Skip to main content

Advertisement

SpringerLink
Log in

Extrathyroidal manifestations of Graves’ disease: a 2014 update

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Introduction

Graves’ orbitopathy (GO), thyroid dermopathy (also called pretibial myxedema) and acropachy are the extrathyroidal manifestations of Graves’ disease. They occur in 25, 1.5, and 0.3 % of Graves’ patients, respectively. Thus, GO is the main and most common extrathyroidal manifestation. Dermopathy is usually present if the patient is also affected with GO. The very rare acropachy occurs only in patients who also have dermopathy. GO and dermopathy have an autoimmune origin and are probably triggered by autoimmunity to the TSH receptor and, likely, the IGF-1 receptor. Both GO and dermopathy may be mild to severe.

Management

Mild GO usually does not require any treatment except for local measures and preventive actions (especially refraining from smoking). Currently, moderate-to-severe and active GO is best treated by systemic glucocorticoids, but response to treatment is not optimal in many instances, and retreatments and use of other modalities (glucocorticoids, orbital radiotherapy, cyclosporine) and, in the end, rehabilitative surgery are often needed. Dermopathy is usually managed by local glucocorticoid treatment. No specific treatment is available for acropachy.

Perspectives

Novel treatments are presently being investigated for GO, and particular attention is paid to the use of rituximab. It is unknown whether novel treatments for GO might be useful for the other extrathyroidal manifestations. Future novel therapies shown to be beneficial for GO in randomized studies may be empirically used for dermopathy and acropachy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bartalena L (2013) Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol 9:724–734

    Article  CAS  PubMed  Google Scholar 

  2. Filipsson Nystrom H, Jansson S, Berg G (2013) Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003–2005. Clin Endocrinol (Oxf) 78:768–776

    Article  Google Scholar 

  3. Bartalena L, Tanda ML (2009) Clinical practice, Graves’ ophthalmopathy. N Engl J Med 360:994–1001

    Article  CAS  PubMed  Google Scholar 

  4. Fatourechi V (2012) Thyroid dermopathy and acropachy. Best Pract Res Clin Endocrinol Metab 26:553–565

    Article  CAS  PubMed  Google Scholar 

  5. Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L (2013) 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 98:1443–1449

    Article  CAS  PubMed  Google Scholar 

  6. Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L (2013) Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 36:444–449

    CAS  PubMed  Google Scholar 

  7. Bartley GB, Fatourechi V, Kadarmas EF, Jacobson SJ, Ilstrup DM, Gorman CA (1996) Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 121:284–289

    CAS  PubMed  Google Scholar 

  8. Fatourechi V, Garrity JA, Bartley GB, Bergstralh EJ, Gorman CA (1993) Orbital decompression in Graves’ opthalmopathy associated with pretibial myxedema. J Endocrinol Invest 16:433–437

    Article  CAS  PubMed  Google Scholar 

  9. Lohiya S, Lohiya V, Stahl EJ (2013) Pretibial myxedema without ophthalmopathy: an initial presentation of Graves’ disease. Am J Med Sci 346:73–75

    Article  PubMed  Google Scholar 

  10. Capsoni F, Minonzio F, Sarzi-Puttini P, Atzeni F, Ambrosi B (2005) Thyroid acropachy: an unusual rheumatic manifestation of Graves’ disease. Clin Exp Rheumatol 23:125–126

    CAS  PubMed  Google Scholar 

  11. Bartley GB, Fatourechi V, Kadarmas EF, Jacobsen SJ, Ilstrup DL, Garrity JA, Gorman CA (1995) The incidence of Graves’ ophthalmopathy in Olmsted County Minnesota. Am J Opthalmol 120:511–517

    CAS  Google Scholar 

  12. Bahn RS (2010) Mechanisms of disease: Graves’ ophthalmopathy. N Engl J Med 362:726–738

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Smith TJ (2010) Pathogenesis of Graves’ orbitopathy: a 2010 update. J Endocrinol Invest 33:414–421

    Article  CAS  PubMed  Google Scholar 

  14. Bartalena L, Pinchera A, Marcocci C (2000) Management of Graves’ ophthalmopathy: reality and perspectives. Endocr Rev 21:168–199

    CAS  PubMed  Google Scholar 

  15. Iyer S, Bahn RS (2012) Immunopathogenesis of Graves’ ophthalmopathy: the role of the TSH receptor. Best Pract Res Clin Endocrinol Metab 26:281–299

