Congenital adrenal hyperplasia
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Congenital adrenal hyperplasia (CAH) refers to a set of hereditary disorders that affect the adrenal glands. Each kidney has one adrenal gland on top of it. The adrenal glands produce vital hormones that the body requires to function properly.
With CAH, the adrenal glands are unable to produce one or more hormones because they lack a specific enzyme. Without this enzyme, the adrenal glands may not produce enough cortisol, aldosterone, or may produce too much androgen. Cortisol is a hormone that aids the body’s response to illness, injury, and stress. Aldosterone maintains proper salt and water levels in the body. While androgens initiate puberty and contribute significantly to normal growth and development.
There are several forms of congenital adrenal hyperplasia. Two main types of CAHs make up 95% of all cases:
- Classic CAH: It can result in severe adrenal problems such as shock and coma. It can be fatal if not detected and treated promptly. This is a more serious variant that is usually diagnosed at birth or early infancy.
- Nonclassic CAH: It usually manifests signs or symptoms later in childhood, adolescence, or adulthood. Symptoms may not be noticeable. This is the milder form and more common form of CAH.
The management strategy for CAH differs based on the particular subtype and the severity of its symptoms. While a complete cure for CAH is not currently available, addressing the symptoms can frequently be accomplished using medications and various therapeutic approaches.
Symptoms
CAH can cause various symptoms. It usually differs depending on which gene has been compromised, the type of CAH, and the level of enzyme deficiency.
- Classic CAH: The signs and symptoms may include:
- Inadequate cortisol production: Classic congenital adrenal hyperplasia (CAH) leads to an inadequate production of cortisol within the body. This can lead to difficulties in sustaining regular blood pressure, blood sugar, and energy levels, as well as complications during periods of physical stress, such as illness.
- Adrenal crisis: This is a fatal condition characterized by a shortage of cortisol, aldosterone, or both. This condition can be fatal.
- Atypical genitalia: Ambiguous genitalia in infants assigned female at birth means that the baby’s external sex organs mirror those of a typical boy, such as an enlarged clitoris that looks like a penis and partially closed labia that looks like a scrotum. However, the child still has typical female internal organs. The uterus, fallopian tubes, and ovaries develop normally. An enlarged penis in infants assigned male at birth is also common in classic CAH.
- Excess androgen: CAH causes the body to produce an excessive amount of androgens. Elevated androgen levels might cause symptoms associated with sexual hormones. Females with extra androgen hormones may develop facial hair, excessive body hair, and a deeper voice. Generally, it can result in low stature and early puberty in both boys and girls. This can include changes in voice, severe acne, and early pubic, armpit, and facial hair.
- Altered growth: During childhood, there may be a period of accelerated growth characterized by a bone age that is advanced, potentially resulting in a final height that falls below the average range.
- Fertility issues: Infertility and abnormal menstrual periods may be caused by classic CAH.
- Nonclassic CAH: This is a milder type of CAH, and some may be completely unaware that they have this condition due to no symptoms. In this type of CAH, cortisol may be the only hormone lacking. The condition usually manifests itself in late childhood or early adulthood.
Nonclassic CAH can manifest similarly in both males and females, with symptoms such as the premature development of pubic hair and other early signs of puberty, severe acne, and accelerated childhood growth accompanied by an advanced bone age, ultimately resulting in a shorter final height than anticipated.
At birth, females with nonclassic CAH might possess outwardly normal genitalia. Nevertheless, as they grow, they could experience the emergence of masculine traits like excessive facial and body hair growth, a deeper voice, and irregular or absent menstrual cycles. These changes might also lead to challenges in achieving pregnancy.
CAH can come to attention when male or female infants display signs of severe illness due to insufficient cortisol, aldosterone, or a combination of both. Classic CAH is commonly identified through routine newborn screening or when infants present with atypical genitalia. In the case of nonclassic CAH, children might display indications of early puberty.
Parents who have concerns about CAH in their children can seek guidance from a healthcare professional for accurate diagnosis and appropriate treatment. Pregnant women with a heightened risk of CAH might receive a recommendation for genetic counseling.
Causes
CAH is occasionally known as 21–hydroxylase deficiency, as the insufficiency of the enzyme 21–hydroxylase is the primary underlying factor of CAH. This enzyme is essential for the production of adequate hormone levels within the body. In rare instances, CAH can result from the absence of another enzyme, known as 11–hydroxylase.
CAH is an autosomal recessive condition. Every gene in the body has two copies, one from each parent. In your body, you inherit a pair of genes for each trait — one from your mother and one from your father. CAH develops when you receive mutated copies of the gene responsible for the deficiency from both of your parents.
Risk factors
Congenital adrenal hyperplasia can affect anyone. However, certain risk factors may increase one’s risk. This include having both parents affected by CAH or carrying the genetic change associated with the condition, as well as belonging to specific ancestral groups like Ashkenazi Jewish, Latino, Mediterranean, Yugoslav, or Yup’ik populations.
