Autoimmune polyendocrine syndrome type 1 is a condition caused in an autosomal recessive manner. Furthermore, it is due to a defect in AIRE gene (which helps to make a protein that is called the autoimmune regulator) mapped to 21q22.3 chromosome location, hence chromosome 21.

In autoimmune polyendocrine syndrome type 1 mechanism one finds that the maintenance of "immunological tolerance" plays a role. Furthermore, upon looking at the AIRE gene, one finds at least 90 mutations in the gene, in those affected with this condition.

Autoimmune polyendocrine syndrome type 1 mechanism also indicates that affected individuals autoantibodies have considerable reactions with both interferon-omega and interferon alpha.

Autoimmune polyendocrine syndromes (APS) occur when more than one autoimmune disease occurs in endocrine glands. These syndromes are also called Polyendocrine Autoimmune Disorders. In Type 3, autoimmune thyroiditis and another endocrine autoimmune disease are present, but the adrenal cortex is not involved.

Immunosuppressive therapy may be used in "type I" of this condition, ketoconazole can be used for "autoimmune polyendocrine syndrome type I" under certain conditions The component diseases are managed as usual, the challenge is to detect the possibility of any of the syndromes, and to anticipate other manifestations. For example, in a person with known Type 2 autoimmune polyendocrine syndrome but no features of Addison's disease, regular screening for antibodies against 21-hydroxylase may prompt early intervention and hydrocortisone replacement to prevent characteristic crises

Each "type" of this condition has a different cause, in terms of IPEX syndrome is inherited in males by an x-linked recessive process. FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of the IPEX condition.

In terms of genetics one finds that autoimmune polyendocrine syndrome type 2 has an autosomal dominant(and recessive) inheritance Furthermore, the human leukocyte antigen involved in this condition are HLA-DQ2(DR3 (DQB*0201)) and HLA-DQ8(DR4 (DQB1*0302)), "genetically speaking", which indicates this is a multifactorial disorder, as well

Should "any" affected organs show chronic inflammatory infiltrate(lymphocytes), this would be an indication. Moreover,

autoantibodies reacting to specific antigens is common, in the immune system of an affected individual

Autoimmune polyendocrine syndrome type 2, a form of autoimmune polyendocrine syndrome also known as Schmidt's syndrome, or APS-II, is the most common form of the polyglandular failure syndromes. It is heterogeneous and has not been linked to one gene. Rather, individuals are at a higher risk when they carry a particular human leukocyte antigen (HLA-DQ2, HLA-DQ8 and HLA-DR4). APS-II affects women to a greater degree than men.

Risk factors for developing antiphospholipid syndrome include:

- Primary APS

- genetic marker HLA-DR7

- Secondary APS

- SLE or other autoimmune disorders

- Genetic markers: HLA-B8, HLA-DR2, HLA-DR3

- Race: Blacks, Hispanics, Asians, and Native Americans

There is an additional elevated risk of adrenal gland bleeds leading to Waterhouse–Friderichsen syndrome (Neisseria meningitidis caused primary adrenal insufficiency). This will require adrenal steroid replacement treatment for life.

The long-term prognosis for APS is determined mainly by recurrent thrombosis, which may occur in up to 29% of patients, sometimes despite antithrombotic therapy.

Outcomes are typically good when treated. Most can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.

Individuals with Addison's disease have more than a doubled mortality rate. Furthermore, individuals with Addison's disease and diabetes mellitus have an almost 4 time increase in mortality compared to individuals with only diabetes.

The frequency rate of Addison's disease in the human population is sometimes estimated at roughly one in 100,000. Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000). Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.

Catastrophic antiphospholipid syndrome (CAPS), also known as Asherson's syndrome, is an acute and complex biological process that leads to occlusion of small vessels of various organs. It was first described by Ronald Asherson in 1992. The syndrome exhibits thrombotic microangiopathy, multiple organ thrombosis, and in some cases tissue necrosis and is considered an extreme or catastrophic variant of the antiphospholipid syndrome.

CAPS has a mortality rate of about 50%. With the establishment of a CAPS-Registry more has been learned about this syndrome, but its cause remains unknown. Infection, trauma, medication, and/or surgery can be identified in about half the cases as a "trigger". It is thought that cytokines are activated leading to a cytokine storm with the potentially fatal consequences of organ failure. A low platelet count is a common finding. Individuals with CAPS often exhibit a positive test to antilipid antibodies, typically IgG, and may or may not have a history of lupus or another connective tissue disease. Association with another disease such as lupus is called a secondary APS unless it includes the defining criteria for CAPS.

