Download PDF
Horm Metab Res 2015; 47(10): 767-772
DOI: 10.1055/s-0035-1555759
Review

Outcome Prediction of Treatment of Graves’ Hyperthyroidism with Antithyroid Drugs

E. Piantanida
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
A. Lai
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
L. Sassi
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
D. Gallo
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
E. Spreafico
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
M. L. Tanda
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
L. Bartalena
1   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Graves’ disease is the most common cause of hyperthyroidism in iodine-replete areas and is ultimately due to antibodies interacting with the TSH receptor on thyroid follicular cells [TSH-receptor antibody (TRAb)]. Antithyroid drugs (ATDs) belonging to the family of thionamides are the first-line treatment in Europe. ATD treatment is commonly continued for 18–24 months. Its major limitation is the high rate of relapses after drug withdrawal. Factors particularly bound to subsequent relapses are the large thyroid volume, smoking habit, persistence of TRAb in the circulation at the end of treatment, and the post-partum period. Under these conditions, consideration should be given to a definitive therapy for hyperthyroidism (radioiodine treatment, thyroidectomy), particularly if the patient is at risk of cardiovascular complications that might be exacerbated by persistence or recurrence of hyperthyroidism.

Key words

Graves’ hyperthyroidism - Graves’ orbitopathy - thionamides - methimazole - TSH-receptor antibody - smoking - goiter


