Discordance between gonadal sex (46,X) and the phenotypic appearance of external genitalia (masculinized) may also result from excessive fetal androgen exposure. his was previously termed female pseudohermaphroditism. In afected individuals, the ovaries and female internal ductal structures such as the uterus, cervix, and upper vagina are present. hus, patients are potentially fertile. he external genitalia, however, are virilized to a varying degree depending on the amount and timing of androgen exposure. he three embryonic structures that are commonly afected by elevated androgen levels or ovarian development disorders are the clitoris, labioscrotal folds, and urogenital sinus. As a result, virilization may range from modest clitoromegaly to posterior labial fusion and development of a phallus with a penile urethra. Degrees of virilization can be described by the Prader score, which ranges from 0 for a normal-appearing female to 5 for a normal, virilized male.
Fetal, placental, or maternal sources can provide the excessive androgen levels. Maternally derived androgen excess may come from virilizing ovarian tumors such as luteoma and Sertoli-Leydig cell tumor or from virilizing adrenal tumors. Fortunately, these neoplasms infrequently cause fetal efects because of the tremendous ability of placental syncytiotrophoblast to convert C19 steroids-androstenedione and testosterone-to estradiol via the enzyme aromatase (Chap. 5, p. 103). As another source, drugs such as testosterone, danazol, and other androgen derivatives may cause fetal virilization.
Of fetal sources, exposure can arise from fetal congenital adrenal hyperplasia (CAH). his stems from a fetal enzyme dei ciency in the steroidogenic pathway that leads to androgen accu mulation. The most common defect is 21-hydroxylase deiciency.
CAH is a frequent cause of virilization and has an incidence approximating 1 in 10,000 to 20,000 live births (Speiser, 2010).
With CAH, phenotypes depend on the location of the enzyme defect in the steroidogenic pathway and on the severity of the resulting enzymatic deiciency (Miller, 201i1). With severe enzymatic deiciency, afected newborns have life-threatening salt wasting and virilization. Other mutations may prompt virilization alone (Auchus, 2015). he mildest abnormalities present later and are described as "nonclassic," "late-onset," or "adult-onset" CAH. In these patients, activation of the adrenal axis at puberty increases steroidogenesis and unmasks a mild enzymatic deficiency. Excess androgen provides negative feedback to gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus. These patients oten present with hirsutism, acne, and anovulation. Thus, lateonset CAH may mimic polycystic ovarian syndrome (McCannCrosby, 2014). In some instances, CAH can be diagnosed antenatally. Early maternal dexamethasone therapy can dampen androgen excess to minimize virilization (Chap. 16, p. 317).
Of rare placental sources, placental aromatase deiciency from a fetal CP 19 gene mutation causes an accumulation of placental androgen and underproduction of placental estrogens (Chap. 5, p. 105) Gones, 2007). Consequently, both the mother and the 46,X fetus are virilized.