Skip to main content
SpringerLink
Log in

Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): Etiopathogenesis, Clinical Manifestations and Diagnosis

  • Chapter
  • First Online:
Thyroid Disorders

  • 1857 Accesses

Abstract

Autoimmune thyroid disease is the most common organ-specific autoimmune disorder affecting 2–5 % of the population in Western countries. Graves-Basedow disease is the most frequent form of hyperthyroidism in iodine sufficient countries; while the exact etiology of thyroid autoimmunity is not known, interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the Major Histocompatibility Complex, Cytotoxic T Lymphocyte Antigen-4, CD40 molecule, Protein Tyrosine Phosphatase-22, TSH receptor and Thyroglobulin. The exact nature of the role environmental factors play in Graves-Basedow disease is still not well known, but the involvement of several factors such as: iodine diet, drugs, stress, and infections has been reported. In Graves-Basedow disease the lymphocytic infiltration of the thyroid leads to activation of TSH Receptor (TSHR)-reactive B-cells that secrete TSHR stimulating antibodies causing hyperthyroidism. These antibodies bind to TSH receptors on the surface of thyroid follicular cells, leading to continuous and uncontrolled thyroid stimulation, associated with excess synthesis of the thyroid hormones T4 and T3, and thyroid hypertrophy. Graves-Basedow disease includes thyrotoxicosis, goiter, exophthalmos, and pretibial myxedema when fully expressed, but can occur with one or more of these features.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Bibliography

  1. Testa AG. Delle malattie del cuore, loro cagioni, specie, segni e cura. 2nd ed, vol. 3. Bologna; 1810.

    Google Scholar 

  2. Flajani G. Sopra un tumor freddo nell’anterior parte del collo broncocele (Osservazione LXVII). Collezione d’osservazioni e reflessioni di chirurgia, Rome, Milano, A Ripa Presso Lino Contedini. 1802;3:270–3.

    Google Scholar 

  3. Basedow CA. Exophthalmos durch Hypertrophie des Zellgewebes in der Augenhöhle. Wochenschrift fur die gesammte Heilkunde Berlin. 1840;6:197–220.

    Google Scholar 

  4. Graves RJ. New observed affection of the thyroid gland in females. London Med Surg J. 1835;7:516–7.

    Google Scholar 

  5. Parry CH. Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart. In: Parry CH, editor. Collections from the unpublished medical writings of H. Parry. London: Underwoods; 1825. p. 111–29.

    Google Scholar 

  6. Young P, Finn BC, Bruetman JE. La enfermedad de Graves, signos y síntomas. An Med Interna (Madrid). 2007;24:505–8.

    CAS  Google Scholar 

  7. McKenna TJ. Graves’ disease. Eponym Lancet. 2001;357:1793–6.

    Article  CAS  PubMed  Google Scholar 

  8. McLeod Donald SA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42:252–65.

    Article  CAS  PubMed  Google Scholar 

  9. Vargas-Uricoechea H, Sierra-Torres CH, Meza-Cabrera IA. Enfermedad de Graves-Basedow. Fisiopatología y diagnóstico. Medicina (Bogotá). 2013;35,1(100):41–66.

    Google Scholar 

  10. Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009;94:1853–78.

    Article  CAS  PubMed  Google Scholar 

  11. Abraham-Nordling M, Torring O, Lantz M, Hallengren B, Ohrling H, Lundell GJ, et al. Incidence of hyperthyroidism in Stockholm, Sweden, 2003–2005. Eur J Endocrinol. 2008;158(6):823–7.

    Article  CAS  PubMed  Google Scholar 

  12. Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, et al. Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab. 2006;91:4873–80.

    Article  CAS  PubMed  Google Scholar 

  13. Ploski R, Szymanski K, Bednarczuk T. The genetic basis of Graves’ disease. Curr Genomics. 2011;12:542–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ban Y. Genetic factors of autoimmune thyroid diseases in Japanese. Autoimmune Dis. 2012;2012:9. doi:10.1155/2012/236981. Article ID 236981.