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Moshkelgosha S, So P-W, Deasy N, Diaz-Cano S, Banga JP (2013) Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of Graves’ orbitopathy induced by thyrotropin receptor plasmid in vitro electroporation. Endocrinology 154:3008–3015

    Article  CAS  PubMed  Google Scholar 

  17. Smith TJ, Huetwell FGL, Hegedus L, Douglas RS (2012) Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab 26:291–302

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wiersinga WM (2011) Autoimmunity in Graves’ ophthalmopathy: the result of an unfortunate marriage between TSH receptors and IGF-1 receptors? J Clin Endocrinol Metab 96:2386–2394

    Article  CAS  PubMed  Google Scholar 

  19. Estcourt S, Quinn AG, Vaidya BJ (2009) Quality of life in thyroid eye disease: impact of quality of care. Eur J Endocrinol 164:649–655

    Article  Google Scholar 

  20. Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, Boschi A, Dickinson AJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Sartini MS, Stahl M, von Arx G (2006) Clinical assessment of patients with Graves’ orbitopathy: the European Group on Graves’ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol 155:387–389

    Article  CAS  PubMed  Google Scholar 

  21. Dolman PJ, Rootman J (2006) VISA classification for Graves’ orbitopathy. Ophthal Plast Reconstr Surg 22:319–324

    Article  PubMed  Google Scholar 

  22. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L (1997) Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 47:9–14

    Article  CAS  Google Scholar 

  23. Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM (2008) Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158:273–285

    Article  CAS  PubMed  Google Scholar 

  24. Bartalena L (2012) Prevention of Graves’ ophthalmopathy. Best Pract Res Clin Endocrinol Metab 26:371–379

    Article  PubMed  Google Scholar 

  25. Pfeilschifter J, Ziegler R (1996) Smoking and endocrine ophthalmopathy: impact of smoking severity and current versus lifetime cigarette consumption. Clin Endocrinol (Oxf) 45:477–481

    Article  CAS  Google Scholar 

  26. Prummel MF, Wiersinga WM, Mourits MP, Koornneef L, Berghout A, van der Gaag R (1990) Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 150:1098–1101

    Article  CAS  PubMed  Google Scholar 

  27. Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell’Unto E, Bruno-Bossio G, Nardi M, Bartolomei MP, Lepri A, Rossi G, Martino E, Pinchera A (1998) Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 338:73–78

    Article  CAS  PubMed  Google Scholar 

  28. Lai A, Sassi L, Compri E, Marino F, Sivelli P, Piantanida E, Tanda ML, Bartalena L (2010) Lower dose prednisone prevents radioiodine-associated exacerbation of initially mild or absent Graves’ orbitopathy: a retrospective cohort study. J Clin Endocrinol Metab 95:1333–1337

    Article  CAS  PubMed  Google Scholar 

  29. Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Tørring O (2008) TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 158:69–75

    Article  CAS  PubMed  Google Scholar 

  30. Marcocci C, Bartalena L (2013) Role of oxidative stress and selenium in Graves’ hyperthyroidism and orbitopathy. J Endocrinol Invest 36(10):15–20

    CAS  PubMed  Google Scholar 

  31. Kohrle J (2013) Pathophysiological relevance of selenium. J Endocrinol Invest 36(10):1–7

    CAS  PubMed  Google Scholar 

  32. Nacamulli D, Petricca D, Mian C (2013) Selenium and autoimmune thyroiditis. J Endocrinol Invest 36(10):8–14

    CAS  PubMed  Google Scholar 

  33. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, Altea MA, Nardi M, Pitz S, Boboridis K, Sivelli P, von Arx G, Mourits MP, Baldeschi L, Bencivelli W, Wiersinga M, European Group on Graves’ Orbitopathy (2011) Selenium and the course of mild Graves’ orbitopathy. N Engl J Med 364:1920–1931

    Article  CAS  PubMed  Google Scholar 

  34. Eckstein A, Schittkowski M, Esser J (2012) Surgical treatment of Graves’ ophthalmopathy. Best Pract Res Clin Endocrinol Metab 26:339–358

    Article  PubMed  Google Scholar 

  35. Zang S, Ponto KA, Kahaly GJ (2011) Intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 96:320–332

    Article  CAS  PubMed  Google Scholar 

  36. Zang S, Ponto KA, Pitz S, Kahaly GJ (2011) Dose of intravenous steroids and therapy outcome in Graves’ orbitopathy. J Endocrinol Invest 34:876–880

