Autoimmune polyendocrine syndrome overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Historical Perspective
In 19th century physicians first focussed their attention on constellation of symptoms associated with autoimmune polyendocrine syndrome. In 1855, Thomas Addison identified patients with Addison's disease who also appeared to have coexisting pernicious anemia. In 1956, Roitt and Doniach found that patients with Hashimoto's thyroiditis had circulating autoantibodies reacting with thyroid gland. In 1980, Neufeld and Blizzard first developed the classification for polyglandular failure and in 1982 categorised autoimmune polyendocrine syndrome into type 1 and type 2.
Classification
On the basis of organ involvement, autoimmune polyendocrine syndrome (APS) can be classified into APS type 1, APS type 2 and APS type 3. APS type 1 commonly presents with mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. APS type 2 commonly presents with Addison's disease, autoimmune thyroiditis and diabetes mellitus type 1. APS type 3 commonly presents with autoimmune thyroiditis, diabetes mellitus type 1 and pernicious anemia.
Pathophysiology
Autoimmune polyendocrine syndrome (APS) are a group of autoimmune disorders against multiple (poly) endocrine organs, although non endocrine organs may be affected. Autoimmune polyendocrine syndrome is also known as polyglandular autoimmune syndrome and polyendocrine autoimmune syndrome. In autoimmune polyendocrine syndrome there is loss of self tolerance and the immune system attacks various endocrine and nonendocrine organs throughout the body. APS is seen in genetic susceptible individuals who when exposed to certain environmental triggers (such as infection) leads to autoimmunity. The involvement of endocrine glands can be simultaneous or sequential. The autoimmune reaction can either be humoral or cell mediated which may lead to partial or complete destruction of the tissue involved. The common endocrine glands involved are parathyroids, adrenals, thyroid, and pancreas. However any other non endocrine gland/tissue of the body may be involved.
Causes
Common causes of autoimmune polyendocrine syndrome include mutation in AIRE gene, FOXP3 gene and certain HLA alleles such as DR3/DQ2, DR4/DQ8 and DRB1*0404.
Differentiating ((Page name)) from Other Diseases
Epidemiology and Demographics
Autoimmune polyendocrine syndrome (APS) are a group of rare autoimmune disorders. APS type 2 is the most commonly seen autoimmune polyendocrine syndrome. The incidence of APS type 2 is estimated to be 1-2 per 100,000 individuals worldwide. The prevalence of APS type 2 is estimated to be 1-4 per 100,000 individuals worldwide. Most cases of APS type 1 and type 2 are symptomatic by early thirties, while APS type 3 is generally seen in 40-60 years of age. APS usually affects individuals of the caucasian race. In APS type 1, type 2 and type 3 females are more commonly affected than men.
Risk Factors
There are no established risk factors for autoimmune polyendocrine syndrome. However, patients with single autoimmune disorder are at an increased risk of having another autoimmune disorder. Any autoimmune endocrine disorder such as Addison's disease, type 1 diabetes mellitus, autoimmune thyroiditis, hypogonadism (usually autoimmune oophoritis), vitiligo, pernicious anemia, chronic atrophic gastritis, chronic active hepatitis puts the patient at an increased risk of autoimmune polyendocrine syndrome.
Screening
Screening is an important aspect in early diagnosis and management of autoimmune polyendocrine syndrome (APS). The onset of APS is often with a single endocrine disorder and the subsequent involvement of other endocrine/non-endocrine organs may take up to years or decades. In patients of APS, high clinical suspicion should be maintained for presence of other autoimmune disorders. Once a patient has been diagnosed with a single autoimmune endocrine disorder, screening should be done for presence of other auto-antibodies such as 21- hydroxylase or 17-hydroxylase.
Natural History, Complications, and Prognosis
If left untreated, patients with autoimmune polyendocrine syndrome (APS) may progress to involve other endocrine and nonendocrine organs. APS can be a life threatening condition if vital hormone producing organs of the body are involved such as adrenal glands, thyroid, parathyroid glands. The complications of APS depends upon the subtype and organ system involved. Common complication of APS include those arising from hypoparathyroidism, Addison's disease and autoimmune thyroiditis. The prognosis of APS is variable and depends upon the duration and severity of endocrine/non-endocrine organ involved. Patients of APS with endocrine involvement generally require lifelong hormone(s) replacement therapy.
Diagnosis
Diagnostic Criteria
The diagnosis of autoimmune polyendocrine syndrome (APS) is made in the presence of organ-specific antibodies (serological measurement) followed by functional testing. Few examples of organ specific antibodies include autoantibodies against 21-hydroxylase, 17-hydroxylase, GAD, islet cells, thyroglobulin, thyroid peroxidase, intrinsic factor and tyrosinase. Genetic analysis may be done in suspected patients of APS for AIRE or FOXP3 gene mutation. Patients presenting with a single endocrine pathology should always be considered for other endocrine organ dysfunction. Patients with autoimmune endocrine disorder are always at a risk of developing autoimmune conditions of other endocrine organs.
History and Symptoms
Obtaining history may help in early diagnosis of autoimmune polyendocrine syndrome (APS). Autoimmune polyendocrine syndrome patients generally have an early onset. In such cases, history from the caregivers may be obtained. An important aspect involves obtaining family history about the presence of APS in family members since APS can be transmitted in genetic mode. Patients with autoimmune polyendocrine syndrome (APS) have varied symptoms depending upon the subtype. The most common symptoms of APS-1 include mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. The most common symptoms of APS-2 include Addison's disease with autoimmune thyroiditis or diabetes mellitus type 1. The most common symptoms of APS 3 include autoimmune thyroiditis, diabetes mellitus type 1, pernicious anemia and/or with involvement of a nonendocrine organ.
Physical Examination
Laboratory Findings
Electrocardiogram
An ECG may be helpful in the diagnosis of autoimmune polyendocrine syndrome (APS) associated hypoparathyroidism which may present with cardiac dysfunction. Hypoparathyroidism may lead to hypocalcemia which may alter cardiac conduction system. Findings on an ECG suggestive of cardiac dysfunction due to hypoparathyroidism include prolongation of QT interval.
X-ray
There are no x-ray findings associated with autoimmune polyendocrine syndrome.
CT scan
A CT scan may be helpful in the diagnosis of autoimmune polyendocrine syndrome (APS) associated hypoparathyroidism and Addison's disease. Hypoparathyroidism on CT may present with increased volumetric bone mineral density (vBMD) of both cortical and trabecular bones. Addison's disease on CT scan may present with small adrenal remnants bilaterally (suggestive of autoimmune adrenalitis) or as atrophied adrenal glands.
MRI
Brain MRI may be helpful in the diagnosis of autoimmune polyendocrine syndrome associated hypopituitarism and hypogonadism. Findings on MRI suggestive of autoimmune polyendocrine syndrome include hypopituitarism and hypogonadism. MRI is the imaging procedure of choice in the diagnosis of hypopituitarism. It is preferred over the CT scan as optic chiasm, pituitary stalk, and cavernous sinuses can be seen in MRI. An MRI lesion needs to be related to clinical and lab findings. The absence of an MRI lesion mostly indicates a non-organic etiology. Autoantibodies against pituitary gland results in hemorrhage into the pituitary gland which presents as a high-intensity signal on both T1- and T2-weighted images.