pediatrics
Congenital Adrenal Hyperplasia Caused by 21 Hydroxylase Deficiency
Symptoms and Signs
The salt-wasting form causes hyponatremia (sometimes severe), hyperkalemia, and hypotension as well as virilization. If undiagnosed and untreated, this form can lead to life-threatening adrenal crisis, with vomiting, diarrhea, hypoglycemia, hypovolemia, and shock. With either form of classic 21-hydroxylase deficiency, female neonates have ambiguous external genitals, with clitoral enlargement, fusion of the labia majora, and a urogenital sinus rather than distinct urethral and vaginal openings. Male infants typically have normal genital development, which can delay the diagnosis of the salt-wasting form; affected boys are often identified only through routine newborn screening. Unless detected by newborn screening, boys with the simple virilizing form may not be diagnosed for several years, when they develop signs of androgen excess. Signs of androgen excess may include early appearance of pubic hair and increase in growth velocity in both sexes, clitoral enlargement in girls, and penile enlargement and earlier deepening of voice in boys. Children with nonclassic 21-hydroxylase deficiency do not have symptoms at birth and usually do not present until childhood or adolescence. Affected females may have early pubic hair development, advanced bone age, hirsutism, oligomenorrhea, and/or acne; these symptoms may resemble the manifestations of Polycystic Ovary Syndrome (PCOS) . Affected males may have early pubic hair development, growth acceleration, and advanced bone age. In affected females, especially those with the salt-wasting form, reproductive function may be impaired as they reach adulthood; they may have labial fusion and anovulatory cycles or amenorrhea. Some males with the salt-wasting form are fertile as adults, but others may develop testicular adrenal rest tumors (benign intratesticular masses composed of adrenal tissue that hypertrophies under chronic ACTH stimulation), Leydig cell dysfunction, decreasedtestosterone, and impaired spermatogenesis. Most affected males with the non–salt-wasting form, even if untreated, are fertile, but in some, spermatogenesis is impaired. 