Congenital Adrenal Hyperplasia: A Handbook for Parents

Congenital - present at birth
Adrenal - involving the adrenal glands
Hyperplasia - this word means that the adrenal glands are overgrown.

In CAH, the child is born with overgrown adrenal glands. The adrenal glands of babies with CAH are unable to make enough cortisol, which is the principal adrenal gland hormone. In an effort to make enough cortisol, the adrenal gland enlarges, or overgrows.

Adrenal Glands

The adrenal glands (Figure 1) are a pair of small organs, each about the size of a walnut, located on top of the kidneys just below the ribs in the back. They produce various hormones, or chemical messengers, which are released into the bloodstream. The inner core (medulla) of the adrenal gland makes adrenalin and is not affected in CAH. The outer portion (cortex) normally makes three different products: cortisol (hydrocortisone), aldosterone (salt-retaining hormone), and androgens (male-type hormones).

Figure 1

Hormones Made By The Adrenal Glands

Cortisol (Hydrocortisone)

Normal adrenal glands produce and release cortisol continuously into the blood stream. Cortisol is essential for life as it is needed to maintain an adequate energy supply and blood sugar level. Cortisol is also called a "stress hormone" because our adrenal glands make lots more of it when we are under physical or emotional stress to protect our body from the effects of illness or injury.

Aldosterone (salt retaining hormone)

Another important hormone made by the adrenal gland is called aldosterone or salt-retaining hormone. Aldosterone is used by the kidney to help the body maintain normal levels of the salt minerals, sodium and potassium. Normal levels of sodium and potassium are necessary for all cells to work normally. If the adrenal gland cannot make this hormone too much salt and water is lost in the urine, leading to salt deficiency and dehydration.

Androgen (male sex hormone)

The adrenals of both males and females make several types of male-like hormones, which are thought to be important in normal growth.

The hormones produced by the adrenal gland are made in a series of steps or chemical reactions. Just as oil is the raw product which must be refined into gasoline or kerosene, cholesterol is the "raw product" which is "refined" into cortisol, aldosterone, and androgens. Each step in the refining process is controlled by a special protein called an enzyme. There are at least 5 enzymes needed to make cortisol from the raw material (cholesterol). If any of these enzymes are faulty, the adrenals cannot make enough cortisol to satisfy the body's needs.

Adrenal-Pituitary Thermostat Control

Although cortisol is made in the adrenal gland, control over its production is found in the brain in a gland called the pituitary or master gland (Figure 2). The pituitary is a pea-sized gland located on the underside of the brain and about two inches behind the bridge of the nose. Despite its small size, it is one of the most powerful glands in the body. It directs the activities of practically all the hormone-producing glands including the thyroid, adrenals and sex glands. The pituitary gland senses the amount of cortisol in the bloodstream. If it decides that not enough cortisol is present, the pituitary releases a hormone called adrenocoricotrophic hormone (or ACTH, for short). ACTH travels through the blood stream and acts on the adrenal glands, stimulating them to make more cortisol. The increased amount of cortisol in the blood can then be sensed by the pituitary, which then lowers the amount of ACTH it releases. The lowered level of ACTH will in turn decrease the stimulation of the adrenal glands to make cortisol. This mechanism is very similar to that of a thermostat: when cortisol levels are appropriate, productions shuts down; when cortisol levels fall, production is increased to restore the level to normal.

Figure 2

CAH results from three disturbances:

Figure 3

1. Lack of cortisol
2. Lack of salt retaining hormone
3. Too much androgen

Lack of cortisol
The adrenal glands of persons with CAH have insufficient amounts of one of the enzymes that is needed to manufacture cortisol. The pituitary gland senses decreased cortisol output and tries to overcome it by sending signals (in the form of ACTH) to stimulate the adrenal. The adrenal glands sense this stimulation and enlarge in an effort to produce cortisol, but because a necessary enzyme is deficient, not enough cortisol is made; the thermostat mechanism does not. The body which lacks cortisol cannot mobilize sugar efficiently. Low blood sugar can cause drowsiness and coma.