    Google Scholar 

  15. Davies TF, Latif R, Yin X. New genetic insights from autoimmune thyroid disease. J Thyroid Res. 2012;2012:6. doi:10.1155/2012/623852. Article ID 623852.

    Article  Google Scholar 

  16. Clayton DG, McKeigue PM. Epidemiological methods for studying genes and environmental factors in complex diseases. Lancet. 2001;358:1357–60.

    Article  Google Scholar 

  17. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003;33:177–82.

    Article  CAS  PubMed  Google Scholar 

  18. Płoski R, Szymański K, Bednarczuk T. The genetic basis of Graves’ disease. Curr Genomics. 2011;12:542–63.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gu LQ, Zhu W, Zhao SX, Zhao L, Zhang MJ, Cui B, Song HD, Ning G, Zhao YJ. Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves’ disease. Clin Endocrinol (Oxf). 2010;72(2):248–55.

    Article  CAS  Google Scholar 

  20. Sibarani RP. Genetics of Graves’ disease: the lost concept. Acta Med Indones. 2009;41(1):37–40.

    PubMed  Google Scholar 

  21. Brand OJ, Gough SCL. Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions. Curr Genomics. 2011;12(8):526–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nagayama Y, Nakahara M, Abiru N. Animal models of Graves’ disease and Graves’ orbitopathy. Curr Opin Endocrinol Diabetes Obes. 2015;22(5):381–6.

    Google Scholar 

  23. Nagayama Y, Nakahara M, Abiru N, Manson JE, Michels K, et al. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch Intern Med. 2005;165:1606–11.

    Article  Google Scholar 

  24. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Graves’ disease. J Clin Endocrinol Metab. 2002;87:3315–20.

    CAS  PubMed  Google Scholar 

  25. Brent GA. Clinical practice. Graves’ disease. N Engl J Med. 2008;358(24):2594–605.

    Article  CAS  PubMed  Google Scholar 

  26. Fadel BM, Ellahham S, Ringel MD, Lindsay J, Wartofsky L, Burman KD. Hyperthyroid heart disease. Clin Cardiol. 2000;23:402–8.

    Article  CAS  PubMed  Google Scholar 

  27. Mansourian AR. A review of literature on the adverse effects of hyperthyroidism on the heart functional behavior. Pak J Biol Sci. 2012;15:164–76.

    Article  PubMed  Google Scholar 

  28. Ebert EC. The thyroid and the gut. J Clin Gastroenterol. 2010;44(6):402–6.

    CAS  PubMed  Google Scholar 

  29. Maser C, Toset A, Roman S. Gastrointestinal manifestations of endocrine disease. World J Gastroenterol. 2006;12(20):3174–9.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Burman KD, McKinley-Grant L. Dermatologic aspects of thyroid disease. Clin Dermatol. 2006;24(4):247–55.

    Article  PubMed  Google Scholar 

  31. Doshi DN, Blyumin ML, Kimball AB. Cutaneous manifestations of thyroid disease. Clin Dermatol. 2008;26(3):283–7.

    Article  PubMed  Google Scholar 

  32. Niepomniszcze H, Amad RH. Skin disorders and thyroid diseases. J Endocrinol Invest. 2001;24(8):628–38.

    Article  CAS  PubMed  Google Scholar 

  33. Yudiarto FL, Muliadi L, Moeljanto D, Hartono B. Neuropsychological findings in hyperthyroid patients. Acta Med Indones. 2006;38(1):6–10.

    PubMed  Google Scholar 

  34. Canton A, de Fabregas O, Tintore M, Mesa J, Codina A, Simo R. Encephalopathy associated to autoimmune thyroid disease: a more appropriate term for an underestimated condition? J Neurol Sci. 2000;176:65–9.

