II. Causes: Physiologic in Newborn, Puberty, Older men

  1. Physiologic Mechanisms
    1. Estrogen excess
    2. Decreased androgen to Estrogen ratio
  2. Physiologic syndromes (25% of cases)
    1. Gynecomastia in the newborn
      1. Common response to maternal Estrogens
      2. Breast enlargement usually resolves in weeks
      3. May be accompanied by milk discharge (witch's milk)
    2. Benign Gynecomastia of Adolescence
      1. Frequently occurs in boys at mid to late Puberty
      2. Asymmetric Breast involvement and tenderness
      3. Resolves spontaneously within 1-2 years
    3. Familial Gynecomastia
      1. Common X-Linked recessive or dominant trait
      2. Limited Breast development during Puberty
      3. No further evaluation unless Hypogonadism present
    4. Gynecomastia of aging
      1. Common in men over age 65 years (40-72%)
      2. Decreased androgen to Estrogen ratio

III. Causes: Secondary (75% of cases)

  1. See Medication Causes of Gynecomastia (10-25% of cases)
  2. Idiopathic (25% of cases)
  3. Cirrhosis (8% of causes)
  4. Hypogonadism
    1. Klinefelter's Syndrome
    2. Kallman Syndrome
    3. Congenital anorchia
    4. 5a-reductase deficiency
    5. Androgen insensitivity
    6. Hemochromatosis
    7. Testicular Trauma (e.g. Testicular Torsion)
    8. Orchitis
  5. Chronic Renal Failure (1% of cases)
    1. Gynecomastia resolves with Renal Transplant (improves partially with Dialysis)
  6. Hyperthyroidism (2% of cases)
    1. Gynecomastia resolves within 2 months of treatment
  7. Obesity
    1. Causes both pseudogynecomastia and Gynecomastia
  8. Primary tumor
    1. Adrenal tumor
    2. Testicular Tumor (e.g. Leydig, Sertoli cell tumor)
    3. Prolactin-Secreting adenomas
  9. Ectopic Hormone production (hcg Secreting tumors)
    1. Lung Cancer
    2. Stomach Cancer
    3. Liver cancer
    4. Renal Cell Cancer
  10. Miscellaneous causes
    1. Familial Gynecomastia
    2. Human Immunodeficiency Virus (HIV)
    3. Ulcerative Colitis
    4. Cystic Fibrosis
    5. Lead Toxicity
    6. Phthalate Toxicity

IV. History: Red flags suggestive of non-physiologic Gynecomastia

  1. Persistent Gynecomastia for >2 years
  2. Nipple Discharge
  3. Breast Skin Changes
  4. Rapid Breast enlargement
  5. Firm Breast Mass
  6. Testicular Mass
  7. Weight loss

V. Signs

  1. Firm Breast swelling that is concentric centered under nipple and areola
  2. Bilateral involvement is most common (typically left sided when unilateral)

VI. Labs

  1. All patients
    1. Thyroid Stimulating Hormone (TSH)
    2. Serum Creatinine
    3. Serum AST and ALT
  2. Hormonally active tumor suspected
    1. Serum Beta hCG
    2. Serum Dehydroepiandrosterone
    3. Urinary 17-ketosteroid
  3. Hypogonadism
    1. Serum Testosterone (total and free)
    2. Serum Estradiol
    3. Follicle Stimulating Hormone (FSH)
    4. Luteinizing Hormone (LH)
  4. Other labs to consider
    1. Serum Prolactin

VII. Differential Diagnosis

  1. Pseudogynecomastia (fatty tissue predominance)
  2. Breast Cancer
  3. Lipoma
  4. Sebaceous Cyst
  5. Mastitis
  6. Dermoid Cyst
  7. Trauma-related swelling (fat necrosis or Hematoma)

VIII. Imaging

  1. Testicular Ultrasound indications
    1. Palpable Testicular Mass
    2. Gynecomastia size >5 cm
    3. Persistent Gynecomastia without obvious cause
    4. Serum HCG increased
  2. Breast Ultrasound (and possibly FNA) indications
    1. Breast Mass suspected
  3. MRI Brain
    1. Prolactinoma suspected (increased Serum Prolactin)

IX. Management

  1. Evaluate for underlying cause
    1. Physiologic cause is a diagnosis of exclusion
  2. Observation
    1. Indicated in most cases
    2. Routine follow-up on an every 6 month basis
  3. Medical management
    1. Indicated in symptomatic or distressing Gynecomastia
    2. Tamoxifen 10 mg daily for 3 months
    3. Raloxifene (Evista) 60 mg daily for 3-9 months
    4. Dihydrotestosterone
    5. Danazol
    6. Clomiphene (Clomid)
  4. Surgical management
    1. Indicated in prolonged, severe, refractory to medication cases

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