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Autoanticorpi anti-surrene nell’insufficienza corticosurrenalica primitiva

Adrenal autoantibodies in primary adrenal insufficiency

  • Rassegna
  • Published:
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine

Riassunto

Il morbo di Addison autoimmune (MAA) è causato dalla distruzione immuno-mediata delle cellule steroidosecernenti della corteccia surrenalica. Il MAA può essere isolato o essere una componente della sindrome poliendocrina di tipo 1 (SPA1) o di tipo 2 (SPA2). La SPA1 è causata da mutazioni del gene AutoImmune Regulator (AIRE) che codifica per un attivatore della trascrizione, Aire, che induce l’espressione di autoantigeni nelle cellule epiteliali della midollare timica, permettendo lo sviluppo di tolleranza immunologica. Il MAA isolato e la SPA2 sono patologie genetiche complesse causate da una distruzione delle cellule adrenocorticali mediata dai linfociti T, con un principale contributo da parte di geni del sistema HLA. Le cellule bersaglio del processo autoimmune partecipano attivamente alla reazione immune producendo chemochine, quali CXCL-10, che attraggono cellule di tipo Th1. Il principale marcatore del processo autoimmune surrenalico è rappresentato dalla comparsa in circolo di autoanticorpi contro l’enzima della steroidogenesi 21-idrossilasi (21OHAb). La determinazione dei 21OHAb è utile clinicamente per discriminare il MAA da altre forme di insufficienza corticosurrenalica primitiva. I 21OHAb sono inoltre il miglior marcatore attualmente disponibile per l’identificazione di una ooforite autoimmune in donne con insufficienza ovarica primitiva. La comparsa in circolo dei 21OHAb in pazienti con malattie endocrine autoimmuni definisce il cosiddetto MAA preclinico. Un’alterata risposta al test di stimolo con ACTH sintetico predice la futura progressione verso un MAA clinico in oltre l’80% dei casi.

Summary

Autoimmune Addison’s disease (AAD) is caused by the immuno-mediated destruction of adrenocortical cells. AAD may be isolated or a component of the autoimmune polyendocrine syndromes type 1 (APS1) and type 2 (APS2). APS1 is caused by mutations of the AutoImmune Regulator (AIRE) gene which encodes an activator of transcription, Aire, that induces expression of autoantigens in thymic medullary epithelial cells and promotes immunological tolerance. Isolated AAD and APS2 are complex genetic pathologies caused by a T-cell mediated destruction of adrenocortical cells, with major contribution of HLA genes. The target cells in the adrenal cortex participate in the immune reaction by releasing chemokines, such as CXCL-10, that are attracting Th1 cells. The major immune marker of the adrenal autoimmune process is the presence of circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase (21OHAb). Determination of 21OHAb is clinically useful to discriminate AAD from other causes of primary adrenal insufficiency. 21OHAb are also the best immune marker for identification of autoimmune oophoritis in women with primary ovarian insufficiency. Appearance of 21OHAb in patients with endocrine autoimmune diseases defines the so-called pre-clinical AAD. An impaired response to an ACTH stimulation test predicts progression towards clinical AAD in over 80% of cases.

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Bibliografia

  1. Laureti S, Vecchi L, Santeusanio F, Falorni A (1999) Is the prevalence of Addison’s disease underestimated? J Clin Endocrinol Metab 84:1762

    PubMed  CAS  Google Scholar 

  2. Løvas K, Husebye ES (2002) High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol (Oxf) 56:787–791

    Google Scholar 

  3. Oelkers W (1996) Adrenal insufficiency. N Engl J Med 335:1206–1212

    PubMed  CAS  Google Scholar 

  4. Falorni A, Minarelli V, Morelli S (2013) Therapy of adrenal insufficiency: an update. Endocrine 43:514–528

    PubMed  CAS  Google Scholar 

  5. Addison T (1855) On the constitutional and local effects of disease of the suprarenal capsules. New Sydenham Society, London. In a collection of the published writing of the late Thomas Addison, M.D., physician to Guy’s Hospital (1868). Reprinted (1937) Med Classics 2:244–293

