Autoimmune polyendocrinopathy broadly describes three main disorders in which deficient functioning of multiple endocrine organs occurs. The pathogenesis involves various autoimmune mechanisms and the following medical entities are enclosed in this group [1] [2] [3] [4] [5] [6]:

• Autoimmune polyendocrine syndrome type 1 (APS1) - APS1 arises from autosomal recessive mutations in the autoimmune regulator (AIRE) gene located on chromosome 21 [4] [5]. It is described as a rare disorder in clinical practice [4], with the presentation starting in early childhood, whereas virtually all patients develop complaints by the end of the first two decades of life [1] [4]. The three cardinal components of APS1 are hypothyroidism, adrenal insufficiency (Addison's disease), and mucocutaneous candidiasis, which is why the term autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is often used [1] [3] [4]. In a variable number of cases, additional features such as diabetes mellitus type 1, pituitary dysfunction, gonadal failure, asplenism, gastrointestinal malabsorption, dysplasia of enamel tissue, hepatitis, and alopecia are encountered [1] [2] [3] [6].
• Autoimmune polyendocrine syndrome type 2 (APS2) - Although Addison's disease is a constitutive feature of APS2, similarly to APS1, distinguishing characteristics are - a more frequent prevalence of diabetes (50% of all patients develop type 1 diabetes compared to only 20% in APS1), an adult-onset (third or fourth decade of life), a predilection toward female gender, and the absence of candidiasis or hypoparathyroidism [1] [2] [4]. Celiac disease, vitiligo, autoimmune gastritis and thyroid disease (eg. Hashimoto thyroiditis) are seen in APS2, but also in a proportion of APS1 individuals [1] [2] [4].
• Immunodysregulation polyendocrinopathy enteropathy X-Linked syndrome (IPEX) - A very early onset (up to 2 years of age) of chronic diarrhea is the hallmark of IPEX [1] [2]. Autoimmune-mediated enteropathy, thyroiditis (mainly hypothyroidism), glomerulonephritis, dermatitis (presenting as eczema), and diabetes mellitus are seen, with symptoms occurring in a relapsing and remitting course [1] [2].

• Fatigue

  Addison disease can cause fatigue, muscle weakness, weight loss, low blood pressure, and changes in skin coloration. There are numerous other symptoms which can also occur in people with PAS-1. [counsyl.com]

  […] of circulating calcium Addison disease, an insufficiency of the adrenal glands, presenting with changes in skin pigmentation, loss of appetite and weight loss, fatigue, low blood pressure and fatigue. [dermnetnz.org]

  However, most people with endocrine disease complain of fatigue and weakness. Blood and urine tests to check your hormone levels can help your doctors determine if you have an endocrine disorder. [webmd.com]

  These include symptoms of AD (hyperpigmentation, fatigue), T1DM (polyuria, polydipsia and polyphagia), pernicious anemia (problems with coordination), hypothyroidism (fatigue, weight gain, hair changes), and celiac disease (abdominal pain, anemia) among [healio.com]

  Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue. [ghr.nlm.nih.gov]

• Myxedema

  Autoimmune Syndrome, Type 2 [Nom commun] Polyglandular Deficiency Syndrome, Type 2 [Nom commun] Schmidt Syndrome [Nom commun] Syndrome, Schmidt [Nom commun] Autoimmune Polyendocrine Syndrome, Type 2 [Nom commun] Diabetes Mellitus, Addison's Disease, Myxedema [idref.fr]

  Información en español Title Other Names: Diabetes mellitus, Addison's disease, myxedema; Multiple endocrine deficiency syndrome, type 2; Polyglandular autoimmune syndrome, type 2; Diabetes mellitus, Addison's disease, myxedema; Multiple endocrine deficiency [rarediseases.info.nih.gov]

• Male Hypogonadism

  Self-Abs against scc, but not 17 α -OH, were associated with hypogonadism (16). Researches revealed that the testis-expressed protein TSGA10 is also a target of immune reactions in male hypogonadal patients (59). [doi.org]

• Abdominal Pain

  He had no associated diarrhoea, abdominal pain, or fever and there was no history of recent travel, contact with unwell persons or consumption of unusual foods. [endocrine-abstracts.org]

  View/Print Table TABLE 2 Diagnosis of Adrenal Insufficiency Symptoms Common: fatigue, weakness, anorexia, nausea, vomiting Less common: abdominal pain, salt craving, diarrhea, constipation, syncope Signs Weight loss, cutaneous and mucosal pigmentation [aafp.org]

  On further review of symptoms, you note the patient has persistent polydipsia, headaches, nausea/vomiting, intermittent abdominal pain, and hyperpigmentation. [healio.com]

