PDF herunterladen
Exp Clin Endocrinol Diabetes 2010; 118(10): 678-684
DOI: 10.1055/s-0030-1253420
Review

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Medical Treatment of Hyperthyroidism: State of the Art

A. Fumarola1 , A. Di Fiore1 , M. Dainelli1 , G. Grani1 , A. Calvanese1
  • 1Dipartimento di Medicina Sperimentale, UOC Endocrinologia A, “Sapienza” Universitá di Roma, Rome, Italy
Weitere Informationen

Publikationsverlauf

received 30.11.2009 first decision 21.01.2010

accepted 15.02.2010

Publikationsdatum:
21. Mai 2010 (online)

Auch verfügbar auf
   Lizenzen und Reprints
Preview

Abstract

Methimazole (MMI) and propylthiouracil (PTU) are the main antithyroid drugs used for hyperthyroidism. They inhibit the synthesis of thyroid hormone at various levels and are used as the primary treatment for hyperthyroidism or as a preparation before radioiodine therapy or thyroidectomy. MMI is the drug of choice because of its widespread availability, longer half-life and small number of severe side effects. Drugs of second choice are potassium perchlorate, beta blockers, iodine, lithium carbonate and glucocorticoids. Rituximab, a monoclonal antibody directed against human CD20, was recently proposed as a biological therapy for cases of Graves’ disease unresponsive to traditional drugs.

