congenital adrenal hyperplasia
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Congenital Adrenal Hyperplasia
CAH 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.
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 and 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 deepens 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, including vomiting, dehydration, electrolyte (a compound such as sodium or calcium that separates to form ions when dissolved in water) changes, and cardiac arrhythmia.
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. However, sometimes there are no symptoms.
CAH is diagnosed by a careful examination of the genitals and blood and urine tests that 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. For some forms of CAH, prenatal diagnosis is possible through chronic villus sampling in the first trimester and by measuring certain hormones in the amniotic fluid during the second trimester.
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, and prednisone or dexamethasone is prescribed for older patients. For patients with salt-wasting CAH, fludrocortisone, which acts like aldosterone (the missing hormone), 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 that lead to increases in the dose of steroids prescribed. Side effects of steroids include stunted growth. Steroid therapy should not be suddenly stopped, since adrenal insufficiency results.
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 hydrocortisone 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 (2.5 cm) 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.
Adrenal glands — The two endocrine glands located above the kidney that secrete hormones and epinephrine.
Aldosterone — A hormone secreted by the adrenal glands that is important for maintaining salt and water balance in the body.
Androgens — Steroid hormones that cause masculinization.
Congenital — Present at birth.
Cortisol — A steroid hormone secreted by the adrenal cortex that is important for maintenance of body fluids, electrolytes, and blood sugar levels.
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 four-ring structure.
CAH can be controlled and successfully treated in most patients as long as they remain on drug therapy.
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. Since there is very little data on the effectiveness and safety of prenatal therapy, it should only be offered to patients who clearly understand the risks and benefits and who are capable of complying with strict monitoring and follow-up throughout pregnancy and after the child is born.
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.
American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000.
National Adrenal Diseases Foundation. 510 Northern Boulevard, Great Neck, NY 11021. (516) 487-4992. 〈http://medhlp.netusa.net/www/nadf.htm〉.
The Johns Hopkins Children's Center. "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency." http://www.med.jhu.edu/pedendo/cha/printable.html.
con·gen·i·tal a·dre·nal hy·per·pla·si·a
a group of autosomal recessively inherited disorders associated with a deficiency of one of the enzymes involved in cortisol biosynthesis, resulting in elevation of ACTH levels and overproduction and accumulation of cortisol precursors proximal to the block; androgens are produced in excess, causing virilization. The most common disorder is the 21-hydroxylase deficiency, caused by mutation in the cytochrome P450 21-hydroxylase gene (CYP21) on chromosome 6p. There are three major types with some clinical similarities but distinctive genetic and biochemical differences: the salt-losing form [MIM*201710, MIM*201810, and MIM*202110]; the simple virilizing form [MIM*201910]; and the late onset form. All three forms are associated with abnormalities of the 21-hydroxylase gene.