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Frequently Asked Questions

Frequently Asked Questions about Congenital Adrenal Hyperplasia (CAH)

Q: Who gets CAH?

A: Individuals of both sexes may be affected by CAH. As this is a disorder which is passed from mother and father to child, both parents must be carriers of the gene defect in order for their child to be affected.

Q: What causes CAH?

A: Mutations in the genes that encode the enzymes necessary to make steroid hormones result in CAH. There are six enzyme defects that cause different forms of CAH.

Q: How is CAH diagnosed?

A: The diagnosis of CAH can be made by measurement of hormones and DNA analysis. Identification of genes and mutations has made diagnosis more precise. Screening of family members is sometimes useful.

Q: How frequent is CAH?

A: The commonest form of CAH (21-hydroxylase deficiency) occurs in 1 in 15,000 live births worldwide in its classical form. There is newborn screening for this disorder in most of the United States . The mild ("nonclassical") form of 21-hydroxylase deficiency is much more frequent and may not be detected by newborn screening. In the diverse population of New York City, it occurs in 1 in 100 people.

Q: Is CAH more common in any ethnic group?

A: Nonclassical CAH is more common in persons of Ashkenazi Jewish and Mediterranean descent.

Q: Can CAH be detected during pregnancy?

A: Yes. 21-Hydroxylase deficiency CAH can be diagnosed prenatally following amniocentesis or chorionic villus sampling. Classical CAH can be treated prenatally. This can prevent masculinization of the genitalia of affected females. Change to " 21-Hydroxylase deficiency and 11b-hydroxylase deficiency CAH"

Q: Will my child look normal when he/she grows up?

A: Children affected with CAH, provided that they are well managed by their endocrinologists, grow and develop normally. Affected girls look like normal girls as they grow up, and affected boys look like normal boys. Nothing in their overall appearance distinguishes them from other boys and girls.

There are two provisos to this, however. Girls with the classical disorder generally are born with an enlarged clitoris and with their vaginal opening inside, not appearing on the surface. Some parents opt for early corrective surgery for this, while others elect to wait and allow their daughters to make the decision in adolescence about what surgery to have and when to have surgery. If they leave the decision for the daughter to make later, there are likely to be some issues that the parents and later the child will have to deal with, as her genitalia will not appear normal when she is nude, in underwear or wearing a bathing suit.

The second proviso is related to classically affected males primarily, but occasionally to females as well. Simple virilizing males are often not diagnosed in early life (in states not having neonatal screening) since they look like normal boys and don't get sick from loss of salt. As a result, these infants and children are not treated in early life, but may see a doctor later in childhood because of tall stature and/or signs of precocious adrenarche (early pubic hair or hair under the arms, enlargement of the penis). Girls are nearly always are diagnosed as infants because of an enlarged clitoris at birth, but if they were missed, they may be diagnosed later in life due to of tall stature and further enlargement of their clitoris and possibly the early growth or appearance of pubic hair. These symptoms in both boys and girls are caused by excess testosterone made by their adrenal glands. Unfortunately, excess testosterone causes both tall stature and an advanced bone age, which means that a child's bones are developed far beyond the average for his or her age. This advancement in bone age can be severe in some children. If not managed correctly, these children will stop growing early and end up as short adults, which in some cases may be quite severe. It is very important for all CAH patients, classical and nonclassical, boys and girls, to have regular bone age measurements done by their doctors.

Q: Will my affected daughter want to change her sex when she grows up?

A: When someone feels unhappy in the sex they are, or feels that they were assigned to the wrong sex at birth, it is called gender dysphoria . Gender dysphoria is extremely rare in CAH-affected individuals, and in fact the frequency in CAH-affected individuals may not be much greater than in the normal population.

Q: What do I do when my classically affected child gets sick?

A: For low-grade fever of 101°F to 102°F, the daily dose of hydrocortisone should be doubled. For high-grade fever greater than 102°F, the daily dose should be tripled and an antipyretic (Tylenol or Advil) should be given. Aspirin should not be given to a child. The child should be evaluated by his or her endocrinologist for the source of the fever and for signs of dehydration or adrenal crisis. If the child is unable to tolerate oral hydrocortisone because of vomiting, the endocrinologist should be notified and the parent should know how to give intramuscular hydrocortisone (Solucortef), in the event that it becomes necessary. In case of severe illness, unconsciousness, or trauma, intramuscular hydrocortisone should be given immediately and the child should be evaluated in the emergency room.