  Other symptoms consistent with adrenal insufficiency include dizziness and orthostasis, anorexia, weakness, nausea, emesis and abdominal pain, salt craving [1]. [hopkinsguides.com]

  Recurrent diarrhea, morning nausea, and intermittent abdominal pain occurred from age 9, and he became Cushingoid because of frequent stress doses of hydrocortisone. [pediatrics.aappublications.org]

• Nausea

  View/Print Table TABLE 2 Diagnosis of Adrenal Insufficiency Symptoms Common: fatigue, weakness, anorexia, nausea, vomiting Less common: abdominal pain, salt craving, diarrhea, constipation, syncope Signs Weight loss, cutaneous and mucosal pigmentation [aafp.org]

  The patient began to suffer from nausea, vomiting, and visual disturbances, and she was transferred to Tampere University Hospital. [edmcasereports.com]

  Recurrent diarrhea, morning nausea, and intermittent abdominal pain occurred from age 9, and he became Cushingoid because of frequent stress doses of hydrocortisone. [pediatrics.aappublications.org]

  Deficiencies of these hormones may lead to weakness, muscle cramps, faintness, diarrhea, nausea and vomiting, low blood pressure, dehydration, and salt craving. [rarediseases.org]

  Other symptoms consistent with adrenal insufficiency include dizziness and orthostasis, anorexia, weakness, nausea, emesis and abdominal pain, salt craving [1]. [hopkinsguides.com]

• Failure to Thrive

  Severe autoimmune enteropathy manifests with intractable secretory diarrhea leading to malabsorption, electrolyte disturbance and failure to thrive. Vomiting, ileus, gastritis or colitis can also be observed. [orpha.net]

  It can cause failure to gain weight and grow at the expected rate (failure to thrive) and general wasting and weight loss (cachexia). People with IPEX syndrome frequently develop inflammation of the skin, called dermatitis. [ghr.nlm.nih.gov]

  Symptoms of diarrhoea and failure to thrive began during the first year of life and led to a biopsy confirmed diagnosis of coeliac disease at 18 months of age. [jmg.bmj.com]

• Hypertension

  […] of Hypertension 1485 Evaluation of Hypertension in Childhood Diseases 1519 Management of the Hypertensive Child 1541 Pathogenesis of Acute Renal Failure 1579 Clinical Evaluation of Acute Kidney Injury in Children 1603 Management of Acute Kidney Failure [books.google.de]

  These included severe hypertension, renal insufficiency, cardiac hypertrophy, and sepsis related to indwelling catheters. [jmg.bmj.com]

  […] irritation (pneumonitis), dry mouth and dry eyes (Sjogren-like syndrome), inflammation of the eyes (keratitis), kidney problems (nephritis), vitamin B12 deficiency, hair loss (alopecia), loss of skin color in blotches ( vitiligo ), high blood pressure (hypertension [ghr.nlm.nih.gov]

  Hypertension developed 3 months after commencing cyclosporin. Investigations revealed normal renin and electrolytes indicating appropriate fludrocortisone dose. [pediatrics.aappublications.org]

• Hypotension

  In patients with addisonian crisis, the initial goal is to reverse hypotension and electrolyte abnormalities, and to treat shock when it occurs. [aafp.org]

  Decreased insulin requirements, hypotension, weight loss, hyperpigmentation, and vitiligo may be present. [hopkinsguides.com]

  […] polydipsia 多飲 polyglandular autoimmune syndrome 多腺性自己免疫症候群 polyneuropathy 多発ニューロパチー polyneuropathy 多発神経障害 polyphagia 多食 polyunsaturated fatty acid 多価不飽和脂肪酸 polyunsaturated fatty acid / saturated fatty acid ratio 多価不飽和脂肪酸/飽和脂肪酸比 polyuria 多尿 postural hypotension [jds.or.jp]

  The patient was anuric and hypotensive, and i.v. fluids were administered. During the next few days, she experienced headache and dizziness. Diuresis restarted on day six after the onset of fever. [edmcasereports.com]

  Addison’s disease •Characteristic symptoms include :Fatigue, salt craving, hypotension, weight loss and an increased pigmentation of the skin and mucous membranes Kisand K, Peterson P. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. [slideshare.net]

• Eczema

  Autoimmune-mediated enteropathy, thyroiditis (mainly hypothyroidism), glomerulonephritis, dermatitis (presenting as eczema), and diabetes mellitus are seen, with symptoms occurring in a relapsing and remitting course. [symptoma.com]

  The symptoms of IPEX syndrome include severe diarrhea, diabetes, skin conditions (such as eczema, erythroderma, or psoriasis ), and thyroid disease ( thyroiditis ). [rarediseases.info.nih.gov]

