Laboratory Evaluation for Gynecomastia
Order a core hormonal panel including total testosterone, estradiol, LH, and hCG in all adult men presenting with gynecomastia, with additional tests guided by initial results and clinical context. 1, 2
Essential Initial Laboratory Tests
The following labs should be ordered in every patient with gynecomastia:
- Total testosterone (morning sample): Identifies hypogonadism as a contributing factor 1, 2, 3
- Estradiol (E2): Detects hyperestrogenism from various causes including obesity, liver disease, or tumors 1, 2, 4, 3
- Luteinizing hormone (LH): Distinguishes primary testicular failure (elevated LH) from secondary hypogonadism (low/normal LH) 1, 2, 3
- Human chorionic gonadotropin (hCG): Screens for testicular germ cell tumors 2, 3
- Prolactin: Identifies hyperprolactinemia, particularly if testosterone is low with low/normal LH 1, 2, 3
Additional Tests Based on Clinical Context
When testosterone is borderline or results are unclear:
- Sex hormone-binding globulin (SHBG): Allows calculation of free testosterone and identifies cases where elevated SHBG contributes to gynecomastia 1, 2, 4, 5
- Free testosterone: Either by equilibrium dialysis or calculated using total testosterone, SHBG, and albumin 1
When secondary hypogonadism is suspected (low testosterone with low/normal LH):
- Follicle-stimulating hormone (FSH): Further characterizes pituitary-gonadal axis dysfunction 1, 2, 3
When systemic disease is suspected:
- Thyroid-stimulating hormone (TSH): Hyperthyroidism can cause gynecomastia through increased SHBG expression 2, 5, 3
- Liver function tests (transaminases, bilirubin): Hepatic dysfunction causes hyperestrogenism and is found in 11% of gynecomastia cases 2, 4, 3
- Renal function tests (creatinine, urea): Chronic kidney disease can alter sex hormone metabolism 2, 3
When testicular tumor is suspected:
In specific populations:
- Dehydroepiandrosterone (DHEA): Consider when adrenal tumor is suspected 3
- Chromosomal analysis: Consider in young men with small testes and elevated FSH/LH to evaluate for Klinefelter syndrome 3
Clinical Context That Guides Testing
Anabolic steroid use (30% of cases):
Expect suppressed LH with elevated testosterone and estradiol 4
Obesity-related gynecomastia (47.5% of cases):
Typically shows elevated estradiol and/or decreased testosterone due to peripheral aromatization 4
Hepatogenic gynecomastia (11% of cases):
Characterized by hyperestrogenism with abnormal liver function tests 4
Elevated SHBG (7.5% of cases):
May occur with thyroid dysfunction or as an isolated finding 4, 5
Mandatory Endocrinology Referral
Refer all patients with elevated baseline estradiol measurements to an endocrinologist to determine the underlying hormonal cause. 1 The endocrinologist will assess for testosterone deficiency, abnormal LH levels, and hyperprolactinemia, and may order additional specialized testing. 1
Important Considerations
- Measure serum estradiol before starting testosterone therapy in all testosterone-deficient patients presenting with breast symptoms or gynecomastia 1
- Perform testicular ultrasound in addition to physical examination, as palpation has low sensitivity for detecting testicular tumors 2, 3
- In men with diabetes, morning total testosterone should be measured with a reliable assay as the primary baseline test, as diabetic men have lower testosterone levels than age-matched controls 1
- Proper investigation reveals underlying pathology in 45-50% of adult gynecomastia cases, making thorough laboratory evaluation essential 2, 3
Common Pitfalls to Avoid
- Do not assume medication-induced gynecomastia without completing the full diagnostic workup, as an apparent cause does not preclude underlying pathology 2
- Do not skip testicular ultrasound even if physical examination is normal, as tumor detection by palpation alone has low sensitivity 2
- Do not order imaging before laboratory evaluation is complete, as hormonal testing guides further management 1, 2