Q: What is the chance that I have nonclassical CAH if I have acne, hirsutism, hair loss, infertility, or irregular periods?

The frequency of nonclassical CAH in the general population of New York City is 1:100. That makes this the most common genetic disorder known in humans. Any or all of the these symptoms (acne, hirsutism, hair loss, infertility, or irregular periods) appear in women with nonclassical CAH. Symptoms of men affected with nonclassical CAH include short stature or infertility. If you suspect you might have nonclassical CAH, you should discuss it with an endocrinologist and ask for hormonal testing and DNA analysis so that an accurate diagnosis may be made. Nonclassical frequency is even higher in certain ethnic groups. If you belong to one of these groups and have any of the symptoms listed above, your chances of being affected are even higher. In Ashkenazi Jews the frequency is 1:27; in Hispanics it is 1:40 and in Slavs it is 1:50.

Q: If my child has tall stature in childhood, could this be a sign of his (or her) having nonclassical CAH?

A: Absolutely. Individuals with nonclassical CAH are born looking completely normal, but have a mild hormonal defect that causes symptoms over time if not diagnosed and treated. Early tall stature with later irreversible short stature is one of these. By about age 15 in girls and 17 in boys the bones have lost their potential for growth. In children exposed to excess testosterone the bones age faster than usual, so their bones will stop growing long before age 15 in girls and age 17 in boys. Growth potential can be lost with every year that the child is untreated. However, since nonclassical is also a very variable disorder, some people will have very severe symptoms and some very mild symptoms. The only way to determine the severity of a given child's growth problems once diagnosed is to check the bone age. If your doctor has looked into your child's tall stature and found there is an advanced bone age, the diagnosis of CAH should be considered and ruled out.

Q: How reliable are the various testing methods?

A: The most common laboratory test performed in patients with CAH due to 21-hydroxylase deficiency is measurement of the 17-hydroxyprogesterone (17OHP) level in the blood. For the 11b-hydroxylase deficiency the main test is the deoxycorticosterone (DOC) level. If only these hormones are measured, they may not always be very reliable. However, measuring other adrenal hormones, such as androstenedione and testosterone, and considering the relationships among the hormones provides a much more reliable indication of control than measuring one hormone alone. All of the hormone levels vary according to the time of day they are measured and the time that medication was taken. In order to improve reliability, there should be consistency in the timing of the blood draw.

Q: What is the best time of day to have blood drawn for patients?

A: Stimulation of the adrenal glands by adrenocorticotrophic hormone (ACTH) is highest in the morning. Therefore, the best time of day to determine adequate adrenal control is in the morning. Most practitioners prefer to draw the adrenal hormone levels about 1-2 hours after the morning dose of hydrocortisone because that is when the medication has its peak effect, and it provides the most reliable measure of whether or not the dose of medication is correct. Other practitioners measure the adrenal hormone levels immediately prior to taking the medication; however, there is not as much data on what values indicate good control when drawn prior to taking the medication.

Q: What does it mean when the doctor says the adrenal glands are "suppressed"?

A: The term "congenital adrenal hyperplasia" refers to over production of sex steroids by the adrenal glands in response to under production of cortisol by the adrenal glands due to an inherited enzyme deficiency. When there is inadequate cortisol in the body, the brain stimulates the adrenal gland to make more cortisol. Because of the enzyme deficiency in patients with CAH, however, the adrenal gland cannot make more cortisol and instead makes more sex steroids in excessive amounts. In order to control, or suppress , the production of excess sex steroids, cortisol must be supplied by outside means, e.g., hydrocortisone, prednisone, or dexamethasone taken orally. When a patient with CAH takes the correct amount of cortisol replacement, the stimulus to the adrenal glands is suppressed and the production of sex steroids diminishes. The adrenal glands can be oversuppressed if too much cortisol replacement is given, or undersuppressed if not enough cortisol replacement is given.

