(Autoimmune polyglandular syndromes; polyendocrine deficiency syndrome)

Polyglandular deficiency syndromes (PDS) are characterized by sequential or simultaneous defects in the function of various endocrine glands, which have a common cause. The etiology is almost always autoimmunogen. The classification depends on the combination of the various pathological features that fall in one of three types. For diagnosis, the measurement of hormone levels, and the determination of antibodies against the relevant endocrine glands is necessary. The therapy involves the substitution of missing or in too small an amount of existing hormones and sometimes immunosuppressants.

Polyglandular deficiency syndromes (PDS) are characterized by sequential or simultaneous defects in the function of various endocrine glands, which have a common cause. The etiology is almost always autoimmunogen. The classification depends on the combination of the various pathological features that fall in one of three types. For diagnosis, the measurement of hormone levels, and the determination of antibodies against the relevant endocrine glands is necessary. The therapy involves the substitution of missing or in too small an amount of existing hormones and sometimes immunosuppressants. Etiology The etiology is almost always autoimmunogen. Risk factors for the development of autoimmunity include Genetic factors triggering factors in the environment to genetic factors include the AIRE gene mutation that causes type 1, and certain HLA subtypes that are important for the development of type 2 and 3 , The environmental triggers include viral infections, nutritional factors and other unknown factors. Pathophysiology autoimmune response underlying includes autoantibodies against endocrine tissue, cell-mediated autoimmunity, or both, leading to inflammation, lymphocytic infiltration and partial or complete destruction of the gland. It is more than involved an endocrine gland, although the clinical manifestations occur not always the same. The autoimmune response and the associated immune system dysfunction can also damage the nonendocrine tissue. Classification Three patterns of autoimmune disorders have been described (see Table: Characteristics of types 1, 2 and 3 Polyglandular deficiency syndrome), which probably reflect different autoimmune abnormalities. Some experts combine types 2 and 3 into a single group. Type 1 Type 1 usually begins in childhood. It is defined by the presence of ? 2 of the following factors: Chronic mucocutaneous candidiasis Hypoparathyroidism Adrenal insufficiency (Addison’s disease) candidiasis is usually the first clinical manifestation and occurs most often in patients <5 years. Hypoparathyroidism presented next, usually in patients <10 years. Finally, there is an adrenal insufficiency in patients <15 years. Accompanying endocrine and nonendocrine disorders (see Table: Characteristics of types 1, 2 and 3 Polyglandular insufficiency syndrome) continues to occur, at least until the patients over 40 years old sind.Typ 2 (Schmidt syndrome) Type 2 occurs usually in adults ; the highest incidence is 30 years. The disorder occurs three times more often in women. They typically manifests with the following symptoms: adrenal insufficiency hypothyroidism or hyperthyroidism type 1 diabetes (autoimmune etiology) Other less common features can also be present (see Table: Characteristics of types 1, 2 and 3 Polyglandular insufficiency syndrome) .typ 3 Type 3 is characterized by glandular failure in adults, particularly middle-aged women hypothyroidism least one of a plurality of other diseases (see Table: characteristics of types 1, 2 and 3 Polyglandular deficiency syndrome) type 3 does not affect the adrenal cortex. Characteristics of types 1, 2 and 3 Polyglandular insufficiency syndromes characterized by Type 1 Type 2 Type 3 Demographic factors Age of onset Childhood (3-5 years) adults (peak 30 years) adults (especially middle-aged women) Female: Male 4: 3 3: 1 N / A Genetics HLA types can influence the development of specific components of the disease in the first place, B8, DW3, DR3, DR4 Other in certain disorders DR3, DR4 inheritance Autosomal recessive mutation of AIRE gene Multigenic Multigenic glands affected Frequently Nebenschil ddrüsen adrenal gonads adrenal thyroid pancreas thyroid pancreatic Less common pancreatic gland gonads variable clinical adrenal insufficiency (Addison's disease) 73-100% 100% Not seen alopecia 26-32% Not noticed * Celiac rare incidence ambiguous * Chronic active hepatitis 20% Not noticed N / A Chronic mucocutaneous Candidiasi is frequent. 