Genetic disorders such as congenital adrenal hyperplasia (CAH) affect the adrenal glands on top of the kidneys. Among the hormones produced by the adrenal glands are cortisol, aldosterone, and androgens, which are essential to the body's functions. A deficiency of an enzyme needed to make these hormones results in a hormonal imbalance in CAH.
One of the genes that code for adrenal hormone synthesis enzymes is mutated, causing CAH. The most common type of CAH is caused by a deficiency of the enzyme 21-hydroxylase, which converts a precursor hormone called 17-hydroxyprogesterone into cortisol and aldosterone. If 21-hydroxylase is not present enough, the body accumulates excess 17-hydroxyprogesterone, which is then converted into androgens.
As CAH is an autosomal recessive gene, both parents must carry a copy of the mutated gene and pass it on to their children. If both parents are professionals, the risk of having a child with CAH is 25%, 50% if one parent is a professional and the other one is a professional, and 100% if both parents have CAH.
The symptoms of CAH vary depending on the type and severity of the enzyme deficiency, as well as the sex of the affected person. The two main types of CAH are classic and nonclassic.
A more severe form of CAH, known as classic CAH, is usually diagnosed at birth or in early infancy. It can cause life-threatening complications if not treated promptly.
Insufficient cortisol: This can lead to low blood sugar, low blood pressure, fatigue, weakness, and poor stress response.
Insufficient aldosterone: This can lead to dehydration, salt loss, high potassium levels, and low blood volume.
An excess of androgens can lead to abnormal sexual development and early puberty in females, as well as ambiguous genitalia in males, such as an enlarged clitoris and fused labia that resemble a scrotum. It can also cause an enlarged penis and early testicular growth in males. The effects can be seen in both sexes, including early growth spurts, pubic hair, acne, and deep voice.
In classic CAH, there are two types: salt-wasting and simple-virilizing. Salt-wasting CAH affects both cortisol and aldosterone production while simple-virilizing CAH affects only cortisol production.
This form of CAH is milder and more common than classic CAH. It may be diagnosed in childhood or adulthood, or it may remain undiagnosed for a long time. Symptoms of nonclassic CAH include:
Mild cortisol deficiency: This can cause fatigue, low blood pressure, and poor stress response.
Mild aldosterone deficiency: This can cause salt craving, dehydration, and low blood volume.
Virilization and early puberty are symptoms of mild androgen excess. Females may experience irregular periods, infertility, acne, hirsutism (excess body hair), and alopecia (hair loss). Males may experience early pubic hair, acne, and premature ejaculation as a result.
CAH can be diagnosed by various methods, depending on the age and symptoms of the affected person. The methods include:
In developed countries, newborns are screened for classic CAH by measuring their blood levels of 17-hydroxyprogesterone. This test can detect most cases of classic CAH, but not nonclassic CAH.
Prenatal testing: A pregnant woman who has a high risk of having CAH during pregnancy can undergo prenatal testing to determine if her fetus has CAH. A sample of amniotic fluid or placenta can be taken, and the cells can then be examined for gene mutations using amniocentesis or chorionic villus sampling.
The physical examination can reveal signs of abnormal sexual development, such as ambiguous genitalia, enlarged genitals, or early puberty. Blood pressure measurements can also indicate low or high blood pressure caused by cortisol or aldosterone deficiency.
It can help confirm the diagnosis and determine the type and severity of CAH by measuring hormone levels and electrolytes in the body, such as cortisol, aldosterone, androgens, sodium, potassium, and glucose.
Genetic test: A genetic test can identify the specific gene mutation that causes CAH. This can help confirm the diagnosis and provide information for genetic counseling.
The treatment of CAH aims to restore the normal balance of hormones in the body and prevent or correct the complications of the disorder. The treatment options include:
Medication: People with CAH need to take medication for life to replace the hormones that their body cannot produce. The medication includes:
The body's metabolism, blood pressure, and immune system are regulated by corticosteroids, which are synthetic versions of cortisol. Examples include hydrocortisone, prednisone, and dexamethasone. Corticosteroids are prescribed based on the individual's needs, which may vary with stress, illness, and injury.
A mineralocorticoid is a synthetic version of aldosterone that helps regulate the body's salt and water balance. Fludrocortisone is an example. Salt-wasting CAH patients must take mineralocorticoids daily to avoid dehydration and electrolyte imbalances. They may also need salt supplements or increase their salt intake.
In females, androgen blockers can reduce virilization signs and improve fertility. Examples include spironolactone, finasteride, and flutamide.
Surgery: Some people with CAH may need surgery to correct the appearance or function of their genitals. This can include:
Women with ambiguous genitalia may undergo reconstructive surgery to reduce the size of the clitoris and separate the labia and urethra. The surgery is usually performed in infancy or early childhood, but can also be performed later in life. This can improve cosmetic and psychological outcomes for the affected person.
Those who wish to enhance their feminine appearance, or those who wish to reduce their penis size, will undergo cosmetic surgery. In addition to improving self-esteem, this surgery can also improve sexual function. It is usually performed after puberty has been completed in adolescence or adulthood.
Women with CAH may need to undergo fertility surgery, which consists of removing ovarian cysts, restoring ovulation, or performing in vitro fertilization (IVF). The surgery is usually performed in adulthood, when the person is ready to conceive.
It is common for CAH patients to experience anxiety, depression, low self-esteem, body image issues, or gender identity issues. Psychological support can help them cope with these challenges and improve their quality of life. It can include counseling, therapy, support groups, or education. These can all be used to help people cope with these challenges and improve their quality of life.
There is no way to prevent CAH, as it is a genetic disorder that is present from birth. However, there are ways to reduce the risk of having a child with CAH or to detect it early. These include:
Before starting a family, individuals with a history of CAH or those who carry the mutation of the gene can consult a genetic counselor. A genetic counselor can provide information about the inheritance pattern, the risk of having a child with CAH, and the available testing and treatment options.
Women who are at risk of having a child with CAH can undergo prenatal diagnosis to detect CAH in the fetus. The information will allow them to make informed decisions about the pregnancy, such as whether to continue it or end it. It can also help them prepare for the delivery and treatment of the child.
Screening newborns for CAH can save lives and prevent complications. Early diagnosis and treatment improve the health and development of the child and prevent adrenal crisis, which can be fatal.
