Journal of Endocrinological Investigation

, Volume 38, Issue 3, pp 283–294 | Cite as

Role of genetic and non-genetic factors in the etiology of Graves’ disease

  • M. MarinòEmail author
  • F. Latrofa
  • F. Menconi
  • L. Chiovato
  • P. Vitti


In spite of the advancements in understanding the pathogenic mechanisms of Graves’ disease (GD), its ultimate cause remains elusive. The majority of investigators agree that GD is likely a multifactorial disease, due to a complex interplay of genetic and non-genetic factors that lead to the loss of immune tolerance to thyroid antigens and to the initiation of a sustained autoimmune reaction. Twin and family studies support a role of genetic factors, among which the HLA complex, CD40, CTLA-4, PTPN22, FCRL3, thyroglobulin, and the TSH receptor may be involved. Among non-genetic factors, iodine, infections, psychological stress, gender, smoking, thyroid damage, vitamin D, selenium, immune modulating agents, and periods of immune reconstitution may contribute the development of the diseases. Here we review in detail the respective role of genetic and non-genetic factors in the etiology of GD, taking advantage of the great bulk of data generated especially over the past 30 years.


Graves’ disease Hyperthyroidism Autoimmunity Genetics Environment 


Conflict of interest

The authors declare that they do not have any conflict of interest that could be perceived as prejudicing the impartiality of the manuscript.


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Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • M. Marinò
    • 1
    • 2
    Email author
  • F. Latrofa
    • 1
    • 2
  • F. Menconi
    • 1
    • 2
  • L. Chiovato
    • 3
  • P. Vitti
    • 1
    • 2
  1. 1.Department of Clinical and Experimental MedicineUniversity Of PisaPisaItaly
  2. 2.Endocrinology UnitUniversity Hospital of PisaPisaItaly
  3. 3.Unit of Endocrinology, Department of Internal Medicine and Medical TherapyUniversity of Pavia, Fondazione Salvatore Maugeri IRCCSPaviaItaly

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