, Volume 12, Issue 1, pp 39–45 | Cite as

Thyroid autoimmunity and polyglandular endocrine syndromes

  • Jean-Louis WémeauEmail author
  • Emmanuelle Proust-Lemoine
  • Amélie Ryndak
  • Laura Vanhove


Even though autoimmune thyroiditis is considered as the most emblematic type of organ-specific autoimmune disorder of autoimmunity, autoimmune thyroid diseases can be associated with other autoimmune endocrine failures or non-endocrine diseases (namely vitiligo, pernicious anemia, myasthenia gravis, autoimmune gastritis, celiac disease, hepatitis). Thyroid disorders, which are the most frequent expression of adult polyendocrine syndrome type 2, occur concomitantly with or secondarily to insulinodependent diabetes, premature ovarian failure, Addison’s disease (Schmidt syndrome, or Carpenter syndrome if associated with diabetes). Testicular failure and hypoparathyroidism are unusual. The disease is polygenic and multifactorial. Disorders of thyroid autoimmunity are, surprisingly, very rare in polyendocrine syndrome type 1 (or APECED) beginning during childhood. They are related to mutations of the AIRE gene that encodes for a transcriptional factor implicated in central and peripheral immune tolerance. Hypothyroidism can also be observed in the very rare IPEX and POEMS syndromes.

