Skip to main content

Advertisement

SpringerLink
Log in

The thyroid, the eyes and the gut: a possible connection

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

Abstract

Introduction

Graves’ disease (GD) is an autoimmune disorder responsible for 60–90% of thyrotoxicosis, with an incidence of 1 to 2 cases per 1000 population per year in England. Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation, not provoked directly by abnormal thyroid hormone levels, but by the consequence of the underlying autoimmune process. The aetiology of autoimmune disorders is due to an interplay between susceptibility genes and environmental factors, such as infections and stress. What triggers the autoimmune reaction to a specific site of the body is not yet clearly understood. The lack of knowledge in GD and GO pathogenesis implicates therapies that only limit damage but do not prevent disease onset.

Material and methods

We performed on PubMed and the Cochrane Library a literature search for the articles published until July 2016 by using the search terms ‘graves disease’ and ‘microbiome’, ‘orbitopathy’ and ‘autoimmune pathogenesis’. Reference lists of relevant studies were hand-searched for additional studies.

Conclusion

In this scenario, a Marie Sklodowska–Curie funded project INDIGO (http://www.indigo-iapp.eu/) is investigating the role of the gut bacteria in GD and GO pathogenesis. The gut is the first and the widest area of bacteria access, with the highest concentration of T cells in the human body and trained to react to microorganisms. Interestingly, all the environmental factors involved in GD and GO pathogenesis can alter the balance within the microorganisms located in the gut, and influence the immune system, in particular the proportions of regulatory Treg and inflammatory TH17 cells. It is hoped that investigating GD and GO pathogenesis from this novel aspect will identify new targets for prevention and treatment.

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

Similar content being viewed by others

References

  1. DeGroot LJ (2016) Graves’ disease and the manifestations of thyrotoxicosis in www.thyroidmanager.com, last update 14 July 2016. Published by ENDOCRINE EDUCATION Inc, South Dartmouth, MA

  2. Bartalena L, Fatourechi V (2014) Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Investig 37(8):691–700. doi:10.1007/s40618-014-0097-2

    Article  CAS  Google Scholar 

  3. Potgieser PW, Wiersinga WM et al (2015) Some studies on the natural history of Graves’ orbitopathy: increase in orbital fat is a rather late phenomenon. Eur J Endocrinol 173(2):149–153. doi:10.1530/EJE-14-1140

    Article  CAS  PubMed  Google Scholar 

  4. Abraham-Nordling M, Byström K et al (2011) Incidence of hyperthyroidism in Sweden. Eur J Endocrinol 165(6):899–905. doi:10.1530/EJE-11-0548

    Article  CAS  PubMed  Google Scholar 

  5. Laurberg P, Berman DC et al (2012) Incidence and clinical presentation of moderate to severe graves’ orbitopathy in a Danish population before and after iodine fortification of salt. J Clin Endocrinol Metab 97(7):2325–2332. doi:10.1210/jc.2012-1275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Perros P, Žarković M et al (2015) 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. doi:10.1136/bjophthalmol-2015-306733

    PubMed  Google Scholar 

  7. Wang Y, Smith TJ (2014) Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Investig Ophthalmol Vis Sci 55(3):1735–1748. doi:10.1167/iovs.14-14002

    Article  CAS  Google Scholar 

  8. Marinò M, Latrofa F, Menconi F, Chiovato L, Vitti P (2015) Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig 38(3):283–294. doi:10.1007/s40618-014-0214-2

    Article  Google Scholar 

  9. Rapoport B, McLachlan SM (2014) Graves’ hyperthyroidism is antibody-mediated but is predominantly a Th1-type cytokine disease. J Clin Endocrinol Metab 99(11):4060–4061. doi:10.1210/jc.2014-3011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ludgate M (2000) Animal models of Graves’ disease. Eur J Endocrinol 142:1–8

    Article  CAS  PubMed  Google Scholar 

  11. Nagayama Y (2007) Graves’ animal models of Graves’ hyperthyroidism. Thyroid 17(10):981–988

    Article  CAS  PubMed  Google Scholar 

  12. Jenkins RC, Weetman AP (2002) Disease associations with autoimmune thyroid disease. Thyroid 12(11):977–988

    Article  PubMed  Google Scholar 

  13. Draman MS, Ludgate M (2016) Thyroid eye disease-an update. Expert Rev Ophthalmol. doi:10.1080/17469899.2016.1202113

    Google Scholar 

  14. Zhang L, Baker G et al (2006) Biological effects of thyrotropin receptor activation on human orbital preadipocytes. Investig Ophthalmol Vis Sci 47(12):5197–5203

