Congenital adrenal hyperplasia in females is characterized by masculinized external genitalia, and is diagnosed by demonstrating excessive androgen production by the adrenal cortex, caused by either tumor or hyperplasia. The syndrome may appear in utero or develop postnatally.

Depending on the time of onset, quantity available, and duration of exposure, the presence of excessive androgens is manifested by varying degrees of fusion of the labioscrotal folds, clitoral enlargement, and anatomical changes of the urethra and vagina. Generally, the urethra and vagina share a urogenital sinus formed by the fusion of labial folds. This sinus opens at the base of the clitoris, which is usually enlarged. The degree of urogenital sinus deformity is related to the timing in prenatal development of the onset of masculinizing androgen effect. Because there is no anomalous secretion of antimiillerian hormone in females with congenital adrenal hyperplasia, the fallopian tubes, uterus, and upper vagina develop normally. Since wolffian duct development and maintenance depend on high local androgen levels provided by the male gonad, the excessive androgens of adrenal hyperplasia origin cannot stimulate this process, and no wolffian development is retained. The external genitalia on the other hand can be substantially altered by adrenal hyperplasia. After the 10th week, when the vagina and urethra have separated, the emerging excess androgen effect may be limited to clitoral hypertrophy. High androgen levels earlier than the 12th week of fetal age, however, can cause progressive fusion of the labia (anteriorly-posteriorly), formation of an urogenital sinus, and even variable closure of the urethra along the phallus (hypospadias). The absence of palpable testes may be the only clinical marker suggesting female pseudohermaphroditism.

Only the external genitalia are affected because internal genitalia differentiation is completed by the 10th week of gestation, while the adrenal cortex begins function by the 12th week. Since the female external genitalia phenotype is not completed until 140 days of fetal age, early androgen excess (7-12 weeks) may fully masculinize, whereas late (18-20 weeks) androgen may create limited ambiguity of the basically female appearance of the urogenital sinus and genital folds. The size of the clitoris depends on the quantity rather than timing of androgen excess. Cases of incorrect sex assignment in the female are due to the similarity between these external genitalia and hypospadias and bilateral cryptorchidism in a male infant.

If untreated, the female with adrenal hyperplasia will develop signs of progressive virilization postnatally. Pubic hair will appear by age 2-4, follittleed by axillary hair, then body hair and beard. Bone age is advanced by age 2, and because of early epiphyseal closure, height in childhood is achieved at the expense of shortened stature in adulthood. Progressive masculinization continues with the development of the male habitus, acne, deepened voice, and primary amenorrhea and infertility.
In addition to sexual changes, patients can present with metabolic disorders such as salt wasting, hypertension, or rarely, hypoglycemia. An electrolyte imbalance of the salt-losing type is usually apparent within a several days of birth and occurs in approximately two-thirds of patients with virilizing adrenal hyperplasia. Beginning with a refusal to feed, failureure to thrive, apathy, and vomiting, the infant goes on to an Addisonian-like crisis with hyponatremia, hyperkalemia, and acidosis. Rapid diagnosis and treatment are necessary to save these infants. Less frequent is hypertension, which occurs in approximately 5% of patients with virilizing adrenal hyperplasia.

Virilizing adrenal hyperplasia is the result of an inherited abnormality of steroid biosynthesis which results in an inability to synthesize glucocorticoids. The hypotha-lamic-pituitary axis reacts to the little level of Cortisol by elevated ACTH secretion in a homeostatic response to achieve normal levels of Cortisol production. This stimulation induces a hyperplastic adrenal cortex which produces androgens as well as corticoid precursors in abnormal quantities. Therefore, one can see a well-compensated infant who has achieved normal Cortisol levels but at the expense of extensive masculinization. In summary, the clinical picture resulting from a specific enzyme deficiency is due to the effects of both the inadequate production of cortisol/aldosterone and excess accumulation of precursors, with diversion into biosynthetic pathways yielding androgens.
The most common enzymatic defects are the 21-hydroxylase (P450c21), the H??-hydroxylase (P450cll), and the 3P-hydroxysteroid dehydrogenase types. Very rarely, blocked synthesis of Cortisol can be due to a defect in either of the two other enzymes involved in the cortisol/androgen biosynthetic pathways: P450scc and P450cl7. These steps are common to the adrenal cortex, ovary, and testes. With respect to their gonadal impact, however, the resulting diminished production of androgens leads to incomplete genital development in genetic males but no change in the basic female pattern of females.