A 38-year-old man comes to the office with headaches, loss of libido, and erectile dysfunction for the last 3 months. The patient has no chronic medical conditions and takes no prescription or over-the-counter medications. He does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. The examination is notable for peripheral vision loss, bilateral gynecomastia, and soft testes without masses. Laboratory evaluation shows normal serum prolactin, normal β-hCG, low serum LH, and low serum testosterone. Which of the following is the most likely mechanism for this patient's gynecomastia?

Question

A 38-year-old man comes to the office with headaches, loss of libido, and erectile dysfunction for the last 3 months.  The patient has no chronic medical conditions and takes no prescription or over-the-counter medications.  He does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  The examination is notable for peripheral vision loss, bilateral gynecomastia, and soft testes without masses.  Laboratory evaluation shows normal serum prolactin, normal β-hCG, low serum LH, and low serum testosterone.  Which of the following is the most likely mechanism for this patient's gynecomastia?

Quizplus · Accepted Answer

This patient's headaches and peripheral vision loss (ie, bitemporal hemianopsia) suggest a pituitary mass with compression of the optic chiasm. In addition, he has features of hypogonadism, including decreased libido, erectile dysfunction, testicular atrophy, and a low circulating testosterone level; his low LH level confirms secondary (central) hypogonadism. Secondary hypogonadism is common in patients with pituitary masses. Potential etiologies include the following: High prolactin levels from a prolactin-secreting adenoma (prolactinoma) can suppress secretion of GnRH, leading to decreased LH secretion and lower testosterone production Non-prolactin-secreting tumors can disrupt the inhibitory dopaminergic regulation of prolactin secretion, leading to hyperprolactinemia and (usually mild) hypogonadism Direct compression of gonadotrope cells with loss of LH secretion (independent of prolactin effect), which is likely in this patient with a normal prolactin level Gynecomastia is the abnormal growth of male breast tissue, typically due to an increased estrogen/testosterone ratio. This patient has low testosterone, but production of estrogen precursors (eg, androstenedione, dehydroepiandrosterone [DHEA], DHEA sulfate) continues uninterrupted in the zona reticularis of the adrenal cortex. These steroid hormones are subsequently aromatized to estrogens in peripheral tissues. When testosterone levels are normal, the inhibitory effect of testosterone prevents breast growth, but when testosterone is low, the adrenal-derived estrogens can produce significant gynecomastia. (Choice A) Estrogen is cleared primarily in the liver. Patients with cirrhosis commonly develop gynecomastia due to decreased clearance of estrogen along with increased production and aromatization of estrogen precursors. However, this patient has no risk factors for cirrhosis (eg, alcohol use), and his bitemporal hemianopsia suggests a pituitary etiology. (Choice B) Androgen receptor defects typically present at birth with a female phenotype or ambiguous genitalia (with 46,XY karyotype), although some variants (partial androgen insensitivity syndrome) may present in adulthood with gynecomastia and undervirilization (eg, decreased facial and pubic hair). However, androgen production is unaffected, and testosterone levels would be normal to high. (Choice C) Testosterone biosynthetic defects generally present at birth or during development with abnormal genitalia and/or undervirilization in males. Biochemical testing shows primary hypogonadism (ie, low testosterone, high LH). (Choice D) Estrogen is synthesized in the testes by the aromatization of androgens, producing high local concentrations. However, this patient has decreased testicular testosterone production, so subsequent estrogen synthesis would also be low. Educational objective: The adrenal cortex produces estrogen precursors (eg, androstenedione, dehydroepiandrosterone [DHEA], DHEA sulfate), which are subsequently aromatized to estrogens in peripheral tissues. In men with hypogonadism (low testosterone), the resulting elevation in the estrogen/testosterone ratio can produce gynecomastia.

A 38-Year-Old Man Comes to the Office with Headaches, Loss