What is the recommended lab workup for a patient presenting with gynecomastia?

Laboratory Workup for Gynecomastia

The recommended laboratory workup includes testosterone, estradiol, SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests, though this should be guided by clinical findings rather than ordered reflexively in all cases. 1, 2

When to Order Laboratory Testing

Laboratory investigation is warranted when:

• Gynecomastia presents in adulthood, as underlying pathology is identified in approximately 45-50% of adult cases 1, 2
• The clinical examination suggests an underlying hormonal disorder or systemic disease 1
• There is no obvious reversible cause (such as medication-induced gynecomastia) 2

Important caveat: Even when an apparent cause is identified (such as medication use), this should not preclude detailed investigation in adult patients 2

Core Laboratory Panel

The following tests form the foundation of the hormonal workup:

Primary Hormonal Assessment

• Serum testosterone - to identify hypogonadism 1, 2
• Serum estradiol - particularly important in testosterone-deficient patients and should be measured before starting testosterone therapy 1, 2
• SHBG (sex hormone-binding globulin) - to calculate free testosterone and assess the estrogen-to-androgen ratio 2
• LH (luteinizing hormone) - to differentiate primary from secondary hypogonadism 1, 2
• FSH (follicle-stimulating hormone) - to complete the gonadotropin assessment 1, 2

Secondary Hormonal and Systemic Assessment

• Prolactin - if testosterone is low with low/normal LH, as hyperprolactinemia can cause gynecomastia 1, 3, 2
• TSH (thyroid-stimulating hormone) - to rule out thyroid disease as an underlying cause 1, 2
• hCG (human chorionic gonadotropin) - to screen for testicular tumors 1, 2
• AFP (alpha-fetoprotein) - additional tumor marker for testicular malignancy 1, 2
• Liver function tests - as liver cirrhosis increases gynecomastia risk through altered hormone metabolism 3, 2
• Renal function tests - to identify renal dysfunction as a contributing factor 1, 2

Clinical Context Matters

Do not order all tests reflexively. The laboratory workup should be tailored based on:

• Age of presentation: Pubertal gynecomastia (affecting ~50% of mid-pubertal boys) typically resolves spontaneously within 24 months and rarely requires extensive workup 2
• Duration: Gynecomastia present since adolescence without recent changes may not warrant full investigation 1
• Associated symptoms: Pain, rapid growth, or signs of systemic disease warrant more comprehensive testing 1, 2

Critical Management Points Based on Lab Results

Elevated Estradiol

Mandatory endocrinology referral for all patients with elevated baseline estradiol measurements 1

Low Testosterone with Low/Normal LH

• Consider selective estrogen receptor modulator therapy 1
• Particularly relevant for patients wishing to preserve fertility 1
• Perform reproductive health evaluation (testicular exam, FSH measurement) before treatment 1

Elevated hCG or AFP

• Suggests testicular tumor requiring urgent urological evaluation 1, 2
• Physical examination has low sensitivity for detecting testicular tumors, so testicular ultrasound is recommended as part of the evaluation 2

Common Pitfalls to Avoid

• Do not skip testicular ultrasound: Physical examination alone has low sensitivity for detecting testicular tumors, which can present with gynecomastia 2
• Do not assume medication-induced gynecomastia excludes other pathology: Even with obvious medication causes (spironolactone, antiandrogens, etc.), adult patients warrant investigation 4, 2
• Do not order breast imaging routinely: Most men with clinical findings consistent with gynecomastia do not require imaging unless differentiation from breast cancer cannot be made clinically 1
• Measure estradiol before starting testosterone therapy in all testosterone-deficient patients presenting with breast symptoms, as testosterone can worsen gynecomastia through aromatization to estrogen 1, 4

Special Populations Requiring Enhanced Workup

• Klinefelter syndrome patients: Have significantly elevated risk (relative risk 24.7) and warrant comprehensive evaluation 3
• BRCA2 mutation carriers: Higher risk of male breast cancer necessitating lower threshold for imaging and biopsy 3
• Patients on androgen deprivation therapy: Gynecomastia incidence up to 80% on estrogen therapy; prophylactic measures should be considered 4