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Radiopraxis 2020; 13(02): E32-E48
DOI: 10.1055/a-1130-1573
CPD-Fortbildung

Update endokrine Orbitopathie

Anja Eckstein
,
Michael Oeverhaus
,
Mareile Stöhr
,
Dirk Dekowski
,
Utta Berchner-Pfannschmidt
,
Joachim Esser
,
Lars Möller
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Die endokrine Orbitopathie (EO) ist die häufigste extrathyreoidale Manifestation des Morbus Basedow. Für Therapieentscheidungen wird die Erkrankung in eine aktive und eine inaktive Phase eingeteilt sowie eine Unterscheidung zwischen einer milden, moderaten und schweren visusbedrohenden Manifestation vorgenommen, wobei die Lebensqualität der Patienten bei den beiden letzteren erheblich eingeschränkt ist.



Publication History

Article published online:
13 August 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • Literatur

  • 1 Bahn RS. Current Insights into the Pathogenesis of Graves’ Ophthalmopathy. Horm Metab Res 2015; 47: 773-778
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Davies TF, Ando T, Lin RY. et al. Thyrotropin receptor-associated diseases: from adenomata to Graves disease. J Clin Invest 2005; 115: 1972-1983
    CrossrefPubMedGoogle Scholar
  • 3 Bahn RS. Thyrotropin receptor expression in orbital adipose / connective tissues from patients with thyroid-associated ophthalmopathy. Thyroid 2002; 12: 193-195
    CrossrefPubMedGoogle Scholar
  • 4 Kumar S, Iyer S, Bauer H. et al. A stimulatory thyrotropin receptor antibody enhances hyaluronic acid synthesis in Graves’ orbital fibroblasts: inhibition by an IGF-I receptor blocking antibody. J Clin Endocrinol Metab 2012; 97: 1681-1687
    CrossrefPubMedGoogle Scholar
  • 5 Kumar S, Nadeem S, Stan MN. et al. A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves’ ophthalmopathy. J Mol Endocrinol 2011; 46: 155-163
    CrossrefPubMedGoogle Scholar
  • 6 Kumar S, Schiefer R, Coenen MJ. et al. A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves’ orbital preadipocyte fibroblasts. Thyroid 2010; 20: 59-65
    CrossrefPubMedGoogle Scholar
  • 7 Krieger CC, Neumann S, Marcus-Samuels B. et al. TSHR / IGF-1 R Cross-Talk, Not IGF-1 R Stimulating Antibodies, Mediates Graves’ Ophthalmopathy Pathogenesis. Thyroid 2017; 27: 746-747
    CrossrefPubMedGoogle Scholar
  • 8 Krieger CC, Place RF, Bevilacqua C. et al. Thyrotropin / IGF-1 receptor crosstalk in Graves’ ophthalmopathy pathogenesis. J Clin Endocrinol Metab 2016; 10: 2340-2347
    CrossrefPubMedGoogle Scholar
  • 9 Hiromatsu Y, Yang D, Bednarczuk T. et al. Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2000; 85: 1194-1199
    PubMedGoogle Scholar
  • 10 Shan SJ, Douglas RS. The pathophysiology of thyroid eye disease. J Neuroophthalmol 2014; 34: 177-185
    CrossrefPubMedGoogle Scholar
  • 11 Plohn S, Edelmann B, Japtok L. et al. CD40 enhances sphingolipids in orbital fibroblasts: potential role of sphingosine-1-phosphate in inflammatory T-cell migration in Graves’ orbitopathy. Invest Ophthalmol Vis Sci 2018; 59: 5391-5397
    CrossrefPubMedGoogle Scholar
  • 12 Gortz GE, Horstmann M, Aniol B. et al. Hypoxia-dependent HIF-1 activation impacts on tissue remodeling in Graves’ ophthalmopathy-implications for smoking. J Clin Endocrinol Metab 2016; 101: 4834-4842
    CrossrefPubMedGoogle Scholar
  • 13 Banga JP, Moshkelgosha S, Berchner-Pfannschmidt U. et al. Modeling Graves’ orbitopathy in experimental Graves’ disease. Horm Metab Res 2015; 47: 797-803
