A 34-year-old man comes to the office due to lack of sexual desire and erectile dysfunction for 3 months. Medical history is significant for opioid use disorder, for which he has been taking methadone for 2 years. The patient has gained 4.5 kg (10 lb) over the past 6 months. Vital signs are normal. BMI is 24.5 kg/m². On examination, the testes are small and soft. There is no gynecomastia. Visual field and thyroid examination findings are normal. Laboratory results are as follows: Which of the following is the most likely cause of this patient's symptoms?

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11ec25c8_d0c5_4a1c_bc81_69c4c3b62eb7_MD0003_00 This patient has secondary hypogonadism presenting with low libido, erectile dysfunction, and a low serum testosterone level. Secondary (ie, pituitary, hypothalamic) hypogonadism can be differentiated from primary hypogonadism by a low or inappropriately normal LH. In primary hypogonadism, the elevated gonadotropin (eg, LH) levels stimulate aromatization of estrogen precursors (eg, androstenedione) from the adrenal gland, leading to gynecomastia; in contrast, breast enlargement in secondary hypogonadism is less prominent. Secondary hypogonadism is a common adverse effect of opioids. Opioids suppress GnRH and LH secretion, leading to reduced Leydig cell testosterone synthesis, decreased spermatogenesis, and testicular atrophy. Additional manifestations can include depression, hot flashes, and osteoporosis. In women, menstrual irregularities are common. (Choice A) Klinefelter syndrome (47,XXY) is a common chromosomal disorder that causes primary hypogonadism. It manifests with small, firm testes; low serum testosterone; and elevated LH levels. Gynecomastia is often present. (Choice C) Pituitary mass lesions can cause secondary hypogonadism due to disruption of the hypophyseal portal vessels or direct injury to the LH-secreting gonadotrophs. However, these disorders typically cause a mild to moderate elevation in prolactin (20-200 ng/mL) due to disruption of dopaminergic neurons in the pituitary stalk. (Choice D) Rapid or severe weight loss (eg, anorexia nervosa) can cause secondary hypogonadism due to the suppression of GnRH secretion. Although overweight and obese patients may have mildly low testosterone levels, moderate weight gain in a patient with a normal BMI would not cause symptomatic hypogonadism. Educational objective: Secondary hypogonadism in men presents with low libido, erectile dysfunction, a low serum testosterone level, and a low or inappropriately normal LH level. Secondary hypogonadism is a common adverse effect of opioids, which suppress GnRH and LH secretion, leading to reduced Leydig cell testosterone synthesis. References: Testosterone deficiency in non-cancer opioid-treated patients. (http://www.ncbi.nlm.nih.gov/pubmed/30343356)

A 34-Year-Old Man Comes to the Office Due to Lack