Gynaecomastia

Physiological Causes

Neonatal Gynaecomastia: Common due to maternal estrogen crossing the placenta; usually resolves spontaneously.
Pubertal Gynaecomastia: Occurs in up to 60% of boys during puberty due to hormonal fluctuations; typically resolves within 6 months to 2 years.
Age-Related (Senile) Gynaecomastia: Seen in older men due to increased adipose tissue converting androgens to estrogens, and declining testosterone levels.

Pathological Causes

Testicular Tumors: Can produce estrogens or hCG, leading to gynaecomastia; seminomas and Leydig cell tumors are common examples.
Liver Disease: Chronic liver disease can impair estrogen metabolism, leading to gynaecomastia; seen in conditions like cirrhosis.
Hyperthyroidism: Increased SHBG leads to higher estrogen levels relative to androgens, causing breast tissue proliferation.
Chronic Kidney Disease: Reduced testosterone and increased estradiol levels in men with CKD can lead to gynaecomastia.
Hypogonadism: Primary or secondary hypogonadism leads to low testosterone and a relative increase in estrogen activity.
Obesity: Increased aromatase activity in adipose tissue converts androgens to estrogens, contributing to gynaecomastia.
Klinefelter Syndrome: A genetic condition (47,XXY) associated with hypogonadism and gynaecomastia; patients may have small testes and are often infertile.
HIV: Antiretroviral therapy, particularly protease inhibitors, can cause gynaecomastia in patients with HIV.
Malnutrition and Refeeding: Starvation reduces testosterone levels, and refeeding increases insulin, leading to transient gynaecomastia.
Idiopathic Gynaecomastia: No identifiable cause, but may be due to individual sensitivity to normal circulating estrogens.

Drug-Induced Gynaecomastia

Spironolactone: A potassium-sparing diuretic with anti-androgen effects, leading to increased estrogen effects.
Anti-Androgens: Medications like flutamide, bicalutamide, and finasteride can lead to gynaecomastia by blocking testosterone action.
Anabolic Steroids: Exogenous androgens can suppress endogenous testosterone production, leading to estrogen dominance when discontinued.
Cimetidine: An H2 receptor antagonist with weak anti-androgen effects, previously used for peptic ulcer disease.
Antipsychotics: Drugs like risperidone and haloperidol can increase prolactin levels, indirectly causing gynaecomastia.
Antidepressants: Some SSRIs, particularly paroxetine, have been associated with gynaecomastia.
Calcium Channel Blockers: Medications like verapamil can cause gynaecomastia through unclear mechanisms.
Others: Include ketoconazole, digoxin, methadone, and some chemotherapeutic agents.

Symptom Onset and Duration

Onset: Rapid onset may suggest a testicular tumor or drug-induced gynaecomastia, while gradual onset is more common in physiological or chronic conditions.
Duration: Long-standing gynaecomastia is less likely to resolve spontaneously and may require surgical intervention.
Pain or Tenderness: Painful gynaecomastia is more often associated with rapid growth, such as during puberty or with certain medications.
Bilateral vs. Unilateral: Bilateral gynaecomastia is more common with systemic causes, while unilateral enlargement may require exclusion of a breast or testicular tumor.
Associated Symptoms: Inquire about symptoms like testicular pain, weight loss, or systemic symptoms like fever or night sweats, which could indicate an underlying malignancy or infection.
History of Weight Gain: Obesity can contribute to gynaecomastia and may mask underlying pathological causes.
Pubertal History: In adolescents, assess the timing of puberty and whether gynaecomastia is isolated or part of broader pubertal development.

Background

Past Medical History: Consider conditions such as liver disease, hyperthyroidism, kidney disease, and hypogonadism.
Drug History: Detailed review of current and past medications, including over-the-counter and herbal supplements, is crucial to identify potential drug-induced causes.
Family History: Ask about a family history of breast or testicular cancer, as well as genetic conditions like Klinefelter syndrome.
Social History: Consider alcohol use, recreational drug use (e.g., anabolic steroids), and lifestyle factors that might contribute to hormonal imbalances.
Sexual History: Evaluate for signs of hypogonadism, such as decreased libido, erectile dysfunction, or infertility.
Occupational History: Certain occupations may increase exposure to estrogens or estrogen-like substances (e.g., pesticides).
Psychological Impact: Assess the psychological and emotional impact of gynaecomastia on the patient, particularly in adolescents.
Breast Cancer Risk: Although rare, male breast cancer should be considered, especially in older patients or those with a strong family history.

Blood Tests

Serum Testosterone: Low levels suggest hypogonadism as a potential cause.
Serum Estradiol: Elevated levels may indicate a testicular tumor or other estrogen-producing conditions.
Serum hCG: Elevated in testicular tumors and some lung cancers; a crucial test if malignancy is suspected.
Serum LH and FSH: Elevated levels may suggest primary hypogonadism, while low levels could indicate secondary causes (e.g., pituitary tumors).
Liver Function Tests: To assess for liver disease, which can impair estrogen metabolism.
Thyroid Function Tests: Hyperthyroidism can increase SHBG and lead to relative estrogen excess.
Renal Function Tests: Chronic kidney disease can disrupt hormonal balance and contribute to gynaecomastia.
Prolactin Levels: Elevated in pituitary adenomas, which can cause gynaecomastia.
Karyotyping: Consider in suspected Klinefelter syndrome (47,XXY).
Serum SHBG: Elevated levels suggest a hormonal imbalance contributing to gynaecomastia.
Serum DHEAS: May be elevated in adrenal tumors.

Imaging and Other Tests

Testicular Ultrasound: First-line imaging for suspected testicular tumors.
Mammography/Ultrasound of the Breast: Indicated if there is suspicion of male breast cancer, particularly in unilateral gynaecomastia or when there is a hard mass.
Chest X-Ray: May reveal lung masses if a paraneoplastic syndrome is suspected.
Abdominal Ultrasound/CT: Consider if there is a suspicion of adrenal tumors or liver disease contributing to gynaecomastia.
MRI Pituitary: Indicated if there is a suspicion of a pituitary adenoma causing hypogonadism.
DEXA Scan: To assess bone mineral density in patients with long-standing hypogonadism.
Biopsy: Considered if imaging is inconclusive and there is a strong suspicion of malignancy.
Semen Analysis: In patients with suspected hypogonadism, to assess fertility status.

Endocrine & metabolic