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Bartley GB, Fatourechi V, Kadrmas EF. et al. Long-term follow-up of Graves ophthalmopathy in an incidence cohort. Ophthalmology 1996; 103: 958-962
    CrossrefPubMedGoogle Scholar
  • 15 Dederichs B, Dietlein M, Jenniches-Kloth B. et al. Radioiodine therapy of Graves’ hyperthyroidism in patients without preexisting ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy? Exp Clin Endocrinol Diabetes 2006; 114: 366-370
    Article in Thieme ConnectPubMed
  • 16 Uddin JM, Rubinstein T, Hamed-Azzam S. Phenotypes of thyroid eye disease. Ophthalmic Plast Reconstr Surg 2018; 34: S28-S33
    CrossrefPubMedGoogle Scholar
  • 17 Wiersinga WM. Quality of life in Graves’ ophthalmopathy. Best Pract Res Clin Endocrinol Metab 2012; 26: 359-370
    CrossrefPubMedGoogle Scholar
  • 18 Eckstein AK, Losch C, Glowacka D. et al. Euthyroid and primarily hypothyroid patients develop milder and significantly more asymmetrical Graves ophthalmopathy. Br J Ophthalmol 2009; 93: 1052-1056
    CrossrefPubMedGoogle Scholar
  • 19 McKeag D, Lane C, Lazarus JH. et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol 2007; 91: 455-458
    CrossrefPubMedGoogle Scholar
  • 20 Saeed P, Tavakoli Rad S, Bisschop P. Dysthyroid optic neuropathy. Ophthalmic Plast Reconstr Surg 2018; 34 (Suppl. 01): S60-S67
    CrossrefPubMedGoogle Scholar
  • 21 Regensburg NI, Wiersinga WM, Berendschot TT. et al. Do subtypes of Graves’ orbitopathy exist? Ophthalmology 2011; 118: 191-196
    CrossrefPubMed
  • 22 Perros P, Crombie AL, Kendall-Taylor P. Natural history of thyroid associated ophthalmopathy. Clin Endocrinol (Oxf) 1995; 42: 45-50
    CrossrefPubMedGoogle Scholar
  • 23 Mourits MP, Koornneef L, Wiersinga WM. et al. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73: 639-644
    CrossrefPubMedGoogle Scholar
  • 24 Bartalena L, Baldeschi L, Boboridis K. et al. The 2016 European Thyroid Association / European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J 2016; 5: 9-26
    CrossrefPubMedGoogle Scholar
  • 25 Bartalena L, Baldeschi L, Dickinson A. et al. Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008; 158: 273-285
    CrossrefPubMedGoogle Scholar
  • 26 Dolman PJ, Rootman J. VISA Classification for Graves’ orbitopathy. Ophthal Plast Reconstr Surg 2006; 22: 319-324
    CrossrefPubMedGoogle Scholar
  • 27 Wiersinga WM. Combined thyroid eye clinic: the importance of a multidisciplinary health care in patients with Graves’ orbitopathy. Pediatr Endocrinol Rev 2010; 7 (Suppl. 02): 250-253
    PubMedGoogle Scholar
  • 28 Bartalena L, Martino E, Marcocci C. et al. More on smoking habits and Graves’ ophthalmopathy. J Endocrinol Invest 1989; 12: 733-737
    CrossrefPubMedGoogle Scholar
  • 29 Prummel MF, Wiersinga WM. Smoking and risk of Graves’ disease. JAMA 1993; 269: 479-482
    CrossrefPubMedGoogle Scholar
  • 30 Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf) 1996; 45: 477-481
    CrossrefPubMedGoogle Scholar
  • 31 Traisk F, Tallstedt L, Abraham-Nordling M. et al. Thyroidassociated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009; 94: 3700-3707
    CrossrefPubMedGoogle Scholar
  • 32 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: 73-78
    CrossrefPubMedGoogle Scholar
  • 33 Bartalena L, Marcocci C, Tanda ML. et al. Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 1998; 129: 632-635
    CrossrefPubMedGoogle Scholar
  • 34 Eckstein A, Quadbeck B, Mueller G. et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol 2003; 87: 773-776
    CrossrefPubMedGoogle Scholar
