• Neonatal: transient palpable breast tissue developing in newborns due to the high estrogen levels in the feto-placental unit. This condition resolves as estrogen levels decline.
• Pubertal: benign transient gynecomastia occurring in otherwise healthy adolescent males. Breast tissue in pubertal gynecomastia measuring less than 4 cm in diameter has a high likelihood of spontaneous regression.
• Involutional: breast enlargement occurring in elderly men.

• Drug-induced
  • Hormones: estrogen, androgens, gonadotropins, anabolic steroids, growth hormone, anti-androgens
  • Anti-infective agents: ethionamide, isoniazid, ketoconazole, metronidazole
  • Anti-ulcer drugs: cimetidine, ranitidine, omeprazole
  • Chemotherapeutic agents: alkylating agents, methotrexate, vinca alkaloids
  • Cardiovascular agents: amiodarone, captopril, digitoxin, diltiazem, enalapril, methyldopa, nifedipine, reserpine, spironolactone, verapamil
  • Psychotropic agents: diazepam, haloperidol, phenothiazines, tricyclic antidepressants
  • Drugs of abuse: alcohol, amphetamines, heroin, marijuana, methadone
  • Miscellaneous: metoclopramide, phenytoin, penicillamine, theophylline
• Hypogonadism: primary or secondary
• Tumors: testicular, adrenal, ectopic hCG-producing tumors
• Chronic disease: hyperthyroidism, renal failure, liver disease, malnutrition with refeeding, HIV infection
• Congenital disorders: Klinefelter syndrome, vanishing testes syndrome (also known as anorchia, gonadal agenesis, or testicular regression), androgen resistance syndromes, true hermaphroditism, excessive peripheral tissue aromatase
• Chest wall trauma
• Intercostal nerve damage following surgery or herpes zoster
• Psychological stress
• Spinal cord injury

• Increased estrogen concentration (endogenous or exogenous)
• Normal estrogen levels with decreased androgen concentrations
• Congenital reduction in estrogen receptors
• Pharmacological blockade of androgen receptors
• Increased breast or peripheral tissue aromatase (aromatase converts androgens to estrogens)
• Testicular dysfunction
• High serum gonadotropins or increased sex hormone binding globulin
• Elevated estrogen levels lead to proliferation of the ducts and surrounding mesenchymal tissue resulting in breast enlargement.
• Mechanism of drug-induced gynecomastia depends on drug type. Reversibility with drug withdrawal is the rule.

• Two peaks in age distribution occur in the pediatric population: in the neonatal period and in puberty.
• Neonatal gynecomastia occurs in 60% to 90% of all newborns
• 40% of boys develop transient gynecomastia (measuring >0.5 cm) during puberty
• Peak incidence at 14 years (range 10–16 years)
• No racial differences exist

• Physical pain, which may interfere with sports
• Psychological pain
• Embarrassment
• Skin erosion of the nipple due to rubbing against clothing
• Breast cancer: patients with Klinefelter syndrome have a 16-fold increased risk of breast cancer; other causes of gynecomastia are not associated with an increased risk of breast cancer

• Overall, good
• Pubertal gynecomastia: 75% disappears spontaneously within 2 years, and 90% within 3 years
• Neonatal gynecomastia usually resolves within the first year of life

• Breast abscess

• Breast neoplasm
• Neurofibroma
• Lymphangioma
• Lipoma
• Neuroblastoma metastasis

• Hematoma

• Pseudogynecomastia: excessive adipose tissue only; no discrete subareolar tissue
• Dermoid cyst

Question: Time of onset relative to puberty?
Significance: Genitalia development will be present for at least 6 months before onset of breast development.

Question: Rate of progression?
Significance: Rapidly enlarging, painful gynecomastias with acute onset is more concerning than long-standing enlargement.

Question: Drug exposures, including alcohol and substance abuse?
Significance: Marijuana and heroin addiction may cause gynecomastia.

• Symptoms suggestive of hyperthyroidism? 30% of young men with hyperthyroidism develop gynecomastia.
• Symptoms suggestive of liver disease?
• Symptoms suggestive of renal failure?
• Symptoms suggestive of neoplastic disease? In patients <10 yrs of age, consider pituitary adrenal or testicular tumor.
• Symptoms suggestive of hypogonadism, such as decreased libido, decreased erectile function, and infertility suggest abnormal estrogen to androgen ratio.

• Assess height, weight, growth velocity, and blood pressure.
• Assess for malnourishment. Malnourishment may result in hepatic dysfunction causing higher estrogen to androgen ratio.

Finding: Perform a complete breast examination
Significance: With patient in the supine position, grasp the breast between the thumb and forefinger and move digits toward the nipple: look for a firm, rubbery, mobile, disk-like mound of tissue arising concentrically below the nipple and areola. Measure the diameter of the disk of glandular tissue. Asymmetry and tenderness are common.