Clinically, the syndrome affects at least three organs and may affect many organs systems. Peripheral thrombosis may be encountered affecting veins and arteries. Intraabdominal thrombosis may lead to pain. Cardiovascular, nervous, kidney, and lung system complications are common. The affected individual may exhibit skin purpura and necrosis. Cerebral manifestations may lead to encephalopathy and seizures. Myocardial infarctions may occur. Strokes may occur due to the arterial clotting involvement. Death may result from multiple organ failure.

Treatments may involve the following steps:

- Prevention includes the use of antibiotics for infection and parenteral anticoagulation for susceptible patients.

- Specific therapy includes the use of intravenous heparin and corticosteroids, and possibly plasma exchanges, intravenous immunoglobulin.

- Additional steps may have to be taken to manage circulatory problems, kidney failure, and respiratory distress.

- When maintaining survival of the disease treatments also include high doses of Rituxan (Rituximab) to maintain stability.

All causes in this category are genetic, and generally very rare. These include mutations to the "SF1" transcription factor, congenital adrenal hypoplasia due to "DAX-1" gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). "DAX-1" mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when "DAX-1" is deleted together with a number of other genes.

Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse-Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.

For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addison's Disease), tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.

Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease). Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.

Adrenoleukodystrophy can also cause adrenal insufficiency.

Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage).

Re-entry ventricular arrhythmia is a type of paroxysmal tachycardia occurring in the ventricle where the cause of the arrhythmia is due to the electric signal not completing the normal circuit, but rather an alternative circuit looping back upon itself. There develops a self-perpetuating rapid and abnormal activation. ("Circus Movement" is another term for this.) Conditions necessary for re-entry include a combination of unidirectional block and slowed conduction. Circus movement may also occur on a smaller scale within the AV node (dual AV nodal physiology), a large bypass tract is not necessary.

Re-entry is divided into two major types: [Anatomically Defined] re-entry and [Functionally Defined] re-entry. The circus movement can occur around an anatomical or functional core. Either type may occur alone, or together.

"Anatomically" defined re-entry has a fixed anatomic pathway. Anomalous conduction via accessory pathways (APs) create the re-entry circuit (which are also called bypass tracts), that exist between the atria and ventricles. Wolff–Parkinson–White syndrome (WPW) is an example of anatomically defined re-entry. WPW syndrome is an atrioventricular re-entrant tachycardia (AVRT), secondary to an accessory pathway that connects the epicardial surfaces of the atrium and ventricle along the AV groove. The majority of time symptomatic WPW fits the definition of AVRT (Supraventricular tachycardia) however AVNRT (dual AV nodal physiology) exist in ~10% of patients with WPW syndrome creating the possibility of spontaneous atrial fibrillation degenerating into ventricular fibrillation (VF). The fact that WPW patients are young and do not have structural heart disease, lead to using catheter ablation of the APs with the elimination of the atrial fibrillation as well as the episodes of re-entrant ventricular tachycardia. This elimination of the atrial fibrillation with ablation implies APs have some pathophysiologic role in the development of a-fib in the WPW patient.

"Functionally" defined re-entry does not require the alternative anatomically defined circuit accessory pathways and it may not reside in just one location. Ventricular fibrillation (VF) following ventricular tachycardia (VT) may be described as a functionally defined re-entry problem caused by multiple mini re-entrant circuits spontaneously created within the ventricular myocardium. The original re-entrant circuit breaks down into multiple mini reentrant circuits. (VF becoming the grand finale of a single prolonged VT larger circus movement, propagating change in the "functional core" of the ventricular myocardium, dissipating mini reentrant circuits, exhibited as ventricular fibrillation.) Ischemia, electrolyte, pH abnormalities, or bradycardia are potential causes of functionally defined re-entry due to changes in the properties of the cardiac tissue's functional core. (No accessory pathway required)

Perfectionism, in psychology, is a personality trait characterized by a person's striving for flawlessness and setting high performance standards, accompanied by critical self-evaluations and concerns regarding others' evaluations. It is best conceptualized as a multidimensional characteristic, as psychologists agree that there are many positive and negative aspects. In its maladaptive form, perfectionism drives people to attempt to achieve an unattainable ideal, while their adaptive perfectionism can sometimes motivate them to reach their goals. In the end, they derive pleasure from doing so. When perfectionists do not reach their goals, they often fall into depression.

Perfectionists strain compulsively and unceasingly toward unobtainable goals, and measure their self-worth by productivity and accomplishment. Pressuring oneself to achieve unrealistic goals inevitably sets the person up for disappointment. Perfectionists tend to be harsh critics of themselves when they fail to meet their standards.