The Congenital adrenal hyperplasia The CAH (" Congenital adrenal hyperplasia A") belongs to the group of autosomal recessive diseases from genetic mutations.
Specifically, enzymes involved in the production of glucocorticoids, mineralocorticoids or sexual steroids are altered by the action of the adrenal glands. (Warrell, 2005). That is, a mutation or deletion of any gene encoding enzymes that synthesize cortisol or aldosterone results in this disease. (Wilson, 2015).
Primarily, this disease is going to cause by excess or by defect an abnormal production of Sexual steroids .
For this reason, the person with congenital adrenal hyperplasia will show an altered development of the characteristics Primary sexual Y high schools. (Milunsky, 2010). The phenotype will depend on the sex of the subject and the severity of the mutation. (Wilson, 2015)
What are adrenal glands?
They are small organs that are located just above the kidneys. Its function is to produce hormones that are fundamental for the proper functioning of the organism (Spanish Society of Pediatric Endocrinology), like the sex hormones or the Cortisol. The latter is important for responding to stress and other functions.
What types exist?
This disease presents numerous variations according to the sex and the affected genes. Therefore, there are several ways to classify it.
The most common classification encompasses alterations in the levels of different enzymes:
- Congenital Adrenal Hyperplasia 21-Hydroxylase , Which is the most frequent. In turn, it can be divided clinically into 3 phenotypes: loss of salt, simple virilizing, and non-classical. (Wilson, 2015).
- Congenital Adrenal Hyperplasia 11-beta-hydroxylase
- Congenital Adrenal Hyperplasia 3-beta-hydroxysteroid dehydrogenase
- Congenital Adrenal Hyperplasia 17-alpha-hydroxylase
- Congenital Adrenal Hyperplasia Lipoid (Desmolesa 20, 22).
It can be cataloged also according to the moment in which the symptoms appear, being able to be:
- Classical : If the symptoms are already expressed in the newborn.
- Not classical : If symptoms occur in more advanced stages of life, such as puberty. According to the Spanish Society of Pediatric Endocrinology, within this type can be given a less severe form called"cryptic form". It refers to cases that are detected by a family study, examining parents or siblings who already have this disease. In cryptic cases there are also enzymatic alterations that are usually overlooked due to the absence or lightness of symptomatic expression.
What is its prevalence?
Classical adrenal hyperplasia occurs in 1 in 13000 to 1 in every 15,000 live births in the world. Specifically, the non-classical subtype of 21-hydroxylase deficiency is the most common, with autosomal recessive disease being more common in humans.
According to Wilson (2005), it accounts for 90% of cases. The second most frequent subtype is 11β-hydroxylase deficiency, which accounts for between 5 and 8% of cases. The other types are very rare cases.
It should be noted that the frequency of subtypes of congenital adrenal hyperplasia depends on certain populations and has a high ethnic specificity. (New, 2013).
As for sex, men and women suffer this disease with the same frequency. However, depending on the accumulation of precursor hormones or the synthesis of testosterone related to each sex, phenotypic manifestations will vary between women and men (Wilson, 2015).
What are its causes?
It is produced mainly by the action of cholesterol in 3 ways: the glucocorticoid route, the mineralocorticoid route and, finally, that of the sex steroids.
It appears that in congenital adrenal hyperplasia there is a decrease in the release of cortisol, from Aldosterone Or both (Wilson, 2015). It is known that lack of cortisol increases the secretion of ACTH (or corticotropin, a hormone that stimulates the growth of the adrenal cortex). (New, 2013).
Two copies of an abnormal gene are needed for this disease to arise, and it is important to note that not all partial deletions or mutations originate. (Wilson, 2015)
It is important to mention that the clinical phenotype will change according to enzyme deficiency, accumulation of precursor hormones, the production of these hormones and their physiological action when the enzymes do not function correctly (Speiser, 2015).
What signs and symptoms does it present?
Signs of congenital adrenal hyperplasia may already manifest from birth and vary by subtype.
Symptoms in women
- In the case of classical virilizing adrenal hyperplasia, masculinized genitalia are found with abnormalities such as: complete or partial fusion of the labioscrotal folds, pharyngeal urethra or Clitoromegaly .
