Congenital Adrenal Hyperplasia (CAH) is a term combining several rare, genetic autosomal recessive disorders that are inherited by children when both of the parents are carriers of a mutated gene. The carriers of the mutated gene typically do not show any symptoms of the disorder. CAH affects the genes that are responsible for enzyme production, needed for the adrenal glands to produce a sufficient amount of hormones to maintain bodily functions. A deficiency in these enzymes may cause low production of cortisol and/or aldosterone, as well as an overproduction of androgens.
There are several subdivisions of CAH, each affected by a different mutated gene. The forms of each disorder range from mild to severe and affect males and females differently. There are screening tests for newborns for CAH caused by the enzyme 21-hydroxylase deficiency, which is the most common, causing 90% of CAH disorders. Early testing allows for quicker and more accurate treatment.
Congenital Adrenal Hyperplasia affects the hormone producing adrenal glands, located on top of the two kidneys. A deficiency in the amount of cortisol produced by the adrenal glands affect regulation of blood pressure, blood sugar, as well as the body’s ability to respond to stress and any inflammatory processes. A lack in production of aldosterone may cause low blood pressure, low sodium levels, and a higher than normal potassium level. Low levels of aldosterone cause too much salt and water to be washed out by the kidneys, resulting in dehydration and extremely low blood pressure. This type of CAH disorder if often called the “salt-wasting” type. CAH may also cause an overproduction of androgens, affecting both girls and boys.
Classical CAH is usually diagnosed in the postnatal period. Newborn girls can present with “masculinized” genitalia (enlarged clitoris, fused labia). Newborn boys can have a mostly normal physical exam with some hyperpigmentation to genitalia/arm pits and/or enlargement of penis and testes. In the non-classical type (late onset) girls may develop excess hair on the face and body, severe acne, male pattern baldness , and irregular periods. Boys may develop excess hair on the body at an early age, as well as an early growth of facial hair and severe acne. In more severe cases, such as the salt-wasting type of CAH, both girls and boys may experience severe dehydration and heart problems due to low blood pressure. Excess production of androgens may also cause rapid “maturation” and early puberty in children, resulting in shorter than average height in their adult age due to the sooner than normal closing of the growth plates. Females who may have Polycystic Ovary Syndrome may also exhibit symptoms similar to those with CAH.
The cause for CAH disorders is genetic. There are several types of gene mutations that cause different forms of CAH. The most common type is a gene mutation that causes deficiency in the production of enzyme 21-hydroxylase, occurring in 1:15,000 births worldwide.
The non-classical form is relatively common, it has an incidence rate of 1:1,000 in Caucasians and up to 2% in inbred populations, such as Eastern European (Ashkenazi) Jews. Both, males and females are affected equally.
Other, less common subdivisions of CAH are: 11-Beta hydroxylase deficiency, 17a-hydroxylase deficiency, 3-Beta-hydroxysteroid dehydrogenase deficiency, congenital lipoid adrenal hyperplasia, and p450 oxidoreductase deficiency.
Several tests may be performed to diagnose CAH in fetuses. These tests are suggested for parents who have a history of CAH in their family. Aminocentesis is a test that involves withdrawing a sample of amniotic fluid from the womb. Chorionic villus is another prenatal test in which cells are withdrawn from the placenta. Both of these prenatal tests allow for a quicker diagnoses and more accurate treatment early on. Diagnostic tests used for children to diagnose CAH are blood and urine tests that measure the levels of hormones produced by the adrenal glands. Post-natally, CAH is usually diagnoses by the Newborn Screening rest. Non-classical CAH is usually diagnoses later in life (due to clinical symptoms) and could be confirmed by genetic testing.
CAH requires life-long hormonal replacement therapy. Earlier treatment can lower the risk for an onset of a potentially fatal adrenal crisis.
Patients diagnosed with CAH have a normal life expectancy, provided they receive proper and ongoing treatment.
Ongoing studies have been performed to provide better and more efficient treatment of patients with CAH. The Eunice Kennedy Shriver National Institute of Child Health and Human Development based in the United States is currently conducting clinical trials for better screening and evaluation methods, taking into account genetic aspects. NICHD is also providing support for studies evaluating new treatment options, as well as medication options for patients who have complications such as hypoglycemia and metabolic syndrome.