Polyendocrine autoimmune diseases represent a heterogeneous group of autoimmune disorders in which multiple endocrine and nondocrine organs may be affected simultaneously. These diseases occur very rarely and probably all have a genetic background. Treatment is not causative, but only symptomatic by hormone replacement of missing hormones.
What are polyendocrine autoimmune diseases?
Polyendocrine autoimmune diseases are characterized by a multitude of concurrent autoimmune diseases of endocrine glands. Often, additional nondocrine organs are also affected. These are diseases with completely different causes. What they all have in common is that the body’s own immune system attacks various organs of the body simultaneously. If endocrine organs are damaged as a result, hormone-related secondary diseases result. Synonymous with the term “polyendocrine autoimmune diseases“, the terms APS for autoimmune pluriglandular syndromes, pluriglandular insufficiencies or polyendocrine autoimmunopathies are also used. The polyendocrine autoimmune disorders are classified into APS types I through IV. Type I APS is also called juvenile autoimmune syndrome because it has been present since the beginning of birth. The other types of APS are classified as adult polyglandular syndromes. Type I APS is also known as APECED syndrome. Here, Addison’s disease is usually combined with hypoparathyroidism and fungal involvement of the skin and muscles. Other autoimmune diseases such as type I diabetes may also occur. APECED syndrome is extremely rare and has only been observed in Finland. Type II APS occurs in two subtypes, Schmidt syndrome and Schmidt-Carpender syndrome. While Schmidt’s syndrome combines Addison’s disease and autoimmune thyroid disease, Schmidt-Carpender syndrome is associated with type I diabetes mellitus. Type III APS represents very rare combination of autoimmune diseases of the thyroid, pancreas, kidneys, blood, skin, vessels, and muscles. Type IV APS includes autoimmune diseases that cannot be assigned to any of the other three types.
Causes
Genetic factors are thought to be the cause of all polyendocrine autoimmune diseases. APECED syndrome is the only known syndrome caused by mutation of a single gene. It is inherited in an autosomal recessive manner. This gene encodes the so-called AIRE protein. The AIRE protein is a self-antigen produced by thymic stomatal cells. It is an autoimmune regulator by stimulating the production of several thousand different tissue-specific autoantigens. The autoantigens that have bound to MHCI proteins present themselves at the cell surface for attack by T cells. This induces apoptosis (cell suicide) in the T cells. This results in negative selection with the result that these autoantigens are tolerated by the immune system. If a defective AIRE protein is encoded by the gene mutation, this adaptation does not take place, so that many autoimmune diseases can develop. The causes of the so-called Schmidt syndrome or Schmidt-Carpenter syndrome are again not known. Polygenic factors are suspected. The most severe and rarest form of polyendocrine autoimmune disease is XPID. The term XPID stands for the abbreviation of the English term X-linked polyendocrinopathy, immunodeficiency and diarrhea syndrome. As the name suggests, it is a gene mutation on the X chromosome. Therefore, only boys are affected by the severe form. In girls, the disease is usually milder because the mutated gene from the mother is compensated by a healthy gene from the father. The affected gene is the FOXP3 gene.
Symptoms, symptoms, and signs
Polyendocrine autoimmune diseases show all the symptoms that would be seen in single autoimmune diseases. Patients with APECED syndrome have symptoms of Addison’s disease, hypoparathyroidism, and mucocutaneous candidiasis. Sometimes type I diabetes may also be present. In Addison’s disease, the adrenal cortex is destroyed. There is a cortisol deficiency and a deficiency of aldosterone. The production of ACTH is increased. The patient suffers from feelings of weakness, nausea, vomiting, weight loss, hypoglycemia, and electrolyte imbalances.At the same time, hypoparathyroidism leads to calcium deficiency with numbness and pawing of the hands. In addition, there are digestive disorders, cataracts, headaches and sometimes dementia. Mucocutaneous candidiasis manifests as malabsorption, diarrhea, chronic hepatitis, localized hair loss, or pernicious anemia. Schmidt syndrome is mainly Addison’s disease combined with Hashimoto’s thyroiditis. In addition to the symptoms of Addison’s syndrome, the symptoms of chronic thyroiditis are also present. The thyroid gland is attacked by its own immune system. In this process, hyperthyroidism initially develops in the context of Hashimoto’s syndrome because stored thyroid hormones are rapidly released. After extensive destruction of the thyroid gland, too little thyroid hormone is then produced, with the typical symptoms of hypothyroidism. The most severe form of polyendocrine autoimmune disease, XPID syndrome, is characterized by the combination of diabetes and severe diarrhea. The disease begins in early childhood, usually affecting boys. Due to autoimmune reactions against many internal organs, death often occurs early.