    Google Scholar 

  6. 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

    PubMed  CAS  Google Scholar 

  7. Neufeld M, Blizzard RM (1980) Polyglandular autoimmune diseases. In: Pinchera A, Doniach D, Fenzi GF, Baschieri L (eds) Symposium on autoimmune aspects of endocrine disorders. Academic Press, New York, pp 357–365

    Google Scholar 

  8. The Finnish-German APECED Consortium (1997) An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. Nat Genet 17:399–403

    Google Scholar 

  9. Nerup J (1974) Addison’s disease-clinical studies. A report of 108 cases. Acta Endocrinol 76:127–141

    PubMed  CAS  Google Scholar 

  10. Kong MF, Jeffcoate W (1994) Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf) 41:757–761

    CAS  Google Scholar 

  11. Irvine WJ, Stewart AG, Scarth L (1967) A clinical and immunological study of adrenocortical insufficiency (Addison’s disease). Clin Exp Immunol 2:31–69

    PubMed  CAS  PubMed Central  Google Scholar 

  12. McHardy-Young S, Lessof MH, Maisey MN (1974) Serum TSH and thyroid studies in Addison’s disease. Clin Endocrinol (Oxf) 1:45–56

    Google Scholar 

  13. Irvine WJ, Toft AD, Feek CM (1979) Addison’s disease. In: James VHT (ed) The adrenal gland. Raven Press, New York, pp 131–164

    Google Scholar 

  14. De Rosa G, Corsello SM, Cecchini L et al. (1987) A clinical study of Addison’s disease. Exp Clin Endocrinol 90:232–242

    PubMed  Google Scholar 

  15. Papadopoulos KI, Hallengren B (1990) Polyglandular autoimmune syndrome type II in patients with idiopathic Addison’s disease. Acta Endocrinol 122:472–478

    PubMed  CAS  Google Scholar 

  16. Kasperlik-Zaluska AA, Migdalska B, Czarnocka B et al. (1991) Association of Addison’s disease with autoimmune disorders—a long-term observation of 180 patients. Postgrad Med J 67:984–987

    PubMed  CAS  PubMed Central  Google Scholar 

  17. Zelissen PM, Bast EJ, Croughs RJ (1995) Associated autoimmunity in Addison’s disease. J Autoimmun 8:121–130

    PubMed  CAS  Google Scholar 

  18. Söderbergh A, Winqvist O, Norheim I et al. (1996) Adrenal autoantibodies and organ-specific autoimmunity in Addison disease. Clin Endocrinol (Oxf) 45:453–460

    Google Scholar 

  19. Neufeld M, MacLaren NK, Blizzard RM (1981) Two types of autoimmune Addison’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore) 60:355–362

    CAS  Google Scholar 

  20. La Marca A, Brozzetti A, Sighinolfi G et al. (2010) Primary ovarian insufficiency: autoimmune causes. Curr Opin Obstet Gynecol 22:277–282

    PubMed  Google Scholar 

  21. Falorni A, Minarelli V, Bartoloni E et al. (2014) Diagnosis and classification of autoimmune hypophysitis. Autoimmun Rev 13:412–416

    PubMed  CAS  Google Scholar 

  22. Falorni A, Brozzetti A, La Torre D et al. (2008) The association of genetic polymorphisms and autoimmune Addison’s disease. Expert Rev Clin Immunol 4:441–456

    PubMed  CAS  Google Scholar 

  23. Yu L, Brewer KW, Gates S et al. (1999) DRB1∗04 and DQ alleles: expression of 21-hydroxylase autoantibodies and risk of progression to Addison’s disease. J Clin Endocrinol Metab 84:328–335

    PubMed  CAS  Google Scholar 

  24. Myhre AG, Undlien DE, Løvås K et al. (2002) Autoimmune adrenocortical failure in Norway autoantibodies and human leukocyte antigen class II associations related to clinical features. J Clin Endocrinol Metab 87:618–623