    Article  Google Scholar 

  15. Kumar S, Nadeem S et al (2011) A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves’ ophthalmopathy. J Mol Endocrinol 46(3):155–163. doi:10.1530/JME-11-0006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wakelkamp IM, Gerding MN et al (2000) Both Th1- and Th2-derived cytokines in serum are elevated in Graves’ ophthalmopathy. Clin Exp Immunol 121:453–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Eckstein AK, Plicht M et al (2006) Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 91(9):3464–3470

    Article  CAS  PubMed  Google Scholar 

  18. Banga JP, Moshkelgosha S et al (2015) Modeling Graves’ orbitopathy in experimental Graves’ disease. Horm Metab Res 47(10):797–803. doi:10.1055/s-0035-1555956. (Erratum in: Horm Metab Res 2015 Sep 47(10):e4)

  19. Berchner-Pfannschmidt U, Moshkelgosha S et al (2016) Comparative assessment of female mouse model of graves’ orbitopathy under different environments, accompanied by proinflammatory cytokine and T-cell responses to thyrotropin hormone receptor antigen. Endocrinology 157(4):1673–1682. doi:10.1210/en.2015-1829

    Article  CAS  PubMed  Google Scholar 

  20. Smith TJ, Huetwell FGL et al (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  PubMed Central  Google Scholar 

  21. Song D, Wang R et al (2012) Locally produced insulin-like growth factor-1 by orbital fibroblasts as implicative pathogenic factor rather than systemically circulated IGF-1 for patients with thyroid-associated ophthalmopathy. Graefes Arch Clin Exp Ophthalmol 250:433–440

    Article  CAS  PubMed  Google Scholar 

  22. Krieger CC, Neumann S et al (2015) Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by Graves’ disease immunoglobins. J Clin Endocrinol Metab 100(3):1071–1077. doi:10.1210/jc.2014-3566

    Article  CAS  PubMed  Google Scholar 

  23. Villanueva R, Greenberg DA et al (2003) Sibling recurrence risk in autoimmune thyroid disease. Thyroid 13(8):761–764

    Article  CAS  PubMed  Google Scholar 

  24. Brix TH, Kyvik KO et al (2001) Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab 86:930–934

    CAS  PubMed  Google Scholar 

  25. Lee HJ, Li CW et al (2015) Immunogenetics of autoimmune thyroid diseases: a comprehensive review. J Autoimmun. doi:10.1016/j.jaut.2015.07.009

    Google Scholar 

  26. Effraimidis G, Wiersinga WM (2014) Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol 170(6):R241–R252. doi:10.1530/EJE-14-0047

    Article  CAS  PubMed  Google Scholar 

  27. Nakano A, Watanabe M et al (2007) Apoptosis-induced decrease of intrathyroidal CD4(+)CD25(+) regulatory T cells in autoimmune thyroid diseases. Thyroid 17(1):25–31

    Article  CAS  PubMed  Google Scholar 

  28. Marazuela M, Garcia-Lopez MA et al (2006) Regulatory T cells in human autoimmune thyroid disease. J Clin Endocrinol Metab 91(9):3639–3646

    Article  CAS  PubMed  Google Scholar 

  29. Glick AB, Wodzinski A et al (2013) Impairment of regulatory T-cell function in autoimmune thyroid disease. Thyroid 23(7):871–878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kula D, Bednarczuk T et al (2006) Interaction of HLA-DRB1 alleles with CTLA-4 in the predisposition to Graves’ disease: the impact of DRB1*07. Thyroid 16(5):447–453

    Article  CAS  PubMed  Google Scholar 

  31. Ban Y, Tozaki T et al (2005) The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase-22 gene does not contribute to autoimmune thyroid disease susceptibility in the Japanese. Thyroid 15(10):1115–1118

    Article  CAS  PubMed  Google Scholar 

  32. Lopez ER, Zwermann O et al (2004) A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and type 1 diabetes mellitus in Germans. Eur J Endocrinol 151(2):193–197

