Adrenogenital syndrome

Definition

Congenital adrenal hyperplasia is a genetic disorder characterized by a deficiency in the hormones cortisol and aldosterone and an over-production of the hormone androgen, which is present at birth and affects sexual development.

Description

Congenital adrenal hyperplasia (CAH) is a form of adrenal insufficiency in which the enzyme that produces two important adrenal steroid hormones, cortisol and aldosterone, is deficient. Because cortisol production is impeded, the adrenal gland instead overproduces androgens (male steroid hormones). Females with CAH are born with an enlarged clitoris and normal internal reproductive tract structures. Males have normal genitals at birth. CAH causes abnormal growth for both sexes; patients will be tall as children and short as adults. Females develop male characteristics and males experience premature sexual development.

In its most severe form, called salt-wasting CAH, a life-threatening adrenal crisis can occur if the disorder is untreated. Adrenal crisis can cause dehydration, shock, and death within 14 days of birth. There is also a mild form of CAH that occurs later in childhood or young adult life in which patients have partial enzyme deficiency.

CAH, a genetic disorder, is the most common adrenal gland disorder in infants and children, occurring in one in 10,000 total births worldwide. It affects both females and males. It is also called adrenogenital syndrome.

Causes & symptoms

CAH is an inherited disorder. It is a recessive disease, which means that a child must inherit one copy of the defective gene from each parent who is a carrier; when two carriers have children, each pregnancy carries a 25% risk of producing an affected child.

In females, CAH produces an enlarged clitoris at birth, and masculinization of features as the child grows, such as deepening of the voice, facial hair, and failure to menstruate or abnormal periods at puberty. Females with severe CAH may be mistaken for males at birth. In males, the genitals are normal at birth, but the child becomes muscular, the penis enlarges, pubic hair appears, and the voice depends long before normal puberty, sometimes as early as two to three years of age.

In the severe salt-wasting form of CAH, newborns may develop symptoms shortly after birth: vomiting, dehydration, electrolyte (a compound such as sodium or calcium that separates to form ions when dissolved in water) changes, and cardiac arrhythmias.

In the mild form of CAH which occurs in late childhood or early adulthood, symptoms include: premature development of pubic hair, irregular menstrual periods, unwanted body hair, or severe acne. Sometimes, there are no symptoms.

Diagnosis

CAH is diagnosed by a careful examination of the genitals and blood and urine tests which measure the hormones produced by the adrenal gland. A number of states in the United States perform a hormonal test (a heel prick blood test) for CAH and other inherited diseases, within a few days of birth. In questionable cases, genetic testing can provide a definitive diagnosis.

Treatment

The goal of treatment for CAH is to return the androgen levels to normal. This is usually accomplished through drug therapy, although surgery is an alternative. Lifelong treatment is required.

Drug therapy consists of a cortisol-like steroid medication called a glucocorticoid. Oral hydrocortisone is prescribed for children, prednisone or dexamethasone for older patients. For patients with salt-wasting CAH, flurdocortisone is also prescribed. Infants and small children may also receive salt tablets, while older patients are told to eat salty foods. Medical therapy achieves hormonal balance most of the time, but CAH patients can have periods of fluctuating hormonal control, which leads to increases in the dose of steroids prescribed. Side effects of steroids include stunted growth.

Patients with CAH should see a pediatric endocrinologist frequently. The endocrinologist will assess height, weight, and blood pressure, and order an annual x ray of the wrist (to assess bone age), as well as assess blood hormone levels. CAH patients with the milder form of the disorder are usually effectively treated with hydrodcortisone or prednisone, if they need medical treatment at all.

Females with CAH who have masculine external genitalia require surgery to reconstruct the clitoris and/or vagina. This is usually performed between the ages of one and three.

An experimental type of drug therapy--a three-drug combination, with an androgen blocking agent (flutamide), an aromatase inhibitor (testolactone), and low dose hydrocortisone--is currently being studied by physicians at the National Institutes of Health. Preliminary results are encouraging, but it will be many years before the safety and effectiveness of this therapy is fully known.

Adrenalectomy, a surgical procedure to remove the adrenal glands, is a more radical treatment for CAH. It was widely used before the advent of steroids. Today, it is recommended for CAH patients with little or no enzyme activity and can be accomplished by laparoscopy. This is a minimally invasive type of surgery done through one or more small (1 in) incisions and a laparoscope, an instrument with a fiber-optic light containing a tube with openings for surgical instruments. Adrenalectomy is followed by hormone therapy, but in lower doses than CAH patients not treated surgically receive.

Prognosis

CAH can be controlled and successfully treated in most patients as long as they remain on drug therapy.

Prevention

Prenatal therapy, in which a pregnant woman at risk for a second CAH child is given dexamethasone to decrease secretion of androgens by the adrenal glands of the female fetus, has been in use for about 10 years. This therapy is started in the first trimester when fetal adrenal production of androgens begins, but before prenatal diagnosis is done that would provide definitive information about the sex of the fetus and its disease status. This means that a number of fetuses are exposed to unnecessary steroid treatment in order to prevent the development of male-like genitals in female fetuses with CAH. Several hundred children have undergone this treatment with no major adverse effects, but its long-term risks are unknown.

Parents with a family history of CAH, including a child who has CAH, should seek genetic counseling. Genetic testing during pregnancy can provide information on the risk of having a child with CAH.

Key Terms

Adrenal glands

The two endocrine glands located above the kidney that secrete hormones and epinephrine.

Congenital

Present at birth.

Hormone

A chemical messenger produced by the endocrine glands or certain other cells. Hormones are usually carried in the blood stream and regulate some metabolic activities.

Steroids

Hormones, including aldosterone, cortisol, and androgens, derived from cholesterol that share a 4-ring structure.

Further Reading

For Your Information

Books

• "Fetal Adrenal Development." In Williams Obstetrics, 20th ed. Stamford, CT: Appleton & Lange, 1997.
• "Fetal Treatment." In Medical Genetics, edited by Lynn B. Jorde, John C. Carey, and Raymond L. White. St. Louis: Mosby, 1995.
• Hay, William W., Jr., et al., eds. Current Pediatric Diagnosis and Treatment. Stamford, CT: Appleton & Lange, 1997.

  Periodicals

• Gussinye, Miquel, et al. "Bone Mineral Density in Prepubertal and in Adolescent and Young Adult Patients with the Salt-Wasting Form of Congenital Adrenal Hyperplasia." Pediatrics. 100 (October 1997): 671.

  Organizations

• National Adrenal Diseases Foundation. 510 Northern Boulevard, Great Neck, NY 11021. (516) 487-4992. http://medhlp.netusa.net/www/nadf.htm

  Other

• Applied Medical Informatics Inc."Congenital Adrenal Hyperplasia." (1997). http://www.healthanswers.com/database/ami/converted/000411.html (28 May, 1998).
• National Adrenal Diseases Foundation. "New Developments in the Treatment and Diagnosis of Congenital Adrenal Hyperplasia." http://www.medhelp.org/222/nadf5.htm (28 May 1998).

Gale Encyclopedia of Medicine. Gale Research, 1999.