A 17-year-old boy comes to the office for evaluation of gynecomastia. Examination shows sparse facial and pubic hair. Laboratory studies show: Semen analysis reveals severe oligospermia. Which of the following mechanisms is the most likely cause of this patient's condition?

Question

A 17-year-old boy comes to the office for evaluation of gynecomastia.  Examination shows sparse facial and pubic hair.  Laboratory studies show:  Semen analysis reveals severe oligospermia.  Which of the following mechanisms is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_3afe_efc6_9249_078fd4cd58ba_MD0001_00 This patient has an elevated testosterone level, but his gynecomastia and sparse facial and pubic hair suggests lack of the expected physiologic response. Androgen insensitivity syndrome (AIS) is caused by loss-of-function mutations of the androgen receptor (AR) gene on the X chromosome. Complete AIS is characterized by female body habitus and external genitalia (but with absence of internal Mullerian derivatives) and cryptorchid testes. In contrast, partial AIS has a variable phenotype; typical findings include: Undervirilization of the external genitalia, ranging from phenotypically female to phenotypically male (often with microphallus and hypospadias) Decreased facial, axillary, and pubic hair (which is driven by androgens in both males and females) Oligospermia Gynecomastia Dysfunction of the AR in the hypothalamus and pituitary leads to loss of feedback inhibition of gonadotropin-releasing hormone (GnRH), FSH, and LH. This results in the following hormonal findings: GnRH induces increased LH secretion, which leads to increased testosterone production in the testes. FSH secretion is increased by GnRH but suppressed by inhibin from the seminiferous tubules and is often normal. Estrogen, which is derived by aromatization of testosterone, may be normal or elevated. (Choices B and E) Testicular disorders can affect the Leydig cells, seminiferous tubules, or both. The Leydig cells are the primary site of testosterone production; reduced Leydig cell function can cause gynecomastia and elevated LH but would be associated with low (not high) testosterone. Injury to the seminiferous tubules leads to loss of inhibin feedback of FSH secretion and an elevated FSH. (Choice C) Ejaculatory duct obstruction can be caused by congenital defects or infection (eg, Chlamydia trachomatis). Sperm counts are low but testicular endocrine function (ie, testosterone level) is typically normal. (Choice D) Abuse of exogenous androgens can reduce spermatogenesis (due to reduced local testicular testosterone levels) and cause gynecomastia (due to aromatization of excess androgens to estrogens). However, this would be associated with suppression of LH levels. Educational objective: Androgen receptor dysfunction in patients with partial androgen insensitivity syndrome leads to decreased facial, axillary, and pubic hair; oligospermia; gynecomastia; and undervirilization of external genitalia (eg, microphallus). Loss of feedback inhibition of gonadotropin-releasing hormone results in elevated LH and testosterone levels.

A 17-Year-Old Boy Comes to the Office for Evaluation of Gynecomastia