Q: My child is growing slowly - why?

A: An excessive amount of cortisol causes a decline in growth. If a child with CAH is growing more slowly than normal, then he/she may be taking too much medication.

Q: My child's face appears rounder than previously - why?

A: An excessive amount of cortisol can cause increased weight gain, particularly around the face and trunk. If your child has these symptoms, it may mean that he/she is receiving too much medication.

Q: What's the difference between 17a-hydroxylase and 21-hydroxylase?

A: The most common form of CAH is due to an inherited deficiency of the enzyme 21-hydroxylase, which is one of the enzymes necessary for the production of cortisol and aldosterone (salt-retaining hormone). When there is not enough 21-hydroxylase, there is build-up of the hormone 17-hydroxyprogesterone (17OHP). The second most common form of CAH is due to an inherited deficiency of the enzyme 11b-hydroxylase, which is another enzyme necessary for the production of cortisol and aldosterone. When there is not enough 11b-hydroxylase, there is a build-up of the hormone deoxycorticosterone (DOC) which can cause hypertension. Both 21-hydroxylase and 11b-hydroxylase deficiency cause build-up of male hormones, e.g., testosterone. In contrast, the enzyme 17a-hydroxylase is another enzyme in the adrenal gland that is involved in the production of sex steroids. A deficiency of this enzyme is very rare and causes a completely different disorder (see below).

Q: What do I need to tell the school about my child's medical condition?

A: In general we advise parents to inform the school that their child has adrenal insufficiency and is on steroid treatment. The term "adrenal insufficiency" is used for several reasons. The most important is that CAH (or congenital adrenal hyperplasia) might not be a term known to all emergency room doctors. However, all such professionals know how to treat adrenal insufficiency and would be able to provide care if the child were in an accident or were ill and needing urgent cortisol treatment. In addition, some parents prefer not to give the school the specific name of their child's disorder, feeling that could violate their child's right to confidentiality.

Q: Are medical alert pendants, bracelets, etc., important for my child to wear if he (or she) has nonclassical CAH, or are they just for patients with classical CAH?

A: For many years it was thought that medical alert charms only needed to be worn by classical patients, but it is now thought that all patients on steroid replacement therapy (i.e., cortisol, prednisone, dexamethasone, etc.) should wear medical alert charms in case of accident or serious illness. Indicate on the bracelet that the child has adrenal insufficiency and is on steroid treatment.

Q: Can my child participate in sports if he (she) has CAH?

A: There are no restrictions on sports or other activities in children or adults with either the classical or nonclassical form of CAH. However, particularly in the salt-wasting classical form, if the sports are played in hot weather, the patient should carry some salt packets (like those used in cafeterias) and take extra salt if he or she feels queasy or faint. This usually is not necessary in the simple virilizing and nonclassical forms.

Q: I have been told that someone in my extended family has CAH, what does this mean for me? What, if anything should I do?

A: If you have a family member who has been diagnosed with CAH, there is a chance that you may be a carrier. The closer to you the family member is, the greater the likelihood that you could carry the gene. Since as a rule carriers do not have symptoms from CAH, being a carrier per se is not a problem for you or for your health and you do not need medication. However, if you plan to have children, you should be tested for the CAH genes. If you turn out to be a carrier, your partner should then be tested. If you are a carrier and your partner is not, your only concern is to remember to tell your children when they are grown that some of them might be carriers and they should also be tested before starting a family.

When you are tested, you will also be told whether the gene you carry is for a mild or for a severe form of CAH. If your spouse also turns out to be a carrier he or she will also be told the severity of the gene. If you are both carriers your probability of having an affected child is one if four. That does not mean that one-fourth of your children will be affected. It means only that out of thousands of children born to families where both parents are carriers, roughly one-fourth of the children will be affected, half will be carriers, and one-fourth will neither have CAH nor carry it. In your own family you might have no affected children, or several in a row. If you flip two coins four times, and count how often they both come down heads, you can get an idea of how genetic inheritance works. Imagine that two heads is an affected child, one head is a carrier, and two tails is a child that has two normal genes. The process of genetic inheritance is like this coin toss - you may be able to predict how often parents with certain genes will have affected children, but there is no way to control or predict the genes a specific child will inherit.