Finding: Pseudogynecomastia
Significance: If pseudogynecomastia (fatty enlargement of breasts) is present, no glandular disk will be palpable.

Finding: Check for galactorrhea
Significance: Seen with drug ingestion and pituitary tumor.

Finding: Determine if macrogynecomastia (disk diameter >5 cm with a secondary mound above the level of the breast) is present.
Significance: Macrogynecomastia may be physiological or pathological, and is unlikely to regress.

Finding: Examine the thyroid gland for the presence of a goiter
Significance: Gynecomastia seen in puberty and hyperthyroidism.

Finding: Determine the Tanner staging
Significance: Perform a careful testicular examination with measurement of size. Rule out Klinefelter syndrome if testes less than 3 cm in length or 8 mL in volume.

• None indicated for pubertal and neonatal gynecomastia.
• Renal, hepatic, and/or thyroid function tests if indicated.

Test: Karyotype
Significance: Klinefelter syndrome suspected.

Test: Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, testosterone, and hCG.
Significance: To determine if hypogonadism, precocious puberty, or macrogynecomastia present.

Test: Prolactin level
Significance: To rule out a prolactin-secreting pituitary tumor: if galactorrhea present or if decreased testosterone with decreased or normal LH.

Test: Testicular ultrasound
Significance: If elevated hCG, elevated estradiol or asymmetric testes on physical examination to rule out testicular tumor.

Test: Chest x-ray with abdominal CT
Significance: If hCG elevated and testicular ultrasound is normal to rule out extragonadal germ cell tumor or hCG-secreting nontrophoblastic neoplasm.

Test: Adrenal CT or MRI
Significance: To rule out adrenal neoplasm, if estradiol elevated, LH decreased or normal, and testicular ultrasound normal

Test: Skull x-ray, brain MRI or CT
Significance: If pituitary tumor is suspected.

• Reassurance for patients with pubertal gynecomastia measuring more than 4 cm. Treatment guidelines are variable for gynecomastia measuring 4 to 5 cm. Consultation in these patients should be considered.
• Re-examine at 3-month intervals
• Discontinue any drugs known to induce gynecomastia and follow-up in 1 month.
• Correct any underlying disorders (hyperthyroidism, malnutrition, etc.).

• The effectiveness of drugs in the treatment of gynecomastia has been difficult to evaluate due to the high prevalence of spontaneous regression
• Generally, drug therapy should proceed under the guidance of an endocrinologist
• Tamoxifen and testolactone have shown some benefit in adolescents with benign pubertal gynecomastia
• If gynecomastia has been present for more than 1 year, pharmacological therapy is of little benefit. After 1 year, regardless of the etiology of gynecomastia, epithelial growth becomes less prominent while periductal fibrosis and hyalinization are more evident. Because of the increase in fibrosis, gynecomastia of longer duration is less amenable to medical treatment.
• Surgery is the therapy of choice for macrogynecomastia, or persistent gynecomastia resistant to medical therapy
• Surgical options include periareolar incision with adjunctive liposuction or glandular tissue removal through two incisions in the anterior axillary regions

• Watch for signs of psychological stress
• Watch for symptoms of chronic disease, abnormal physical changes

• Mistaking pseudogynecomastia (i.e., fatty enlargement of the breasts) from true gynecomastia
• Overlooking a potentially drug-related etiology. Drug-related gynecomastia is usually reversible if diagnosed within 1 year of onset.

Q: When should a patient with gynecomastia be referred to a specialist?
A: If macrogynecomastia is present, if there is an abnormal hormonal work-up or an abnormal imaging study, or if there is an abnormal rate of progression

Q: For how long does neonatal gynecomastia persist?
A: Studies of healthy term infants have shown that the diameter of the breast tissue may actually increase during the first 2 weeks of life. The breast tissue then decreases to an average diameter of 10 mm until about 4 to 6 months of age. The breast tissue of female infants is generally larger and may persist longer than in males. Occasionally, the breast tissue will fail to regress and remain after the first year of life.

Q: Is it normal for a newborn baby’s breasts to secrete milk?
A: In the later stages of gestation, the developing breast undergoes a small amount of secretory activity. This produces the so-called “witch’s milk” that is expressed from the breasts of many full-term infants from the fifth to seventh day of life. Witch’s milk may persist for 1 to 7 weeks after birth. As fetal prolactin, placental estrogen, and progesterone decline, the breast tissue regresses.

Q: How is gynecomastia distinguished from breast cancer?
A: Breast cancer usually presents as a unilateral, eccentric hard or firm mass that is fixed to underlying tissues. Associated findings can include dimpling of the skin, retraction of the nipple, nipple discharge, or axillary lymphadenopathy. The incidence of breast cancer in the pediatric population is extremely low. Less than 0.1% of all breast cancers occur in patients less than 20 years of age. Benign tumors, such as fibroadenomas, are much more common than malignant breast tumors.