Salt-wasting
Some children with CAH are also unable to make enough aldosterone. These "salt wasters" lose large amount of salt in their urine. A large salt imbalance could cause repeated vomiting, dehydration, extreme muscle weakness, and weakness of the heart muscle. Some children are able to make small amounts of aldosterone. Salt imbalance can lead to poor growth. Salt-wasting occurs in about 75% (3out of 4) children with CAH. It is believed to be due to a more complete loss of enzyme function than in non salt-wasting CAH which occurs in 25% of cases or 1 out of 4 children with CAH.

Figure 4

Too much androgen
Unfortunately, ACTH signals the entire adrenal gland to work harder, not just the part that makes cortisol. The faulty enzyme causes a bottleneck in the chemical assembly line that makes cortisol, resulting in a piling up of "raw products" for making the final adrenal hormones. These substances spill over into other production lines which do not use the faulty enzyme: the production lines for androgens (male hormones). The pituitary ACTH control (which senses low cortisol but is insensitive to too much male hormone) continues to make ACTH. The stimulated adrenal cannot make cortisol but continues to make too much male hormone (Figure 3).

This overproduction of male hormone can affect the baby before birth. The genitals of the male infant may appear normal at birth, but the external genitals of the female baby may take on a male appearance, with enlargement of the clitoris and partial closing of the opening between the labia, or vaginal lips (Figure 5). However, the internal parts (uterus, fallopian tubes, and ovaries) are quite normal.

Figure 5

Without treatment, the clitoris will continue to enlarge into a male-like penile structure. For this reason, girls with CAH are more likely to be diagnosed earlier than boys.

Excessive male hormone in childhood can cause early sexual hair, acne and a growth rate which is too rapid. Boys and girls with CAH can develop pubic hair and growth of the penis or clitoris in the preschool years. Children's bones have growth plates at the end of the long bones which allow for growth.

As the child matures these growth plates close, and growth stops. High levels of androgens made by the adrenal cause rapid early growth. The child will appear tall as a preschooler and young school-aged child. If these high levels of male-like hormones are allowed to continue, the growth plates will close up prematurely. After the growth plates close, no further growth is possible. The result is a very short adult (Figure 6).

Figure 6

High levels of male-like hormones continue to affect the adolescent. The girl with untreated CAH will not have normal menstrual periods because the male-like hormones interfere with the work of the ovary. The testicles of the boy cannot function well and will not make sperm normally.

There are two forms of CAH. The classical and non-classical forms. Non-classical CAH refers to a condition in which the enzyme defect is less severe. Individuals with this form of CAH are typically normal at birth but begin to suffer mild effects of too much male hormone in childhood or adolescence. This is also called "late onset" CAH.

CAH is never "outgrown"; treatment is required for life. The treatment for CAH is by replacement with hormone medications. The amount of medication needed will be different for each child and will need to be adjusted as the child grows. Two types of hormone medicines are used to correct the problems of CAH.

These hormones are given daily by mouth either as a pill or liquid. They usually have to be given two or three times a day. The amount of medication given is no more than that made normally by the body itself. It is not harmful.

The risks associated with cortisol-like medications occur only with the very high dosages used to treat some illnesses such as severe asthma or arthritis.

The lack of cortisol is treated with a hormone medication similar to cortisol naturally occurring in the body. Some examples of this type of medication are hydrocortisone, cortisone, prednisone and dexamethasone. They differ in strength and duration of action. Cortisone and hydrocortisone are short acting while prednisone and dexamethasone last much longer.

Both boys and girls need cortisol-like medication to control the excessive male-type hormone production. When the child takes cortisol-like medication, the adrenal glands will produce normal amounts of male hormone. Soon after therapy begins, rapid growth stops, and the penis of the boy and the clitoris of the girls will decrease slowly in size. The clitoris may not return completely to normal size, however, and the vaginal opening may remain closed because of the joined labial folds. As such, surgery may be needed in girls who have a marked male-like appearance to their external genitals. The age at which surgery is done is determined on an individual basis, depending on the severity of the problem.

