A 17-year-old boy is brought to the office due to bilateral breast enlargement. The patient first noticed it a few months ago and says that it is slightly painful. His parents are concerned that the breast tissue is gradually becoming more prominent. The patient is in special education classes due to a long history of learning disabilities. Height is at the 95th percentile, and weight is at the 25th percentile. Examination shows symmetric glandular tissue under both nipple-areolar complexes. The lungs are clear bilaterally, and the abdomen is soft without organomegaly. The testicles appear small and firm. Neurologic examination is unremarkable. Which of the following laboratory findings is most likely to be present in this patient?
Klinefelter syndrome | |
Pathogenesis |
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Clinical features |
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Laboratory findings |
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Breast enlargement in adolescent boys, or gynecomastia, is often physiologic during puberty. However, a pathologic cause should be suspected when the onset is outside of midpuberty (eg, Tanner 1 or 5), the tissue is rapidly enlarging, or other abnormalities on physical examination suggest a systemic disorder. In this case, the patient is age 17 but has small/firm testes, a sign of hypogonadism. His learning disability and tall height make Klinefelter syndrome, the most common cause of primary hypogonadism, the most likely diagnosis.
Patients with Klinefelter syndrome (47,XXY karyotype) typically have atrophied, hyalinized seminiferous tubules, resulting in low inhibin levels, and damaged Leydig cells, resulting in low testosterone levels. The lack of feedback inhibition results in excess gonadotropin production (ie, increased FSH and LH). Elevated FSH upregulates aromatase, the enzyme that converts androgens into estrogens, and therefore causes increased estradiol levels (Choice A). The increase in the estrogen/testosterone ratio is responsible for breast tissue growth.
Other phenotypic findings in patients with Klinefelter syndrome include tall stature and absent secondary sex characteristics (eg, deep voice, facial/pubic hair). Cognitive impairment is typical and characterized by learning disabilities and impaired social skills.
(Choice B) Increased androstenedione levels due to anabolic steroid use can cause irreversible gynecomastia and testicular atrophy. However, exogenous steroids would also cause acne, male pattern baldness, and aggressive behavior, none of which are seen in this patient. In addition, hastened epiphyseal closure (ie, reduced height potential) is characteristic with adolescent steroid use.
(Choice C) Testicular germ cell tumors produce excessive β-hCG, which can result in gynecomastia. However, a rapidly growing testicular mass, not small, firm testes, would be present on examination.
(Choice E) Hyperprolactinemia due to a prolactinoma can result in gynecomastia; high prolactin suppresses GnRH, which leads to reduced LH and testosterone secretion. However, this diagnosis is uncommon and often delayed in male patients, usually resulting in associated neurologic findings (eg, headache, vision changes) due to local tumor growth. In addition, hyperprolactinemia is not associated with learning disabilities or tall stature.
Educational objective:
Pathologic gynecomastia should be suspected in patients who also have signs of hypogonadism (eg, small/firm testes, absent pubic hair). Klinefelter syndrome (47,XXY) is the most common cause of primary hypogonadism, and patients have low testosterone, elevated gonadotropin (FSH, LH), and relatively increased estradiol levels.