    Article  CAS  PubMed  Google Scholar 

  33. Cuddihy RM, Dutton CM, Bahn RS (1995) A polymorphism in the extracellular domain of the thyrotropin receptor is highly associated with autoimmune thyroid disease in females. Thyroid 5:89–95

    Article  CAS  PubMed  Google Scholar 

  34. Kotsa KD, Watson PF, Weetman AP (1997) No association between a thyrotropin receptor gene polymorphism and Graves’ disease in the female population. Thyroid 7:31

    Article  CAS  PubMed  Google Scholar 

  35. Hiratani H, Bowden DW et al (2005) Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves’ disease. J Clin Endocrinol Metab 90(5):2898–2903

    Article  CAS  PubMed  Google Scholar 

  36. Dechairo BM, Zabaneh D et al (2005) Association of the TSHR gene with Graves’ disease: the first disease specific locus. Eur J Hum Genet 13(11):1223–1230

    Article  CAS  PubMed  Google Scholar 

  37. Płoski R, Brand OJ et al (2010) Thyroid stimulating hormone receptor (TSHR) intron 1 variants are major risk factors for Graves’ disease in three European Caucasian cohorts. PLoS ONE 5(11):e15512. doi:10.1371/journal.pone.0015512

    Article  PubMed  PubMed Central  Google Scholar 

  38. Huber AK, Jacobson EM et al (2008) Interleukin (IL)-23 receptor is a major susceptibility gene for Graves’ ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 93:1077–1081

    Article  CAS  PubMed  Google Scholar 

  39. Khalilzadeh O, Anvari M et al (2009) Graves’ ophthalmopathy and gene polymorphisms in interleukin-1alpha, interleukin-1beta, interleukin-1 receptor and interleukin-1 receptor antagonist. Clin Exp Ophthalmol 37:614–619

    Article  PubMed  Google Scholar 

  40. Daroszewski J, Pawlak E et al (2009) Soluble CTLA-4 receptor an immunological marker of Graves’ disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms. Eur J Endocrinol 161:787–793

    Article  CAS  PubMed  Google Scholar 

  41. Alevizaki M, Mantzou E et al (2009) The Pro12Ala PPARgamma gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO). Clin Endocrinol (Oxf) 70:464–468

    Article  CAS  Google Scholar 

  42. Vannucchi G, Covelli D et al (2013) The therapeutic outcome to intravenous steroid therapy for active Graves’orbitopathy is influenced by the time of response but not polymorphisms of the glucocorticoid receptor. Eur J Endocrinol 170(1):55–61. doi:10.1530/EJE-13-0611

    Article  PubMed  Google Scholar 

  43. Feldon SE, Park DJJ et al (2005) Autologous T-lymphocytes stimulate proliferation of orbital fibroblasts derived from patients with Graves’ ophthalmopathy. Investig Ophthalmol Vis Sci 46:3913–3921

    Article  Google Scholar 

  44. Antonelli A, Ferrari SM et al (2015) Autoimmune thyroid disorders. Autoimmun Rev 14(2):174–180. doi:10.1016/j.autrev.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  45. Campi I, Tosi D et al (2015) B cell-activating factor (BAFF) and Baff receptor expression in autoimmune and non autoimmune thyroid diseases. Thyroid 25(9):1043–1049. doi:10.1089/thy.2015.0029

    Article  CAS  PubMed  Google Scholar 

  46. Prabhakar BS, Bahn RS, Smith TJ (2003) Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev 24:802–835

    Article  CAS  PubMed  Google Scholar 

  47. Ajjan AR, Weetman AP (2004) New understanding of the role of cytokines in the pathogenesis of Graves’ ophthalmopathy. J Endocrinol Investig 27:237–245

    Article  CAS  Google Scholar 

  48. Salvi M, Campi I (2015) Medical treatment of Graves’ orbitopathy. Horm Metab Res 47(10):779–788. doi:10.1055/s-0035-1554721

    Article  CAS  PubMed  Google Scholar 

  49. Schmidt M, Gorbauch E et al (2006) Incidence of postradioiodine immunogenic hyperthyroidism/Graves’ disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease. Thyroid 16(3):281–288