    Article  CAS  PubMed  Google Scholar 

  35. Doherty C. Neurologic manifestations of thyroid disease. Neurologist. 2001;7:147–57.

    Article  Google Scholar 

  36. Wiersinga WM, Smit T, van der Gaag R, Mourits M, Koornneef L. Clinical presentation of Graves’ ophthalmopathy. Ophthalmic Res. 1989;21:73–82.

    Article  CAS  PubMed  Google Scholar 

  37. Pérez Moreiras JV, Prada Sánchez MC, Coloma J, et al. Oftalmopatía distiroidea. En: Pérez Moreiras JV, Prada Sánchez C. Patología orbitaria. Exploración, diagnóstico y cirugía. Barcelona: Edika Med 2002;2:940–90.

    Google Scholar 

  38. Gaddipati RV, Meyer DR. Eyelid retraction, lid lag, lagophthalmos, and von Graefe’s sign. Quantifying the eyelid features of Graves’ ophthalmopathy. Ophthalmology. 2008;115:1083–8.

    Article  PubMed  Google Scholar 

  39. Fernández-Hermida RV, Pinar S, Muruzábal N. Manifestaciones clínicas de la oftalmopatía tiroidea. An Sist Sanit Navar. 2008;31(Supl. 3):45–56.

    PubMed  Google Scholar 

  40. Li JH, Safford RE, Aduen JF, Heckman MG, Crook JE, Burger CD. Pulmonary hypertension and thyroid disease. Chest. 2007;132(3):793–7.

    Article  PubMed  Google Scholar 

  41. Armigliato M, Paolini R, Aggio S, Zamboni S, Galasso MP, Zonzin P, Cella G. Hyperthyroidism as a cause of pulmonary arterial hypertension: a prospective study. Angiology. 2006;57(5):600–6.

    Article  PubMed  Google Scholar 

  42. Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol. 2012;23(1):22–6.

    Article  CAS  PubMed  Google Scholar 

  43. Dhanwal DK. Thyroid disorders and bone mineral metabolism. Indian J Endocrinol Metab. 2011;15:S107–12.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mosekilde L, Eriksen EF, Charles P. Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am. 1990;19:35–63.

    CAS  PubMed  Google Scholar 

  45. Kendall-Taylor P. Thyrotoxicosis. In: Grossman A, editor. Clinical endocrinology. Oxford: Blackwell Science; 1998. p. 328–58.

    Google Scholar 

  46. Trzepacz PT, Klein I, Roberts M, Greenhouse J, Levey GS. Graves’ disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms. Am J Med. 1989;87:558–61.

    Article  CAS  PubMed  Google Scholar 

  47. Hegazi MO, Ahmed S. Atypical clinical manifestations of Graves’ disease: an analysis in depth. J Thyroid Res. 2012;2012:8. doi:10.1155/2012/768019. Article ID 768019.

    Article  Google Scholar 

  48. Kalra S, Khandewal SK, Goyal A. Clinical scoring scales in thyroidology: a compendium. Indian J Endocrinol Metab. 2011;15 Suppl 2:S89–94.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Klein I. Clinical, metabolic and organ-specific indices of thyroid function. Endocrinol Metab Clin North Am. 2001;30(2):415–27.

    Article  CAS  PubMed  Google Scholar 

  50. Klein I, Trzepacz PT, Roberts M, Levey GS. Symptom rating scale for assessing hyperthyroidism. Arch Intern Med. 1988;148:387–90.

    Article  CAS  PubMed  Google Scholar 

  51. Nayak B, Hodak SP. Hyperthyroidism. Endocrinol Metab Clin North Am. 2007;36(3):617–56.

    Article  CAS  PubMed  Google Scholar 

  52. Ross DS. Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease. Endocrinol Metab Clin North Am. 2001;30(2):245–64.

    Article  CAS  PubMed  Google Scholar 

  53. Dufour RD. Laboratory tests of thyroid function: uses and limitations. Endocrinol Metab Clin North Am. 2007;36:579–94.

