Hyperprolactinemia Low levels of LH and FSH may be associated with hyperprolactinemia. As noted, galactorrhea cannot occur in the absence of complete breast development. Pituitary prolactinomas are rare during adolescence but must be considered when certain signs and symptoms are present. Many individuals with prolactinomas have a history of delayed menarche. The association between the ingestion of certain drugs (most often psychotropic agents and opiates in this age group) is well established. Primary hypothyroidism is associated with hyperprolactinemia because increased levels of thyrotropin-releasing hormone (TRH) stimulate secretion of prolactin. The empty sella syndrome, in which the sella turcica is enlarged but is replaced by cerebrospinal ﬂuid, may be associated with hyperprolactinemia.
Use of Chemotherapeutic Agents As survival rates following treatment for childhood malignancy improve, the effects of cancer therapy become more important. Both radiation therapy to the abdomen and systemic chemotherapeutic agents, particularly alkylating agents, have toxic effects on germ cells. Although prepubertal gonads appear less vulnerable than those of adults, ovarian failure is common. An argument can be made for endocrine assessment as early as 1 year following completion of therapy to identify children who will suffer from hypogonadism. Spontaneous ovarian activity can resume even years after therapy.
Asynchronous Puberty Asynchronous pubertal development is characteristic of androgen insensitivity (i.e., testicular feminization). Affected individuals typically present with breast development (usually only to Tanner stage 3) out of proportion with the amount of pubic and axillary hair present (Fig. 29.15). In this disorder, 46,XY individuals have bilateral testes, female external genitalia, a blindly ending vagina (often foreshortened and sometimes absent), and no m¨ullerian derivatives (i.e., uterus and fallopian tubes) (64). Infrequently, patients may have clitoral enlargement and labioscrotal fusion at puberty, which is referred to as incomplete androgen insensitivity.
Asynchronous puberty is heterogeneous but is always related to some abnormality of the androgen receptor or of androgen action (65). In perhaps 60% to 70% of cases, androgen receptors cannot be detected (i.e., the patient is receptor negative). In the remaining cases, androgen receptors are present (i.e., receptor positive), but mutations in the androgen receptor are detected or there is a defect at a more distal step in androgen action (i.e., a postreceptor defect). Receptor-positive individuals are indistinguishable clinically from receptor-negative individuals. Several different mutations in the androgen receptor gene, most of which occur within the androgen-binding domain of the receptor, are identified in affected individuals who are receptor positive. Severe X-linked androgen receptor gene mutations cause complete androgen insensitivity, whereas mild mutations impair virilization with or without infertility, and moderate mutations result in a wide phenotypic spectrum of expression among siblings (66).
Because the Sertoli cells of the testes make antim¨ullerian hormone (AMH), m¨ullerian derivatives are absent in this disorder; thus, m¨ullerian regression occurs normally. The testes are often normal in size and may be located anywhere along the path of embryonic testicular descent—in the abdomen, inguinal canal, or labia. Half of all individuals with androgen insensitivity develop inguinal hernias. Recognizing that most such girls will be 46,XX, it is important to determine the karyotype in prepubertal girls with inguinal hernias, especially if a uterus cannot be detected with certainty by ultrasound.