Diagnosis
The diagnosis of congenital adrenal hyperplasia (CAH) varies depending on the type of CAH. For classic CAH, the diagnosis usually happens during the regular newborn screening, while nonclassic CAH are often detected during childhood, or later in life usually when one starts showing symptoms.
- Prenatal testing: Pregnant women with one child already diagnosed with CAH may opt for prenatal genetic testing. A healthcare provider can perform CAH screening using procedures such as amniocentesis or chorionic villus sampling.
- Amniocentesis: During the procedure, extracting a sample of amniotic fluid from the womb with a needle and then analyzing the cells.
- Chorionic villus sampling: The procedure entails removing cells from the placenta for analysis.
The confirmation of a CAH diagnosis involves conducting tests after the baby’s birth.
- Newborns and infants: For female infants displaying severe atypical genitalia, chromosome analysis can be conducted to determine their genetic sex, and a pelvic ultrasound can also be employed to detect the presence of female reproductive organs like the uterus and ovaries.
Newborn screening detects the classic form of CAH but not the nonclassic variant. During the first few days of life, routine screening of all newborns for hereditary 21–hydroxylase deficiency is recommended.
- Children and young adults: CAH diagnosis in children and adolescents includes:
- Physical examination: To diagnose suspected CAH, the child’s blood pressure and heart rate may be checked. The healthcare provider may also need to assess all the existing symptoms.
- Blood and urine tests: These tests measure electrolyte levels, which are minerals like sodium that help regulate the body’s water balance. Generally, these tests are requested to examine the levels of hormones from the adrenal glands to see if they are too high or too low.
- Genetic testing: A genetic testing helps to detect mutations in genes, chromosomes, or proteins. These mutations can indicate whether or not one has a genetic problem. This may be required to confirm CAH diagnosis.
Treatment
While a definitive cure for CAH is lacking, symptom relief can be achieved through medications and therapeutic interventions.
In cases of classic CAH, the aim of treatment is to ensure proper growth and sexual maturation. For nonclassic CAH, individuals with mild symptoms might require low–dose medication, while those without symptoms might not need any treatment. The management of CAH can encompass medication usage, reconstructive surgery, and psychological assistance.
- Medications: CAH medications are administered daily. Additional drugs or larger doses may be required during periods of illness or extreme stress, such as surgery. The purpose of these medications is to treat CAH to minimize excess androgen production and replenish deficient hormones.
People with the classic CAH can successfully control the condition for the rest of their lives by using hormone replacement drugs. While nonclassic CAH patients may not require treatment or may just require low–dose corticosteroids.
Medications that may be prescribed include salt supplements, corticosteroids to replace cortisol, and mineralocorticoids to replace aldosterone and aid in salt retention and potassium elimination.
Evaluating the medication’s efficacy involves following a set schedule for assessment:
- Physical examination: Regular health checks are necessary throughout one’s life. Growth and development, such as changes in height, weight, blood pressure, and bone growth require monitoring in children with CAH.
- Monitoring for side effects: Some medications, such as high and prolonged doses of steroid–type replacement medications, may have potential side effects. The healthcare provider will conduct regular monitoring to detect side effects like diminished bone density and growth issues associated with these drugs.
- Blood tests to check hormone levels: Children who have not yet entered puberty require enough cortisol to inhibit androgens and allow them to develop to a normal height. To eliminate undesired masculine traits in girls with CAH, androgens must be suppressed. Cortisol excess, on the other hand, can result in Cushing syndrome. In people with CAH, regular blood tests are required to ensure that hormone levels are regulated.
Individuals with classic CAH must adhere to a lifelong daily medication regimen. Ceasing the medication intake will lead to the reappearance of symptoms. Wearing a medical identification badge could be benefitial for proper treatment.
- Reconstructive surgery: Surgery presents a choice for addressing ambiguous genitalia. It can be employed to enhance the appearance and functionality of the child’s genitals between two to six months following birth. In some instances, the surgery might be delayed for a number of years.
Generally, performing genital surgery is more feasible when a child is very young, but certain parents opt to delay the procedure until their child reaches an age where they can comprehend the associated risks and have a say in their gender assignment. Complications from surgery to fix ambiguous genitalia include infection, hemorrhage, scarring, among others.
During the procedure, the clitoris may be reduced in size and the vaginal aperture may be rebuilt. Females who have reconstructive genital surgery may require more aesthetic surgery in the future.
- Psychological support: Providing psychological support is crucial for promoting the emotional well–being and social adjustment of individuals, whether they are children or adults, living with CAH. With early detection and medication, one can lead a healthy, productive life with CAH.
- Research: Administering synthetic corticosteroids during pregnancy that can pass through the placenta to reach the fetus is regarded as an experimental approach. Further research is being conducted to assess the long–term safety of synthetic corticosteroids and their impact on embryonic brain development.
