Congenital Adrenal Hyperplasia

Definition

The term congenital adrenal hyperplasia (CAH) refers to a complex series of rare but well-studied enzymatic errors of metabolism with deficient levels of different enzymes involved in the synthesis of cortisol (hydrocortisone).

Description

CAH comprises a group of disorders resulting from defective synthesis of adrenal corticosteroids. Lack of glucocorticoids, especially cortisol, causes various kinds of metabolic problems. The response to low levels of cortisol is increased production of corticotropin (ACTH). Lack of mineralocorticoids, primarily aldosterone (steroid hormone), causes sodium and water imbalance which, in some cases, can be fatal. The various forms of CAH represent defects in the different stages of corticosteroid synthesis, usually hydroxylation reactions at certain positions on the original cholesterol molecule.

Causes and Risk Factors

The cause of CAH is unknown.

Symptoms

In several forms of CAH in which adrenomegaly produces abnormally large amounts of androgen (a hormone that stimulates the activity of male sex organs), abnormalities of sexual development may be the most conspicuous consequence, particularly masculinization of the external genitalia in females.

Deficiencies of glucocorticoids occur in some cases despite the adrenal hypertrophy, causing symptoms of Addison's disease. These include weakness, nausea, vomiting, anorexia, irritability, depression, darkening or pigmentation of the skin, hypotension, lack of resistance to cold, and inability to respond physiologically to stress.

Even patients who produce adequate corticosteroids under normal conditions usually cannot meet the increased requirement. Life-threatening Addisonian crisis can then occur. A deficiency of aldosterone can lead to sodium depletion, dehydration, and circulatory collapse.

In congenital lipoid hyperplasia (adrenal cortex with male pseudo-hermaphroditism [false presence of both ovarian and testicular tissue]), the most prominent feature is male pseudohermaphroditism.

The disorder is characterized by failure of the external male genitalia to masculinize, and by hypospadias (one having the orifice of the penis too low). There is accompanying impaired androgen action. Infant survival is very poor in this form of CAH.

Female pseudohermaphroditism is the most common form of CAH. Although both males and females are affected, this disorder is not usually apparent in males until later in life.

Females are born with abnormalities of the external genitalia that range from mild clitoromegaly to fusion of the labia so that the infant appears to have a phallus with undescended testes. Internally, the female reproductive organs are present; however, labial fold fusion may seal off the vagina from the exterior.

These children are often raised as boys until the small size of the phallus becomes apparent at about age 4. Very rarely, genetic females have lived their lives as males.

Untreated females do not menstruate and are infertile. Physical growth may initially be rapid, but retardation occurs fairly soon, and adult stature is short. Untreated females may have psychological problems.

Male infants appear normal. At age 3 to 4, certain characteristics become apparent: unusually rapid growth, acne, deepening voice, penile enlargement, and pubic and underarm hair growth. High levels of androgens suppress hormones required for normal puberty, testicular and sperm development. Since the disorder is not initially apparent in boys there is risk of an unanticipated, potentially fatal gluco- or mineralocorticoid deficiency crisis.

Diagnosis

Diagnosis is usually suspected in a clinical exam by a physician and confirmed through blood tests.

Treatment

The fundamental step in the treatment of CAH is the administration of enough glucocorticoid to suppress ACTH and reverse the metabolic abnormalities. A mineralocorticoid is required in the salt-losing form.

Plastic surgery may be necessary in females with ambiguous genitalia. This should be performed early in life.

Oral corticosteroid therapy corrects the endocrine deficiency and must continue throughout life.

Questions to Ask Your Doctor

What tests need to be done to diagnose and to determine which corticosteroids are affected?

What corticosteroids are affected?

What treatment will you be recommending?

Will you be prescribing any medications? What are the side effects?

What is the prognoses of lifetime corticosteroid therapy?

Will any of the physical appearances disappear after treatment?