Diagnosis and course of the disease
Diagnosis of polyendocrine autoimmune disease results from the variety of organ involvement.
Complications
In these diseases, affected individuals suffer from a number of different symptoms and complaints. In most cases, however, this involves a feeling of weakness and, further, vomiting or nausea. Weight loss may also occur, so that the affected persons may also show deficiency symptoms. Patients also suffer from severe headaches or numbness and other sensory disturbances. Furthermore, the symptoms also occur in the region of the stomach and intestines, so that diarrhea or constipation may occur. The disease-related hair loss leads to a significantly reduced aesthetic appearance of the patient, so that in many cases the affected persons suffer from inferiority complexes or a reduced self-esteem. Similarly, hypothyroidism or hyperthyroidism may occur. If these symptoms are not treated, the patient usually dies. Causal treatment of the disease is not possible. With the help of replacement hormones, the symptoms can usually be limited. However, in most cases, this significantly reduces the patient’s life expectancy.
When should one go to the doctor?
Fatigue, an internal weakness, as well as a decrease in physical performance are signs of impaired health. A visit to the doctor is necessary if the complaints persist over several weeks or increase. A doctor should be consulted in case of nausea, vomiting, a general feeling of malaise as well as a feeling of illness. If there is an unwanted weight loss, this is to be understood as a warning signal of the organism, which should be followed up. Disturbances of the digestive tract, persistent diarrhea, constipation, and sleep disorders should be examined and treated. If the affected person complains of headaches, impaired memory or hormonal irregularities occur, a doctor is needed. If left untreated, the disorders can lead to the premature demise of the affected person. Therefore, a visit to the doctor should be made if symptoms persist or the health condition worsens. Unusual hair loss, sensory disturbances on the skin or a feeling of numbness should be presented to a physician. A characteristic feature of polyendocrine autoimmune diseases is pawing of the hands. If this can be observed, a visit to the doctor should be made immediately. If, in addition to the physical abnormalities, emotional or mental complaints develop, a doctor should also be consulted. In the case of behavioral changes, a withdrawal, a depressed mood or a steadily decreasing sense of well-being, clarification of the symptoms by a physician is recommended.
Treatment and therapy
Causative treatment of polyendocrine autoimmune disease is not currently available. The main focus is on hormone replacement therapies. These, of course, depend on the diseases present. Thus, in Addison’s disease, lifelong substitution with cortisol and aldosterone occurs.In hypoparathyroidism, calcium levels must be stabilized by peroral calcium administration.
Prevention
Because polyendocrine autoimmune diseases are genetic, there are no recommendations for preventive measures. If there are previous cases of multiple autoimmune diseases in the family, human genetic counseling and genetic analyses can be used to assess the risk to offspring if children are desired.
Follow-up
There is no cure for polyendocrine autoimmune disease. There is no appropriate therapy to date. Affected individuals must carry an emergency kit at all times. In addition, sufferers must be strict about not losing too much weight due to the nausea and vomiting, or the body will experience deficiency symptoms. Sick people must eat a diet that is light and rich in vitamins and consume many portions of fluids. Examples include water, soups or spritzers. Sufferers should also make sure that the food they eat contains salt, as this binds the fluids to the body. As a result of the disease, many sufferers suffer from inferiority complexes and feel disadvantaged by life. This can lead to a high impairment of the quality of life. In this case, it is important that those affected maintain a social environment so that there is always contact with friends and family and help can be sought if needed. Consulting a psychologist can also be very helpful. This person can teach affected persons how to live with the disease. If affected individuals maintain a desire to have children, they should undergo human genetic counseling. There, it can be determined if the children will also have the polyendocrine autoimmune disease, if applicable.
Here’s what you can do yourself
The diseases grouped under this term are not curable. This means that those affected will need to substitute hormones for the rest of their lives. They would do well to make this a habit, because poor compliance also worsens the health condition. Any emergency kits must be carried at all times. In addition, patients with polyendocrine autoimmune disease should be careful not to lose too much weight, even during periods of nausea and vomiting, or they risk deficiency symptoms such as vitamin or mineral loss. Patients benefit from a light diet rich in vitamins and many portions of fluids distributed throughout the day. Water, teas, spritzers or thin soups are recommended. Salt in the diet is also recommended so that the body can bind the absorbed fluid. It is possible that the disease causes patients to feel inferior or disadvantaged by life. The possibly reduced life expectancy can also be very stressful. Sufferers should then not be afraid to seek psychotherapeutic help. Most polyendocrine autoimmune diseases are genetically determined. If affected patients have a desire to have children, they should seek human genetic counseling with their partner. Genetic analysis can provide a clue as to whether or not the potential offspring will also have polyendocrine autoimmune disease.
