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Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is an inherited disorder that affects the adrenal glands. These glands help keep the body in balance by making the right amounts of cortisol, aldosterone, and androgens. But in CAH, production of cortisol is blocked. Some children with CAH also lack aldosterone. These imbalances cause the adrenal gland to make too much androgen.

Symptoms

Too little cortisol may cause tiredness and nausea. During illness or injury, low cortisol levels can lead to low blood pressure and even death. Lack of aldosterone, which occurs in three out of four patients with classic CAH, upsets salt levels. This imbalance may cause dehydration (too little fluid within the body), and possibly death. Chronic salt imbalance may also cause abnormal growth.

Too much androgen causes abnormal physical development in children. Boys and girls with CAH may grow too fast, develop early pubic hair and acne, and stop growing too soon, causing short stature. Girls exposed to high levels of androgens before birth may have abnormal external genitalia at birth. Although their internal female organs are normal, excess androgens may also affect puberty and cause irregular menstrual periods.

Too much cortisol replacement also causes abnormal development in children. Side effects include obesity and short stature. Also, too much hydrocortisone, the medicine given to replace cortisol in the body, can cause decreased bone density (osteoporosis).

Types

There are many types of CAH. The severe form is called classic CAH, while the mild form is called nonclassic CAH.

Classic CAH

The most common is 21-hydroxylase deficiency (95 percent of cases). A child with this type of CAH has adrenal glands that cannot make enough cortisol and may or may not make aldosterone. As a result, the glands over-work trying to make these hormones and end up making too much of what they can make: androgens.

The second most common form of CAH is 11-hydroxylase deficiency. A child with this type of CAH has adrenal glands that make too much androgen and not enough cortisol. Children with this type of CAH may also have high blood pressure. These patients do not have aldosterone deficiency.

Rare other types of CAH include 3-beta-hydroxy-steroid dehydrogenase deficiency, lipoid CAH, and 17-hydroxylase deficiency.

Classic CAH occurs in 1 in 15,000 births.

Nonclassic (late-onset) CAH

This type of CAH is a mild form of CAH and is almost always due to 21-hydroxylase deficiency. Only a handful of people have been described as having nonclassic (mild) CAH due to other causes.

People with nonclassic 21-hydroxylase deficiency make enough cortisol and aldosterone, but they make excess androgens. Symptoms come and go, beginning at any time but typically in late childhood or early adulthood. Boys often do not need treatment. Girls usually need treatment to suppress their excess androgens.

Nonclassic CAH is common. One in every 1,000 people has nonclassic 21-hydroxylase deficiency. Incidence is higher in certain ethnic groups including Ashkenazic Jews, Hispanics, Yugoslavs, and Italians.

How is CAH inherited?

CAH is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell must be altered in order for the disease to occur.

Treatment

The standard treatment for classic 21-hydroxylase deficiency is hydrocortisone which replaces cortisol, and fludrocortisone (Florinef) which replaces aldosterone. For 11-hydroxylase deficiency, the treatment is only hydrocortisone. Patients can be started on longer-acting forms of hydrocortisone (i.e. prednisone or dexamethasone) when they are done growing.

Patients with the nonclassic form of CAH need only hydrocortisone (or a longer-acting form of hydrocortisone). Some patients with nonclassic CAH are able to come off medication as adults, but patients with classic CAH need lifelong treatment.

 

Source

NIH Clinical Center, USA.