73-97% Not observed N / A diabetes mellitus (type 1) 2-30% 52% * gonadal failure In men, 15-25% in women 60% 3.5% * hypoparathyroidism 76-99% Not observed Not observed malabsorption 2 2-24% non noticed N / A myasthenia gravis Not noticed incidence ambiguous * Pernicious anemia 13-30% <1% * sarcoidosis Not noticed Not noticed * thyroid disease † 10-11% 69% 100% vitiligo N / A * Associated 4-30% 5-50%; Incidence not unique. † Usually chronic lymphocytic thyroiditis but also Graves' disease. N / A = Data not available. Data from Husebye ES, Perheentupa J, Rautemaa R Kampe O: Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type 1. Journal of Internal Medicine 265: 519-529, 2009; Trence DL, Morley JE, Handwerger BS: Polyglandular autoimmune syndromes. American Journal of Medicine 77 (1): 107-116, 1984; Leshin M: Polyglandular autoimmune syndromes. American Journal of Medical Sciences290 (2): 77-88, 1985; Dittmar M, Kahaly GJ: Polyglandular autoimmune syndromes: Immunogenetics and long-term follow-up. Journal of Clinical Endocrinology and Metabolism 88: 2983-2992, 2003; and Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. New England Journal of Medicine 350: 2068-2079, 2004. Symptoms and signs The clinical presentation of patients with PDS is the sum of the individual endocrine deficiencies and associated nichtendokrinen disorders. The symptoms and complaints are discussed elsewhere in MSDManual. The defects do not always occur at the same time and it may require a period of several years until they manifest themselves. In such cases, they do not follow a particular sequence. Diagnostic measurement of hormone levels Sometimes autoantibody titers is diagnosed clinically and confirmed by the determination of the (reduced) hormone levels. Among the other causes of multiple endocrine deficiencies hypothalamic-pituitary dysfunction and randomly existing endocrine disorders by separate causes (eg. as tuberculous hypoadrenalism not autoimmune hypothyroidism in the same patient). The detection of autoantibodies to each affected glandular tissue can help differentiate PDS from other causes and elevated levels of pituitary hormones (eg. As thyroid-stimulating hormone) suggest that the hypothalamic-pituitary axis is intact (though some patients with type 2 PDS have a hypothalamic-pituitary insufficiency). Because it can take decades to all manifestations occur, a lifelong follow-up is smart. A hypoparathyroidism or adrenal insufficiency, which remain undetected, can be life-threatening. Relatives should be informed of the diagnosis and possibly studied. Attempts to follow the relatives of patients with type 1 diabetes on the development of autoimmunity, currently running at. Therapy Hormone Replacement Therapy Treatment of the various functions of the glands is discussed elsewhere in the MSD Manual. The treatment of multiple defects may be more complex than a single endocrine deficiency. Thus, treatment of hypothyroidism with thyroid hormone replacement in patients for example, can create with an undiagnosed adrenal insufficiency adrenal crisis. Chronic mucocutaneous candidiasis usually makes a lifelong antifungal therapy necessary. (. Z. B oral fluconazole, or ketoconazole) Clinical intervention studies to slow the autoimmune process in patients with type 1 diabetes have shown some positive results in the delay of the complete destruction of the insulin-producing beta cells. Among the treatments that were evaluated include immunotherapy and cord blood transplantation. Treatments are still experimental (1, 2). Treatment Information Cai J, Wu Z, Xu X, et al.Umbilical cord mesenchymal stromal cell with autologous bone marrow cell transplantation in established type 1 diabetes: A pilot randomized controlled open-label clinical study to assess safety and impact on insulin secretion. Diabetes Care39: 1149-157, 2016. Haller MJ, Gitelman SE, Gottlieb PA, et al. An anti-thymocyte globulin / G-CSF treatment receives the ?-cell function in patients with established type 1 diabetes. J Clin Invest 125 (1): 448-455, 2015. Important points Polyglandular deficiency syndrome (PDS) include defects in the function of various endocrine glands, which may occur simultaneously or sequentially. Non-endocrine organs may also be affected. Most cases are autoimmune; the triggers are often unknown, but may include viruses or substances in food. PDS are differentiated depending on the affected glands.

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