Adrenogenital syndrome is referred to as “congenital androgenital disorder associated with enzyme deficiency” according to the WHO catalog number E25.0. It is caused by disorders in the synthesis of hormones in the adrenal cortex and results in a deficiency of cortisol in the body.
What is adrenogenital syndrome?
Adrenogenital syndrome is caused by disorders in the synthesis of hormones in the adrenal cortex and results in a deficiency supply of cortisol to the body. Adrenogenital syndrome is characterized by disruption of the interplay between the adrenal cortex, thyroid gland, and the hypothalamus and pituitary gland. All four are involved in the provision of hormones in the human body. In the main, the hormones cortisol as well as aldosterone are affected by the malfunction. If aldosterone is absent, for example, this can also be accompanied by a considerable loss of salt. Another characteristic of adrenogenital syndrome is found in adolescents. In male patients, the sex organs develop earlier than normal and female patients show distinct male features. Disturbances in cortisol levels cause sleep disturbances and severely limit performance throughout the day. This can lead to chronic fatigue syndrome.
Causes
Depending on which enzyme is specifically affected, adrenogenital syndrome can be classified into five types based on the cause. In type 1, the production of StAR protein is impaired. One subtype shows disturbances in cholesterol monooxygenase, but so far this has only been demonstrated in a single case. In type 2, 3beta-hydroxysteroid dehydrogenase is impaired. Type 3 occurs with a significant frequency and is manifested by a disturbance of 21-hydroxylase. Type 4, in which serological changes in 11-beta-hydroxylase can be detected, ranks second in frequency. 17alpha-hydroxylase is disturbed in type 5, which is diagnosed quite rarely. Regional differences are also observed. For example, type 1 adrenogenital syndrome is very rare in Europe, whereas it is found with a marked frequency in South Korea and Japan.
Symptoms, complaints, and signs
Classic adrenogenital syndrome is manifested by prenatal masculinization of the external genitalia in female individuals. In males, the main symptom is salt wasting. Depending on whether it is a form with or without salt loss, failure to thrive or shock may occur. In the worst case, the child falls into a coma. In both sexes, excessive male hormones are formed during childhood, resulting in tall stature, acne, premature voice change and genital hair, a lack of menstrual periods, and other symptoms. Untreated children achieve short stature and often suffer from obesity, metabolic changes and infertility in adulthood. They are also at increased risk for cardiovascular problems and other complications. Late-onset AGS is not usually associated with prenatal masculinization. However, it can also cause symptoms such as premature pubic hair and acne. Affected individuals often suffer from tall stature and are usually infertile. Furthermore, adrenogenital syndrome can be recognized by external malformations or deformities. For example, in some cases the genitals are excessively small or large. In girls, the growth of the breasts may be disturbed. Other symptoms depend on the particular form of AGS.
Diagnosis and course
For diagnosis, the first means after a general medical history is a so-called blood gas analysis. This involves checking the ratio of bases and acids in the blood. A determination of electrolytes is also performed to determine how far salt loss has progressed in the metabolism. In a second step, parallel examinations of the blood and urine are performed, through which indications of a disturbance in the provision of 17-hydroxy-progesterone are obtained. Evidence of changes in cortisol levels can now also be obtained by salivary tests, and changes can also be found throughout the day, indicating adrenal insufficiency. The ACTH test is used as a further diagnostic tool.In babies, this test is one of the standard tests performed in Germany immediately after birth. In the unborn child, diagnostics can be performed via tests of the amniotic fluid.
Complications
Primarily, in adrenogenital syndrome, the patient suffers from severe androgenization. Especially in women, this is an enormous problem and can lead to severe disturbances of self-esteem and inferiority complexes. Often there is also the development of a pseudo-penis. Those affected suffer from fatigue and sleep disturbances. Likewise, they are more affected by infectious diseases and become ill more often. The body grows relatively quickly and strongly. The masculinization leads to bullying and teasing, especially in childhood, which can result in severe psychological complaints and depression. Often psychological treatment of the child and parents is necessary to cope with this syndrome. Unfortunately, the syndrome cannot be cured causally, so treatment is aimed only at limiting the symptoms. This mainly involves replacing the missing hormones to counteract the syndrome. Since the missing hormones are not produced by the body at all, the patient usually has to take them for the rest of his life. No further complications occur. If the disease is detected during pregnancy, the mother can also take medication. The life expectancy is not reduced in this case. The development of the child also usually takes place.
When should you go to the doctor?