  • 35 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; 326: 1733-1738
    CrossrefPubMedGoogle Scholar
  • 36 Meyer Zu Horste M, Pateronis K, Walz MK et al. The effect of early thyroidectomy on the course of active Graves’ orbitopathy (GO): A retrospective case study. Horm Metab Res 2016 48. 433-439
    PubMed
  • 37 Vannucchi G, Campi I, Covelli D. et al. Graves’ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab 2009; 94: 3381-3386
    CrossrefPubMedGoogle Scholar
  • 38 Lai A, Sassi L, Compri E. et al. Lower dose prednisone prevents radioiodine-associated exacerbation of initially mild or absent Graves’ orbitopathy: a retrospective cohort study. J Clin Endocrinol Metab 2010; 95: 1333-1337
    CrossrefPubMedGoogle Scholar
  • 39 Kahaly GJ, Bartalena L, Hegedus L. et al. 2018 European Thyroid Association Guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J 2018; 7: 167-186
    CrossrefPubMedGoogle Scholar
  • 40 Perros P, Kendall-Taylor P, Neoh C. et al. A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active Graves’ ophthalmopathy. J Clin Endocrinol Metab 2005; 90: 5321-5323
    CrossrefPubMedGoogle Scholar
  • 41 Menconi F, Marino M, Pinchera A. et al. Effects of total thyroid ablation vs near-total thyroidectomy alone on mild to moderate Graves’ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 2007; 92: 1653-1658
    CrossrefPubMedGoogle Scholar
  • 42 Menconi F, Leo M, Vitti P. et al. Total thyroid ablation in Graves’ orbitopathy. J Endocrinol Invest 2015; 38: 809-815
    CrossrefPubMedGoogle Scholar
  • 43 Marcocci C, Kahaly GJ, Krassas GE. et al. Selenium and the course of mild Graves’ orbitopathy. The New England journal of medicine 2011; 364: 1920-1931
    CrossrefPubMedGoogle Scholar
  • 44 Kahaly GJ, Pitz S, Hommel G. et al. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab 2005; 90: 5234-5240
    CrossrefPubMedGoogle Scholar
  • 45 Bartalena L, Krassas GE, Wiersinga W. et al. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 2012; 97: 4454-4463
    CrossrefPubMedGoogle Scholar
  • 46 Zhu W, Ye L, Shen L. et al. A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 2014; 99: 1999-2007
    CrossrefPubMedGoogle Scholar
  • 47 Oeverhaus M, Witteler T, Lax H. et al. Combination therapy of intravenous steroids and orbital irradiation is more effective than intravenous steroids alone in patients with Graves’ orbitopathy. Horm Metab Res 2017; 49: 739-747
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Mourits MP, van Kempen-Harteveld ML, Garcia MB. et al. Radiotherapy for Graves’ orbitopathy: randomised placebocontrolled study. Lancet 2000; 355: 1505-1509
    CrossrefPubMedGoogle Scholar
  • 49 Johnson KT, Wittig A, Loesch C. et al. A retrospective study on the efficacy of total absorbed orbital doses of 12, 16 and 20 Gy combined with systemic steroid treatment in patients with Graves’ orbitopathy. Graefes Arch Clin Exp Ophthalmol 2010; 248: 103-109
    CrossrefPubMedGoogle Scholar
  • 50 Bartalena L, Veronesi G, Krassas GE. et al. Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves’ orbitopathy? J Endocrinol Invest 2017; 40: 547-553
    CrossrefPubMed
  • 51 Salvi M, Vannucchi G, Curro N. et al. Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves’ orbitopathy: a randomized controlled study. J Clin Endocrinol Metab 2015; 100: 422-431
    CrossrefPubMedGoogle Scholar
  • 52 Rajendram R, Taylor PN, Wilson VJ. et al. Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 x 2 factorial, double-blind, randomised controlled trial. Lancet Diabet Endocrinol 2018; 6: 299-309