    PubMed  CAS  Google Scholar 

  25. Gambelunghe G, Kockum I, Bini V et al. (2005) Retrovirus-like long terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes mellitus and autoimmune Addison’s disease. Diabetes 54:900–905

    PubMed  CAS  Google Scholar 

  26. Gambelunghe G, Falorni A, Ghaderi M et al. (1999) Microsatellite polymorphism of the MHC class I chain-related (MIC-A and MIC-B) genes marks the risk for autoimmune Addison’s disease. J Clin Endocrinol Metab 84:3701–3707

    PubMed  CAS  Google Scholar 

  27. Gambelunghe G, Ghaderi M, Tortoioli C et al. (2001) Two distinct MIC-A gene markers discriminate major autoimmune diabetes types. J Clin Endocrinol Metab 86:3754–3760

    PubMed  CAS  Google Scholar 

  28. Skinningsrud B, Husebye ES, Gervin K et al. (2008) Mutation screening of PTPN22: association of the 1858T-allele with Addison’s disease. Eur J Hum Genet 16:977–982

    PubMed  CAS  Google Scholar 

  29. Brozzetti A, Marzotti S, Tortoioli C et al. (2010) Cytotoxic T Lymphocyte Antigen-4 Ala17 polymorphism is a genetic marker of autoimmune adrenal insufficiency: Italian association study and meta-analysis of European studies. Eur J Endocrinol 162:361–369

    PubMed  CAS  Google Scholar 

  30. Petrone A, Suraci C, Capizzi M et al. (2008) The Protein Tyrosine Phosphatase Non receptor (PTPN22) is associated with high GAD antibody titre in adult onset autoimmune diabetes. Diabetes Care 31:534–538

    PubMed  Google Scholar 

  31. Ghaderi M, Gambelunghe G, Tortoioli C et al. (2006) MHC2TA single nucleotide polymorphism and genetic risk for autoimmune adrenal insufficiency. J Clin Endocrinol Metab 91:4107–4111

    PubMed  CAS  Google Scholar 

  32. Skinningsrud B, Husebye E, Pearce SH et al. (2008) Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency. J Clin Endocrinol Metab 93:3310–3317

    PubMed  CAS  Google Scholar 

  33. Harton JA, Ting JP (2000) Class II transactivator: mastering the art of major histocompatibility complex expression. Mol Cell Biol 20:6185–6194

    PubMed  CAS  PubMed Central  Google Scholar 

  34. Mitchell AL, Macarthur KDR, Gan EH et al. (2014) Association of autoimmune Addison’s disease with alleles of STAT4 and GATA3 in European Cohort. PLoS ONE 9:e88991

    PubMed  PubMed Central  Google Scholar 

  35. Magitta NF, Bøe Wolff AS, Johansson S et al. (2009) A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun 10:120–124

    PubMed  CAS  Google Scholar 

  36. Freeman M, Weetman AP (1992) T and B cell reactivity to adrenal antigens in autoimmune Addison’s disease. Clin Exp Immunol 88:275–279

    PubMed  CAS  PubMed Central  Google Scholar 

  37. Hayashi Y, Hiyoshi T, Takemura T et al. (1989) Focal lymphocytic infiltration in the adrenal cortex of the elderly: immunohistological analysis of infiltrating lymphocytes. Clin Exp Immunol 77:101–105

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Nerup J, Andersen V, Bendixen G (1969) Anti-adrenal, cellular hypersensitivity in Addison’s disease. Clin Exp Immunol 4:355–363

    PubMed  CAS  PubMed Central  Google Scholar 

  39. Nerup J, Andersen V, Bendixen G (1970) Anti-adrenal, cellular hypersensitivity in Addison’s disease. IV. In vivo and in vitro investigations on the mitochondrial fraction. Clin Exp Immunol 6:733–739

    PubMed  CAS  PubMed Central  Google Scholar 

  40. Rabinowe SL, Jackson RA, Dluhy RG, Williams GH (1984) Ia-positive T lymphocytes in recently diagnosed idiopathic Addison’s disease. Am J Med 77:597–601

