Congenital adrenal hyperplasia Health Article

Definition

Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive genetic conditions that result from an abnormality in one of the enzymes required by the adrenal glands to convert cholesterol into cortisol, aldosterone, and androgens.

Description

The first likely description of congenital adrenal hyperplasia (CAH) occurred in 1865 when an anatomist named Luigi De Crecchio reported on a cadaver who had what appeared to be a penis with the urinary opening on its underside and undescended testicles. What was remarkable about this cadaver was that it also had a vagina, a uterus, fallopian tubes, ovaries and very enlarged adrenal glands. From four years of age until his death, this person had lived his life as a male although at birth he was declared a female. He died in his 40s after many episodes of vomiting, diarrhea, and prostration. This genetic female with masculinized external genitals and abnormalities in regulating the amount of salt in her body had all the symptoms of a textbook case of a severe and untreated CAH.

Congenital adrenal hyperplasia (CAH), formerly called adrenogenital syndrome, results from an abnormality in one of the enzymes required by the adrenal glands to convert cholesterol into cortisol, aldosterone, and androgens such as testosterone. These three hormones are very necessary for normal health. Cortisol helps the body to cope with stress such as injury or illness, aldosterone helps to insure that the body retains normal amounts of salt, and androgens such as testosterone are involved in the production of masculine traits such as body hair and the development of male sex organs.

There are many different enzymes necessary for the normal production of cortisol, aldosterone, and testosterone. Each type of CAH results from a deficiency in one of these enzymes. One of the most important enzymes involved in the breakdown of cholesterol is 21-hydroxylase. 21-hydroxylase is involved in the conversion of cholesterol to cortisol and aldosterone but is not involved in the conversion of cholesterol to testosterone. Ninety to ninety-five percent of people with CAH have a deficiency or absence of 21-hydroxylase (21-hydroxylase deficiency).

A deficiency or absence of 21-hydroxylase (CAH21) results in the production of decreased levels of cortisol and aldosterone, which prompts the body to compensate by forcing the adrenal glands to increase the conversion of cholesterol. This does not result in significantly increased levels of cortisol and aldosterone, but does result in increased levels of testosterone, which is produced by another enzyme. Both men and women normally produce some testosterone, although men typically produce larger amounts of this hormone.

Increased levels of testosterone can result in premature puberty in males and females and can cause the absence of a menstrual period and increased amounts of body hair in women. Females who produce high levels of this hormone in utero can be born with masculinized external genitals. Decreased levels of cortisol can also result in increased levels of two other hormones called 17-hydroxyprogesterone and androstenedione. Increased levels of 17-hydroxyprogesterone in conjunction with decreased levels of aldosterone can result in an inability of the body to retain normal amounts of salt.

The three major types of 21-hydroxylase deficiency (CAH21) are: (1) the classic salt-losing form, (2) the classic non-salt-losing form, and (3) the non-classical form (later onset form). The classic forms of the disorder, if untreated, can result in premature puberty in boys and can cause girls to be born with an enlarged clitoris or external male genitals. Men and women with untreated classical CAH21 can have increased growth in childhood but short adult height. The salt-losing form of CAH21 results in reduced levels of salt in the body, which can sometimes result in an adrenal crisis. An adrenal crisis is a life threatening condition characterized by severe dehydration, very low blood pressure, and vomiting. The nonclassic form, which is milder and has a later onset, can cause women to have an absence of menstruation and increased body hair and can cause a low sperm count in men.