Careful history taking and physical examination (the relevant elements of which are presented in ) often reveal that patients actually are presenting with pseudogynecomastia, which means accumulation of subareolar fat without real proliferation of glandular tissue. Examination of these patients reveals diffuse breast enlargement without a subareolar palpable nodule. These patients do not need additional work-up and only require reassurance. Gynecomastia is usually bilateral,3,9
but patients may present with asymmetrical or unilateral findings. Palpation usually demonstrates a palpable, tender, firm, mobile, disclike mound of tissues1,4
that is not as hard as breast cancer and is located centrally under the nipple-areolar complex. When palpable masses are unilateral, hard, fixed, peripheral to the nipple, and associated with nipple discharge, skin changes, or lymphadenopathy, breast cancer should be suspected and thorough evaluation is recommended. Anthropometric measurements (eg, body mass index) may also be helpful because obesity can be associated with increased peripheral conversion of androgens to estrogens and is associated with a higher prevalence of gynecomastia.3,10
The presence of varicoceles has also been strongly associated with gynecomastia.9
A family history of gynecomastia has been elicited in 58% of patients with persistent pubertal gynecomastia. History may also reveal a clear and temporal association with a causative drug and obviate the need for extensive and costly evaluation. If the association with a drug is unclear, then evaluation is recommended. depicts the numerous medications that have been associated with gynecomastia. It has also been associated with the use of alcohol and illicit drugs, such as marijuana, heroin, methadone, and amphetamines.4
Several herbal supplements, particularly those containing phytoestrogen, may also cause gynecomastia.12
Elements of Patient History and Physical Examination Relevant for Evaluation of Gynecomastia
Drugs Associated With Gynecomastiaa
In one case series, history and physical examination detected a predisposing medical condition or causative medication in 83% of cases of gynecomastia.13
All breast cancer cases in that series presented with a dominant mass on clinical examination or other signs suggestive of malignancy.
After initial history and examination exclude pseudogynecomastia and other obvious explanatory conditions, mammography can differentiate true gynecomastia from a mass that requires tissue sampling to exclude malignancy. Mammography was found to be fairly accurate in distinguishing between malignant and benign male breast diseases and can substantially reduce the need for biopsies. The sensitivity and specificity of mammography for benign and malignant breast conditions exceed 90%; however, the positive predictive value for malignant conditions is low (55%) because of the low prevalence of malignancy in patients presenting with gynecomastia.14
Imaging of the scrotum is only recommended if palpable masses are present.
Laboratory investigations are pursued in cases of true gynecomastia without clear explanation. Liver, kidney, and thyroid function tests exclude the respective medical conditions. Hormonal testing measures levels of total and bioavailable testosterone, estradiol, prolactin, luteinizing hormone, and hCG, and its findings can direct toward pituitary, gonadal, and extragonadal endocrinopathies and neoplasms as seen in the stepwise algorithm depicted in the . If all testing is unrevealing, idiopathic gynecomastia is diagnosed.
FIGURE. Diagnostic algorithm for gynecomastia. CT = computed tomography; E2 = estradiol; hCG = human chorionic gonadotropin; LFT = liver function test; LH = luteinizing hormone; Prl = prolactin; T = testosterone; TSH = thyroid-stimulating hormone; US = ultrasonography. (more ...)
The differential diagnosis of a palpable breast mass in a male patient includes pseudogynecomastia, gynecomastia, breast cancer, and numerous other benign conditions. A review of all mammographic findings for men for a period of 5 years at Mayo Clinic in Jacksonville, FL, revealed a 1% rate of malignancy. Most cases were due to benign causes; of these, gynecomastia represented 62%, with other causes including lipomas, dermoid cysts, sebaceous cysts, lymphoplasmacytic inflammation, ductal ectasia, hematomas, and fat necrosis.13
In contrast, the differential diagnosis of gynecomastia per se, as demonstrated in a series of young adult patients with gynecomastia aged 19 through 29 years, includes idiopathic gynecomastia (58%), hypogonadism (25%), hyperprolactinemia (9%), chronic liver disease (4%), and drug-induced gynecomastia (4%).10
The frequency distribution of these etiologies is imprecise because of the small number of cases reported in the literature and may vary widely across publications and practice settings.