    PubMed  CAS  Google Scholar 

  41. Kriegel MA, Lohmann T, Gabler C et al. (2004) Defective suppressor function of human CD4+CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199:1285–1291

    PubMed  CAS  PubMed Central  Google Scholar 

  42. Coles AJ, Thompson S, Cox AL et al. (2005) Dehydroepiandrosterone replacement in patients with Addison’s disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells. Eur J Immunol 35:3694–3703

    PubMed  CAS  Google Scholar 

  43. Husebye ES, Bratland E, Bredholt G et al. (2006) The substrate-binding domain of 21-hydroxylase, the main autoantigen in autoimmune Addison’s disease, is an immunodominant T cell epitope. Endocrinology 147:2411–2416

    PubMed  CAS  Google Scholar 

  44. Rotondi M, Chiovato L, Romagnani S et al. (2007) Role of chemokines in endocrine autoimmune diseases. Endocr Rev 28:492–520

    PubMed  CAS  Google Scholar 

  45. Rotondi M, Falorni A, De Bellis A et al. (2005) Elevated serum interferon-γ-inducible chemokine-10/CXC chemokine ligand-10 in autoimmune primary adrenal insufficiency and in vitro expression in human adrenal cells primary cultures after stimulation with proinflammatory cytokines. J Clin Endocrinol Metab 90:2357–2363

    PubMed  CAS  Google Scholar 

  46. Vendrame F, Segni M, Grassetti D et al. (2006) Impaired caspase-3 expression by peripheral T cells in chronic autoimmune thyroiditis and in autoimmune polyendocrine syndrome-2. J Clin Endocrinol Metab 91:5064–5068

    PubMed  CAS  Google Scholar 

  47. Vendrame F, Santangelo C, Misasi R et al. (2005) Defective lymphocyte caspase-3 expression in type 1 diabetes mellitus. Eur J Endocrinol 152:119–125

    PubMed  CAS  Google Scholar 

  48. Anderson JR, Goudie RB, Gray KG, Timbury GC (1957) Autoantibodies in Addison’s disease. Lancet 1:1123–1124

    Google Scholar 

  49. Blizzard RM, Kyle M (1963) Studies of the adrenal antigens and autoantibodies in Addison’s disease. J Clin Invest 42:1653–1660

    PubMed  CAS  PubMed Central  Google Scholar 

  50. Goudie RB, Anderson JR, Gray KK, Whyte WG (1966) Autoantibodies in Addison’s disease. Lancet 1:1173–1176

    Google Scholar 

  51. Andrada JA, Bigazzi PL, Andrada E et al. (1968) Serological investigation on Addison’s disease. Clin Sci 206:1535–1541

    CAS  Google Scholar 

  52. Blizzard RM, Chee D, Davis W (1967) The incidence of adrenal and other autoantibodies in the sera of patients with idiopathic adrenal insufficiency (Addison’s disease). Clin Exp Immunol 2:19–30

    PubMed  CAS  PubMed Central  Google Scholar 

  53. Wuepper KD, Weigienka LC, Hugh Fudenberg H (1969) Immunologic aspect of adrenocortical insufficiency. Am J Med 46:206–216

    PubMed  CAS  Google Scholar 

  54. Irvine WJ, Barnes EW (1974) Addison’s disease and associated conditions: with particular references to premature ovarian failure, diabetes mellitus and hypoparathyroidism. In: Gell PH, Coombs RRA, Lachman P (eds) Clinical aspects of immunology. Blackwell, Oxford, pp 1301–1354

    Google Scholar 

  55. Elder M, Maclaren N, Riley W (1981) Gonadal autoantibodies in patients with hypogonadism and/or Addison disease. J Clin Endocrinol Metab 52:1137–1142

    PubMed  CAS  Google Scholar 

  56. Sotsiou F, Bottazzo GF, Doniach D (1980) Immunofluorescence studies on autoantibodies to steroid-producing cells, and to germline cells in endocrine disease and infertility. Clin Exp Immunol 39:97–111

