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What is Polyglandular syndromes type I, II, III

Polyglandular syndromes type I, II, III (PDS) is characterized by sequential or simultaneous deficiencies in the function of several endocrine glands that have a common cause. Etiology (cause, set of causes) is most often autoimmune. Polyglandular deficiency syndromes (PDS) involve deficiencies in the function of several endocrine glands, which may occur simultaneously or sequentially. Nonendocrine organs also may be affected. Most cases are autoimmune; triggers are often unknown but may involve viruses or dietary substances. PDS is distinguished by the glands affected. Categorization depends on the combination of deficiencies, which fall within 1of 3 types. Diagnosis requires measurement of hormone levels and autoantibodies against affected endocrine glands. Treatment includes replacement of missing or deficient hormones and sometimes immunosuppressants. Risk factors for the development of autoimmunity include Genetic factors and Environmental triggers. Genetic factors include the AIRE gene mutation, which is causative of type 1, and certain HLA subtypes, which are important in the development of types 2 and 3. Environmental triggers include viral infections, dietary factors, and other as yet unknown exposures.

For type II, see also Schmidt syndrome

Autoimmune polyglandular syndrome type 1 is an inherited autoimmune condition that affects many of the body’s organs. Symptoms often begin in childhood or adolescence and may include mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. This syndrome can cause a variety of additional signs and symptoms, such as weak teeth (enamel hypoplasia) and chronic diarrhea or constipation.[1] Also, about 60% of the women with APS-1 who are younger than 30 years of age develop primary ovarian insufficiency.[2]

Complications of APS-1 can affect the bones, joints, skin, and nails, the gonads (ovaries and testicles), the eyes, the thyroid, and several internal organs (kidneys, liver, lungs and the spleen). Anemia may also be present due to a lack of production of the red blood cells.[2] Type 1 diabetes also occurs in some patients with this condition.[1] APS-1 is progressive, with symptoms appearing at different time intervals (chronic mucocutaneous candidiasis and hypoparathyroidism classically appear early in childhood, whereas adrenal insufficiency usually start in the second decade of life). Diagnosis is suspected when there are at least two of these features, specially in young people. [2][3] APS-1 is caused by variations (mutations) in the AIRE gene. Inheritance is autosomal recessive.[1] Treatment may include hormone-replacement, and medication for candidiasis, as well as specific treatment of any complications. Patients with APS-1 are best followed by an endocrinologist and other specialists.[2]

Most people with APS-1, develop earlier and more severe symptoms than people with a related disease known as autoimmune polyendocrine syndrome type 2 (APS-2).

Autoimmune polyglandular syndrome type 2 is an autoimmune disorder that affects many hormone-producing (endocrine) glands.[1] It is characterized by the presence of Addison’s disease along with autoimmune thyroid disease and/or type 1 diabetes.[1] Affected individuals may also have problems with other endocrine glands and other common features include primary hypogonadism, myasthenia gravis, and celiac disease. Autoimmune polyglandular syndrome type 2 is diagnosed in adulthood, typically around age 30.[2] The cause of autoimmune polyglandular syndrome type 2 is unknown, although it may involve a combination of genetic and environmental factors. This condition occurs more often in women than men. About 10% of patients with APS-2 and Addison’s disease had a relative with adrenal insufficiency, and about 10% of patients with APS-2 and type 1 diabetes had a sibling with the same disease, and, or with autoimmune thyroid disease.[1][3]

Currently, there are no unique tests to detect APS-2, but testing for autoantibodies may be helpful in assessing disease risk, since the relevant autoantibodies (such as antibodies to thyroid peroxidase in autoimmune thyroid disease, or to glutamic acid decarboxylase in type 1 diabetes) are frequently detectable years before disease onset. Treatment is mainly with hormone replacement therapy.[1][3][2]

Autoimmune polyglandular syndrome (APS) type 3 is an autoimmune condition that affects the body’s endocrine glands. The syndrome, which typically affects women during middle age, results from failure of the glands to produce their hormones. This condition is characterized by autoimmune thyroiditis along with another organ-specific autoimmune disease.[1][2][3] The other autoimmune diseases may include diabetes mellitus, pernicious anemia, vitiligo, alopecia, myasthenia gravis, and Sjogren’s syndrome.[2] The adrenal cortex (the outer layer of the adrenal gland) is not involved.[1][2][3] There are three types of autoimmune polyglandular syndrome type 3:[1][2]
– APS3A – Autoimmune thyroiditis with immune-mediated diabetes mellitus (IMDM)
– APS3B – Autoimmune thyroiditis with pernicious anemia
– APS3C – Autoimmune thyroiditis with vitiligo and/or alopecia and/or other organ-specific autoimmune disease

The cause is still unknown, but it is believed that it may be an autoimmune disease, where environmental factors (such as viral infections) and genetic factors (such as variations in the HLA II genes) are also involved in the disease. In many cases more than one member of the same family is affected with PAS III, suggesting that its inheritance could be autosomal dominant, and therefore, familiar screening is recommended. It is very important that people with APS3 are monitored closely by their doctors for early detection of any glandular problems. Treatment includes lifelong hormone replacement therapy for any established glandular failure.[1]

This information is provided by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD).

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