Women with adrenogenital syndrome should seek advice from a human geneticist if they wish to have children. This person will perform a DNA analysis and help assess the risk of disease for the unborn child. If this is increased due to heterozygosity of the partner, prenatal therapy is performed. This prevents masculinization symptoms in girls. In boys, the symptoms are more inconspicuous and usually only appear when a life-threatening salt wasting crisis occurs. If affected children appear listless, vomit frequently or fall into a coma, this is to be classified as an emergency. This requires immediate action. Further care and drug therapy is provided by the pediatric endocrinologist. An adrenal crisis can also occur in adults. Symptoms such as high blood pressure, nausea, vomiting or shock require immediate medical attention. Women should see a gynecologist if they suffer from infertility or lack of menstruation. If they also develop signs of virilization, the right contact is an internal endocrinologist. If late-onset AGS is suspected, the physician will perform various tests. Increased sweating, pronounced acne and slight weight gain are not in themselves a cause for concern. These signs may be a normal consequence of puberty or hormonal imbalance.
Treatment and therapy
Treatment in the sense of correcting the cause is not possible for adrenogenital syndrome because it is a congenital genetic defect. Symptomatic treatment is therefore given, consisting of replacement of the missing hormones. This must be lifelong, although with regard to the dosage it should be noted that it must be temporarily increased in stressful situations. In the main, preparations with fludrocortisone and mineral corticoids are used. These hormone replacement therapies should be started as early as possible. This has led to the development of technologies to provide corticosteroids to girls while they are still in the womb.
Outlook and prognosis
Usually, this syndrome results in very severe masculinization of the patient. In the process, pseudopenis may also develop in the female as the disease progresses. The body grows relatively fast and puberty occurs early. In most cases, those affected also suffer from psychological complaints and sometimes depression. In children, teasing and bullying may occur. There is also severe fatigue, which is caused by sleep disturbances. The patient is also highly susceptible to various infections and diseases and suffers from inflammation more often. The quality of life of the affected person is greatly reduced by the syndrome. The treatment of this syndrome is carried out with the help of hormone therapy, which usually leads to success.Further complications and complaints do not occur. The patient can be provided with the necessary hormones while still in the womb, so that the symptoms are greatly reduced after birth. The syndrome can be completely limited in the further course of treatment, so that there is no further discomfort for the patient.
Prevention
Because a genetic defect has been identified as the cause, prevention in the strict sense is not possible. But with some measures, the effects can be alleviated. Consistent stress avoidance plays an important role here. Nutrition can also make a significant contribution to relieving the metabolism. One should know that thereby some of the references of the WHO to the healthy nutrition are turned completely on the head. Particularly interesting here is the Logi method of nutrition, which was developed by Harvard University. Instead of three meals one should distribute its food admission evenly over the day. In this way, fluctuations in the cortisol balance due to the time of day are balanced out.
Follow-up
As a rule, no special measures or options for aftercare are available to the patient with this syndrome. In this regard, the affected person is primarily dependent on early detection and diagnosis of these complaints in order to prevent further complaints or to complications. It is also not possible for the disease to heal itself, so that early detection is the most important factor in this disease. If the affected person wishes to have children, genetic counseling can also be performed in order to possibly prevent the syndrome from being passed on to the descendants. Since this is a hereditary disease, it is not possible to provide a complete or even a causal treatment. Possibly, the life expectancy of the affected person is also reduced by this syndrome. The treatment itself is usually carried out through the administration of medication. The affected person should pay attention to a correct dosage and also to a regular intake. A doctor should always be consulted first if there are any questions or uncertainties. Further aftercare measures are neither necessary nor possible. In the case of children, it is primarily the parents who must ensure that the medication is taken correctly.
What you can do yourself
People who have adrenogenital syndrome need medical treatment for the rest of their lives. In everyday life, an active lifestyle and an adapted diet are recommended. The physician will recommend a steady diet with sufficient vitamins and minerals. In addition, the patient must consume enough fluids to minimize the risk of a medical emergency. AGS patients must also carry an emergency identification card. In the event of a medical emergency, first responders can immediately call emergency medical services and provide first aid. The emergency ID card must also be carried after medication treatment is completed. Because medication for AGS often must be continued for life, attention should be paid to any side effects and interactions. Especially in the first weeks and months after starting treatment, it is important to recognize complications and adjust the medication. After a few months, the medication should be optimally adjusted to the symptom pattern, minimizing hormonal complaints and reducing the risk of a medical emergency. However, if unusual symptoms do occur, it is best to contact emergency medical services or an urgent care physician immediately.