    PubMed  CAS  PubMed Central  Google Scholar 

  57. Stechmesser E, Scherbaum WA, Grossman T, Berg PA (1985) An ELISA method for the detection of autoantibodies to adrenal cortex. J Immunol Methods 80:67–76

    Google Scholar 

  58. Kosowicz J, Gryczynska M, Bottazzo GF (1986) A radioimmunoassay for the detection of adrenal autoantibodies. Clin Exp Immunol 63:671–679

    PubMed  CAS  PubMed Central  Google Scholar 

  59. Betterle C, Volpato M, Pedini B et al. (1999) Adrenal-cortex autoantibodies (ACA) and steroid-producing cells autoantibodies (StCA) in patients with Addison’s disease: comparison between immunofluorescence and immunoprecipitation assays. J Clin Endocrinol Metab 84:618–622

    PubMed  CAS  Google Scholar 

  60. Falorni A, Laureti S, Nikoshkov A et al. (1997) 21-Hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison’s disease. Clin Exp Immunol 107:341–345

    PubMed  CAS  PubMed Central  Google Scholar 

  61. Furmaniak J, Talbot D, Reinwein D et al. (1988) Immunoprecipitation of human adrenal microsomal antigen. FEBS Lett 232:25–28

    Google Scholar 

  62. Winqvist O, Karlsson FA, Kämpe O (1992) 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 339:1559–1562

    PubMed  CAS  Google Scholar 

  63. Baumann-Antczak A, Wedlock N, Bednarek J et al. (1992) Autoimmune Addison’s disease and 21-hydroxylase. Lancet 340:429–430

    PubMed  CAS  Google Scholar 

  64. Bednarek J, Furmaniak J, Wedlock N et al. (1992) Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison’s disease. FEBS Lett 309:51–55

    PubMed  CAS  Google Scholar 

  65. Krohn K, Uibo R, Aavik E et al. (1992) Identification by molecular cloning of an autoantigen associated with addison’s disease as steroid 17α-hydroxylase. Lancet 339:770–773

    PubMed  CAS  Google Scholar 

  66. Winqvist O, Gustafsson J, Rorsman F et al. (1993) Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison’s disease. J Clin Invest 92:2377–2385

    PubMed  CAS  PubMed Central  Google Scholar 

  67. Falorni A, Nikoshkov A, Laureti S et al. (1995) High diagnostic accuracy for idiopathic Addison’s disease with a sensitive radiobinding assay for autoantibodies against recombinant human 21-hydroxylase. J Clin Endocrinol Metab 80:2752–2755

    PubMed  CAS  Google Scholar 

  68. Colls J, Betterle C, Volpato M et al. (1995) Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. Clin Chem 41:375–380

    PubMed  CAS  Google Scholar 

  69. Tanaka H, Perez MS, Powell M et al. (1997) Steroid 21-hydroxylase autoantibodies: measurements with a new immunoprecipitation assay. J Clin Endocrinol Metab 82:1440–1446

    PubMed  CAS  Google Scholar 

  70. Chen S, Sawicka J, Prentice L et al. (1998) Analysis of autoantibody epitopes on steroid 21-hydroxylase (21-OH) using a panel of monoclonal antibodies. J Clin Endocrinol Metab 83:2977–2986

    PubMed  CAS  Google Scholar 

  71. Nikoshkov A, Falorni A, Lajic S et al. (1999) A conformation-dependent epitope in Addison’s disease and other endocrinological autoimmune diseases maps to a carboxyl-terminal functional domain of human steroid 21-hydroxylase. J Immunol 162:2422–2426

    PubMed  CAS  Google Scholar 

  72. Asawa T, Wedlock N, Baumann-Antczak A et al. (1994) Naturally occurring mutations in human steroid 21-hydroxylase influence adrenal autoantibody binding. J Clin Endocrinol Metab 79:372–376