In times of illness, surgery, or major injury, CAH patients of all ages need closer medical attention. At these times, more cortisol is needed to help recovery and to keep up with the body's increased demands. Two or three times the normal daily dose of medication needs to be given when a child with CAH has high fever, vomiting, severe diarrhea, suffers a major injury, or undergoes even minor surgery. If the child cannot keep the medication down because of vomiting or is unconscious from the surgical anesthesia or from an accident, an injection of rapid acting cortisol is necessary and may be lifesaving. Even though extra cortisol-like medication is not usually needed for mild colds or minor cuts and scratches, it should be given for severe injuries such as broken bones. If in doubt, it is always better to give the extra medication than not to give it. Every person who takes cortisone should wear a medical Alert bracelet or necklace which says, "adrenal insufficiency: in emergency give cortisone." These can be obtained at most pharmacies. They may be lifesaving in emergency situations when parents or relatives are not present.

Some children will also need a salt-retaining hormone medication. The substitute medication for aldosterone is fludrocortisone (trade name: florinef).

Some infants with severe salt-wasting may also require extra salt in the milk formula along with the salt-retaining hormone medication. Extra salt will not cause high blood pressure in children with salt wasting CAH.

The exact dose of these medications needs to be adjusted as the child grows and matures. Some children with non-classical CAH may not need to take medication all the time. The growth and maturation of all children with CAH needs to be checked regularly, and blood tests need to be done regularly for cortisol, ACTH, and other hormones to make sure that just the right amount of medication is being given. Infants and children with CAH need to be followed closely by a specialist in pediatric endocrinology to prevent complications of the disease and to assure optimal growth and maturation.

With regular medication, your child with CAH can lead a normal life. There are no known intellectual disabilities associated with CAH. The life expectancy is normal. Women with CAH (if they take their medications are directed) have no difficulties becoming pregnant or carrying a baby, and men who take their medications appropriately have normal fertility.

CAH is a genetic disorder. This means that the enzyme defect in CAH is inherited. Inherited disorders are passed from parents to children through genes contained in the egg and sperm which join to form the baby. Genes come in twos with one gene inherited from the mother and one gene inherited from the father. The baby with CAH has two abnormal genes (one from each parent). 

Figure 7  

Parents of babies with CAH rarely show the condition because each parent has usually only one gene for CAH together with a normal gene (Figure 7). Each parent is said to "carry the CAH trait". In the general population about one person in 50 carries the CAH gene (trait).

For each baby born of two parents carrying the CAH trait, the odds are one in four. If you have had a child with CAH and are currently pregnant you should request the prenatal test for CAH.

Each sibling who does not have CAH has a two out of three chance of being a "carrier" for CAH. If they want to know whether they carry the trait, there are both gene test and special hormone tests which may answer this question.

It would be very unusual for a person with CAH to marry a person who has CAH or who even carries the trait. The chance of your child with CAH having a child with CAH is roughly one in 200.

If your baby was born with abnormalities of the genitals you may wish to tell family and friends that your baby has a minor defect which will delay the doctors in being able to confirm the sex of the child for a few days. Reassure them that the baby is healthy and normal in every other way. You may wish to add that your baby has a hormone imbalance that will require treatment.

Issues relating to sexuality may cause concerns which are difficult to talk about. Be reassured that the little girl with CAH will grow up to function as a normal woman. Likewise, be reassured that the little boy with CAH who is taking medication to prevent excessive adrenal male-type hormone is still making plenty of male hormone!

In infancy it is important to remember that other than needing regular medications, your baby should be treated as you would any baby. The baby does not need a special diet nor protection from "germs." The baby should get immunizations according to your doctor's recommended schedule. Toddlers at times like to take extra medication; be sure to keep all medications where they cannot be reached by the child.

As your child gets older you should begin to explain to him or her the nature of his condition. When you give the CAH medications to the four- or five-year-old you may wish to say: "Most people's body can make this special stuff, but yours can't so you need to take it in a pill."

Older children need to know the importance of taking their medication regularly. They need to know that if they skip their medications, they may not grow normally and may not develop the normal changes of adolescence. When their questions show that they want to learn more, you may wish to read this booklet with them or provide a time for them to talk with their endocrinologist.