Key words

Hyperthyroidism - Graves' disease - Thionamides

References

  • 1 Abraham P, Avenell A, Park CM. et al . A systematic review of drug therapy for Graves’ hyperthyroidism.  Eur J Endocrinol. 2005;  153 489-498
    Suche in Google Scholar
  • 2 Allannic H, Fauchet R, Orgiazzi J. et al . Antithyroid drugs and Graves’ disease: a prospective randomized evaluation of the efficacy of treatment duration.  J Clin Endocrinol Metab. 1990;  70 675-679
    Suche in Google Scholar
  • 3 Andersohn F, Konzen C, Garbe E. Systematic Review: Agranulocytosis Induced by Nonchemotherapy Drugs.  Ann Intern Med. 2007;  146 657-665
    Suche in Google Scholar
  • 4 Arnold DM, Dentali F, Crowther MA. et al . Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura.  Ann Intern Med. 2007;  146 25-33
    Suche in Google Scholar
  • 5 Bahn RS, Burch HS, Cooper DS. et al . The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration.  Thyroid. 2009;  19 (7) 673-674
    Suche in Google Scholar
  • 6 Bandyopadhyay U, Biswas K, Banerjee RK. Extrathyroidal actions of antithyroid thionamides.  Toxicol Lett. 2002;  128 117-127
    Suche in Google Scholar
  • 7 Bauch K. Epidemiology of functional autonomy.  Exp Clin Endocrinol Diabetes. 1998;  106 S16-S22
    Suche in Google Scholar
  • 8 Berkman EM, Orlin JB, Wolfsdorf J. An anti-neutrophil antibody associated with a propylthiouracil-induced lupus-like syndrome.  Transfusion. 1983;  23 135-138
    Suche in Google Scholar
  • 9 Bonnema SJ, Bennedbaek FN, Gram J. et al . Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomised clinical trial.  Eur J Endocrinol. 2003;  149 485-492
    Suche in Google Scholar
  • 10 Boye J, Elter T, Engert A. An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab.  Ann Oncol. 2003;  14 520-535
    Suche in Google Scholar
  • 11 Burch HB, Solomon BL, Cooper DS. et al . The effect of antithyroid drug pre-treatment on acute changes in thyroid hormone levels after 131I ablation for Graves’ disease.  J Clin Endocrinol Metab. 2001;  86 3016-3021
    Suche in Google Scholar
  • 12 Byrd JC, White CA, Link B. et al . Rituximab therapy in Waldenstrom's macroglobulinemia: preliminary evidence of clinical activity.  Ann Oncol. 1999;  10 1525-1527
    Suche in Google Scholar
  • 13 Carr DR, Heffernan MP. Off-label uses of rituximab in dermatology.  Dermatol Ther. 2007;  20 277-287
    Suche in Google Scholar
  • 14 Carson KR, Focosi D, Major EO. et al . Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project.  Lancet Oncol. 2009;  10 816-824
    Suche in Google Scholar
  • 15 Chiovato L, Fiore E, Vitti P. et al . Outcome of thyroid function in Graves’ patients treated with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced thyroid damage.  J Clin Endocrinol Metab. 1998;  83 40-46
    Suche in Google Scholar
  • 16 Cooper DS, Goldminz D, Levin AA. et al . Agranulocytosis associated with antithyroid drugs. Effects of patient age and drug dose.  Ann Intern Med. 1983;  98 26-29
    Suche in Google Scholar
  • 17 Cooper DS, Rivkees SA. Putting propylthiouracil in perspective.  J Clin Endocrinol Metab. 2009;  94 (6) 1881-1882
    Suche in Google Scholar
  • 18 Cooper DS. Antithyroid Drugs in the Management of Patients with Graves’ Disease: An Evidence-Based Approach to Therapeutic Controversies.  J Clin Endocrinol Metab. 2003;  88 3474-3481
    Suche in Google Scholar
  • 19 Cooper DS. Antithyroid drugs.  N Engl J Med. 2005;  352 905-917
    Suche in Google Scholar
  • 20 Cooper DS. The side-effects of antithyroid drugs.  Endocrinologist. 1999;  9 457-467
    Suche in Google Scholar
  • 21 D’Arcy CA, Mannik M. Serum sickness secondary to treatment with the murine-human chimeric antibody IDEC-C2B8 (rituximab).  Arthritis Rheum. 2001;  44 1717-1718
    Suche in Google Scholar
  • 22 Dasgupta S, Savage MW. Evaluation of management of Graves’ disease in District General Hospital: achievement of consensus guidelines.  Int J Clin Pract. 2005;  59 1097-1100
    Suche in Google Scholar
  • 23 Dass S, Vital EM, Emery P. Development of psoriasis after B cell depletion with rituximab.  Arthritis Rheum. 2007;  56 2715-2718
    Suche in Google Scholar