Publication History

Received: 07 April 2015

Accepted: 28 May 2015

Article published online:
21 July 2015

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol 2013; 9: 724-734
    CrossrefPubMedGoogle Scholar
  • 2 Bartalena L, Fatourechi V. Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Invest 2014; 37: 691-700
    CrossrefPubMedGoogle Scholar
  • 3 Bahn RS. Graves’ ophthalmopathy. N Engl J Med 2010; 362: 726-738
    CrossrefPubMedGoogle Scholar
  • 4 Johnson KTM, Wiesweg B, Schott M, Ehlers M, Müller M, Minich WB, Nagayama Y, Gulbins E, Eckstein AK, Berchner-Pfannschmidt U. Examination of orbital tissues in murine models of Graves’ disease reveals expression of UCP-1 and the TSHR in retrobulbar adipose tissues. Horm Metab Res 2013; 45: 401-407
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Wiesweg B, Johnson KTM, Eckstein AK, Berchner-Pfannschmidt U. Current insights into animal models of Graves’ disease and orbitopathy. Horm Metab Res 2013; 45: 549-555
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L. Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 2013; 36: 444-449
    PubMedGoogle Scholar
  • 7 Marinò M, Latrofa F, Menconi F, Chiovato L, Vitti P. An update on the medical treatment of Graves’ hyperthyroidism. J Endocrinol Invest 2014; 37: 1041-1048
    CrossrefPubMedGoogle Scholar
  • 8 Bartalena L, Burch HB, Burman KD, Kahaly GJ. A 2013 European survey of clinical practice patterns in the management of Graves’ disease. Clin Endocrinol (Oxf) 2014; Dec 8 DOI: 10.1111/cen.12688[Epub ahead of print].
    CrossrefPubMedGoogle Scholar
  • 9 Burch HB, Burman KD, Cooper DS. A survey of clinical practice patterns in the management of Graves’ disease. J Clin Endocrinol Metab 2012; 97: 4549-4558
    CrossrefPubMedGoogle Scholar
  • 10 Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore E, Rocchi R, Martino E, Pinchera A. Clinical features of patients with Graves’ disease undergoing remission after antithyroid drug therapy. Thyroid 1997; 3: 369-375
    CrossrefPubMedGoogle Scholar
  • 11 Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SCL, Franklyn JA. Age and gender predict the outcome of treatment for Graves’ hyperthyroidism. J Clin Endocrinol Metab 2000; 85: 1038-1042
    PubMedGoogle Scholar
  • 12 Sundaresh V, Brito JP, Wang Z, Prokop LJ, Stan MN, Mirad MH, Bahn RS. Comparative effectiveness of therapies for Graves’ hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab 2013; 98: 3671-3677
    CrossrefPubMedGoogle Scholar
  • 13 Ohye H, Mainagawa A, Yoshimura Noh J, Mukasa K, Kunji Y, Watanabe N, Matsumoto M, Suzuki M, Yoshihara A, Ito Ko, Ito Ku. Antithyroid drug treatment for Graves’ disease in children: a long-term retrospective study at a single institution. Thyroid 2014; 24: 200-207
    CrossrefPubMedGoogle Scholar
  • 14 Mohlin E, Filipsson Nystrom H, Eliasson M. Long-term prognosis after medical treatment of Graves’ disease in a northern Swedish population 2000-2010. Eur J Endocrinol 2014; 170: 419-427
    CrossrefPubMedGoogle Scholar
  • 15 Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev 2010; DOI: 10.1002/14651858.CD003420.pub4.
    CrossrefPubMedGoogle Scholar
  • 16 Brent GA. Clinical Practice: Graves’ disease. N Engl J Med 2008; 358: 2594-2605
    CrossrefPubMedGoogle Scholar
  • 17 Aizawa T, Ishihara M, Hashizume K, Takasu N, Yamada T. Age-related changes of thyroid function and immunologic abnormalities in patients with hyperthyroidism due to Graves’ disease. J Am Geriatr Soc 1989; 37: 944-948
    CrossrefPubMedGoogle Scholar
  • 18 Winsa B, Dahlberg PA, Jansson R, Agren H, Karlsson FA. Factors influencing the outcome of thyrostatic drug therapy in Graves’ disease. Acta Endocrinol (Copenh) 1990; 122: 622-628
    PubMedGoogle Scholar
  • 19 Nedrebo BG, Holm PI, Uhlving S, Sorheim JI, Skeie S, Eide GE, Husebye ES, Lien EA, Aanderud S. Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves’ disease. Eur J Endocrinol 2002; 147: 583-589
    CrossrefPubMedGoogle Scholar
  • 20 Anagnostis P, Adamidou F, Polyzos SA, Katergari S, Karathanasi E, Zouli C, Panagiotou A, Kita M. Predictors of long-term remission in patients with Graves’ disease: a single center experience. Endocrine 2013; 44: 448-453
    CrossrefPubMedGoogle Scholar
  • 21 Wang P-W, Chen I-Y, Juo S-HH, His E, Liu R-T, Hsieh C-J. Genotype and phenotype predictors of relapse of Graves’ disease after antithyroid drug withdrawal. Eur Thyroid J 2012; 1: 251-258
    CrossrefPubMedGoogle Scholar
  • 22 Benker G, Reinwein D, Kahaly G, Tegler L, Alexander WD, Fassbinder J, Hirche H. and the Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs . Is there a a methimazole dose effect on remission rate in Graves’ disease? Results from a long-term prospective study. Clin Endocrinol (Oxf) 1998; 49: 451-457