- If the 21-hydroxylase deficiency is milder, the symptoms are seen in late childhood and consist of: accelerated skeletal growth and maturation, early pubic hair appearance and clitoromegaly. This type would be called Simple Virilizing Adrenal Hyperplasia.
- Another less serious type begins to reveal in adolescence or early adulthood. It is identified by oligomenorrhea (delayed menstruation), Hirsutism (Excessive appearance of hair) and / or infertility (non-classical adrenal hyperplasia).
- On the other hand, if there is deficiency of the 17-hydroxylase enzyme; The phenotype is female at birth, but in adolescence menstruation does not appear nor develop the breasts. Hypertension is often present here.
- They can show (especially in the virilizing form) interests considered socially of the masculine sort.
Symptoms in men
- Men develop male genitalia in most cases. Although there is deficiency in the androgenic regulation of 3-beta-hydroxysteroid dehydrogenase (3β-HSD) or 17-hydroxylase, ambiguous or feminized genitalia may be present. In these cases, it is customary that they are educated as if they were girls and that they go to the doctor after several years for lack of growth of the sines or hypertension .
- In the most severe cases, one can observe between the first and fourth week after birth developmental delay, vomiting, dehydration, Hypotension , Hyponatremia (low sodium level), hyperkalemia (high level of potassium in the blood) that is consistent with the diagnosis of classical salt-losing adrenal hyperplasia.
- A milder lack of the 21-hydroxylase enzyme already manifests itself in childhood through an accelerated development characterized by early pubic hair growth, rapid skeletal maturation and phallic enlargement. (Simple Virilizing Adrenal Hyperplasia). (Wilson, 2015)
- Testicular tumors and oligospermia (poor sperm secretion) may occur (Speiser, 2015).
Other general symptoms of the classic and nonclassical type (Kivi and Rogers, 2016)
- Deep voice.
- Weightloss.
- Dehydration.
- Vomiting.
- High cholesterol.
- Severe acne.
- Low bone density.
What complications can occur?
In classic congenital adrenal hyperplasia there may be a complication called"adrenal crisis,"which means that the adrenal glands do not produce enough cortisol.
This condition must be taken care of immediately. It is necessary to clarify that it usually occurs in children and does not happen in adults with the non-classic subtype.
Its signs and symptoms would be the following:
- Diarrhea.
- Vomiting.
- Dehydration.
- Low levels of sugar and sodium in the blood.
Shock.
Long-term complications include:
- Infertility.
- Permanent risk of adrenal crisis.
- Sexual problems, such as pain during intercourse ( Dyspareunia ).
How is it detected?
Over time, methods have been changing in order to improve the predictive value of these tests and to be able to detect the disease more accurately.
For example, there are some screening programs where blood tests are repeated after several weeks. In this way, they make sure to diagnose cases that have been overlooked.
Due to these developments, child mortality has improved significantly; All thanks to the improvement of an early diagnosis (which will allow the treatment to be started as soon as possible).
- In most developed countries, all newborns are heel tested for 21-hydroxylase deficiency and other disorders.
- Immunoassays are also used, which are useful for detecting 17-hydroxyprogesterone.
- An approach to the diagnosis of this disorder in the fetus can be made in the second trimester of pregnancy. To do this, hormone levels of amniotic fluid are measured (Kivi and Rogers, 2016).
- Genotyping of fetal DNA in maternal serum: it consists of detecting a possible case of congenital adrenal hyperplasia before the 7th week of pregnancy to start treatment as soon as possible (Spanish Society of Pediatric Endocrinology). So far it has not been considered profitable and does not fall into the diagnostic routine (Speiser, 2015).
How is the forecast?
According to Wilson (2005), if the correct medical and / or surgical treatment is received, the prognosis may be good.
However, there are usually psychological problems that need to be addressed, as these people may experience dissatisfaction due to genital abnormalities common in some types of congenital adrenal hyperplasia.
In addition, difficulties may arise in terms of gender identity because some of these young patients are usually raised according to a gender in which they feel they do not fit.
It is important in this case to provide adequate psychological, medical and surgical support; As well as providing you with enough information to understand the disease and make the right decisions.
People with adrenal hyperplasia often have low fertility and fecundity compared to those who do not have this disease (Speiser, 2015), although with adequate metabolic control it can be improved.
Premature death may occur in some cases if doses of Glucocorticoids Necessary at key moments.
