. Thyroid. 2019 Nov;29(11):1545–1557.
  • Tajiri J, Noguchi S, Murakami T, et al. Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. Arch Intern Med. 1990;150(3):621–624.
  • van Veenendaal NR, Rivkees SA. Treatment of pediatric Graves’ disease is associated with excessive weight gain. J Clin Endocrinol Metab. 2011;96(10):3257–3263.
  • Krassas GE, Segni M, Wiersinga WM. Childhood Graves’ ophthalmopathy: results of a European questionnaire study. Eur J Endocrinol. 2005 Oct;153(4):515–521.
  • Jankauskiene J, Jarusaitiene D. The influence of juvenile graves’ ophthalmopathy on Graves’ disease course. J Ophthalmol. 2017;2017:4853905.
  • Diana T, Brown RS, Bossowski A, et al. Clinical relevance of thyroid-stimulating autoantibodies in pediatric graves’ disease-a multicenter study. J Clin Endocrinol Metab. 2014 May;99(5):1648–1655.
  • Leger J, Kaguelidou F, Alberti C, et al. Graves’ disease in children. Best Pract Res Clin Endocrinol Metab. 2014;28(2):233–243.
  • Shulman DI, Muhar I, Jorgensen EV, et al. Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and responses to medical therapy. Thyroid. 1997;7(5):755–760.
  • Glaser NS, Styne DM. Predicting the likelihood of remission in children with Graves’ disease: a prospective, multicenter study. Pediatrics. 2008;121(3):e481–8.
  • Gastaldi R, Poggi E, Mussa A, et al. Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers. J Pediatr. 2014;164(5):1189–1194.e1.
  • Jevalikar G, Solis J, Zacharin M. Long-term outcomes of pediatric Graves’ disease. J Pediatr Endocrinol Metab. 2014;27(11–12):1131–1136.
  • Kuś A, Radziszewski M, Glina A, et al. Paediatric-onset and adult-onset Graves’ disease share multiple genetic risk factors. Clin Endocrinol (Oxf). 2019;90(2):320–327.
  • Kuś A, Szymanski K, Peeters RP, et al. The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves’ disease. Clin Endocrinol (Oxf). 2015 Oct;83(4):556–562.
  • Vos XG, Wiersinga WM, Endert E, et al. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with Graves’ hyperthyroidism. J Clin Endocrinol Metab. 2016;101(4):1381–1389.
  • Wang PW, Chen IY, Juo SH, et al. Genotype and phenotype predictors of relapse of graves’ disease after antithyroid drug withdrawal. Eur Thyroid J. 2013;1(4):251–258.
  • Hayashi M, Kouki T, Takasu N, et al. Association of an A/C single nucleotide polymorphism in programmed cell death-ligand 1 gene with Graves’ disease in Japanese patients. Eur J Endocrinol. 2008;158(6):817–822.
  • Glowacka D, Loesch C, Johnson KT, et al. The T393C polymorphism of the Galphas gene (GNAS1) is associated with the course of Graves’ disease. Horm Metab Res. 2009;41(6):430–435.
  • Struja T, Kaeslin M, Boesiger F, et al. External validation of the GREAT score to predict relapse risk in Graves’ disease: results from a multicenter, retrospective study with 741 patients. Eur J Endocrinol. 2017;176(4):413–419.
  • Segni M. Disorders of the thyroid gland in infancy, childhood and adolescence. In: Feingold KR, Anawalt B, Boyce A, editors. Endotext. South Dartmouth MA: MDText.com, Inc.; 2000.
  • Saravanan P, Chau WF, Roberts N, et al. Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol (Oxf). 2002;57(5):577–585.
  • Samuels MH, Schuff KG, Carlson NE, et al. Health status, psychological symptoms, mood, and cognition in L-thyroxine-treated hypothyroid subjects. Thyroid. 2007;17(3):249–258.
  • Wekking EM, Appelhof BC, Fliers E, et al. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol. 2005;153(6):747–753.
  • Lee JA, Grumbach MM, Clark OH. The optimal treatment for pediatric Graves’ disease is surgery. J Clin Endocrinol Metab. 2007;92(3):801–803.
  • Read CH Jr., Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves’ patients. J Clin Endocrinol Metab. 2004;89(9):4229–4233.
  • Cohen RZ, Felner EI, Heiss KF, et al. Outcomes analysis of radioactive iodine and total thyroidectomy for pediatric Graves’ disease. J Pediatr Endocrinol Metab. 2016;29(3):319–325.
  • Kitahara CM, de Gonzalez AB, Bouville A, et al. Association of radioactive iodine treatment with cancer mortality in patients with hyperthyroidism. JAMA Intern Med. 2019;179(8):1034–1042.
  • Khan SR, Chaker L, Ruiter R, et al. Thyroid function and cancer risk: the rotterdam study. J Clin Endocrinol Metab. 2016;101(12):5030–5036.
  • Dobyns BM, Sheline GE, Workman JB, et al. Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism: a report of the cooperative thyrotoxicosis therapy follow-up study. J Clin Endocrinol Metab. 1974;38(6):976–998.
  • Tallstedt L, Lundell G, Torring O, et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The thyroid study group. N Engl J Med. 1992 June 25;326(26):1733–1738.
  • Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med. 1998;338(2):73–78.
  • Donovan PJ, McLeod DS, Little R, et al. Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves’ disease. Eur J Endocrinol. 2016;175(6):595–603.
  • Nordenström E, Bergenfelz A, Almquist M. Permanent hypoparathyroidism after total thyroidectomy in children: results from a national registry. World J Surg. 2018;42(9):2858–2863.
  • Gschwandtner E, Seemann R, Bures C, et al. How many parathyroid glands can be identified during thyroidectomy? Eur Surg. 2018 Feb 01;50(1):14–21.
  • Okamura K, Sato K, Fujikawa M, et al. Remission after potassium iodide therapy in patients with Graves’ hyperthyroidism exhibiting thionamide-associated side effects. J Clin Endocrinol Metab. 2014;99(11):3995–4002.
  • Uchida T, Goto H, Kasai T, et al. Therapeutic effectiveness of potassium iodine in drug-naive patients with Graves’ disease: a single-center experience. Endocrine. 2014;47(2):506–511.
  • Neumann S, Nir EA, Eliseeva E, et al. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology. 2014;155(1):310–314.
  • Pearce SHS, Dayan C, Wraith DC, et al. Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves’ hyperthyroidism: a phase I study. Thyroid. 2019;29(7):1003–1011.
  • Furmaniak J, Sanders J, Young S, et al. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2011;3(1):19–25.

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