    Article  CAS  PubMed  Google Scholar 

  37. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G, Azzolini C, Boboridis KG, Mourits MP, Soeters MR, Baldescxhi L, Nardi M, Currò N, Boschi A, Bernard M, von Arx G, European Group on Graves’ Orbitopathy (2012) Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 97:4454–4463

    Article  CAS  PubMed  Google Scholar 

  38. Le Moli R, Baldeschi L, Saeed P, Regensburg N, Mourits MP, Wiersinga WM (2007) Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves’ ophthalmopathy. Thyroid 17:357–362

    Article  PubMed  Google Scholar 

  39. Bartalena L (2010) What to do for moderate-to-severe and active Graves’ orbitopathy if glucocorticoids fail? Clin Endocrinol (Oxf) 73:149–152

    CAS  Google Scholar 

  40. Tanda ML, Bartalena L (2012) Efficacy and safety of orbital radiotherapy for Graves’ orbitopathy. J Clin Endocrinol Metab 97:3857–3865

    Article  CAS  PubMed  Google Scholar 

  41. Prummel MF, Mourits MP, Berghout L (1989) Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy. N Engl J Med 321:1353–1359

    Article  CAS  PubMed  Google Scholar 

  42. Estcourt S, Hickey J, Perros P, Dayan C, Vaidya B (2009) The patient experience of services for thyroid eye disease in the UK: results of a nationwide survey. Eur J Endocrinol 161:483–487

    Article  CAS  PubMed  Google Scholar 

  43. Verma S, Rongioletti F, Braun-Falco M, Ruzicka T (2013) Preradial myxedema in a euthyroid male: a distinct rarity. Dermatol Online J 19:9

    PubMed  Google Scholar 

  44. Schwartz KM, Fatourechi V, Ahmed DF, Pond GR (2002) Dermopathy of Graves’ disease (pretibial myxedema): long term outcome. J Clin Endocrinol Metab 87:438–446

    CAS  PubMed  Google Scholar 

  45. Karoutsou E, Polymeris A (2011) Pathogenesis of Graves’ disease focusing on Graves’ ophthalmopathy. Endocr Regul 45:209–220

    Article  CAS  PubMed  Google Scholar 

  46. Shih SR, Lin MS, Li HY, Yang HY, Hsiao YL, Chang MT, Chen CM, Chang TC (2011) Observing pretibial myxedema in patients with Graves’ disease using digital infrared thermal imaging and high-resolution ultrasonography: for better records, early detection, and further investigation. Eur J Endocrinol 164:605–611

    Article  CAS  PubMed  Google Scholar 

  47. Fatourechi V (2005) Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol 6:295–309

    Article  PubMed  Google Scholar 

  48. Zhao P, Deng Y, Gu P, Wang Y, Zhou H, Hu Y, Chen P, Fan X (2013) Insulin-like growth factor 1 promotes the proliferation and adipogenesis of orbital adipose-derived stromal cells in thyroid-associated ophthalmopathy. Exp Eye Res 107:65–73

    Article  CAS  PubMed  Google Scholar 

  49. Rapoport B, Alsabeh R, Aftergood D, McLachlan SM (2000) Elephantiasic pretibial myxedema: insights into and a hypothesis regarding the pathogenesis of extrathyroidal manifestations of Graves’ disease. Thyroid 10:685–692

    Article  CAS  PubMed  Google Scholar 

  50. Davies TF (2000) Trauma and pressure explain the clinical presentation of the Graves’ disease Triad. Thyroid 10:620–630

    Google Scholar 

  51. Rice SA, Peden NR, McGlynn S, Morton C (2010) Atypical presentation of infiltrative thyroid dermopathy. Clin Exp Dermatol 35:56–58

    Article  CAS  PubMed  Google Scholar 

  52. Stan MN, Bahn RS (2010) Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid 20:777–783

    Article  PubMed Central  PubMed  Google Scholar 

  53. Lois N, Abdelkader E, Reglitz K, Garden C, Ayres JG (2008) Environmental tobacco smoke exposure and eye disease. Br J Ophthalmol 92:1304–1310

    Article  CAS  PubMed  Google Scholar 

  54. Hegedus L, Brix TH, Vestergaard P (2004) Relationship between cigarette smoking and Graves’ ophthalmopathy. J Endocrinol Invest 27:265–271

    Article  Google Scholar 

  55. Fatourechi V, Ahmed DD, Schwartz KM (2002) Thyroid acropachy report of 40 patients treated in a single institution in a 26-year period. J Clin Endocrinol Metab 87:5435–5441