  Skin involvement consists of a generalized pruriginous eruption resembling eczema, psoriasis, and/or atopic or exfoliative dermatitis. Less frequently, alopecia or onychodystrophy can be observed. [orpha.net]

  Clinical features are highly variable and include early onset type 1 diabetes, hypothyroidism, severe enteropathy, eczema, anaemia and thrombocytopenia. Haemopoietic stem cell transplantation has sometimes been effective in its treatment. [diapedia.org]

• Ulcer

  […] autoimmune polyglandular syndrome type 3 variant in the Japanese population. ( 22466347 ) Horie I....Kawakami A. 2012 10 Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III. ( 22616341 ) Choudhury B.K....Saikia M. 2011 11 Ulcerative [malacards.org]

  27, 28 Arthritis also occurred in our case 3 and ulcerative colitis in case 1. [jmg.bmj.com]

  A family history of autoimmune diseases including systemic lupus erythematosus, Sjogren syndrome, ulcerative colitis, and thyroid disease was present in first- and second-degree relatives. [pediatrics.aappublications.org]

• Urticaria

  Addobbati C.J....Sandrin-Garcia P. 2015 5 Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III. ( 26782418 ) de AzevA-do Silva J....BrandALo L.A. 2015 6 A case of autoimmune urticaria [malacards.org]

  Figure 3 Urticaria-like eruption (red arrows). [jmedicalcasereports.biomedcentral.com]

  Indeed, in a restricted number of cases a maculopapular, or morbilliform, or urticaria-like skin rash, eventually accompanied by fever, splenomegaly and arthralgia, has been reported [ 2, 3, 6 – 18 ]. [doi.org]

  Other reported cutaneous features include urticaria-like erythema with fever, lymphoplasmacytic vasculitis, Sjogren's syndrome and rarely psoriasis vulgaris. [1], [2], [3] Herein, we describe the rare occurrence of unstable psoriasis (with onset of pustular [ijdvl.com]

  The thyroid and urticaria. Curr Opin Allergy Clin Immunol 5: 408, 2005. PubMed CrossRef Google Scholar 32. Aarli JA, Thunold S, Heimann P. Thyroiditis in myasthenia gravis. Acta Neurol Scand 58: 121, 1978. PubMed CrossRef Google Scholar 33. [link.springer.com]

• Arthralgia

  Indeed, in a restricted number of cases a maculopapular, or morbilliform, or urticaria-like skin rash, eventually accompanied by fever, splenomegaly and arthralgia, has been reported [ 2, 3, 6 – 18 ]. [doi.org]

• Kidney Failure

  1579 Clinical Evaluation of Acute Kidney Injury in Children 1603 Management of Acute Kidney Failure 1619 Pathophysiology of Progressive Renal Disease 1631 Management of Chronic Kidney Disease 1661 Handling of Drugs in Children with Abnormal Renal Function [books.google.de]

The diagnosis of autoimmune polyendocrinopathy syndromes can be made through a detailed clinical, laboratory, and genetic assessment. The physician should obtain a history that will assess the age of symptom onset, presenting complaints, and associated endocrine abnormalities, which may provide useful clues into discriminating between the different types of autoimmune polyendocrinopathy syndromes. After a meticulous laboratory investigation, the detection of multiple abnormalities of endocrine tissue must raise suspicion toward this disorder. The presence of multiple autoantigens (islet cells, thyroid-stimulating hormone receptors, gastric intrinsic factor, gliadin, tyrosinase, etc.) and autoantibodies (antigonadal, antiadrenal, anti-islet, and other organ-specific antibodies) is highly specific for all syndromes belonging to this group of conditions, and is one of the main laboratory criteria [2] [4] [5] [6]. A definite diagnosis, however, rests on genetic studies. Identification of mutations in the AIRE gene on chromosome 21 confirms autoimmune polyendocrine syndrome type 1 as the underlying cause [4] [5]. For IPEX, detection of mutations in the FOX3 gene on chromosome X is diagnostic [1]. Unfortunately, the entire pathogenesis model for APS type 2 remains to be elucidated [1].

• Abnormal Renal Function

  1619 Pathophysiology of Progressive Renal Disease 1631 Management of Chronic Kidney Disease 1661 Handling of Drugs in Children with Abnormal Renal Function 1693 Endocrine and Growth Disorders in Chronic Kidney Disease 1713 Chronic Kidney Disease Mineral [books.google.de]

• Candida

  METHODS: We assessed T(H)17 responses of PBMCs to Candida and non-Candida species stimuli by measuring IL-17, IL-22, IL-21, IL-6, IL-23, and IFN-γ cytokine production using cytokine arrays and intracellular cytokine-producing cell numbers and proliferation [ncbi.nlm.nih.gov]

  Candida was recovered from 14/16 patients and Candida albicans was the only Candida species identified. [tara.tcd.ie]