    Article  CAS  PubMed  Google Scholar 

  54. Kamath C, Adlan MA, Premawardhana LD. The role of thyrotrophin receptor antibody assays in Graves’ disease. J Thyroid Res. Vol. 2012;2012:8. doi:10.1155/2012/525936. Article ID 525936.

    Article  Google Scholar 

  55. Lytton SD, Kahaly GJ. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun Rev. 2010;10(2):116–22.

    Article  CAS  PubMed  Google Scholar 

  56. Soto GD, Halperin I, Squarcia M, Lomeña F, Domingo MP. Update in thyroid imaging. The expanding world of thyroid imaging and its translation to clinical practice. Hormones (Athens). 2010;9(4):287–98.

    Article  Google Scholar 

  57. Chaudhary V, Bano S. Imaging of the thyroid: recent advances. Indian J Endocrinol Metab. 2012;16:371–6.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Meller J, Becker W. The continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound. Eur J Nucl Med. 2002;29 Suppl 2:425–38.

    Article  Google Scholar 

  59. Piga M, Cocco MC, Serra A, Boi F, Loy M, Mariotti S. The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Eur J Endocrinol. 2008;159(4):423–9.

    Article  CAS  PubMed  Google Scholar 

  60. Avci E, Narci H. Coexistence of Graves’ disease and toxic adenoma: a rare presentation of Marine-Lenhart syndrome. J Ayub Med Coll Abbottabad. 2015;27(1):248–50.

    PubMed  Google Scholar 

  61. Lagaru A, McDougall IR. Treatment of thyrotoxicosis. J Nucl Med. 2007;48:379–89.

    Google Scholar 

  62. Intenzo C, Jabbour S, Miller JL, Ahmed I, Furlong K, Kushen M, Kim SM, Capuzzi DM. Subclinical hyperthyroidism: current concepts and scintigraphic imaging. Clin Nucl Med. 2011;36(9):e107–13.

    Article  PubMed  Google Scholar 

  63. Brahma A, Beadsmoore C, Dhatariya K. The oldest case of Marine-Lenhart syndrome? JRSM Short Rep. 2012;3:21. doi:10.1258/shorts.2011.011164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. LiVolsi VA. The pathology of autoimmune thyroid disease: a review. Thyroid. 1994;4:333–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Internal Medicine Department, University of Cauca, Popayán-Cauca, Colombia

    Hernando Vargas-Uricoechea MD, MSc, Ph.Dc

  2. Division of Basic Immunology and Biomedical Sciences, University of Valle, Cali-Valle, Colombia

    Anilza Bonelo-Perdomo BSc, MSc, Ph.D

  3. Division of Genetic and Molecular Epidemiology, University of Cauca, Popayán-Cauca, Colombia

    Carlos Hernán Sierra-Torres Ph.D

  4. Laboratory of Pathology, Hospital Universitario San José, Popayán-Cauca, Colombia

    Ivonne Meza-Cabrera MD

Authors
  1. Hernando Vargas-Uricoechea MD, MSc, Ph.Dc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anilza Bonelo-Perdomo BSc, MSc, Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Hernán Sierra-Torres Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivonne Meza-Cabrera MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hernando Vargas-Uricoechea MD, MSc, Ph.Dc .

Editor information

Editors and Affiliations

  1. Internal Medicine, Al-Mouwasat Hospital, Jubail, Saudi Arabia

    Syed Khalid Imam

  2. School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

    Shamim I. Ahmad

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Vargas-Uricoechea, H., Bonelo-Perdomo, A., Sierra-Torres, C.H., Meza-Cabrera, I. (2016). Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): Etiopathogenesis, Clinical Manifestations and Diagnosis. In: Imam, S., Ahmad, S. (eds) Thyroid Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-25871-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-25871-3_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-25869-0

  • Online ISBN: 978-3-319-25871-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation