Congenital adrenal hyperplasia

The signs and symptoms of congenital adrenal hyperplasia (CAH) vary based on many factors including the type of CAH, the age of diagnosis and the sex of the affected person. For example, girls with the severe form of CAH may be born with ambiguous genitalia, which often allows the condition to be diagnosed before other associated health problems such as poor feeding, vomiting, dehydration, and abnormal heart beat, can develop. Males typically appear unaffected at birth even when they have a severe form of CAH and without proper diagnosis, will develop associated health problems within 2-3 weeks after birth. Both genders can experience other symptoms such as early onset of puberty, fast body growth, and premature completion of growth leading to short stature, if they are not treated in early life.^[4][1][2]

People affected by milder forms may not have any signs and symptoms of CAH during childhood. In these cases, a diagnosis may not be made until adolescence or adulthood when the affected person experiences early signs of puberty or fertility problems. Females with this type may have excessive facial or body hair; irregular menstrual periods; and/or acne.^[4][1][2]

There are two main types of CAH: classic CAH, the more severe form, and a milder form called nonclassic CAH. For a detailed description of the signs and symptoms found in each type of CAH, please click here.^[3]

Congenital adrenal hyperplasia (CAH) is a group of genetic conditions that can be caused by a change (mutation) in several different genes:^[2]

• 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene
• 3-beta-hydroxysteroid dehydrogenase deficiency is caused by mutations in the HSD3B2 gene
• 11-beta-hydroxylase deficiency is caused by mutations in the CYP11B1 gene
• Cytochrome P450 oxidoreductase deficiency is caused by mutations in the POR gene
• 17-hydroxylase deficiency is caused by mutations in the CYP17A1 gene
• Congenital lipoid adrenal hyperplasia is caused by mutations in the STAR gene

Most of these genes encode enzymes that the adrenal glands need to make one or more hormones. The adrenal glands are cone-shaped organs that sit on top of the kidneys and are responsible for releasing various types of hormones that the body needs to function. Mutations in these genes lead to deficient levels of enzymes which cause low levels of hormones such as cortisol and/or aldosterone and an overproduction of androgens (male hormones such as testosterone). Cortisol is a hormone that affects energy levels, blood sugar levels, blood pressure, and the body's response to stress, illness, and injury. Aldosterone helps the body maintain the proper level of sodium (salt) and water and helps maintain blood pressure. Irregular levels of these hormones lead to the signs and symptoms of CAH.^[3][4]

All forms of congenital adrenal hyperplasia (CAH) are inherited in an autosomal recessive manner.^[2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Yes, genetic testing is available for many of the genes known to cause congenital adrenal hyperplasia (CAH).^[5] Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Shortly after birth, all newborns in the United States are screened for a variety of conditions, including 21-hydroxylase deficiency. This is the most common cause of congenital adrenal hyperplasia (CAH) and accounts for 95% of classic CAH cases. Nonclassic CAH is not detected through newborn screening and is often not suspected until signs and symptoms of the condition begin to appear later in childhood or early adulthood. In these cases, a diagnosis of CAH is usually based on physical examination; blood and urine tests that measure hormone levels; and/or genetic testing. An X-ray may also be helpful in confirming the diagnosis in children since CAH can cause bones to grow and develop more quickly than usual (advanced bone age) .^[2][3][4]

The best treatment options for congenital adrenal hyperplasia (CAH) depend on many factors including the type of CAH and the signs and symptoms present in each person. Many people with CAH require steroids to replace the low hormones. These medications will need to be taken daily throughout life or the symptoms of CAH may return. It is important that affected people on medications be closely followed by their healthcare provider because their dose may need to be adjusted at different times in life such as periods of high stress or illness.

Girls with severe CAH who are born with ambiguous genitalia may undergo surgery to ensure proper function and/or to make the genitals look more female.^[2][3][4]

For more information on the treatment of CAH, please click here.

The long-term outlook (prognosis) for people with congenital adrenal hyperplasia (CAH) is usually good. With lifelong treatment, affected people typically have good health and normal lifespans.^[1] However, problems with psychological adjustment are common, particularly in people with genital abnormalities.^[4]