• Colitis

  […] polyglandular syndrome type 3 variant in the Japanese population. ( 22466347 ) Horie I....Kawakami A. 2012 10 Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III. ( 22616341 ) Choudhury B.K....Saikia M. 2011 11 Ulcerative colitis [malacards.org]

  Vomiting, ileus, gastritis or colitis can also be observed. Patients also present with autoimmune endocrinopathies, generally insulin-dependent diabetes mellitus (type 1 DM), but also thryroiditis leading to hypothyroidism or hyperthyroidism. [orpha.net]

  27, 28 Arthritis also occurred in our case 3 and ulcerative colitis in case 1. [jmg.bmj.com]

  Fifteen percent of patients had gastric outlet obstruction, 10% urinary tract obstruction, and 17% colitis/enteritis. Ten percent of X-linked recessive kindreds and 3% of autosomal recessive kindreds had family members with lupus. [scienceopen.com]

Management and treatment The only curative treatment for IPEX is hematopoietic stem cells transplantation (HSCT), which is much more successful when performed in the early stages of the disease. [orpha.net]

In the case of low growth rate, GH should be evaluated by dynamic tests and, if GH deficiency is detected, treatment with hGH must be initiated. [ncbi.nlm.nih.gov]

You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]

This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. [ncbi.nlm.nih.gov]

The clinical presentation, onset of symptoms, organs involved, and the prognosis depends on the underlying subtype. The diagnosis rests on a thorough physical examination, a comprehensive history, and a detailed laboratory assessment. [symptoma.com]

What is the prognosis for a person with Polyglandular Autoimmune Syndrome Type 1? The prognosis for a person with PAS-1 varies depending on the number and severity of his or her symptoms. [counsyl.com]

In addition, the patient developed progressive muscular atrophy of unknown etiology at the beginning of the third decade, and is bedridden at the present time. [ncbi.nlm.nih.gov]

Etiology IPEX syndrome is caused by mutations in the FOXP3 gene (Xp11.23). [orpha.net]

Etiology The etiology is most often autoimmune. [merckmanuals.com]

Rhabdomyolysis: a review of clinical presentation, etiology, diagnosis, and management. Pediatr Emerg Care. 2008;24(4):262–268 doi:10.1097/PEC.0b013e31816bc7b7 [CrossRef]. Egan JJ, Davies AJ, Jones MK. [healio.com]

The presence of antithyroid antibodies (e.g. anti-thyroglobulin antibodies, anti-microsomal antibodies, thyroid stimulating immunoglobulins) can be useful for confirming autoimmune etiology (see thyroid function tests module). [hopkinsguides.com]

Expanded epidemiological investigations based on AIRE gene sequencing are necessary to verify the relevancy of the novel mutation to APECED etiopathogenesis in the Lithuanian population and to prove its diagnostic efficacy in association with clinical [ncbi.nlm.nih.gov]

Epidemiology Frequency United States Approximately 14-20 people per million population are affected by polyglandular autoimmune syndrome type II. [emedicine.medscape.com]

In this article, we discuss the role of AIRE in autoimmune polyendocrine syndrome type-1 and identify issues that still need to be addressed to fully understand the molecular pathophysiology of this complex syndrome. [ncbi.nlm.nih.gov]

Chapters cover both basic pathophysiology informed by studies of animal models as well as current understanding of multiple related clinical diseases—their pathophysiology, diagnosis, and therapy. [books.google.de]

The pathophysiological aspects of this syndrome are discussed. © 1982 S. [karger.com]

Autoimmunity, environmental factors, and genetic factors are the 3 major factors that should be considered in the pathophysiology of PAS III. [emedicine.medscape.com]

We will summarize how AIRE contributes to immunological tolerance, and thus to the prevention of autoimmunity. [ncbi.nlm.nih.gov]

Funding and Disclosures Supported by grants from the National Institutes of Health (DK32083, AI39213, DK55969, DK62718, AI95380, DK32493, DK59097, DK63518, AI46374, and DK61926; a Diabetes Endocrine Research Center grant [P30 DK57516]; an Autoimmunity Prevention [oadoi.org]

1. Husebye ES, Anderson MS. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis. Immunity. 2010;32(4):479-487.
2. Anderson MS. Update in Endocrine Autoimmunity. J Clin Endocrinol Metab. 2008;93:3663–3670.
3. Perheentupa J. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. J Clin Endocrinol Metab. 2006;91:2843–2850
4. Kahaly GJ. Polyglandular autoimmune syndromes. Eur J Endocrinol. 2009;161:11–20.
5. Alimohammadi M, Björklund P, Hallgren A, et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N Engl J Med. 2008;358:1018–1028.
6. Bensing S, Fetissov SO, Mulder J, et al. Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(3):949-954.