Congenital Adrenal Hyperplasia Treatment Center

What is CAH?
Congenital adrenal hyperplasia (CAH), also termed adrenogenital syndrome in older literature, is a common inherited form of adrenal insufficiency. This group of diseases is due to mutations (genetic defects) in the genes coding for several enzymes needed for the production of adrenal cortex hormones. About 95% of cases of CAH are caused by 21-hydroxylase deficiency. This enzyme is necessary for efficient production of two vital adrenal steroid hormones: cortisol and aldosterone. Deficient production of these substances causes disruption in the delicate balance of hormones. Sensing low levels of cortisol, the adrenal, directed by the master hypothalamus and pituitary glands, goes into high gear. Because cortisol production is impeded, the adrenal cortex instead manufactures androgens, or male steroid hormones, an undesired by-product. In short, while one part of the adrenal functions poorly, making inadequate amounts of cortisol and aldosterone, another portion of the gland over-produces androgens. This last feature distinguishes CAH-21-hydroxylase deficiency from Addison's disease, since in Addisonian patients, the adrenals are most often completely non-functional.

How common is congenital adrenal hyperplasia?
The severe form, "classic" forms of CAH occur in 1 in 10,000 to 1 in 15,000 births worldwide. Milder forms of CAH are much more common. The various forms of CAH are described below.

Classic CAH-21-hydroxylase deficiency:
Lack of both cortisol and aldosterone predispose 3/4 of severely affected individuals to "adrenal crises" with dehydration and shock, or even death, if not properly diagnosed and treated. For this reason, most states in this country now perform newborn screening for CAH. Excess adrenal androgen production begins in early fetal life in classic CAH-21 affected infants, and causes abnormal growth of girls' clitoris and masculinization of the genital-urinary structures. Severely affected girls may be mistaken for boys at birth. Affected boys have no genital malformations at birth, but continued androgen excess causes unusually fast body growth. Inappropriately early puberty leads to premature completion of growth and short adult height. Proper medical treatment resets the abnormal balance of hormones, permits near-normal growth and puberty. Proper surgical treatment by an experienced pediatric urologist reconstructs near-normal female genitals. Some surgeons are now able to reconstruct the vagina at the same time as they reduce the size of the clitoris in early infancy, whereas in the past surgery was at least a two-step process, finished in late adolescence. Some families may opt to defer genital surgery.

Nonclassic CAH-21-hydroxylase deficiency:
A milder, non-life-threatening form of CAH-21 becomes manifest in later childhood or even young adult life, and is not characterized by ambiguous genitalia in girls. Rather, these individuals have partial enzyme deficiency, and thus have better cortisol production, normal aldosterone production, and lower levels of adrenal androgens. They do not suffer "adrenal crisis." Generally, such patients seek medical attention because of premature development of pubic hair, irregular menstrual periods, hirsutism (unwanted body hair), or severe acne. Some people affected with nonclassic CAH are not at all symptomatic, and are identified only because of an affected relative. Sometimes, newborn screening tests detect nonclassic forms of CAH. Most endocrinologists prefer not to treat this disorder in infancy or early childhood, unless symptoms are apparent.

Diagnosis:
The diagnosis of CAH has traditionally rested on hormone measurements combined with clinical evaluation, including history and physical examination. A number of states in the U.S. as well as several foreign countries now perform a hormonal test for CAH within the first few days of life. These heel-prick blood specimens are obtained at the time when blood is drawn for thyroid tests and a number of other inherited diseases. The rationale for newborn screening is that mainly in boys, who have no outward sign of the disease, the mortality from "adrenal crisis" is high, and this could be entirely prevented by early diagnosis and medical treatment. Since the incidence of classic CAH is relatively high worldwide, this amounts to a substantial number of potentially preventable infant deaths. These screening programs have achieved their goals. Diagnostic methods are continually being refined, both for the hormonal methods, and for the newer genetic typing discussed below.

Since the advent of molecular genetic technology, we can now examine the genes of CAH patients and family members. This type of study has application for prenatal testing, neonatal screening, and genetic counseling, as well as confirming diagnosis in questionable cases. Molecular diagnosis is available in several specialized laboratories. As DNA diagnosis becomes more widely accepted, these tests will no doubt become more widely available. Just as there are potential inaccuracies in hormonal testing, there are pitfalls in genetic testing, as now has become clear from published reports concerning CAH, as well as in the diagnosis of other diseases, and in forensic use of DNA testing. Nonetheless, for the most part, these techniques are verifiable and accurate in the proper hands. Genetic testing can resolve ambiguities that arise from hormonal testing, and can help provide accurate information to parents of CAH patients as to their risk of having another affected child during the early weeks of pregnancy.

How do you treat CAH?
Currently, standard medical treatment consists of giving a glucocorticoid (a cortisol-like steroid medication, e.g., oral hydrocortisone in children, or prednisone or dexamethasone in older patients). In addition, severely affected individuals with classic CAH often have aldosterone deficiency, and will need another drug, fludrocortisone (Florinef, which acts like the missing hormone, aldosterone) to be able to retain salt. Infants and small children may also receive salt tablets as a dietary supplement, whereas older patients eat salty foods. Your doctor will instruct you as to proper dosing.

All children with CAH should be seen frequently by a pediatric endocrinologist to measure blood hormone levels, and to carefully assesses height, weight, blood pressure, and an annual x-ray of the wrist (bone age x-ray).

Nonclassic CAH patients, if they require medical therapy, are usually effectively treated with low dose hydrocortisone (children) or prednisone (adults) only. They do not require genital surgery.

Some experimental treatments are being tested for CAH, however, none of these is approved for general use at this time.

Are there any side effects to these medications?
As with any medication, there are potential side effects. If proper medical care is given, these should be minimized. The most important side effect of steroids in children is a slow-down of growth, if excessive doses are given. Doctors are now advocating modest treatment doses to preserve height potential. Most CAH children will grow to a normal adult height, but are somewhat shorter than family members.

What happens if a child or adult with CAH is not treated?
Treatment is essential for life in those with severe cases of CAH. Missing even a few doses could be very serious. Patients who cannot take their medication orally must be evaluated urgently and may require intravenous treatment. Please speak with your doctor about emergency management instructions.

The mild forms of nonclassic CAH do not have the same urgent treatment requirements.

What is the long-term outcome?
Most individuals with CAH will live a long and productive life if properly treated. It is important for both men and women with severe CAH to maintain lifelong treatment. Fertility is reduced in some patients, but assisted reproductive techniques can usually enhance fertility.