Congenital adrenal hyperplasia; 21-hydroxylase deficiency
Congenital adrenal hyperplasia refers to a group of inherited disorders relating to the adrenal glands, characterized by a deficiency in the hormones cortisol and aldosterone and an overproduction of androgen.
Causes, incidence, and risk factors
The different types of adrenogenital syndrome are inherited as autosomal recessive diseases and can affect both boys and girls. The defect involves a lack of an enzyme needed by the adrenal gland to make the major steroid hormones of the adrenal cortex: cortisol and aldosterone.
Without these hormones, steroids are ‘diverted’ to becoming androgens, a form of male sex hormones. This causes early (or inappropriate) appearance of male characteristics.
In a newborn girl with this disorder, the clitoris is enlarged, with the urethral opening at the base (ambiguous genitalia, often appearing more male than female). The internal structures of the reproductive tract (ovaries, uterus, and fallopian tubes) are normal. As she grows older, masculinization of some features takes place, such as deepening of the voice, the appearance of facial hair, and failure to menstruate at puberty.
In a newborn boy no obvious abnormality is present, but long before puberty normally occurs, the child becomes increasingly muscular, the penis enlarges, pubic hair appears, and the voice deepens. Affected males may appear to enter puberty as early as 2-3 years of age. At puberty, the testes are small.
Some forms of congenital adrenal hyperplasia are more severe and cause adrenal crisis in the newborn due to salt wasting. In this salt-losing form of congenital adrenal hyperplasia, newborns develop symptoms shortly after birth. These include vomiting, dehydration, electrolyte changes, and cardiac arrhythmias. Untreated, this condition can lead to death within 1-6 weeks after birth.
About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia.
- In girls: o Ambiguous genitalia o Early appearance of pubic and axillary (armpit) hair o Excessive hair growth o Deep voice o Abnormal menstrual periods o Failure to menstruate
- In boys, early development of masculine characteristics: o Well-developed musculature o Enlarged penis o Small testes o Early appearance of pubic and axillary hair
Both boys and girls will be tall as children but significantly shorter than normal as adults.
Signs and tests
- Decreased aldosterone and cortisol in blood
- Elevated urinary 17-ketosteroids
- Normal or decreased urinary 17-hydroxycorticosteroids
- Elevated 17-OH progesterone in blood
- Elevated serum DHEA sulfate
- X-ray for bone age (demonstrates markedly advance bone age above chronological age)
- Abnormal salt levels o in blood (serum electrolytes) o in urine
- Genetic testing is often helpful in diagnosing or confirming the disease and can be useful in the management of the condition.
This disease may also alter the results of the following tests:
- Estriol - urine
- Estriol - serum
The goal of treatment is to return hormone levels to normal. This is achieved by daily administration of forms of cortisol: dexamethasone, fludrocortisone, or hydrocortisone. Additional doses of medicine are required during times of stress such as severe illness or surgery.
The gender of a baby with ambiguous genitalia is determined by examination of the chromosomes (karyotyping). Reconstructive surgery for girls with masculine external genitalia is usually performed between the ages of 1 and 3 months to correct the abnormal appearance.
Parents of children with this disorder need instruction on the side effects of steroid therapy. They should report signs of infection and stress to their health care provider because increases in medication may be required. In addition, steroid medications cannot be stopped suddenly or adrenal insufficiency will result.
National Adrenal Diseases Foundation: (516) 487-4992
CARES (Congenital Adrenal hyperplasia Research, Education, and Support) Foundation: (866) 227-3737 (toll free) or http://www.caresfoundation.com
The outcome is usually associated with good health, but short stature may result even with treatment. Males have normal fertility. Females may have a smaller opening of the vagina and lower fertility.
Medication to treat this disorder must be continued for life.
- Adrenal crisis, including hyponatremia and shock (especially in newborns)
- Abnormal female external genitalia (internal organs are normal)
- Early development of male sexual characteristics
- Short adult stature despite early, rapid childhood growth
- Tumors of the testes in adult men
- High blood pressure
- Low blood sugar
- Side effects of corticosteroids used as treatment
Calling your health care provider
Call for an appointment with your health care provider if your child develops symptoms of this disorder.
Also, if you had a child with this disorder or you have a family history of this disease and you plan to have other children, you should discuss this with your health care provider before conceiving a child. Genetic counseling is important if there is a history of congenital adrenal hyperplasia.
Genetic counseling is indicated for parents with a family history of congenital adrenal hyperplasia (of any type) or a family with a child who has the condition.
Prenatal diagnosis is available for some forms of congenital adrenal hyperplasia. Diagnosis is made in the first trimester by chorionic villus sampling and in the second trimester by measuring hormones such as 17-hydroxyprogesterone in the amniotic fluid.
A newborn screening test is available for the most common form of congenital adrenal hyperplasia and can be done on heelstick blood (as part of the routine screenings done on newborns). This test is not yet widely available.
by Brenda A. Kuper, M.D.
All ArmMed Media material is provided for information only and is neither advice nor a substitute for proper medical care. Consult a qualified healthcare professional who understands your particular history for individual concerns.