Most adolescents with gynecomastia are best managed by reassurance and observation11 (ALGORITHM),3 and no laboratory or radiographic studies are recommended in most cases. Exceptions would be gynecomastia that develops before the onset of puberty; evidence of undervirilization on physical examination; a testicular mass; or persistence of gynecomastia beyond the usual observation period of 12 to 18 months.11
ALGORITHM
Evaluating gynecomastia3
CT, computed tomography; hCG, human chorionic gonadotropin; LH, luteinizing hormone; MRI, magnetic resonance imaging; TSH, thyroid-stimulating hormone.
↑ = elevated; ↓ = lowered; ↔ = normal.
If findings on physical examination are consistent with a breast neoplasm, arrange for mammography immediately. The sensitivity and specificity of mammography for benign and malignant conditions exceed 90%.12 A biopsy may be necessary if uncertainty remains after imaging.
No specific tests are necessary when gynecomastia is clearly associated with intake of a medication known to be associated with the condition, especially if the history and examination are otherwise negative. A prompt regression of gynecomastia after discontinuation of the offending drug will confirm the diagnosis.
If the condition persists in an adolescent or adult and the cause is still unclear, perform renal function tests and measure levels of liver enzymes, early-morning serum human chorionic gonadotropin (hCG), LH, total testosterone, estradiol, TSH, and prolactin.
What lab results may mean. If the total testosterone level is borderline or low-normal (200-350 ng/dL), repeat the test and measure the free testosterone level.
If an elevated hCG level is found, repeat the testicular examination carefully and order ultrasonography. In the absence of a testicular tumor, consider an MRI of the brain and computed tomography (CT) of the abdomen and chest to help identify an extragonadal hCG-secreting tumor.
An elevated LH level and low testosterone level are diagnostic of primary testicular hypogonadism. A karyotype may be necessary in some individuals to diagnose Klinefelter syndrome. Elevated LH and testosterone levels are seen in patients with androgen insensitivity syndromes. These conditions are caused by abnormalities in the androgen receptor with a wide range of possible phenotypes, including ambiguous genitalia.
A low testosterone level with a low or normal LH level indicates secondary hypogonadism of hypothalamic or pituitary origin. An elevated prolactin level in such cases (as was seen in Mr. J.’s case) is usually due to a prolactin secreting pituitary adenoma.
Hereditary hemochromatosis is an important and often overlooked cause of hypogonadism. Obtain iron studies and ferritin levels in this setting.13 Unrecognized hemochromatosis may result in fibrosis and multiple organ failure.
Patients with secondary hypogonadism are best managed by a referral to an endocrinologist, as the potential list of causes is extensive.4,14,15
A low TSH level is consistent with thyrotoxicosis, which may result in increased levels of SHBG and altered metabolism of estrogens and androgens.16 Thus, about 10% of men with thyrotoxicosis present with gynecomastia and erectile dysfunction.16 If the estradiol level is elevated, a testicular ultrasound as well as an adrenal CT scan will help identify a neoplasm.
In a significant number of patients, the diagnostic tests are normal, leading to a diagnosis of idiopathic gynecomastia. In these cases, the alteration in androgen and estrogen levels can be subtle and intermittent.17 Continue surveillance and periodically reevaluate the patient.
Management of gynecomastia
Gynecomastia often results from transient hormonal imbalance and regresses spontaneously. Therefore, no specific treatment is necessary for neonatal, pubertal, or drug-induced gynecomastia. In other situations, prompt diagnosis and treatment are important to maximize the likelihood of successful medical therapy. It has been shown that fibrosis develops 6 to 12 months after the onset of gynecomastia, making it unlikely that medical treatments beyond that stage will result in significant regression of the breast enlargement.18 In such long-standing cases, surgical intervention with subcutaneous mastectomy or liposuction can be considered for patients who have significant psychological problems or esthetic issues. Indications for surgery also include continued growth and tenderness of breast tissue or malignancy.
Available medications include those aimed at decreasing estrogen production or estrogen effect on target breast tissue. Aromatase inhibitors such as testolactone, anastrozole, and letrozole can decrease the synthesis of estrogen by inhibiting aromatization of androgens. Although theoretically promising, results of the few controlled trials with aromatase inhibitors have been generally disappointing.19
Selective estrogen receptor modulators that alter the effect of estrogen on breast tissue are tamoxifen and raloxifene. Tamoxifen is not yet approved for treatment of gynecomastia, but has proven effective in randomized trials.20 At a dose of 20 mg/d for 3 or more months, tamoxifen resulted in complete regression of gynecomastia in 60% of patients and partial regression in 20% of patients.20 Tamoxifen also prevents gynecomastia after medial prostatectomy and treatment with the antiandrogen, bicalutamide.