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Patient Story


A 3400-gram infant is being evaluated by the pediatrician after an uncomplicated term gestation and vaginal delivery. The infant is noted to have ambiguous genitalia, characterized by clitoromegaly, enlarged labia, and no palpable testes. A single urethral/vaginal opening is present (Figure 197-1). A diagnosis of congenital adrenal hyperplasia is suspected based on these findings. A pediatric endocrinologist is consulted, who orders a serum 17-hydroxyprogesterone level, which is markedly elevated, and a rapid karyotype, which reveals a 46 XX karyotype, confirming the diagnosis of CAH caused by 21-hydroxylase deficiency. The infant is treated with glucocorticoids and the parents receive psychosocial and genetic counseling regarding the diagnosis.

FIGURE 197-1

Ambiguous genitalia, manifested by clitoromegaly, enlarged and hyperpigmented labia, fused urogenital opening, in a female infant with congenital adrenal hyperplasia. (Used with permission from Elumalai Appachi, MD.)

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Congenital adrenal hyperplasia (CAH) is an autosomal-recessive disorder most commonly (95%) caused by 21-hydroxylase deficiency. Classic CAH refers to the salt wasting and simple virilizing form, while nonclassic, or late onset CAH, refers to a less severe form of the disorder and may not be apparent until later in life. This chapter will focus on classic CAH caused by 21-hydroxylase deficiency. Patients with the salt-wasting variety of congenital adrenal hyperplasia present with failure to thrive, dehydration, vomiting, and anorexia. In female infants, virilization of the external genitalia leads to an early diagnosis; the condition is often diagnosed later in male infants with the salt-wasting variety (2 to 3 weeks of life) because the external genitalia may appear normal.




Primary adrenal insufficiency, 21-hydroxylase deficiency, pseudohermaphroditism.




  • 21-hydroxylase deficiency accounts for 95 percent of all forms of CAH.

  • The incidence of 21-hydroxylase deficiency is 1 in 15,000 live births and is one of the most common inborn errors of metabolism.13

  • The incidence of CAH is equal among Caucasians and Hispanics and about fourfold less common in African Americans.3


Etiology and Pathophysiology


  • Inherited defects in the enzymatic steps of cortisol biosynthesis (steroidogeneses) result in congenital adrenal hyperplasia.

  • The resulting decrease in cortisol levels increases the secretion of adrenocorticotropic hormone (ACTH), thereby stimulating the production of adrenal steroids up to and including the substrate for the defective enzyme. This chronic ACTH stimulation results in hyperplasia of the adrenal cortex (Figure 197-2).

  • Accumulation of 17-hydroxyprogesterone and other steroid precursors results in shunting into a pathway for androgen biosynthesis, leading to high levels of androstenedione that are converted outside the adrenal gland to testosterone. The effects of this shunting begin in affected fetuses by 8 to 10 weeks of gestation and leads to abnormal genital development in females (Figure 197-3).

  • The clinical manifestations of these ...

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