  • 24 El Fassi D, Banga JP, Gilbert JA. et al . Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies.  Clin Immunol. 2009;  130 252-258
    Suche in Google Scholar
  • 25 El Fassi D, Clemmensen O, Nielsen CH. et al . Evidence of intrathyroidal B-lymphocyte depletion after rituximab therapy in a patient with Graves' disease.  J Clin Endocrinol Metab. 2007;  92 3762-3763
    Suche in Google Scholar
  • 26 El Fassi D, Nielsen CH, Hasselbalch HC. et al . The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option.  Eur J Endocrinol. 2006;  154 623-632
    Suche in Google Scholar
  • 27 El Fassi D, Nielsen CH, Kjeldsen J. et al . Ulcerative colitis following B lymphocyte depletion with rituximab in a patient with Graves’ disease.  Gut. 2008;  57 714-715
    Suche in Google Scholar
  • 28 Fibbe WE, Claas FHJ, Van der Star-Dijkstra W. et al . Agranulocytosis induced by propylthiouracil: evidence of a drug dependent antibody reacting with granulocytes, monocytes and haematopoietic progenitor cells.  Br J Haematol. 1986;  64 363-373
    Suche in Google Scholar
  • 29 Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review.  Crit Rev Oncol Hematol. 2007;  63 47-52
    Suche in Google Scholar
  • 30 Garcia-Mayor RVG, Paramo C, Luna-Cano R. et al . Antithyroid drug and Graves’ hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission.  J Endocrinol Invest. 1992;  15 815-820
    Suche in Google Scholar
  • 31 Goetz M, Atreya R, Ghalibafian M. et al . Exacerbation of ulcerative colitis after rituximab salvage therapy.  Inflamm Bowel Dis. 2007;  13 1365-1368
    Suche in Google Scholar
  • 32 Gunton JE, Stiel J, Clifton-Bligh P. et al . Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication.  Eur J Endocrinol.. 2000;  142 (6) 587
    Suche in Google Scholar
  • 33 Heemstra KA, Toes RE, Sepers J. et al . Rituximab in relapsing Graves’ disease, a phase II study.  Eur J Endocrinol. 2008;  159 609-615
    Suche in Google Scholar
  • 34 Homsanit M, Sriussadaporn S, Vannasaeng S. et al . Efficacy of single the daily dosage of Methimazole vs. Propylthiuracil in the induction of euthyroidism.  Clin Endocrinol (Oxf). 2001;  54 385-390
    Suche in Google Scholar
  • 35 Iagaru A, McDougall R. Treatment of Thyrotoxicosis.  J Nucl Med. 2007;  48 379-389
    Suche in Google Scholar
  • 36 Koenig RJ. Regulation of type 1 iodothyronine deiodinase in health and disease.  Thyroid. 2005;  15 835-840
    Suche in Google Scholar
  • 37 Koornstra JJ, Kerstens MN, Hoving J. et al . Clinical and biochemical changes following 131I teraphy for hyperthyroidism in patients not pretreatred with antithyroid drugs.  Neth J Med. 1999;  55 215-221
    Suche in Google Scholar
  • 38 Kuehn BM. FDA focuses on drugs and liver damage: labeling and other changes for acetaminophen.  JAMA. 2009;  302 (4) 369-371
    Suche in Google Scholar
  • 39 Maugendre D, Gatel A, Campion L. et al . Antithyroid drugs and Graves’ disease–prospective randomized assessment of long-term treatment.  Clin Endocrinol (Oxf). 1999;  50 127-132
    Suche in Google Scholar
  • 40 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;  31 866-872
    Suche in Google Scholar
  • 41 McDermott MT, Kidd GS, Dodson Jr LE. et al . Radioiodine-induced thyroid storm. Case report and literature review.  Am J Med. 1983;  75 353-359
    Suche in Google Scholar
  • 42 McLaughlin P, Grillo-López AJ, Link BK. et al . Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.  J Clin Oncol. 1998;  16 2825-2833
    Suche in Google Scholar
  • 43 Mitsiades N, Poulaki V, Tseleni-Balafouta S. et al . Fas ligand expression in thyroid follicular cells from patients with thionamide-treated Graves’ disease.  Thyroid. 2000;  10 527-532
    Suche in Google Scholar
  • 44 Moriyama K, Tagami T, Usui T. et al . Antithyroid Drugs Inhibit Thyroid Hormone Receptor-Mediated Transcription.  J Clin Endocrinol Metab. 2007;  92 1066-1072
    Suche in Google Scholar
  • 45 Nakamura H, Noh JY, Itoh K. et al . Comparison of Methimazole and Propylthiouracil in Patient with Hyperthyroidism Caused by Graves’ Disease.  J Clin Endocrinol Metab. 2007;  92 2157-2162
    Suche in Google Scholar
  • 46 Nayak B, Burman K. Thyrotoxicosis and thyroid storm.  Endocrinol Metab Clin North Am. 2006;  35 663-686