    CrossrefPubMedGoogle Scholar
  • 53 Kahaly GJ, Riedl M, Konig J. et al. Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabet Endocrinol 2018; 06: 287-298
    CrossrefPubMedGoogle Scholar
  • 54 Stan MN, Garrity JA, Carranza Leon BG. et al. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab 2015; 100: 432-441
    CrossrefPubMedGoogle Scholar
  • 55 Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR. et al. Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant graves orbitopathy: a randomized clinical trial. Am J Ophthalmol 2018; 195: 181-190
    CrossrefPubMedGoogle Scholar
  • 56 Kahaly G, Schrezenmeir J, Krause U. et al. Ciclosporin and prednisone v. prednisone in treatment of Graves’ ophthalmopathy: a controlled, randomized and prospective study. Eur J Clin Invest 1986; 16: 415-422
    PubMedGoogle Scholar
  • 57 Ghadiri N. The management of thyroid eye disease by immunomodulation. The Cambridge regime. International Thyroid Eye Disease Society Symposium 2016
    PubMed
  • 58 Prummel MF, Mourits MP, Berghout A. et al. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 1989; 321: 1353-1359
    CrossrefPubMedGoogle Scholar
  • 59 Wakelkamp I, Baldeschi L, Saeed P. et al. Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ ophthalmopathy? A randomized controlled trial Clin Endocrinol (Oxf) 2005; 63: 323-328
    CrossrefPubMed
  • 60 Curro N, Covelli D, Vannucchi G. et al. Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy. Thyroid 2014; 24: 897-905
    CrossrefPubMedGoogle Scholar
  • 61 Smith TJ, Kahaly GJ, Ezra DG. et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med 2017; 376: 1748-1761
    CrossrefPubMedGoogle Scholar
  • 62 Pearce S, Perros P, Razvi P. et al. Antigen -specific immune modulation using TEH receptor peptides (ATX-GD-59) for Graves’ hyperthyroidism: Results of a first in human study. ETA abstracts 2018
    PubMed
  • 63 Furmaniak J, Sanders J, Rees Smith B. Blocking type TSH receptor antibodies. Auto Immun Highlights 2013; 4: 11-26
    CrossrefPubMedGoogle Scholar
  • 64 Furmaniak J, Ryder MR, Castro MR. et al. Blocking the TSH receptor with the human monoclonal autoantibody K1-70 improves Graves’ ophthalmopathy and aids control of advanced follicular thyroid carcinoma – results of long term treatment under the first in human single patient expended use therapy. European Thyroid Association meeting 2018 in New Castle OP-08-57
  • 65 Neumann S, Nir EA, Eliseeva E. et al. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology 2014; 155: 310-314
    CrossrefPubMedGoogle Scholar
  • 66 Wabbels B, Forl M. Botulinumtoxin bei Überfunktion der Tränendrüse, spastischem Entropium und Oberlidretraktion bei endokriner Orbitopathie. Ophthalmologe 2007; 104: 771-776
    CrossrefPubMedGoogle Scholar
  • 67 Chee E, Chee SP. Subconjunctival injection of triamcinolone in the treatment of lid retraction of patients with thyroid eye disease: a case series. Eye (Lond) 2008; 22: 311-315
    CrossrefPubMedGoogle Scholar
  • 68 Lee SJ, Rim TH, Jang SY. et al. Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy using subconjunctival triamcinolone injections. Graefes Arch Clin Exp Ophthalmol 2013; 251: 261-270
    CrossrefPubMedGoogle Scholar
  • 69 Oeverhaus M, Copei A, Mattheis S. et al. Influence of orbital morphology on proptosis reduction and ocular motility after decompression surgery in patients with Graves’ orbitopathy. PLoS One 2019; 14: e0218701
