What is the recommended workup for gynecomastia?

Workup for Gynecomastia

Initial Clinical Assessment

Begin by determining whether imaging is needed through focused physical examination: palpate for a soft, rubbery, or firm mobile mass directly under the nipple to confirm true gynecomastia versus pseudogynecomastia (fat deposition only), and assess for suspicious features including unilateral presentation, hard or fixed texture, eccentric location, bloody nipple discharge, or skin/nipple retraction. 1

Key Physical Examination Elements

• Differentiate true glandular gynecomastia from pseudogynecomastia by palpating for firm subareolar tissue; pseudogynecomastia consists solely of adipose tissue without glandular proliferation 1, 2
• Assess body habitus and calculate BMI to identify obesity-related increased aromatase activity that converts androgens to estrogens 1
• Perform complete testicular examination to assess size, consistency, and presence of masses (Leydig or Sertoli cell tumors can autonomously produce estrogen) 1, 2
• Examine body hair patterns in androgen-dependent areas to evaluate virilization status and potential hypogonadism 1
• Check for visual field defects (bitemporal hemianopsia) suggesting pituitary disorders 1
• Assess prostate size and morphology to identify abnormalities 1

Critical History Components

• Document all medications, particularly anti-androgens, GnRH agonists (leuprolide, goserelin), digoxin, chemotherapeutic agents, and estrogen-containing compounds 2
• Inquire about alcohol consumption (suppresses testicular steroidogenesis and impairs hepatic steroid clearance) and cannabis use, especially if initiated during adolescence 3, 2
• Ask about anabolic-androgenic steroids, herbal products, and pesticide exposure 4
• Assess duration of symptoms: gynecomastia present <6 months is proliferative/edematous and potentially responsive to medical therapy, whereas >12 months indicates fibrosis requiring surgical intervention 2

Laboratory Workup Algorithm

Step 1: Baseline Hormonal Assessment

Measure morning total testosterone using a reliable assay as the primary baseline test in all patients with gynecomastia. 1

• Obtain luteinizing hormone (LH) and follicle-stimulating hormone (FSH) simultaneously to distinguish primary testicular failure (high LH/FSH, low testosterone) from secondary hypogonadism (low/normal LH/FSH, low testosterone) 3, 1
• Measure serum estradiol in all patients before considering any hormonal therapy 3, 1

Step 2: Additional Testing Based on Initial Results

If testosterone is low with low or normal LH, add prolactin measurement to exclude hyperprolactinemia as a contributing factor 3, 1

If total testosterone results are borderline, assess free testosterone either by equilibrium dialysis or calculated using total testosterone, SHBG, and albumin 1

Step 3: Mandatory Endocrinology Referral

All patients with elevated baseline estradiol measurements must be referred to endocrinology for comprehensive evaluation to determine the underlying hormonal cause, including assessment for adrenal tumors, testicular tumors, or adrenocortical carcinoma 1, 2

Imaging Decision Algorithm

When Imaging is NOT Needed

For patients with clinical findings clearly consistent with gynecomastia or pseudogynecomastia, no imaging is routinely recommended because unnecessary imaging leads to additional benign biopsies without improving outcomes 1

When Imaging IS Indicated

Proceed with imaging if differentiation between benign disease and breast cancer cannot be made clinically, or if presentation includes suspicious features: unilateral mass, hard texture, fixed position, eccentric location, bloody nipple discharge, or retracted skin/nipple 1

Age-Based Imaging Protocol

• Men younger than 25 years: Ultrasound is the initial recommended study; if suspicious features are found, follow with mammography or digital breast tomosynthesis 1
• Men 25 years and older: Mammography or digital breast tomosynthesis is the initial study (sensitivity 92-100%, specificity 90-96%, negative predictive value 99-100%); ultrasound follows if mammogram is indeterminate 1

Biopsy Technique When Tissue Diagnosis Required

Image-guided core needle biopsy is superior to fine-needle aspiration in sensitivity, specificity, and correct histological grading 1

• Use ultrasound guidance for lesions visible on ultrasound (preferred for patient comfort, real-time visualization, no radiation) 1
• Use stereotactic guidance for lesions only visible on mammography 1
• Place post-biopsy marker clip to confirm tissue sampling and aid correlation 1

Special Population Considerations

Adolescents

In boys under 20 years, 79% of gynecomastia is physiological pubertal gynecomastia; conduct limited laboratory workup unless symptoms are painful, rapidly growing, diameter >4 cm, or associated with testicular masses 4

Diabetic Men

Men with diabetes have lower serum testosterone than age-matched non-diabetic men; optimize glycemic control because uncontrolled diabetes further reduces testosterone levels 1

Screen for cardiovascular disease, peripheral neuropathy, and nephropathy as these influence choice of antihyperglycemic agents and overall management 1

Men Interested in Fertility

Perform reproductive health evaluation (testicular exam, FSH measurement) before initiating any treatment for gynecomastia 1

Common Pitfalls to Avoid

Do not assume gynecomastia in elderly patients is physiological: in patients over 26 years with new-onset gynecomastia, the likelihood of pathology is significantly increased 5

Do not rely solely on clinical criteria to exclude pathological causes: 39% of pathological gynecomastias lack the traditional "red flag" signs (pain, rapid growth, >4 cm diameter, testicular masses) that are commonly cited as triggers for investigation 4

Do not skip estradiol and testosterone measurement: even in seemingly benign presentations, these baseline hormonal measurements are essential because they identify the 41% of cases with pathological etiologies including hypogonadism, estrogen-secreting tumors, and medication effects 4