A 29-year-old man is evaluated for gynecomastia present for the past 2 years. He also has fatigue, low libido, weight gain, and erectile dysfunction. He and his wife have been attempting to become pregnant for the past 12 months without success. He has no other symptoms and takes no medications or supplements.
Vital signs are normal. BMI is 27. Muscle mass is decreased, and axillary and pubic hair is scant. Breast palpation demonstrates subareolar glandular tissue approximately 1 cm in diameter in the left breast and 0.8 cm in the right breast. Testicular examination reveals decreased testicular volume.
Which of the following is the most appropriate diagnostic test?
A. Breast biopsy
B. 8 AM Serum testosterone
D. Testicular ultrasonography
E. Thyroid-stimulating hormone
MKSAP Answer and Critique
The correct answer is B. 8 AM Serum testosterone. This content is available to MKSAP 19 subscribers as Question 29 in the Endocrinology and Metabolism section. More information about MKSAP is available online.
The most appropriate diagnostic test is measurement of 8 AM serum testosterone (Option B). In addition to gynecomastia (evidenced by palpation of subareolar glandular tissue >0.5 cm in diameter), this patient displays clinical features of hypogonadism, including fatigue, low libido, erectile dysfunction, infertility, and decreased muscle mass. A morning testosterone test is the next step to confirm that hypogonadism is the etiology of his gynecomastia. In addition to hypogonadism, gynecomastia may be caused by substance use disorders, malnutrition, cirrhosis, testicular germ cell tumors, hyperthyroidism, and chronic kidney disease. Gynecomastia also may result from the use of medications that affect androgen or estrogen levels, such as spironolactone, cimetidine, ketoconazole, estrogens, antiandrogens, 5α-reductase inhibitors, and protease inhibitors, as well as over-the-counter supplements, such as lavender oil and tea tree oil. A thorough medication/supplement history should be taken in all patients with gynecomastia. When the etiology of gynecomastia is not clinically apparent, the initial laboratory evaluation includes measurement of human chorionic gonadotropin (hCG), luteinizing hormone, estradiol, and 8 AM fasting testosterone. The etiology of gynecomastia in this patient is apparent; an early-morning testosterone level will establish the diagnosis.
The patient's physical examination is consistent with gynecomastia rather than breast cancer. Male breast cancer would be suspected if a unilateral, nontender, fixed breast mass were present with nipple involvement or retraction, overlying skin changes or ulceration, and axillary lymphadenopathy. A breast biopsy (Option A) is performed only if a suspicious breast mass was confirmed on imaging. Mammography (Option C) is only indicated if physical examination findings are concerning for breast cancer.
Testicular germ cell tumors can cause gynecomastia. When the etiology of gynecomastia is not apparent, evaluation of hCG as well as a testicular examination for testicular masses should be performed. Testicular ultrasonography (Option D) is indicated if hCG is elevated or a testicular mass is palpated on physical examination. In this case, the patient has an apparent cause of gynecomastia (hypogonadism) and no testicular mass on examination. Therefore, testicular ultrasonography is not indicated.
The patient has classic symptoms of hypogonadism and does not have clinical features of hyperthyroidism (palpitations, tachycardia, tremors, sweating, weight loss, hyperdefecation); therefore, a thyroid-stimulating hormone level (Option E) does not need to be obtained.
- When the etiology of gynecomastia is not clinically apparent, the initial laboratory evaluation includes measurement of human chorionic gonadotropin, luteinizing hormone, estradiol, and 8 AM fasting testosterone.