What is the approach to a patient with gynecomastia?

Approach to a Patient with Gynecomastia

The initial approach to gynecomastia requires clinical differentiation from pseudogynecomastia and breast cancer through physical examination, followed by a targeted medication review and hormonal evaluation only when clinically indicated, with imaging reserved for suspicious presentations. 1

Step 1: Clinical Examination and Differentiation

Physical Examination Technique

• Palpate for true gynecomastia: a soft, rubbery, or firm mobile mass directly under the nipple (often painful if present <6 months), which is bilateral in approximately 50% of cases 1
• Distinguish from pseudogynecomastia: fatty tissue deposition without glandular enlargement, particularly in patients with elevated BMI 1
• Perform complete testicular examination assessing size, consistency, masses, and varicocele presence 1
• Calculate BMI or measure waist circumference to assess for underlying systemic conditions 1
• Examine body hair patterns in androgen-dependent areas to evaluate virilization status and potential hypogonadism 1
• Assess prostate size and morphology for abnormalities 1
• Check visual fields for bitemporal hemianopsia suggesting pituitary disorders 1

Rule Out Malignancy

• Male breast cancer is rare (<1% of all breast cancers, median age 63 years) but must be excluded, especially in older men with suspicious features 1
• Suspicious features include: hard, fixed masses; eccentric location; skin changes; nipple discharge; or lymphadenopathy 1

Step 2: Medication and Substance Review

High-Risk Medications to Identify

• Spironolactone (switch to eplerenone if gynecomastia develops, as it has significantly lower risk) 2
• Antiandrogens: bicalutamide, flutamide, nilutamide (incidence up to 80% with estrogen therapy for prostate cancer) 2
• 5-alpha reductase inhibitors: finasteride, dutasteride 2
• Testosterone or anabolic steroids (conversion to estrogens) 2
• GnRH agonists/antagonists 2
• Ketoconazole 2
• Hyperprolactinemia-inducing drugs 2
• Glucocorticoids 2
• Digoxin (contradictory evidence) 2
• Chronic cannabis use, especially when started young 2

Temporal Relationship

• Assess timing between medication initiation and gynecomastia onset 3
• Discontinuing contributing medications is the mainstay of treatment 4

Step 3: Assess for Underlying Medical Conditions

Systemic Diseases to Evaluate

• Liver cirrhosis 3
• Renal insufficiency 4
• Hypogonadism 3
• Thyroid disease 3
• Hyperprolactinemia 3
• Klinefelter syndrome (relative risk 24.7) 3

Neoplastic Causes

• Adrenal tumors or adrenocortical carcinomas (direct estrogen secretion) 3
• Testicular masses (identified on examination) 1

Step 4: Laboratory Evaluation (Selective, Not Routine)

When to Order Labs

• Refer to endocrinology if elevated baseline estradiol is found 1
• Order hormonal workup for: progressive disease, suspected pathology, or patients >26 years with new-onset gynecomastia 5

Specific Tests

• Serum testosterone levels 1
• Serum estradiol (measure before starting testosterone therapy in patients with breast symptoms) 1
• Luteinizing hormone (LH) 1
• Prolactin (if testosterone is low with low/normal LH) 1

Step 5: Imaging Decision Algorithm

When Imaging is NOT Needed

• Most men with clinical findings consistent with gynecomastia or pseudogynecomastia require no imaging 1
• Clear benign presentation on examination 1

When Imaging IS Indicated

• Cannot differentiate benign disease from breast cancer clinically 1
• Suspicious presentation 1
• Indeterminate breast masses 1

Imaging Modality Selection

For men <25 years:

• Ultrasound as initial study 1
• Follow with mammography/digital breast tomosynthesis (DBT) if suspicious features found 1

For men ≥25 years:

• Mammography or DBT as initial study (sensitivity 92-100%, specificity 90-96%, NPV 99-100%) 1
• Ultrasound if mammogram indeterminate or suspicious 1

Common Pitfall

• Unnecessary imaging in clear gynecomastia cases leads to additional unnecessary benign biopsies 1, 3

Step 6: Management Based on Etiology and Duration

Physiologic Gynecomastia (Pubertal, Neonatal, Senescent)

• Reassurance and observation: spontaneous resolution occurs in up to 50% of cases 1
• Pubertal gynecomastia resolves spontaneously in the majority of adolescents 6

Persistent Painful Gynecomastia

• Monitor testosterone-deficient patients: symptoms sometimes abate on testosterone treatment 1
• Consider estrogen receptor modulators for testosterone-deficient patients with low/low-normal LH 1
• Medical therapy shows good results for short-term trials in adults with persistent painful gynecomastia 6

Preventive Measures for High-Risk Patients

• For patients starting antiandrogen therapy: administer breast irradiation (8-15 Gy in 1-3 fractions) 1-2 weeks before initiation to prevent painful gynecomastia 1

Chronic/Fibrotic Gynecomastia

• Gynecomastia persisting beyond 12 months often becomes fibrotic and less responsive to medical therapy 3
• Surgical removal is treatment of choice for chronic, bothersome gynecomastia 6

Step 7: Special Considerations

Fertility Concerns

• Perform reproductive health evaluation prior to treatment in men interested in fertility 1

Genetic Risk Factors

• BRCA2 mutation carriers have significantly higher risk of male breast cancer and gynecomastia 3
• Family history of male breast disorders increases risk 3

Biopsy Technique (If Needed)

• Core needle biopsy is superior to fine-needle aspiration for sensitivity, specificity, and histological grading 1
• Ultrasound guidance preferred for visible lesions (real-time visualization, no radiation) 1
• Stereotactic guidance for mammography-only visible lesions 1
• Place post-biopsy marker clip to confirm sampling 1