Adrenogenital Syndrome

What is Adrenogenital Syndrome?

Excessive production of adrenal androgens causes adrenogenital syndrome, resulting in masculinization, virilization, and hermaphrodism. In rare, true hermaphrodism the person has both ovarian and testicular tissues, a uterus, and ambiguous gonads distributed in various patterns. Adrenogenital syndrome may be inherited (congenital adrenal hyperplasia [CAH]) or acquired (adrenal virilism), usually as a result of an adrenal tumor.

CAH is the most common adrenal disorder in infants and children; simple virilizing CAH and salt-losing CAH are the most common forms. Adrenal virilism is rare and affects females twice as often as males.

Causes of Adrenogenital Syndrome

CAH is transmitted as an autosomal recessive trait that causes deficiencies in the enzymes needed for adrenocortical secretion of cortisol and, possibly, aldosterone. Compensatory secretion of corticotropin produces varying degrees of adrenal hyperplasia.

In simple virilizing CAH, deficiency of the enzyme 21-hydroxylase results in underproduction of cortisol. In turn, this cortisol deficiency stimulates increased secretion of corticotropin, producing large amounts of cortisol precursors and androgens that don't require 21-hydroxylase for synthesis.

In salt-losing CAH, 21-hydroxylase is almost completely absent. Corticotropin secretion increases, causing excessive production of cortisol precursors, including salt-wasting compounds. Plasma cortisol levels and aldosterone - both dependent on 21-hydroxylase - decrease precipitously and; in combination with the excessive production of salt-wasting compounds, expedite acute adrenal crisis. Corticotropin hypersecretion stimulates adrenal androgens, possibly even more than in simple virilizing CAH, and produces masculinization.

Other rare CAH enzyme deficiencies exist and lead to increased or decreased production of affected hormones.

Signs & Symptoms of Adrenogenital Syndrome

The following symptoms are listed common:

(1) In girls:

• Ambiguous genitalia
• Early appearance of pubic and axillary hair
• Excessive hair growth
• Abnormal menstrual periods
• Failure to menstruate

(2) In boys early development of masculine characteristics:

• Well-developed musculature
• Enlarged penis
• Small testes
• Early appearance of pubic and axillary hair

Both boys and girls will be tall as children but Significantly shorter than normal as adults.

Diagnostic tests

The following test findings are needed to confirm adrenogenital syndrome:

• elevated levels of urine 17 -ketosteroids (17 -KS). Which can be suppressed by administering oral dexamethasone
• increased urine metabolites of hormones, particularly pregnanetriol
• elevated levels of plasma 17 -hydroxyprogesterone and dehydroepiandrosterone sulfate
• hyperkalemia, hyponatremia, and hypochloremia on the presence of elevated levels of urine 17 -KS and pregnanetriol and decreased aldosterone levels. which confirm salt-losing CAH in any infant with Signs and symptoms of adrenal hypofunction or adrenal crisis in the first week after birth.

Ambiguous external genitalia suggest hermaphrodism; a gonadal biopsy and chromosomal studies are needed to confirm the diagnosis.

Treatment

Simple virilizing CAH necessitates correction of the cortisol deficiency and inhibition of excessive pituitary corticotropin production. This is accomplished through daily administration of cortisone or hydrocortisone. Such treatment returns androgen production to normal levels. Initially, the oral hydrocortisone dosage starts at 25 to 30 mg/m²/day. Then, the dosage is reduced to 10 to 20 mg/m²/day. Infants must receive I.M. cortisone or hydrocortisone until age 18 months; after that, they may take the drug orally.

The infant with salt-losing CAH in adrenal crisis requires immediate I.V. sodium chloride and glucose infusion to maintain fluid and electrolyte balance and to stabilize vital Signs. If this treatment doesn't control symptoms while diagnosis is being established, I.M. desoxycorticosterone and, occasionally, I.V. hydrocortisone are necessary. Later, maintenance therapy includes mineralocorticoid (desoxycorticosterone) and glucocorticoid (cortisone or hydrocortisone) replacement.

Based on the anatomy of the external genitalia and chromosomal evaluation, sexual assignment and reconstructive surgery may be recommended. For example, the female with masculine external genitalia requires reconstructive surgery such as correction of the labial fusion and of the urogenital sinus. Such surgery is usually scheduled between ages 1 and 3 after the effect of cortisone therapy has been assessed.

Prevention Tips

• Genetic counseling is indicated for parents with a family history of congenital adrenal hyperplasia (of any type) or a family with a child who has the condition.
• A newborn screening test is available for the most common form of congenital adrenal hyperplasia and can be done on heelstick blood . This test is not yet widely available.