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Type II Polyglandular Autoimmune Syndrome

  • Author: Surendra Sivarajah, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Aug 28, 2014
 

Background

Polyglandular autoimmune syndrome type II (PGA-II) is the most common of the immunoendocrinopathy syndromes. It is characterized by the obligatory occurrence of autoimmune Addison disease in combination with thyroid autoimmune diseases and/or type 1 diabetes mellitus (also known as insulin-dependent diabetes mellitus, or IDDM). Primary hypogonadism, myasthenia gravis, and celiac disease also are commonly observed in this syndrome.

The definition of the syndrome depends on the fact that if one of the component disorders is present, an associated disorder occurs more commonly than in the general population. The most frequent clinical combination association is Addison disease and Hashimoto thyroiditis, while the least frequent clinical combination is Addison disease, Graves disease, and type 1 diabetes mellitus. The complete triglandular syndrome is sometimes referred to as Carpenter syndrome.

PGA-II occurs primarily in adulthood, usually around the third and fourth decades of life. Middle-aged women have shown an increased prevalence of PGA-II. It is associated with HLA-DR3 and/or HLA-DR4 haplotypes, and the pattern of inheritance is autosomal dominant with variable expressivity.[1]

Two other related autoimmune endocrinopathies exist, namely type I and type III. The former is rare and presents in childhood. It usually consists of mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency (presenting in that order). PGA-I usually is inherited in an autosomal recessive pattern, with variable inheritance; it has no HLA association and, unlike PGA-II, has an equal sex incidence. Type 1 diabetes mellitus is rare in children with PGA-I.

Type III, although ill defined, is the co-occurrence of autoimmune thyroid disease with 2 other autoimmune disorders, including diabetes mellitus type 1, pernicious anemia, or a nonendocrine, organ-specific autoimmune disorder in the absence of Addison disease.[2]

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Pathophysiology

The pathogenesis of polyglandular autoimmune syndrome type II (PGA-II) is poorly understood.[3, 4] The following steps have been postulated:

  • Some degree of genetic susceptibility must exist in the individual. [5]
  • The individual is then exposed to the autoimmune trigger, which could be an environmental or intrinsic factor. The trigger mimics the molecular structure of a self-antigen. An alternative explanation is that a breakdown in normal immunologic tolerogenesis occurs.
  • Next, a subclinical phase of active production of organ-specific autoantibodies occurs.
  • This phase is followed by autoimmune activity in the respective organ, in which there is progressive glandular destruction. The individual is still asymptomatic.
  • Overt clinical disease subsequently develops when extensive organ damage, caused by the aforementioned autoimmune activity, has occurred. Evidence of this autoimmune phenomenon that may be responsible for this syndrome is based on whether the affected organs demonstrate a chronic inflammatory infiltrate composed of lymphocytes (mainly).

Some of the component diseases are associated with immune-response genes encoded by the class II HLA complex.[1] The syndrome is replete with autoantibodies reacting to target tissue-specific antigens.

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Epidemiology

Frequency

United States

Approximately 14-20 people per million population are affected by polyglandular autoimmune syndrome type II. Observations have revealed, however, that the disease is much more prevalent if subclinical forms are included.

Mortality/Morbidity

To date, the mortality and morbidity rates of polyglandular autoimmune syndrome type II (PGA-II) have not been clinically estimated. The mortality and morbidity of PGA-II are believed to equal the mortality and morbidity of the individual component disorders.

Sex

The female-to-male ratio of polyglandular autoimmune syndrome type II is 3-4:1.[6]

Age

Polyglandular autoimmune syndrome type II occurs in the third or fourth decade of life.

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Contributor Information and Disclosures
Author

Surendra Sivarajah, MD Interim Chief, Section of Endocrinology and Metabolism, The Reading Hospital and Medical Center

Surendra Sivarajah, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Olakunle P A Akinsoto, MD, MB, BCh Consulting Staff, Family Health Center

Olakunle P A Akinsoto, MD, MB, BCh is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Chris Y Fan, MD Assistant Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Pennsylvania State University College of Medicine, Practice Site Director, Endocrinology and Nephrology Clinic, Hershey Medical Center

Chris Y Fan, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Medical Association, Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Ghassem Pourmotabbed, MD, MD 

Ghassem Pourmotabbed, MD, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Endocrine Society

Disclosure: Nothing to disclose.

References
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