ENDOCRINOLOGY AND CONGENITAL ADRENAL HYPERPLASIA

Why is CAH an important concern?

Congenital adrenal hyperplasia (CAH) is a relatively common disease that can affect normal growth and development, and may influence how your body deals with the stress of illness or injury. Some forms of the disorder may cause life-threatening illness. A mild form of the disease is a possible cause of infertility in women. Although there is no cure for CAH, effective treatment is available.

What is CAH?

CAH is a group of inherited genetic disorders that cause a block in the body's ability to make enough of the "stress" hormone, cortisol. Cortisol is made in the adrenal glands, which are two walnut-sized organs located on top of each kidney. Cortisol is essential for life and helps regulate body energy, sugar levels, blood pressure and response to body stress (e.g., illness, colds, infections) or injury (e.g., accidents, surgery, etc.). Some patients with CAH also lack aldosterone, another hormone made by the adrenal glands. Aldosterone helps maintain adequate salt levels in the body. In CAH, since the body can't make enough cortisol (and in some cases aldosterone), it winds up producing an excess of other adrenal hormones that are called androgens. Androgens are male-like hormones present in both males and females that affect growth and development.

CAH occurs in two forms: severe or "classical" and mild or "non-classical." The effects of classical CAH occur as a result of the hormonal imbalance of cortisol, aldosterone and androgens. Too little cortisol during a body stress, such as fever or severe injury, can lead to low blood pressure and in some cases may result in a life threatening situation. Lack of aldosterone production (occurring in three out of four classical CAH patients) damages the body's ability to retain enough salt, a condition that could also be life threatening. Excess production of androgen hormones causes abnormal physical development, particularly the expression of more masculine features. Too much androgens causes both boys and girls to grow too fast and stop growing too early, and develop early pubic hair and/or acne. Girls with classical CAH are born with masculine appearing external genitals due to high levels of androgens in-utero. Although their internal organs are normal, excess androgens may affect puberty in girls and result in irregular menstrual periods, excessive hair growth and infertility.

Nonclassical CAH is a mild version of the classical form of the disease. The same gene is affected, but symptoms are much less severe. Patients with nonclassical CAH are not deficient in cortisol and aldosterone, but do produce excess androgens. The symptoms typically appear in childhood or early adulthood but may appear at any time. Girls with nonclassical or late-onset CAH have unusually high blood levels of the androgen hormone testosterone. Among the difficulties it causes are early growth of sexual hair, acne, excessive body hair growth and infertility. Males with nonclassical or late-onset CAH may have early signs of puberty or may never become symptomatic.

In order for an individual to have CAH, he or she must inherit an affected gene from both parents. If only one copy of the affected gene is inherited, from either parent, the child would be a carrier of CAH but would not have any of the associated symptoms of the disorder.

Inheritance of the affected gene causes a deficiency of an enzyme that is necessary for the production of the adrenal hormones. Depending on which enzyme is in low concentration, the hormones affected and the severity and symptoms of the disease may be different in individuals with CAH.

Who is affected?

CAH may be inherited by both males and females. The nonclassical mild form of the disease is relatively common, occurring in one of every 1000 births. In certain ethnic groups it is even more common, occurring as often as every one in 20 births. The classical severe form is rare and occurs in only one in every 15,000 people.

What is the role of the endocrinologist?

Diagnosis: Endocrinologists are doctors with specialized training in recognizing and treating disorders such as CAH. When CAH is suspected, blood tests may be ordered to determine if CAH is present. Special testing, such as amniocentesis during pregnancy, may be done to determine whether or not an unborn child has CAH or is a carrier of CAH. In such cases involving girls, treatment can begin before the baby is born to prevent abnormal genital growth and development.

Treatment: Endocrinologists are experienced in prescribing and monitoring the treatment for CAH. It is essential that throughout life, and especially as newborns, people with classical CAH be treated with steroid drugs and have regular blood tests and visits to the doctor. Endocrinologists use steroids such as hydrocortisone to restore normal hormone levels and prevent the overproduction of androgens. However, careful monitoring of treatment is critical, especially during childhood, when growth can be affected by over or under treatment with steroid drugs. Doctors have also found that the symptoms experienced by people with milder forms of CAH respond well to steroid treatment, although other treatment options are available.