Key Words

APECED IPEX POEMS polyendocrine syndrome thyroid thyroid autoimmunity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Orgiazzi J, 2011 The treatment of Graves’ disease: current views and controversies. Presse Med 40: 1155–1162.CrossRefPubMedGoogle Scholar
  2. 2.
    Carpenter CC, Solomon N, Silverberg SG, et al, 1964 Schmidt’s syndrome (thyroid and adrenal insufficiency). A review of the literature and a report of fifteen new cases including ten instances of coexistent diabetes mellitus. Medicine (Baltimore) 43: 153–180.Google Scholar
  3. 3.
    Neufeld M, Maclaren N, Blizzard R, 1980 Autoimmune polyglandular syndromes. Pediatr Ann 9: 154–162.CrossRefPubMedGoogle Scholar
  4. 4.
    Kahaly GJ, 2009 Polyglandular autoimmune syndromes. Eur J Endocrinol 161: 11–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Proust-Lemoine E, Sangier-Veber L, Wémeau JL, 2012 Polyglandural autoimmune syndrome type 1. Presse Med 41: e651–e662.CrossRefPubMedGoogle Scholar
  6. 6.
    Proust-Lemoine E, Saugier-Véber P, Lefranc D, et al, 2010 Autoimmune polyendocrine syndrome type 1 in north-western France: AIRE gene mutation specificities and severe forms needing immunosuppressive therapies. Horm Res Paediatr 74: 275–284.CrossRefPubMedGoogle Scholar
  7. 7.
    Whitaker J, Landing BH, Esselborn VM, Williams RR, 1956 The syndrome of familial juvenile hypoadrenocorticism, hypoparathyroidism and superficial moniliasis. J Clin Endocrinol Metab 16: 1374–1387.CrossRefPubMedGoogle Scholar
  8. 8.
    Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J, 1990 Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 322: 1829–1836.CrossRefPubMedGoogle Scholar
  9. 9.
    Aaltonen J, Björses P, Sandkuijl L, Perheentupa J, Peltonen L, 1994 An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nat Genet 8: 83–87.CrossRefPubMedGoogle Scholar
  10. 10.
    Puel A, Döffinger R, Natividad A, 2010 Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 207: 291–297.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kisand K, Bøe Wolff AS, Podkrajsek KT, 2010 Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med 207: 299–308.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Alimohammadi M, Dubois N, Sköldberg F, et al, 2009 Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. Proc Natl Acad Sci U S A 106: 4396–4401.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Jovic NS, Nesovic M, Vranjesevic DN, Ciric J, Marinkovic DM, Bonaci B, 1996 The Vogt-Koyanagi-Harada syndrome: association with autoimmune polyglandular syndrome type 1. Postgrad Med J 72: 495–497.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Podkrajsek KT, Bratanic N, Krzisnik C, Battelino T, 2005 Autoimmune regulator-1 messenger ribonucleic acid analysis in a novel intronic mutation and two additional novel AIRE gene mutations in a cohort of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. J Clin Endocrinol Metab 90: 4930–4935.CrossRefPubMedGoogle Scholar
  15. 15.
    Betterle C, Zanchetta R, 2003 Update on autoimmune polyendocrine syndromes (APS). Acta Biomed 74: 9–33.PubMedGoogle Scholar
  16. 16.
    Perheentupa J, 2006 Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 91: 2843–2850.CrossRefPubMedGoogle Scholar
  17. 17.
    Dominguez M, Crushell E, Ilmarinen T, et al, 2006 Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the Irish population. J Pediatr Endocrinol Metab 19: 1343–1352.CrossRefPubMedGoogle Scholar
  18. 18.
    Cetani F, Barbesino G, Borsari S, et al, 2001 A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 86: 4747–4752.CrossRefPubMedGoogle Scholar
  19. 19.
    Betterle C, Dal Pra C, Mantero F, Zanchetta R, 2002 Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 23: 327–364. Erratum in: Endocr Rev 23: 579CrossRefPubMedGoogle Scholar
  20. 20.
    Sasso FC, Carbonara O, Di Micco P, Coppola L, Torella R, Niglio A, 2003 A case of autoimmune polyglandular syndrome developed after interferon-alpha therapy. Br J Clin Pharmacol 56: 238–239.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Krysiak R, Boldys A, Okopien B, 2011 Autoimmune polyglandular syndrome type 2 induced by treatment with interferon alpha. Am J Med Sci 341: 504–507.CrossRefPubMedGoogle Scholar
  22. 22.
    Eisenbarth GS, Gottlieb PA, 2004 Autoimmune polyendocrine syndromes. N Engl J Med 350: 2068–2079.CrossRefPubMedGoogle Scholar
  23. 23.
    Donner H, Rau H, Walfish PG, et al, 1997 CTLA4 alanine-17 confers genetic susceptibility to Graves’ disease and to type 1 diabetes mellitus. J Clin Endocrinol Metab 82: 143–146.PubMedGoogle Scholar
  24. 24.
    Donner H, Braun J, Seidl C, et al, 1997 Codon 17 polymorphism of the cytotoxic T lymphocyte antigen 4 gene in Hashimoto’s thyroiditis and Addison’s disease. J Clin Endocrinol Metab 82: 4130–4132.PubMedGoogle Scholar
  25. 25.
    Ostrov DA, Shi W, Schwartz JC, Almo SC, Nathenson SG, 2000 Structure of murine CTLA-4 and its role in modulating T cell responsiveness. Science 290: 816–819.CrossRefPubMedGoogle Scholar
  26. 26.
    Robles DT, Fain PR, Gottlieb PA, Eisenbarth GS, 2002 The genetics of autoimmune polyendocrine syndrome type II. Endocrinol Metab Clin North Am 31: 353–368.CrossRefPubMedGoogle Scholar
  27. 27.
    Begovich AB, Carlton VE, Honigberg LA, et al, 2004 A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75: 330–337.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fourati H, Bouzzid D, Abida O, et al, 2012 Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients. Human Immunol. 73: 740–746.CrossRefGoogle Scholar
  29. 29.
    Horie I, Kawasaki E, Ando T, et al, 2012 Clinical and Genetic Characteristics of Autoimmune Poyglandular Syndrome Type 3 Variant in the Japanese Population. J Clin Endocrinol Metab 97: 1043–1045.CrossRefGoogle Scholar
  30. 30.
    Porretti S, Giavoli C, Ronchi C, et al, 2002 Recombinant human GH replacement therapy and thyroid function in a large group of adult GH-deficient patients: when does L-T(4) therapy become mandatory? J Clin Endocrinol Metab 87: 2042–2045.CrossRefPubMedGoogle Scholar
  31. 31.
    Lania A, Giavoli C, Ferrante E, Beck-Peccoz P, 2008 Central hypothyroidism and growth hormone treatment: clinical care. J Endocrinol Invest 31: 66–70.PubMedGoogle Scholar
  32. 32.
    Sjöberg S, Werner S, 1999 [Increased level of TSH can be a sign of adrenal cortex failure. Not necessarily thyroid gland disease]. Lakartidningen 96: 464–465.PubMedGoogle Scholar
  33. 33.
    Faber J, Cohn D, Kirkegaard C, et al, 1979 Subclinical hypothyroidism in Addison’s disease. Acta Endocrinol (Copenh) 91: 674–679.CrossRefGoogle Scholar
  34. 34.
    Abdullatif HD, Ashraf AP, 2006 Reversible subclinical hypothyroidism in the presence of adrenal insufficiency. Endocr Pract 12: 572.CrossRefPubMedGoogle Scholar
  35. 35.
    Dittmar M, Libich C, Brenzel T, Kahaly GJ, 2011 Increased familial clustering of autoimmune thyroid diseases. Horm Metab Res 43: 200–204.CrossRefPubMedGoogle Scholar
  36. 36.
    Wildin RS, Smyk-Pearson S, Filipovich AH, 2002 Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 39: 537–545.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Bennett CL, Christie J, Ramsdell F, et al, 2001 The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27: 20–21.CrossRefPubMedGoogle Scholar
  38. 38.
    Yong PL, Russo P, Sullivan KE, 2008 Use of sirolimus in IPEX and IPEX-like children. J Clin Immunol 28: 581–587.CrossRefPubMedGoogle Scholar
  39. 39.
    Soubrier MJ, Dubost JJ, Sauvezie BJ, 1994 POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS Syndrome. Am J Med 97: 543–553.CrossRefPubMedGoogle Scholar
  40. 40.
    Dun XY, Zhou F, Xi H, Yuan ZG, Hou J, 2009 Thyroid function and its clinical significance in POEMS syndrome. Leuk Lymphoma 50: 2013–2016CrossRefPubMedGoogle Scholar
  41. 41.
    Huang W, Connor E, Rosa TD, et al, 1996 Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity. J Clin Endocrinol Metab 81: 2559–2563.PubMedGoogle Scholar
  42. 42.
    Dittmar M, Kahaly GJ, 2003 Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up. J Clin Endocrinol Metab 88: 2983–2992.CrossRefPubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2013

Authors and Affiliations

  • Jean-Louis Wémeau
    • 1
    Email author
  • Emmanuelle Proust-Lemoine
    • 1
  • Amélie Ryndak
    • 1
  • Laura Vanhove
    • 1
  1. 1.Clinique Endocrinologique Marc LinquetteService d’Endocrinologie et des Maladies Métaboliques, Hôpital Claude Huriez, 4ème Ouest, CHRULille CedexFrance

Personalised recommendations