    Article  CAS  PubMed  Google Scholar 

  50. Laurberg P, Wallin G et al (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(1):69–75. doi:10.1530/EJE-07-0450

    Article  CAS  PubMed  Google Scholar 

  51. Träisk F, Tallstedt L et al (2009) Thyroid Study Group of TT 96. Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94(10):3700–3707. doi:10.1210/jc.2009-0747

    Article  PubMed  Google Scholar 

  52. Mukuta T, Arreaza G et al (1997) Thyroid xenografts from patients with Graves’ disease in severe combined immunodeficient mice and NIH-beige-nude-xid mice. Clin Investig Med 20:5–15

    CAS  Google Scholar 

  53. Kisiel B, Bednarczuk T et al (2008) Polymorphism of the oestrogen receptor beta gene (ESR2) is associated with susceptibility to Graves’ disease. Clin Endocrinol (Oxf) 68(3):429–434

    Article  CAS  Google Scholar 

  54. Cirello V, Rizzo R et al (2015) Fetal cell microchimerism: a protective role in autoimmune thyroid diseases. Eur J Endocrinol 173(1):111–118. doi:10.1530/EJE-15-0028

    Article  CAS  PubMed  Google Scholar 

  55. Yin X, Latif R et al (2007) Thyroid epigenetics: X chromosome inactivation in patients with autoimmune thyroid disease. Ann N Y Acad Sci 1110:193–200

    Article  CAS  PubMed  Google Scholar 

  56. Carmi G, Amital H (2011) The geoepidemiology of autoimmunity: capsules from the 7th international congress on autoimmunity, Ljubljana, Slovenia, May 2010. Isr Med Assoc J 13(2):121–127

    PubMed  Google Scholar 

  57. Chiovato L, Pinchera A (1996) Stressful life events and Graves’ disease. Eur J Endocrinol 134:680–682

    Article  CAS  PubMed  Google Scholar 

  58. Effraimidis G, Tijssen JG et al (2012) Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study. Psychoneuroendocrinology 37(8):1191–1198. doi:10.1016/j.psyneuen.2011.12.009

    Article  CAS  PubMed  Google Scholar 

  59. Brix TH, Hansen PS et al (2000) Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med 160:661–666

    Article  CAS  PubMed  Google Scholar 

  60. Vestergaard P (2002) Smoking and thyroid disorders: a meta-analysis. Eur J Endocrinol 146:153–161

    Article  CAS  PubMed  Google Scholar 

  61. Cawood TJ, Moriarty P et al (2007) Smoking and thyroid-associated ophthalmopathy: a novel explanation of the biological link. J Clin Endocrinol Metab 92(1):59–64

    Article  CAS  PubMed  Google Scholar 

  62. Wick G, Trieb K et al (1993) Possible role of human foamy virus in Graves’ disease. Intervirology 35:101–107

    Article  CAS  PubMed  Google Scholar 

  63. Hammerstad SS, Tauriainen S et al (2013) Detection of enterovirus in the thyroid tissue of patients with graves’ disease. J Med Virol 85(3):512–518. doi:10.1002/jmv.23476

    Article  CAS  PubMed  Google Scholar 

  64. Tomoyose T, Komiya I et al (2002) Cytotoxic T-lymphocyte antigen-4 gene polymorphisms and human T-cell lymphotrophic virus-1 infection: their associations with Hashimoto’s thyroiditis in Japanese patients. Thyroid 12:673–677

    Article  CAS  PubMed  Google Scholar 

  65. Nagata K, Higaki K et al (2014) Presence of Epstein–Barr virus-infected B lymphocytes with thyrotropin receptor antibodies on their surface in Graves’ disease patients and in healthy individuals. Autoimmunity 47(3):193–200. doi:10.3109/08916934.2013.879863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hargreaves CE, Grasso M et al (2013) Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves’ disease. J Immunol 190(11):5373–5381. doi:10.4049/jimmunol.1203412

    Article  CAS  PubMed  Google Scholar 

  67. Bassi V, Santinelli C et al (2010) Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter 15(6):558–562. doi:10.1111/j.1523-5378.2010.00802.x

    Article  PubMed  Google Scholar 

  68. Wang Y, Zhu S et al (2013) Interaction between gene A-positive Helicobacter pylori and human leukocyte antigen II alleles increase the risk of Graves disease in Chinese Han population: an association study. Gene 531(1):84–89. doi:10.1016/j.gene.2013.07.069

