Congenital Adrenal Hyperplasia

Definition
Congenital adrenal hyperplasia (CAH) is a genetic disorder of the adrenal glands which involves a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both.
Frequency
About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia.
Review of Related Anatomy and Physiology
The adrenal glands are two bean-shaped glands curved over the top of the kidneys. It has a glandular (cortex) and neural tissue (medulla) parts. The central medulla region is enclosed by the adrenal cortex, which contains three separate layers.
The adrenal cortex is responsible for producing three major groups of steroid hormones known as the corticosteroids. The hormones are the following:
1. Mineralocorticoids (aldosterone) – important in regulating the mineral or salt content in the blood, particularly the sodium and the potassium ions. The target organ of this hormone is the kidney tubules which is the one responsible for reabsorbing the minerals selectively or allowing them to be excreted out from the body. Increase aldosterone results to increase sodium retention by the kidney tubules and excretion of the potassium. When sodium increases the water also increases or follows. Thus, mineralocorticoids help in the regulation of water and electrolyte levels (equilibrium) in the body.
2. Glucocorticoids (cortisone and cortisol) – promotes the normal cell metabolism which helps the body to counteract the stressors (long-term) primarily by elevating glucose levels in the blood. These hormones are also called hyperglycemic hormones as their triggers the breaking down of fats and proteins into glucose.
3. Sex hormones (androgens) – produced by the adrenal cortex throughout the life in relatively small amounts. Hypersecretion of the sex hormones leads to masculinization regardless of the sex. Dramatic results are noted in females as they grow beard, a masculine body pattern of hair distribution and other male attributes.
Causes
• Inherited as an autosomal recessive trait
• People with congenital adrenal hyperplasia lack an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone.
Pathophysiology
In congenital adrenal hyperplasia (CAH), the affected individuals lack the enzyme needed by the adrenal glands to form and produce the other two hormones – cortisol and aldosterone. Absence of these hormones results to the increase production of the third hormone produced by the adrenal cortex which is the SEX HORMONES or the ANDROGENS. This causes males characteristics to early in childhood instead of normally appearing during the puberty period. In females, male characteristics appear inappropriately as early as the fetal life.

Signs and Symptoms
Elevated androgen production results to masculinization of the female fetus or an increase of the genital organ size in a male fetus. The process of masculinization begins as early as fetal life.
FEMALE INFANT
1. Born with a clitoris so enlarged that it appears as penis
2. Sinus between vagina and urethra is present
3. Fused labia (ambiguous genitalia; the enlarged clitoris resembles that of an undescended testes and hypospadias)
4. Precocious appearance of pubic and axillary hair and acne
5. Epiphyseal line of the long bones closes early (prevents the child from reaching adult height unless treatment is initiated)
6. No breast development or menstruation at puberty
MALE INFANT
1. Appear normal at birth
2. Signs of sexual precocity appear by 6 months of age
3. Appearance of pubic hair by 4 years of age
4. Enlargement of the penis, scrotum and prostate by 4 years of age
5. Acne and a deep mature voice during childhood
6. No spermatogenesis thus, the child is infertile
Diagnosis
Children with congenital adrenal hyperplasia have increased levels of androgen which is an impartial point for the diagnosis. Determining the levels of other adrenal hormones which is the exact degree of the metabolic defect in production of the cortisol can be measured.
1. A karyotype is essential in the evaluation of an infant with ambiguous genitalia to establish the patient’s chromosomal sex.
2. The diagnosis of congenital adrenal hyperplasia depends on the demonstration of inadequate production of cortisol, aldosterone, or both in the presence of accumulation of excess concentrations of precursor hormones.
3. Newborn screening programs for 21-hydroxylase deficiency
1. Abnormal salt levels in blood and urine
2. High levels of 17-OH progesterone
3. High levels of serum DHEA sulfate
4. High levels of urinary 17-ketosteroids
5. Low levels of aldosterone and cortisol
6. Normal or low urinary 17-hydroxycorticosteroids
7. X-ray for bone age (shows older bones than normal for the person’s age)
8. Chorionic villi sampling at 6-8 weeks of pregnancy to possibly identify the fetus with CAH during pregnancy
9. Amniocentesis at 15 weeks age of gestation to possibly identify the fetus with CAH during pregnancy
Treatment
1. Oral hydrocortisone – both male and female infants are given with this corticosteroid agent to replace the hormones that they cannot produce naturally. Administration of corticosteroids decreases ACTH stimulation, thus, lowering the androgen level to normal limits and no further masculinization occurs.
2. Periodic analysis of cortisol levels to evaluate the effectiveness of the therapy.
3. Periodic growth measurement to evaluate the effectiveness of the therapy.
4. Treatment of the mother with Dexamethasone (a corticosteroid), which crosses the placenta, can prevent the masculization of the fetus for the remainder of pregnancy.
5. Girls with male-looking genitals will usually have surgery between ages 1 month – 3 months to correct the abnormal appearance.