    Article  CAS  PubMed  Google Scholar 

  56. Noppakun N, Bancherun K, Chandarapracert S (1986) Unusual location of localized myxedema in Graves’ disease: report of three cases. Arch Dermatol 12:7117–7721

    Google Scholar 

  57. Siegler M, Retetoff S (1976) Pretibial myxedema: a reversible cause of foot drop due to entrapment of the peroneal nerve. N Engl J Med 294:1383–1384

    Article  CAS  PubMed  Google Scholar 

  58. Eslton DM (2010) Stasis mucinosis. J Cutan Pathol 37:1024

    Article  Google Scholar 

  59. King LR, Braunstein H, Chambers D et al (1959) A case study of peculiar soft-tissue and bony changes in association with thyroid disease. J Clin Endocrinol Metab 19:1323–1330

    Article  CAS  PubMed  Google Scholar 

  60. Cawood TJ, Moriarty P, O’Farrelly C, O’Shea D (2007) Smoking and thyroid-associated ophthalmopathy: a novel explanation of the biological link. J Clin Endocrinol Metab 92:59–64

    Article  CAS  PubMed  Google Scholar 

  61. Farid M, Roch-Levecq AC, Levi L, Brody BL, Granet DB, Kikkawa DO (2005) Psychological disturbance in Graves ophthalmopathy. Arch Ophthalmol 123:491–496

    Article  PubMed  Google Scholar 

  62. Kahaly GJ, Petrak F, Hardt J, Pitz S, Egle UT (2005) Psychosocial morbidity of Graves’ orbitopathy. Clin Endocrinol (Oxf) 63:395–402

    Article  CAS  Google Scholar 

  63. Stan MN, Duraski JM, Brito JP, Bhagra S, Thapa P, Bahn RS (2013) Cohort study on radioactive iodine -induced hypothyroidism: implications for Graves’ ophthalmopathy and optimal timing for thyroid hormone assessment. Thyroid 23:620–625

    Article  CAS  PubMed  Google Scholar 

  64. Bartalena L (2011) The dilemma of how to manage Graves’ hyperthyroidism in patients with associated orbitopathy. J Clin Endocrinol Metab 96:592–599

    Article  CAS  PubMed  Google Scholar 

  65. Menconi F, Marinò M, Pinchera A, Rocchi R, Mazzi B, Nardi M, Bartalena L, Marcocci C (2007) Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Graves’ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 92:1653–1658

    Article  CAS  PubMed  Google Scholar 

  66. Leo M, Marcocci C, Pinchera A, Nardi M, Megna L, Rocchi R, Latrofa F, Altea MA, Mazzi B, Sisti E, Profilo MA, Marinò M (2012) Outcome of Graves’ orbitopathy after total thyroid ablation and glucocorticoid treatment: follow-up of a randomized clinical trial. J Clin Endocrinol Metab 97:E44–E48

    Article  CAS  PubMed  Google Scholar 

  67. De Bellis A, Conzo G, Cennamo G, Pane E, Bellastella G, Colella C, Iacovo AD, Paglionico VA, Sinisi AA, Wall JR, Bizzarro A, Bellastella A (2013) Time course of Graves’ ophthalmopathy after total thyroidectomy alone or followed by radioiodine therapy: a 2-year longitudinal study. Endocrine 41:320–326

    Article  Google Scholar 

  68. Moleti M, Violi MA, Montanini D, Trombetta C, Di Bella B, Sturniolo G, Presti S, Alibrandi A, Campennì A, Baldari S, Trimarchi F, Vermiglio F (2014) Radioiodine ablation of post-surgical thyroid remnants after treatment with recombinant human TSH (rhTSH in patients with moderate-to-severe Graves’ orbitopathy (GO): a prospective, randomized, single-blind clinical trial. J Clin Endocrinol Metab 99:1783–1789

  69. Fatourechi V, Bartley GB, Eghbali-Fatourechi GZ, Pwoel CC, Ahmed DF, Garrity JA (2003) Graves’ dermopathy and acropachy are markers of severe Graves’ ophthalmopathy. Thyroid 13:1141–1144

    Article  PubMed  Google Scholar 

  70. Takasu N, Higa H, Kinjou Y (2010) Treatment of pretibial myxedema (PTM) with topical steroid ointment application with sealing cover (steroid occlusive dressing technique: steroid ODT) in Graves’ patients. Intern Med 49:665–669

    Article  CAS  PubMed  Google Scholar 

  71. Susser WS, Heermans AG, Chapman MS, Baughman RD (2002) Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder. J Am Acad Dermatol 46:723–726