    CrossrefPubMedGoogle Scholar
  • 23 Kaguelidou F, Alberti C, Castanet M, Guitteny M-A, Czernichow P, Léger J. for the French Childhood Graves’ Disease Study Group . Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 2008; 93: 3817-3826
    CrossrefPubMedGoogle Scholar
  • 24 Carlé A, Bulow Pedersen I, Knudsen N, Perrild H, Ovesen L, Banke Rasmussen L, Laurberg P. Epidemiology of subtypes of hyperthyroidism in Denmark: a polulation-based study. Eur J Endocrinol 2011; 164: 801-809
    CrossrefPubMedGoogle Scholar
  • 25 Cappelli C, Gandossi E, Castellano M, Pizzocaro C, Agosti B, Delbarba A, Pirola I, De Martino E, Agabiti Rosei E. Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves’ disease: a 120 months prospective study. Endocrine J 2007; 54: 713-720
    CrossrefPubMedGoogle Scholar
  • 26 Dauksenie D, Dauksa A, Mickuviene N. Independent pretreatment predictors of Graves’ disease outcome. Medicina (Kaunas) 2013; 49: 427-434
    PubMedGoogle Scholar
  • 27 Laurberg P, Buchholtz Hansen PE, Iversen E, Eskjaer Jensen S, Weeke J. Goitre size and outcome of medical treatment of Graves’ disease. Acta Endocrinol (Copenh) 1986; 111: 39-43
    CrossrefPubMedGoogle Scholar
  • 28 Léger J, Gelwane G, Kaguelidou F, Benmerad M, Alberti C. and the French Childhood Graves’ Disease Study Group . 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: 110-119
    CrossrefPubMedGoogle Scholar
  • 29 Choo YK, Yoo WS, Kim DW, Chung H-K. Hypothyroidism during antithyroid drug treatment with methimazole is a favorable prognostic indicator in patients with Graves’ disease. Thyroid 2010; 20: 949-954
    CrossrefPubMedGoogle Scholar
  • 30 Lytton SD, Li Y, Olivo PD, Kohn LD, Kahaly GJ. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins. Clin Exp Immunol 2010; 162: 438-446
    CrossrefPubMedGoogle Scholar
  • 31 Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves’ disease: improvement of diagnostic accuracy over different generation of methods. Systematic review and meta-analysis. Autoimmunity Rev 2012; 12: 107-113
    CrossrefPubMedGoogle Scholar
  • 32 Diana T, Brown RS, Bossowski A, Segni M, Niedziela M, Konig J, Bossowska A, Ziora K, Hale A, Smith J, Pitz S, Kanitz M, Kahaly GJ. Clinical relevance of thyroid-stimulating autoantibodies in pediatric Graves’ disease – a multicenter study. J Clin Endocrinol Metab 2014; 99: 1648-1655
    CrossrefPubMedGoogle Scholar
  • 33 Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Torring O. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008; 158: 69-75
    CrossrefPubMedGoogle Scholar
  • 34 Laurberg P. Remission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism?. Eur J Endocrinol 2006; 155: 783-786
    CrossrefPubMedGoogle Scholar
  • 35 Stefanic M, Karner I. Thyroid peroxidase autoantibodies are associated with a lesser likelihood of late reversion to hyperthyroidism after successful non-ablative treatment of Graves’ disease in Croatian patients. J Endocrinol Invest 2014; 37: 71-77
    CrossrefPubMedGoogle Scholar
  • 36 Feldt-Rassmussen U, Schleusener H, Carayon P. Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves’ disease. J Clin Endocrinol Metab 1994; 78: 98-102
    PubMedGoogle Scholar
  • 37 Barbesino G, Tomer Y. Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab 2013; 98: 2247-2255
    CrossrefPubMedGoogle Scholar
  • 38 Tanda ML, Piantanida E, Liparulo L, Veronesi G, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L. Prevalence and natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed Graves’ hyperthyroidism seen at a single center. J Clin Endocrinol Metab 2013; 98: 1443-1449
    CrossrefPubMedGoogle Scholar
  • 39 Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol 1997; 47: 9-14
    CrossrefPubMedGoogle Scholar
  • 40 Rebelo Pinto E, dos S, Lopes FPPL, de Souza SAL, da Fonseca LMB, Visman M, Gutfilen B, de dos Santos Teixeira PF. A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in Graves’ ophthalmopathy patients with different Clinical Activity Score. Horm Metab Res 2013; 45: 765-768
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Eckstein AK, Lax H, Losch C, Glowacka D, Plicht M, Mann K, Esser J, Morgenthaler NG. Patients with severe Graves’ ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf) 2007; 67: 607-612
    CrossrefPubMedGoogle Scholar
  • 42 Laurberg P, Nygaard B, Andersen S, Carlé A, Karmisholt J, Kerjbjerg A, Bulow Pedersen I, Linding Andersen S. Association between TSH-receptor autoimmunity, hyperthyroidism, goiter, and orbitopathy in 208 patients included in the remission induction and sustenance in Graves’ disease study. J Thyroid Res 2014; Article ID 165487 DOI: 10.1155/2014/165487.
    CrossrefPubMedGoogle Scholar