    Article  CAS  PubMed  Google Scholar 

  69. Gregoric E, Gregoric JA et al (2011) Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens. Endocrine 39(1):41–47. doi:10.1007/s12020-010-9410-9

    Article  CAS  PubMed  Google Scholar 

  70. Tonstad S, Nathan E et al (2015) Prevalence of hyperthyroidism according to type of vegetarian diet. Public Health Nutr 18(8):1482–1487. doi:10.1017/S1368980014002183

    Article  PubMed  Google Scholar 

  71. Dominguez-Bello MG, Costello EK et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107:11971–11975

    Article  PubMed  PubMed Central  Google Scholar 

  72. Smythies LE, Sellers M et al (2005) Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Investig 115:66–75 PMID:15630445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Soderholm JD, Perdue MH (2001) Stress and gastrointestinal tract. II. Stress and intestinal barrier function. Am J Physiol Gastrointest Liver Physiol 280:G7–G13

    CAS  PubMed  Google Scholar 

  74. Lyte M, Vulchanova L, Brown DR (2011) Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res 343:23–32

    Article  CAS  PubMed  Google Scholar 

  75. Biedermann L, Brülisauer K et al (2014) Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH. Inflamm Bowel Dis 20(9):1496–1501

    Article  PubMed  Google Scholar 

  76. Benjamin JL, Hedin CR et al (2012) Smokers with active Crohn’s disease have a clinically relevant dysbiosis of the gastrointestinal microbiota. Inflamm Bowel Dis 18(6):1092–1100

    Article  PubMed  Google Scholar 

  77. Turnbaugh PJ, Ridaura VK et al (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. doi:10.1126/scitranslmed.3000322

    PubMed  PubMed Central  Google Scholar 

  78. Zimmer J, Lange B et al (2012) A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr 66:53–60

    Article  CAS  PubMed  Google Scholar 

  79. De Filippo C, Cavalieri D et al (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from europe and rural africa. Proc Natl Acad Sci USA 107:14691–14696

    Article  PubMed  PubMed Central  Google Scholar 

  80. Rescigno M (2015) Dendritic cell functions: learning from microbial evasion strategies. Semin Immunol 27(2):119–124. doi:10.1016/j.smim.2015.03.012

    Article  CAS  PubMed  Google Scholar 

  81. Williams AM, Probert CS et al (2006) Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse. Immunology 119:470–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gaboriau-Routhiau V, Rakotobe S et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31:677–689. doi:10.1016/j.immuni.2009.08.020

    Article  CAS  PubMed  Google Scholar 

  83. Atarashi K, Tanoue T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341. doi:10.1126/science.1198469

    Article  CAS  PubMed  Google Scholar 

  84. Wei B, Su TT et al (2008) Resident enteric microbiota and CD8 + T cells shape the abundance of marginal zone B cells. Eur J Immunol 38(12):3411–3425. doi:10.1002/eji.200838432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Wu HJ, Wu E (2012) The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3(1):4–14. doi:10.4161/gmic.19320

    Article  PubMed  PubMed Central  Google Scholar 

  86. Shor DB, Orbach H et al (2012) Gastrointestinal-associated autoantibodies in different autoimmune diseases. Am J Clin Exp Immunol 1(1):49–55

    PubMed  PubMed Central  Google Scholar 

  87. Shizuma T (2016) Concomitant thyroid disorders and inflammatory bowel disease: a literature review. Biomed Res Int 2016:5187061. doi:10.1155/2016/5187061

    Article  PubMed  PubMed Central  Google Scholar 

  88. Ponto KA, Schuppan D et al (2014) Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity. Clin Exp Immunol 178(1):57–64. doi:10.1111/cei.12395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Graves’ Orbitopathy Centre, Endocrinology, Department of Clinical Sciences and Community Health, Fondazione Ca’Granda IRCCS, University of Milan, via Sforza 35, 20122, Milan, Italy

    D. Covelli

  2. Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

    M. Ludgate

Authors
  1. D. Covelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Ludgate
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Covelli.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The article does not contain any data using human subjects or animal experiments performed by the authors.

Informed consent

No informed consent.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Covelli, D., Ludgate, M. The thyroid, the eyes and the gut: a possible connection. J Endocrinol Invest 40, 567–576 (2017). https://doi.org/10.1007/s40618-016-0594-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-016-0594-6

Keywords

Search

Navigation