Congenital Adrenal Hyperplasia

What is CAH?
Congenital adrenal hyperplasia (CAH) is a disease caused by a lack of an enzyme that is important for the production of one or more of the steroid hormones made in the adrenal glands. The adrenal glands are glands that sit on top of your kidneys. The adrenal glands make 3 types of steroid hormones: mineralocorticoids, cortisol (hydrocortisone), and androgens. Mineralocorticoids (the main hormone is aldosterone) control salt balance in your body. Hydrocortisone is a natural steroid termed a “glucocorticoid.” The amount of hydrocortisone in the blood normally
rises in the early morning and whenever you are sick or stressed. It maintains your body’s homeostasis (equilibrium) and is essential for life.
People with low hydrocortisone (cortisol) levels can have low blood pressure, nausea, vomiting, and muscle aches and pains. Androgens are sex hormones and are responsible for hair under the arms and in the pubic area as well as for enlargement of the penis and increase in the size of the female equivalent, the clitoris. In most kinds of CAH, the adrenal gland is not able to make cortisol but instead makes too much androgen. CAH is a congenital and inherited disorder. Inheriting 2 abnormal genes—1 from each parent— for an enzyme (a protein) that is needed to make cortisol leads to CAH. The most commonly affected enzyme is produced by the 21-hydroxylase or CYP-21 gene. In the most severe form of CAH caused by 21-hydroxylase deficiency (salt-wasting), patients will lose too much salt in their urine because they do not make enough mineralocorticoids. Girls may be virilized from too much male hormone (androgen), and their external genitals may have some male characteristics. In the non–salt-wasting form, which is milder, children are able to maintain salt balance but still have too much androgen. Both types usually cause symptoms within days to weeks after birth. A much milder form presents later in childhood with early pubic hair or adult-type body odor. This is called nonclassical CAH.

How common is CAH?
In the general population, the most severe form of CAH (classical) occurs in approximately 1 out of 15,000 people. This is an autosomal recessive condition and requires that a defective gene be inherited from each parent, but the parents, who are called carriers, are not affected. When both parents have a defective gene, there is a 25% chance of having an affected child in each pregnancy. The nonclassical form of CAH may be much more common, particularly in some populations.

How is CAH diagnosed?
The classical form of CAH (salt-wasting and non–salt–wasting) is tested for in newborn blood screening in every state in the United States. In baby boys, the disease is not usually suspected at birth. The diagnosis is made when the newborn screening results come back high or the baby becomes sick in the first week to a month of life. In a baby girl, the diagnosis may be suspected if her external genitals show evidence of exposure to high levels of androgen. In such a case, the infant may have an enlarged clitoris, labia that are fused together, or genitals that look very similar to a male except that the testicles are missing.