The risk of germ cell malignancy is 2% in complete androgen insensitivity syndrome (67). Most clinicians believe the risk for gonadal neoplasia is low before 25 years of age; thus, the testes should be left in place until after pubertal feminization, especially because the risk of neoplasia appears to increase with age. Exogenous estrogen should be provided after gonadectomy.
The diagnosis is often suspected by the typical physical findings and strongly suggested by normal (or even somewhat elevated) male levels of testosterone, normal or somewhat elevated levels of LH, and normal levels of FSH. The diagnosis is confirmed by a 46,XY karyotype.
Interacting with the patient and family requires sensitivity and care. It may be inadvisable to begin by informing the patient of the karyotype; the psychological implications may be devastating because the patient was reared as a girl. Family members should be informed initially that m¨ullerian aplasia occurred and that the risk for neoplasia mandates gonadectomy after puberty. Because the disorder can be inherited in an X-linked recessive fashion, families should undergo appropriate genetic counseling and screening to identify the possible existence of other affected family members.
Precocious Puberty Although precocious pubertal development may be classified in several ways, it is perhaps simplest to think of the development as gonadotropin dependent (in which case it is almost invariably of central origin) or gonadotropin independent (of peripheral origin). Precocious puberty is 20 times more common in girls than in boys. In fully 90% of girls, the precocious development is idiopathic, whereas this appears to be true for only 10% of boys. Family history, the rapidity with which secondary sexual characteristics are developing, the rate of growth, and the presence or absence of central nervous system disease should all be considered
Figure 29.15 A: This 17-year-old individual presented with primary amenorrhea and was found to have a blind-ending vagina and bilateral inguinal masses. Circulating levels of testosterone were at the upper limits of the normal range for men and the karyotype was 46,XY, confirming androgen insensitivity. B: Two inguinal testes were found at surgery. (From Simpson JL, Rebar RW. Normal and abnormal sexual differentiation and development. In: Becker KL, ed. Principles and practice of endocrinology and metabolism. 2nd ed. Philadelphia, PA: JB Lippincott, 1995:788–822, with permission.)
LH, FSH, TSH, T4 High LH Low or equivocal LH and FSH High TSH, low T4 Gonadotropin-producing neoplasm Primary hypothyroidism Isosexual development: Estradiol (E2) Heterosexual development: T, DHEAS, 17OHP High E2 E2 normal for development High T High 17OHP or DHEAS Estrogen-producing neoplasm Evaluation of CNS Androgen-producing neoplasm Rule out adrenal hyperplasia
Figure 29.16 Flow diagram for the evaluation of precocious puberty in phenotypic females. LH, luteinizing hormone; FSH, follicle-stimulating hormone; TSH, thyroid-stimulating hormone; T4, thyroxine; T, testosterone; DHEAS, dehydroepiandrosterone sulfate; 17OHP, 17hydroxyprogesterone; CNS, central nervous system. (From Rebar RW. Normal and abnormal sexual differentiation and pubertal development. In: Moore TR, Reiter RC, Rebar RW, et al., eds. Gynecology and obstetrics: a longitudinal approach. New York: Churchill Livingstone, 1993:97–133, with permission.) in deciding whether to pursue evaluation of a girl for precocious puberty. The evaluation of precocious puberty is as follows: 1.