A 35-year-old man comes to the office for evaluation of an enlarged left testis. He also reports decreased libido and erectile potency for the last 2 months. The patient has no chronic medical conditions and takes no medications. Physical examination is notable for significant enlargement of the left testis and bilateral gynecomastia. His other secondary sexual characteristics are normal. Serum β-hCG is markedly elevated and serum TSH is normal. Scrotal ultrasound reveals a 3.1-cm, irregular testicular mass with cystic areas. Which of the following is the most likely cause of this patient's gynecomastia?

Question

A 35-year-old man comes to the office for evaluation of an enlarged left testis.  He also reports decreased libido and erectile potency for the last 2 months.  The patient has no chronic medical conditions and takes no medications.  Physical examination is notable for significant enlargement of the left testis and bilateral gynecomastia.  His other secondary sexual characteristics are normal.  Serum β-hCG is markedly elevated and serum TSH is normal.  Scrotal ultrasound reveals a 3.1-cm, irregular testicular mass with cystic areas.  Which of the following is the most likely cause of this patient's gynecomastia?

Quizplus · Accepted Answer

11ec160b_3cb9_e683_9249_4d9b9042e26d_MD0001_00 Gynecomastia is abnormal growth of breast tissue in males. It is generally due to an increased ratio of estrogens (which cause hyperplasia of breast ductal epithelium and increased fibrosis of stromal tissues) to androgens (which have an inhibitory effect on breast development). In addition to gynecomastia, this patient has hypogonadal symptoms (eg, decreased libido, erectile dysfunction) that suggest decreased testicular androgen production. In light of the large testicular mass and elevated β-hCG level, this likely represents an hCG-secreting germ cell tumor of the testis. Excessive secretion of hCG by testicular germ cell tumors suppresses testosterone production in Leydig cells while increasing aromatase activity and conversion of testosterone to estradiol; the resulting increase in the estrogen/androgen ratio can cause gynecomastia. (Choice A) Inadequate production of adrenal androgens (eg, dehydroepiandrosterone [DHEA], DHEA-sulfate) is seen in patients with 17-alpha-hydroxylase deficiency. In males, this condition usually manifests in childhood with undervirilization and ambiguous (or female) external genitalia. (Choice B) Decreased hypothalamic secretion of GnRH suppresses the entire GnRH-pituitary-gonadal axis, leading to decreased testosterone production. Concurrently, aromatization of weak adrenal androgens to estrogens maintains estrogen levels proportionally high, leading to gynecomastia. However, gynecomastia in patients with germ cell tumors is primarily due to Leydig cell aromatization of androgens. (Choice C) A number of drugs (eg, spironolactone, flutamide, cimetidine) inhibit binding of testosterone and dihydrotestosterone to the androgen receptor, leading to gynecomastia. However, hCG does not affect androgen binding. Educational objective: Secretion of hCG by testicular germ cell tumors impairs testosterone production in Leydig cells while increasing aromatase activity and conversion of androgens to estrogens. The resulting increase in the estrogen/androgen ratio can cause gynecomastia.

A 35-Year-Old Man Comes to the Office for Evaluation of an Enlarged