Q: What is prenatal diagnosis and treatment? Who should consider it?

A: Prenatal diagnosis and treatment is currently available for the 21-hydroxylase and 11b-hydroxylase forms of CAH. Prenatal diagnosis and treatment is usually only necessary for parents who both are carriers, and generally is not necessary unless at least one parent carries a severe gene. Prenatal treatment is possible in CAH to prevent the genital masculinization present in affected salt-wasting and simple virilizing females. The treatment is simple, and thus far has proven safe. The mother takes dexamethasone from the time she knows she is pregnant in a dosage calculated according to her weight. The dexamethasone crosses the placenta and treats the affected fetus, preventing the excess adrenal testosterone that otherwise would masculinize the affected daughter's genitals.

As early as is possible the mother has chorionic villus sampling (a sampling of the chorion surrounding the fetus and placenta that yields fetal cells), done at about 9 to 12 weeks, or amniocentesis, done at about 16 weeks. The results of the sex of the fetus come back first, within days or up to two weeks, depending on the type of test done. If the sex is male, the treatment is stopped, as even if the fetus is affected, only girls have the genital birth defect. If the sex is female, the treatment is continued until the results of the DNA analysis for CAH performed on the fetal cells come back. This takes about a month from the time the lab has received the sample. At that time if the girl is shown to be unaffected, the treatment is stopped; if she is affected, it is continued throughout the pregnancy.

If you know you and your spouse are carriers of genes causing either 21-hydroxylase deficiency or 11b-hydroxylase deficiency CAH and are planning a family, you should discuss the option of prenatal diagnosis and treatment with your endocrinologist.

Frequently Asked Questions about Disorders of Androgen Synthesis or Action

Q: What sex should I raise my child?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. This decision is only reached after a team of physicians, including endocrinologists, urologists, and sometimes psychologists, reviews the case in detail with the parents. Key factors include the amount of androgen exposure to the brain during development, the amount of tissue within the penis to allow for erections, and the potential for further masculinization during puberty.

Q: Will my child want to change his/her gender later in life?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. The two disorders in which this phenomenon occurs regularly are 5a-reductase type 2 deficiency and 17b-hydroxysteroid dehydrogenase type 3 deficiency, where children raised as females masculinize at puberty and may change their social gender to male. Although some general patterns have been observed in the past, it is difficult to predict the behavior of any given individual.

Q: Will my child be able to marry and have children?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. Undervirilized males can have normal sex drive, sometimes requiring hormone replacement therapy, and mildly affected individuals can have erections and ejaculations. Sperm production is normally impaired, so fertility is often very poor but sometimes improved with in vitro fertilization techniques.

Q: When should we start hormone therapy?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. Some males born with a small penis require testosterone from infancy to stimulate penile growth during childhood. In other cases, hormone replacement is begun at the time of expected puberty or following removal of the testes. The types of hormones used depend on the disorder and the social gender of the individual. It is important to recognized that hormone replacement is necessary not only to maintain secondary sexual characteristics but to preserve bone density and other factors contributing to overall health.

Q: Are there long-term complications of taking these hormones?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. There is no evidence that taking normal doses of hormones to replace what the body cannot produce causes long-term problems. On the other hand, there is ample evidence that not taking hormones causes weak bones and other problems. The decisions regarding which and how much hormone to use and for how long are achieved on an individual basis.

Q: Will I have another child with the same problem?

A: The answer to this question depends primarily on the underlying diagnosis. For this reason, it is critical to perform all necessary testing, including genetic studies, prior to reaching conclusions. Many disorders are inherited in an autosomal recessive manner, meaning that each parent carries one copy of the defective gene and one copy of the normal gene. In these cases, there is a 1 in 4 chance that another child will be affected. Other disorders, like AIS, often occur de novo , meaning that the mutation arises spontaneously and that the parents are not carriers of the defective gene. In these cases, the odds that a second child is affected are very low. These issues can be resolved by genetic testing of the child and parents.