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Key Features

Essentials of Diagnosis

  • Adrenal hyperplasia: 21-OHase deficiency

  • Genital virilization in females, with labial fusion, urogenital sinus, enlargement of the clitoris, or other evidence of androgen action

  • Salt-losing crises in infant males or isosexual precocity in older males with infantile testes

  • Increased linear growth and advanced skeletal maturation

  • Elevation of plasma 17-hydroxyprogesterone concentrations in the most common form; may be associated with hyponatremia, hyperkalemia, and metabolic acidosis, particularly in newborns

General Considerations

  • CAH is most commonly (> 90% of patients) the result of homozygous or compound heterozygous mutations in the cytochrome P-450 C21 (CYP21A2) gene causing 21-hydroxylase deficiency

  • The defective gene is present in 1:250–1:100 people and the worldwide incidence of the disorder is 1:15,000, with increased incidence in certain ethnic groups

  • In its severe form, excess adrenal androgen production starting in the first trimester of fetal development causes virilization of the female fetus and life-threatening hypovolemic, hyponatremic shock (adrenal crisis) in the newborn, if untreated

Clinical Findings

  • In females

    • Abnormality of the external genitalia varies from mild enlargement of the clitoris to complete fusion of the labioscrotal folds, forming an empty scrotum, a penile urethra, a penile shaft, and clitoral enlargement sufficient to form a normal-sized glans

    • Signs of adrenal insufficiency (salt loss) typically appear 5–14 days after birth

    • With milder enzyme defects, clinically apparent salt loss may not occur and virilization predominates with accelerated growth and skeletal maturation

    • Pubic hair appears early, acne may be excessive, and voice may deepen

    • Excessive pigmentation may develop

    • Isosexual central precocious puberty may occur if treatment is not initiated before the bone age is significantly advanced

  • In males

    • Infant usually appears normal at birth but may present with salt-losing crisis in the first weeks of life

    • In milder forms, salt-losing crises may not occur and virilization predominates, with enlargement of the penis and increased pigmentation, as well as other symptoms and signs similar to those of affected females

    • Testes are not enlarged unless there are rare adrenal rests in the testes producing asymmetric enlargement

    • In some rare enzyme defects, ambiguous genitalia may be present due to impaired androgen production


Laboratory Findings

  • Hormonal studies are essential for accurate diagnosis

  • Rapid assessment of genetic sex should be obtained in any newborn with ambiguous genitalia since 21-hydroxylase deficiency is the most common cause of ambiguity in females

  • Assessment of urinary steroid metabolites is no longer routine but is reserved for rare forms of CAH


  • Generally not required

  • Ultrasonography, CT scanning, and MRI may be useful in defining pelvic anatomy or to exclude an adrenal tumor



  • Hydrocortisone

    • Initially, 30–50 mg/m2/d is given parenterally or orally until suppression ...

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