    PubMed  CAS  Google Scholar 

  73. Furmaniak J, Kominami S, Asawa T et al. (1994) Autoimmune Addison’s disease. Evidence for a role of steroid 21-hydroxylase autoantibodies in adrenal insufficiency. J Clin Endocrinol Metab 79:1517–1521

    PubMed  CAS  Google Scholar 

  74. Nikfarjam L, Kominami S, Yamazaki T et al. (2005) Mechanism of inhibition of cytochrome P450 C21 enzyme activity by autoantibodies from patients with Addison’s disease. Eur J Endocrinol 152:95–101

    PubMed  CAS  Google Scholar 

  75. Boscaro M, Betterle C, Volpato M et al. (1996) Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity block in vivo. J Clin Endocrinol Metab 81:2801–2804

    PubMed  CAS  Google Scholar 

  76. Laureti S, Candeloro P, Aglietti MC et al. (2002) Dehydroepiandrosterone, 17α-hydroxyprogesterone and aldosterone responses to the low-dose (1 μg) ACTH test in subjects with preclinical adrenal autoimmunity. Clin Endocrinol (Oxf) 57:677–683

    CAS  Google Scholar 

  77. Betterle C, Pra CD, Pedini B et al. (2004) Assessment of adrenocortical function and autoantibodies in a baby born to a mother with autoimmune polyglandular syndrome Type 2. J Endocrinol Invest 27:618–621

    PubMed  CAS  Google Scholar 

  78. Perniola R, Falorni A, Clemente MG et al. (2000) Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Eur J Endocrinol 143:497–503

    PubMed  CAS  Google Scholar 

  79. Falorni A, Laureti S, Candeloro P et al. (2002) Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity. Fertil Steril 78:270–279

    PubMed  Google Scholar 

  80. Dal Pra C, Chen S, Furmaniak J et al. (2003) Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison’s disease. Eur J Endocrinol 148:565–570

    PubMed  CAS  Google Scholar 

  81. Bakalov VK, Anasti JN, Calis KA et al. (2005) Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril 84:958–965

    PubMed  Google Scholar 

  82. Peterson P, Krohn KJ (1994) Mapping of B cell epitopes on steroid 17 alpha-hydroxylase, an autoantigen in autoimmune polyglandular syndrome type I. Clin Exp Immunol 98:104–109

    PubMed  CAS  PubMed Central  Google Scholar 

  83. Liiv I, Teesalu K, Peterson P et al. (2002) Epitope mapping of cytochrome P450 cholesterol side-chain cleavage enzyme by sera from patients with autoimmune polyglandular syndrome type 1. Eur J Endocrinol 146:113–119

    PubMed  CAS  Google Scholar 

  84. Hoek A, Schoemaker J, Drexhage HA (1997) Premature ovarian failure and ovarian autoimmunity. Endocrinol Rev 18:107–134

    CAS  Google Scholar 

  85. Dalla Costa M, Bonanni G, Masiero S et al. (2014) Gonadal function in males with autoimmune Addison’s disease and autoantibodies to steroidogenic enzymes. Clin Exp Immunol 176:373–379

    PubMed  CAS  Google Scholar 

  86. Meager A, Visvalingam K, Peterson P et al. (2006) Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med 3:e289

    PubMed  PubMed Central  Google Scholar 

  87. Meloni A, Furcas M, Cetani F et al. (2008) Autoantibodies against type I Interferons as an additional diagnostic criteria for Autoimmune Polyendocrine Syndrome type I. J Clin Endocrinol Metab 93:4389–4397

    PubMed  CAS  Google Scholar 

  88. Oftedal BE, Wolff AS, Bratland E et al. (2008) Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I. Clin Immunol 129:163–169

    PubMed  CAS  Google Scholar 

  89. Falorni A, Laureti S, De Bellis A et al. (2004) Italian Addison Network Study: update of diagnostic criteria for the etiological classification of primary adrenal insufficiency. J Clin Endocrinol Metab 89:1598–1604

    PubMed  CAS  Google Scholar 

  90. Husebye ES, Allolio B, Arlt W et al. (2014) Consensus statement on the diagnosis, treatment and follow-up o patients with primary adrenal insufficiency. J Intern Med 275:104–115

