This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dittmar, M. Articles by Kahaly, G. J. Search for Related Content PubMed PubMed Citation Articles by Dittmar, M. Articles by Kahaly, G. J.

Polyglandular Autoimmune Syndromes: Immunogenetics and Long-Term Follow-Up

Departments of Medicine I (M.D., G.J.K.) and Biology (M.D.), Gutenberg University, Mainz, Germany 55101

Address all correspondence and requests for reprints to: Prof. George J. Kahaly, Department of Medicine I, Gutenberg University Hospital, Mainz 55101, Germany. E-mail: gkahaly{at}mail.uni-mainz.de.

Polyglandular autoimmune syndromes (PAS) are rare polyendocrinopathies characterized by the failure of several endocrine glands as well as nonendocrine organs, caused by an immune-mediated destruction of endocrine tissues. This article summarizes extensive clinical, epidemiological, serological, and genetic data of a large collective of patients with PAS (n = 360). Since 1988, more than 15,000 adult patients with endocrine diseases have been screened at the endocrine center of the Mainz University, and 151 of 360 patients with PAS have regularly been followed. Type 1 diabetes, Graves’ disease, Hashimoto thyroiditis, Addison’s disease, vitiligo, alopecia, hypogonadism, and pernicious anemia were observed in 61%, 33%, 33%, 19%, 20%, 6%, 5%, and 5%, respectively. The most common disease combination was type 1 diabetes and autoimmune thyroid disease. In most patients, type 1 diabetes was the first manifestation of PAS (48%). The longest time intervals between manifestations of the first and second immune endocrinopathies occurred between type 1 diabetes and thyroid disease (13.3 ± 11.8 yr) and between vitiligo and thyroid disease (16.3 ± 13.3 yr), but a shorter time interval was observed between Addison’s and thyroid diseases. Of the 471 patients with type 1 diabetes screened, 83 (17.6%) were positive for PAS. Subsequently, sera of 126 patients with PAS, 287 with type 1 diabetes, and 303 matched controls were compared for human leukocyte antigens. Patients with PAS had significantly higher frequencies of the human leukocyte antigens A24, A31, B8, B51, B62, DR3, and DR4 (relative risk, 2.35, 2.74, 2.47, 7.17, 2.22, 1.94, and 2.46) vs. controls, and for A31, B15, B52, B55, DR2, DR11, and DR13 (relative risk, 2.51, 7.96, 3.99, 5.36, 4.46, 2.89, and 3.26) vs. type 1 diabetes patients without PAS. In conclusion, patients with autoimmune endocrine disease should be followed on a regular basis. In subjects at risk for PAS, functional screening every 3 yr is warranted. If clinical disease is present, serological measurement of organ-specific antibodies should follow.

This study contains parts of the doctoral theses of S. Drewitz, C. Kautzmann, U. Klein, A. Leischker, and J. Svitek (Endocrine Research Laboratory).

Abbreviations: AIRE, Autoimmune regulator; DR, HLA class locus; GAD, glutamic acid decarboxylase; HLA, human leukocyte antigen; IA2, protein tyrosine phosphatase; ICA, islet cell autoantibodies; 21-OH, 21-hydroxylase; PAS, polyglandular autoimmune syndrome(s); RR, relative risk; Tg, thyroglobulin; Th, T helper cell; TPO, thyroid peroxidase.

This article has been cited by other articles:

				D. Shoback Hypoparathyroidism N. Engl. J. Med., July 24, 2008; 359(4): 391 - 403. [Full Text] [PDF]

				M. Dittmar, M. Ide, M. Wurm, and G. J Kahaly Early onset of polyglandular failure is associated with HLA-DRB1*03. Eur. J. Endocrinol., July 1, 2008; 159(1): 55 - 60. [Abstract] [Full Text] [PDF]

				D. P Macfarlane, S. Forbes, and B. R Walker Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome J. Endocrinol., May 1, 2008; 197(2): 189 - 204. [Abstract] [Full Text] [PDF]

				B. R Walker Glucocorticoids and Cardiovascular Disease Eur. J. Endocrinol., November 1, 2007; 157(5): 545 - 559. [Abstract] [Full Text] [PDF]

				D. J. Wake, R. H. Stimson, G. D. Tan, N. Z. M. Homer, R. Andrew, F. Karpe, and B. R. Walker Effects of Peroxisome Proliferator-Activated Receptor-{alpha} and -{gamma} Agonists on 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Subcutaneous Adipose Tissue in Men J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1848 - 1856. [Abstract] [Full Text] [PDF]

				Y. Loh, Y. Oyama, L. Statkute, K. Quigley, K. Yaung, E. Gonda, W. Barr, B. Jovanovic, R. Craig, D. Stefoski, et al. Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used Blood, March 15, 2007; 109(6): 2643 - 2548. [Abstract] [Full Text] [PDF]

				B. R WALKER and R. ANDREW Tissue Production of Cortisol by 11beta-Hydroxysteroid Dehydrogenase Type 1 and Metabolic Disease Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 165 - 184. [Abstract] [Full Text] [PDF]

				D. J. Wake, N. Z. M. Homer, R. Andrew, and B. R. Walker Acute In Vivo Regulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity by Insulin and Intralipid Infusions in Humans J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4682 - 4688. [Abstract] [Full Text] [PDF]

				C. Cocco, A. Meloni, F. Boi, G. Pinna, R. Possenti, S. Mariotti, and G.-L. Ferri Median Eminence Dopaminergic Nerve Terminals: A Novel Target in Autoimmune Polyendocrine Syndrome? J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4108 - 4111. [Abstract] [Full Text] [PDF]

				R. Andrew, J. Westerbacka, J. Wahren, H. Yki-Jarvinen, and B. R. Walker The Contribution of Visceral Adipose Tissue to Splanchnic Cortisol Production in Healthy Humans Diabetes, May 1, 2005; 54(5): 1364 - 1370. [Abstract] [Full Text] [PDF]

				J. M. Barker, J. Yu, L. Yu, J. Wang, D. Miao, F. Bao, E. Hoffenberg, J. C. Nelson, P. A. Gottlieb, M. Rewers, et al. Autoantibody "Subspecificity" in Type 1 Diabetes: Risk for organ-specific autoimmunity clusters in distinct groups Diabetes Care, April 1, 2005; 28(4): 850 - 855. [Abstract] [Full Text] [PDF]

				M Peracchi, C Gebbia, G Basilisco, M Quatrini, C Tarantino, C Vescarelli, S Massironi, and D Conte Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids Eur. J. Endocrinol., March 1, 2005; 152(3): 443 - 448. [Abstract] [Full Text] [PDF]

				T. C. Sandeep, R. Andrew, N. Z.M. Homer, R. C. Andrews, K. Smith, and B. R. Walker Increased In Vivo Regeneration of Cortisol in Adipose Tissue in Human Obesity and Effects of the 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Carbenoxolone Diabetes, March 1, 2005; 54(3): 872 - 879. [Abstract] [Full Text] [PDF]