  • 43 Abraham P, Avenell A, Park CM, Watson WA, Bevan JS. A systematic review of drug therapy for Graves’ hyperthyroidism. Eur J Endocrinol 2005; 153: 489-498
    CrossrefPubMedGoogle Scholar
  • 44 Vaidya B, Wright A, Shuttleworth J, Donohe M, Warren R, Brooke A, Gericke CA, Ukoumunne OC. Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves’ disease: a retrospective observational study. Clin Endocrinol (Oxf) 2014; 81: 610-613
    CrossrefPubMedGoogle Scholar
  • 45 Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 593-646
    PubMedGoogle Scholar
  • 46 Mazza E, Carlini M, Flecchia D, Blatto A, Zuccarini O, Gamba S, Beninati S, Messina M. 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 dose: a retrospective study. J Endocrinol Invest 2008; 31: 866-872
    CrossrefPubMedGoogle Scholar
  • 47 Elbers L, Mourits M, Wiersinga W. Outcome of very long-term treatment with antithyroid drugs in Graves’ hyperthyroidism associated with Graves’ orbitopathy. Thyroid 2011; 21: 279-283
    CrossrefPubMedGoogle Scholar
  • 48 Laurberg P, Berman DC, Andersen S, Bulow Pedersen I. Sustained control of Graves’ hyperthyroidism during long-term low-dose antithyroid drug therapy of patients with severe Graves’ orbitopathy. Thyroid 2011; 21: 951-956
    CrossrefPubMedGoogle Scholar
  • 49 Vestergaard P. Smoking and thyroid disorders – a meta-analysis. Eur J Endocrinol 2002; 146: 153-161
    CrossrefPubMedGoogle Scholar
  • 50 Wiersinga WM. Smoking and thyroid. Clin Endocrinol (Oxf) 2013; 79: 145-151
    CrossrefPubMedGoogle Scholar
  • 51 Nyirenda MJ, Taylor PN, Stoddart M, Beckett GJ, Toft AD. Thyroid-stimulating hormone-receptor antibody and thyroid hormone concentrations in smokers vs nonsmokers with Graves’ disease treated with carbimazole. JAMA 2009; 301: 162-164
    CrossrefPubMedGoogle Scholar
  • 52 Hou X, Li Y, Li I, Wang W, Fan C, Wang H, Zhang H, Shan Z, Teng W. Development of thyroid dysfunction and autoantibodies in Graves’ multiplex families: an eight-year follow-up study in Chinese Han pedigrees. Thyroid 2011; 12: 1353-1358
    CrossrefPubMedGoogle Scholar
  • 53 Glinoer D, de Nayer P, Bex M. and the Belgian Collaborative Study Group on Graves’ Disease . Effects of L-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves’ hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study. Eur J Endocrinol 2001; 144: 475-483
    CrossrefPubMedGoogle Scholar
  • 54 Kimball LE, Kulinskaya E, Brown B, Johnston C, Farid NR. Does smoking increase relapse rates in Graves’ disease?. J Endocrinol Invest 2002; 25: 152-157
    CrossrefPubMedGoogle Scholar
  • 55 Aagaard-Tyllery KM, Silver R, Dalton J. Immunology of normal pregnancy. Semin Fetal Neonatal Med 2006; 11: 279-295
    CrossrefPubMedGoogle Scholar
  • 56 Davies TF. The thyroid immunology of the post-partum period. Thyroid 1999; 9: 675-684
    CrossrefPubMedGoogle Scholar
  • 57 Amino N, Tada H, Hidaka Y. Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease. Thyroid 1999; 9: 705-713
    CrossrefPubMedGoogle Scholar
  • 58 Rotondi M, Cappelli C, Pirali B, Pirola I, Magri F, Fonte R, Castellano M, Agabiti Rosei E, Chiovato L. The effect of pregnancy on subsequent relapse from Graves’ disease after a successful course of antithyroid drug therapy. J Clin Endocrinol Metab 2008; 93: 3985-3988
    CrossrefPubMedGoogle Scholar
  • 59 Nagakawa Y, Mori K, Hoshikawa S, Yamamoto M, Ito S, Yoshida K. Postpartum recurrence of Graves’ hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy. Clin Endocrinol (Oxf) 2002; 57: 467-471
    CrossrefPubMedGoogle Scholar
  • 60 Weetman AP. Graves’ disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?. Clin Endocrinol (Oxf) 2014; 80: 629-632
    CrossrefPubMedGoogle Scholar
  • 61 Cossburn M, Pace AA, Jones J, Ali R, Ingram C, Baker K, Hirst C, Zajicek J. Scolding N, Boggild M, Pickersgill T, Ben-Shlomo Y, Coles A, Robertson NP. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 2011; 77: 573-579
    CrossrefPubMedGoogle Scholar
  • 62 Daniels GH, Vladic A, Brinar V, Zavalishib I, Valente W, Oyuela P, Palmer J, Margolin DH, Hollenstein J. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab 2014; 99: 80-89
    CrossrefPubMedGoogle Scholar
  • 63 Chen F, Day SL, Metcalfe RA, Sethi G, Kapembwa MS, Brook MG, Churchill D, de Ruiter A, Robinson S, Lacey CJ, Weetman AP. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine (Baltimore) 2005; 84: 98-106
    CrossrefPubMedGoogle Scholar
  • 64 Honda A, Kashiwazaki K, Tsunoda T, Gallant JE, Brown TT. Short communication: CD4 cell count increases during successful treatment of Graves’ disease with methimazole in HIV-affected patients on antiretroviral therapy. AIDS Res Hum Retroviruses 2012; 28: 1627-1629
    CrossrefPubMedGoogle Scholar