    PubMed  CAS  Google Scholar 

  91. Nomura K, Depura H, Saruta T (1994) Addison’s disease in Japan: characteristics and changes revealed in a nationwide survey. Intern Med 33:602–606

    PubMed  CAS  Google Scholar 

  92. do Carmo Silva R, Kater CE, Dib SA et al. (2000) Autoantibodies against recombinant human steroidogenic enzyme 21-hydroxylase, side-chain cleavage and 17α-hydroxylase in Addison’s disease and autoimmune polyendocrine syndrome type III. Eur J Endocrinol 142:187–194

    CAS  Google Scholar 

  93. Bellastella G, Rotondi M, Pane E et al. (2010) Predictive role of the immunostaining pattern of immunofluorescence and the titers of antipituitary antibodies at presentation for the occurrence of autoimmune hypopituitarism in patients with autoimmune polyendocrine syndromes over a 5-year follow-up. J Clin Endocrinol Metab 95:3750–3757

    PubMed  CAS  Google Scholar 

  94. De Bellis A, Pane E, Bellastella G et al. (2011) Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism. Clin Endocrinol (Oxf) 75:361–366

    Google Scholar 

  95. Falorni A, Chen S, Zanchetta R et al. (2011) Measuring adrenal autoantibody response: interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies. Clin Immunol 140:291–299

    PubMed  CAS  Google Scholar 

  96. Aubourg P (1999) On the front of X-linked adrenoleukodystrophy. Neurochem Res 24:515–520

    PubMed  CAS  Google Scholar 

  97. Betterle C, Scalici C, Presotto F et al. (1988) The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J Endocrinol 117:467–475

    PubMed  CAS  Google Scholar 

  98. De Bellis A, Falorni A, Laureti S et al. (2001) Time course of 21-hydroxylase antibodies and long-term remission of subclinical autoimmune adrenalitis after corticosteroid therapy: case report. J Clin Endocrinol Metab 86:675–678

    Google Scholar 

  99. De Bellis A, Bizzarro A, Rossi R et al. (1993) Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies. J Clin Endocrinol Metab 76:1002–1007

    PubMed  Google Scholar 

  100. Betterle C, Volpato M, Rees-Smith B et al. (1997) I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison’s disease. J Clin Endocrinol Metab 82:932–938

    PubMed  CAS  Google Scholar 

  101. Laureti S, De Bellis A, Muccitelli VI et al. (1998) Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison’s disease. J Clin Endocrinol Metab 83:3507–3511

    PubMed  CAS  Google Scholar 

  102. Barker JM, Ide A, Hostetler C et al. (2005) Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison’s disease in a high-risk population. J Clin Endocrinol Metab 90:128–134

    PubMed  CAS  Google Scholar 

  103. Coco G, Dal Pra C, Presotto F et al. (2006) Estimated risk for developing autoimmune Addison’s disease in patients with adrenal cortex autoantibodies. J Clin Endocrinol Metab 91:1637–1645

    PubMed  CAS  Google Scholar 

  104. Arvat E, Di Vito L, Laffranco F et al. (2000) Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: dose–response study. J Clin Endocrinol Metab 88:3141–3146

    Google Scholar 

  105. Laureti S, Arvat E, Candeloro P (2000) Low dose (1 μg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison’s disease. Clin Endocrinol (Oxf) 53:107–115

    CAS  Google Scholar 

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  1. Dipartimento di Medicina, Università di Perugia, Via E. Dal Pozzo, 06126, Perugia, Italia

    Annalisa Brozzetti, Silvia Morelli & Alberto Falorni

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Brozzetti, A., Morelli, S. & Falorni, A. Autoanticorpi anti-surrene nell’insufficienza corticosurrenalica primitiva. Riv Ital Med Lab 10, 141–150 (2014). https://doi.org/10.1007/s13631-014-0063-1

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  • DOI: https://doi.org/10.1007/s13631-014-0063-1

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