    CrossrefPubMedGoogle Scholar
  • 70 Eckstein A, Esser J, Oeverhaus M. et al. Surgical Treatment of Diplopia in Graves Orbitopathy Patients. Ophthalmic Plast Reconstr Surg 2018; 34: S75-S84
    CrossrefPubMedGoogle Scholar
  • 71 Eckstein A, Esser J. Surgical management of extraocular muscle dysfunction in patients with go. In: Bahn RS. , ed. Graves’ Disease. Berlin New York: Springer; 2015: 287-299
    Google Scholar
  • 72 Eckstein A, Esser J, Oeverhaus M. et al. surgical treatment of diplopia in graves orbitopathy patients. Ophthalmic Plast Reconstr Surg 2018; 34: S75-S84
    CrossrefPubMedGoogle Scholar
  • 73 Prummel MF, Wiersinga WM, Mourits MP. et al. Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 1990; 150: 1098-1101
    CrossrefPubMedGoogle Scholar
  • 74 Eckstein AK, Lax H, Losch C. et al. 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
    PubMedGoogle Scholar
  • 75 Masiello E, Veronesi G, Gallo D. et al. Antithyroid drug treatment for Graves’ disease: baseline predictive models of relapse after treatment for a patient-tailored management. J Endocrinol Invest 2018; 41: 1425-1432
    CrossrefPubMedGoogle Scholar
  • 76 Ehlers M, Allelein S, Schott M. TSH-receptor autoantibodies: pathophysiology, assay methods, and clinical applications. Minerva Endocrinol 2018; 43: 323-332
    CrossrefPubMedGoogle Scholar
  • 77 Costagliola S, Morgenthaler NG, Hoermann R. et al. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves’ disease. J Clin Endocrinol Metab 1999; 84: 90-97
    PubMedGoogle Scholar
  • 78 Schott M, Hermsen D, Broecker-Preuss M. et al. Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves’ disease (GD): an international multicentre trial. Clin Endocrinol (Oxf) 2009; 71: 566-573
    CrossrefPubMedGoogle Scholar
  • 79 Giuliani C, Cerrone D, Harii N. et al. A TSHr-LH / CGr chimera that measures functional TSAb in Graves’ disease. The Journal of clinical endocrinology and metabolism 2012; 97: E1106-1115
    CrossrefPubMedGoogle Scholar
  • 80 Frank CU, Braeth S, Dietrich JW. et al. Bridge technology with tsh receptor chimera for sensitive direct detection of TSH receptor antibodies causing Graves’ disease: analytical and clinical evaluation. Horm Metab Res 2015; 47: 880-888
    Article in Thieme ConnectPubMedGoogle Scholar
  • 81 Quadbeck B, Hoermann R, Hahn S. et al. Binding, stimulating and blocking TSH receptor antibodies to the thyrotropin receptor as predictors of relapse of Graves’ disease after withdrawal of antithyroid treatment. Horm Metab Res 2005; 37: 745-750
    Article in Thieme ConnectPubMedGoogle Scholar
  • 82 Carella C, Mazziotti G, Sorvillo F. et al. Serum thyrotropin receptor antibodies concentrations in patients with Graves’ disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and / or thyroid response modify during the observation period. Thyroid 2006; 16: 295-302
    CrossrefPubMedGoogle Scholar
  • 83 Perros P, Zarkovic M, Azzolini C. et al. PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012. Br J Ophthalmol 2015; 99: 1531-1535
    CrossrefPubMedGoogle Scholar
  • 84 Eckstein AK, Plicht M, Lax H. et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 2006; 91: 3464-3470
    CrossrefPubMedGoogle Scholar
  • 85 Eckstein A, Stöhr M, Oeverhaus M. et al. Predicting potential of Anti-TSH-Receptor-autoantibodies (TRAb) measurements for the course of Graves’ hyperthyroidism (GD) and Graves’ orbitopathy (GO) depending on the assay technology. Abstract of the 2019 ETA meeting in Budapest 2019
    PubMed