For all this, the quality of life of patients with this condition has been classified as suboptimal to poor, although methods are currently being developed to continue to maximize the well-being of these people.
How is it treated?
Congenital adrenal hyperplasia is chronic and accompanies the person throughout life. The main goal of treatment in its classical form is to reduce the excess production of adrenal androgens and to replace the deficiency of Cortisol And aldosterone.
In this way it is intended to avoid adrenal insufficiency and virilization, mainly through oral medications composed of mineralocorticoids, glucocorticoids and salt supplements.
It is essential for a correct treatment to perform annual radiographs (observe if the growth is appropriate) and to control the levels of electrolytes, adrenal steroids and plasma renin activity.
According to Kivi and Rogers (2016):
- Medication : Is the most common form of treatment, based on a daily hormone replacement. This reduces symptoms and regulates hormone levels. More than one type of drug may be needed or high doses may be used to treat the patient especially when they become ill, undergo surgery, or are under excessive stress. It is possible that patients with the non-classical subtype do not need treatment because their symptoms are not so obvious.
Hydrocortisone is commonly used, which is given two or three times a day (Speiser, 2015).
- Surgery : You can opt for a surgical method called"feminizing genitoplasty"for girls from 2 to 6 months, which aims to change the functioning and appearance of their genitals. It may be necessary to repeat this operation after puberty. According to one study (Crouch et al., 2004), women who have undergone this intervention are more prone to loss of clitoral sensitivity or to dyspareunia (pain during intercourse)
- Psychological and emotional support : Since it is habitual to have insecurities regarding the physical appearance and to worry about the sexual and reproductive life. It is important to ask for psychological help, and it is useful to consider participating in a support group with people who are in similar conditions.
- It has been suggested to treat pregnant women who carry a fetus with this disease through pharmacological intervention, but this should be handled by professionals who carefully review doses. Specifically, the development of a treatment with dexamethasone has been studied but it is not advised since it can lead to health risks that are still little known, since it is in an experimental phase (Speiser, 2015).
Can it be prevented?
If the family has this disease and are considering having a child, it is recommended that they receive genetic counseling.
It is essential to diagnose the disorder as early as possible (in the prenatal phase) so that you can receive treatment early. As mentioned earlier, if the fetus is diagnosed with congenital adrenal hyperplasia; The pregnant woman can take Corticosteroids During pregnancy.
These drugs work by reducing the amount of Androgens Which produce the affected baby's adrenal glands, and may help the baby develop normal genitalia.
However, we emphasize again that this method is not very widespread since it is currently in the experimental phase, that is, we do not yet know its exact mechanism of action. This could lead to some side effects that endanger the health of both the baby and the mother (Kivi and Rogers, 2016).
Bibliography
- Crouch, N., Minto, C., Laio, L., Woodhouse, C. & Creighton, S. (2004). Genital sensation after feminizing genitoplasty for congenital adrenal hyperplasia: A pilot study. BJU International, 93 (1), 135-138.
- HSC Working Group of the Spanish Society of Pediatric Endocrinology. Guide for patients and families with congenital adrenal hyperplasia (HSC). Retrieved on June 1, 2016.
- Kivi, R. & Rogers, G. (February 18, 2016). Congenital Adrenal Hyperplasia. Obtained from Healthline.
- Adrenal Gland Disorders. (S.f.). Recovered on June 1, 2016, from MedlinePlus.
- Milunsky, A. & Milunsky, J. (2010). Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment. Wiley-Blackwell.
- New, M. L.S. (October 28, 2013). Congenital Adrenal Hyperplasia . Obtained from National Center for Biotechnology Information .
- Speiser, P. (August 20, 2015). Congenital Adrenal Hyperplasia. Obtained from National Center for Biotechnology Information.
- Warrell, D.A. (2005). Oxford textbook of medicine: Sections 18-33. Oxford University Press. Pp. 261.
- Congenital Adrenal Hyperplasia. (S.f.). Retrieved on June 1, 2016, from Wikipedia.
- Wilson, T. (September 3, 2015). Congenital Adrenal Hyperplasia . Obtained from Medscape.
- Congenital Adrenal Hyperplasia . (22 June 2015). Retrieved on June 1, 2016, from Mayoclinic.
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