    Suche in Google Scholar
  • 47 Noh JY, Asari T, Hamada N. et al . Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves’ disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations.  Clin Endocrinol (Oxf). 2001 May;  54 (5) 651-654
    Suche in Google Scholar
  • 48 Okamura K, Ikenoue H, Shiroozu A. et al . Reevaluation of the effects of methylmercaptoimidazole and propylthiouracil in patients with Graves’ hyperthyroidism.  J Clin Endocrinol Metab. 1987;  65 719-723
    Suche in Google Scholar
  • 49 Papadakis KA, Rosenbloom B, Targan SR. Anti-CD20 chimeric monoclonal antibody (rituximab) treatment of immune-mediated thrombocytopenia associated with Crohn's disease.  Gastroenterology. 2003;  124 583
    Suche in Google Scholar
  • 50 Pearce EN, Braderman LE. Hyperthyroidism: advantages and disadvantages of medical therapy.  Surg Clin North Am. 2004;  84 833-847
    Suche in Google Scholar
  • 51 Pearce EN. Diagnosis and management of thyrotoxicosis.  BMJ. 2006;  332 1369-1373
    Suche in Google Scholar
  • 52 Ram R, Bonstein L, Gafter-Gvili A. et al . Rituximab-associated acute thrombocytopenia: an under-diagnosed phenomenon.  Am J Hematol. 2009;  84 247-250
    Suche in Google Scholar
  • 53 Reinwein D, Benker G, Lazarus GH. A prospective randomised trial of antithyroid drugs dose in Graves’ disease therapy.  J Clin Endocrinol Metab. 1993;  76 1516-1521
    Suche in Google Scholar
  • 54 Rodien P. Rituximab in Graves’ disease.  Eur J Endocrinol. 2008;  159 515-516
    Suche in Google Scholar
  • 55 Roy G, Mugesh G. Bioinorganic chemistry in thyroid gland: effect of antithyroid drugs on peroxidase-catalyzed oxidation and iodination reactions.  Bioinorg Chem Appl. 2006;  23214
    Suche in Google Scholar
  • 56 Salvi M, Vannucchi G, Campi I. et al . Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study.  Eur J Endocrinol. 2007;  156 33-40
    Suche in Google Scholar
  • 57 Smolen JS, Keystone EC, Emery P. et al . Consensus statement on the use of rituximab in patients with rheumatoid arthritis.  Ann Rheum Dis. 2007;  66 143-150
    Suche in Google Scholar
  • 58 Streetman DD, Khanderia U. Diagnosis and Treatment of Graves’ disease.  Ann Pharmacother. 2003;  37 1100-1109
    Suche in Google Scholar
  • 59 Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis.  Thyroid. 2004;  14 459-462
    Suche in Google Scholar
  • 60 Takagi S, Hummel BC, Walfish PG. Thionamides and arsenite inhibit specific T3 binding to the hepatic nuclear receptor.  Biochem Cell Biol.. 1990;  68 616-621
    Suche in Google Scholar
  • 61 Thatayatikom A, White AJ. Rituximab: a promising therapy in systemic lupus erythematosus.  Autoimmun Rev. 2006;  5 18-24
    Suche in Google Scholar
  • 62 Toth EL, Mant MJ, Shivji S. et al . Propylthiouracil-induced agranulocytosis: an unusual presentation and a possible mechanism.  Am J Med. 1988;  85 725-727
    Suche in Google Scholar
  • 63 Treon SP, Pilarski LM, Belch AR. et al . CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications.  J Immunother. 2002;  25 72-81
    Suche in Google Scholar
  • 64 Volpe R. The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: a review.  Curr Pharm Des. 2001;  7 451-460
    Suche in Google Scholar
  • 65 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;  334 514-520
    Suche in Google Scholar
  • 66 Wang PW, Luo SF, Huang BY. et al . Depressed natural killer activity in Graves’ disease and during antithyroid medication.  Clin Endocrinol (Oxf). 1988;  28 205-214
    Suche in Google Scholar
  • 67 Weetman AP, Pickerill AP, Watson P. et al . Treatment of Graves’ disease with the block-replace regimen of antithyroid drugs: the effect of treatment duration and immunogenetic susceptibility on relapse.  Q J Med. 1994;  87 337-341
    Suche in Google Scholar
  • 68 Zantut-Wittmann DE, Tambascia MA, da Silva Trevisan MA. et al . Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells in Graves’ disease.  Thyroid. 2001;  11 575-580
    Suche in Google Scholar

Correspondence

Prof. A. Fumarola

Dept. of Experimental Medicine

Sapienza Universitá di Roma

V. le Regina Elena, 324

00161 Rome

Italy

Telefon: + 39/06/4997 2094

Telefon: + 39/06/4997 2586

eMail: angela.fumarola@uniroma1.it