    Article  PubMed  Google Scholar 

  72. Vannucchi G, Campi I, Covelli D, Forzenigo L, Beck-Peccoz P, Salvi M (2013) Treatment of pretibial myxedema with dexamethasone injected subcutaneously by mesotherapy needles. Thyroid 23:626–632

    Article  CAS  PubMed  Google Scholar 

  73. Deng A, Song D (2011) Multipoint subcutaneous injection of long-acting glucocorticid as a cure for pretibial myxedema. Thyroid 21:83–85

    Article  PubMed  Google Scholar 

  74. Heyes C, Nolan R, Leahy M, Gebauer K (2012) Treatment-resistant elephantiasic thyroid dermopathy responding to rituximab and plasmapheresis. Austr J Dermatol 53:e1–e4

    Article  Google Scholar 

  75. Antonelli A, Navarranne A, Palla R, Alberti B, Saracino A, Mestre C, Roger P, Agostini S, Baschieri L (1994) Pretibial myxedema and high-dose intravenous immunoglobulin. Thyroid 4:399–408

    Article  CAS  PubMed  Google Scholar 

  76. Bartalena L (2013) Graves’ orbitopathy: imperfect treatments for a rare disease. Eur Thyroid J 2:259–269

    Article  PubMed Central  PubMed  Google Scholar 

  77. Bartalena L (2014) Rituximab, adalimumab, etanercept, tocilizumab: are biologics the future for Graves’ orbitopathy? Ophthal Plast Reconstr Surg (In press)

  78. Salvi M, Vannucchi G, Beck-Peccoz P (2013) Potential utility of rituximab for Graves’ orbitopathy. J Clin Endocrinol Metab 98:4291–4299

    Article  CAS  PubMed  Google Scholar 

  79. Minakaran N, Ezra DG (2013) Rituximab for thyroid-associated ophthalmopathy. Cochrane Datab Syst Rev 5:CD009226. doi:10.1002/14651858.CD009226.pub2

    Google Scholar 

  80. Paridaens D, van den Bosch WA, van der Loos TL, Krenning EP, van Hagen PM (2005) The effect of etanercept on Graves’ ophthalmopathy: a pilot study. Eye 19:1286–1289

    Article  CAS  PubMed  Google Scholar 

  81. Ayabe R, Rootman DB, Hwuang CJ et al. (2014) Adalimumab as steroid sparing treatment of inflammatory stage thyroid eye disease. Ophthal Plast Reconstr Surg (In press)

  82. Pérez-Moreiras JV, Alvarez-Lopez A, Cardiel Gomez E (2014) Treatment of active corticosteroid-resistant Graves’ orbitopathy. Ophthal Plast Reconstr Surg 30:162–167

    Article  PubMed  Google Scholar 

  83. van Steensel L, Paridaens D, Schrijver B, Dingjan GM, van Daele PL, van Hagen PM, van den Bosch WA, Drexhage HA, Hooijkaas H, Dik WA (2009) Imatinib mesylate and AMN107 inhibit PDGF-signaling in orbital fibroblasts: a potential treatment for Graves’ ophthalmopathy. Invest Ophtalmol Vis Sci 50:3091–3098

    Article  Google Scholar 

  84. Turcu AF, Kumar S, Neumann S, Coenen M, Iyer S, Chiriboga P, Gershengorm MC, Bahn RS (2012) A small molecule antagonist inhibits thyrotropin receptor antibody-induced orbital fibroblasts functions involved in the pathogenesis of Graves’ ophthalmopathy. J Clin Endocrinol Metab 98:2153–2159

    Article  Google Scholar 

  85. Smith TJ (2013) Is IGF-I receptor a target for autoantibody generation in Graves’ disease? J Clin Endocrinol Metab 98:515–518

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was partially supported by grants from the Ministry of Education, University and Research (MIUR, Rome, PRIN n. 2012Z3F7HE_006) to Luigi Bartalena.

Conflict of interest

None to declare.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, Ospedale di Circolo, Viale Borri, 57, 21100, Varese, Italy

    Luigi Bartalena

  2. Department of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA

    Vahab Fatourechi

Authors
  1. Luigi Bartalena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vahab Fatourechi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Luigi Bartalena or Vahab Fatourechi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bartalena, L., Fatourechi, V. Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Invest 37, 691–700 (2014). https://doi.org/10.1007/s40618-014-0097-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-014-0097-2

Keywords

Search

Navigation