GYNECOMASTIA

Definition

• Gynecomastia = enlargement of the male breast from increased glandular tissue (not just adipose).
• Degree can vary from a small, tender subareolar disk to a full female-like breast.
• Differentiate:
  1. True gynecomastia (glandular proliferation)
  2. Pseudogynecomastia (excess adipose).
  3. Breast carcinoma in men.

Histopathology

• Stimulation of ducts, stroma:
  • Ducts: lengthening, branching, budding of new ducts (no alveoli).
  • Epithelial hyperplasia.
  • Increased, often hyalinized stromal tissue.
• Pathogenesis: Decreased androgen : estrogen ratio.

PHYSIOLOGIC (Benign) CAUSES

1. Neonatal
   • Maternal estrogen crosses placenta → slight male breast enlargement, sometimes “witch’s milk.”
   • Typically subsides within weeks.
2. Pubertal Gynecomastia
   • Occurs in ~50% of adolescent boys, often tender and bilateral.
   • Related to enhanced aromatization of androgens to estrogens while testosterone is still at subadult levels.
   • Most common single cause of gynecomastia.
   • Usually resolves spontaneously within 1–2 years in >90% of cases.
   • Persistence into adulthood is called persistent pubertal gynecomastia.
3. Involutional (Aging)
   • Mild breast enlargement in older men, likely due to decreasing testosterone production with age.

PATHOLOGIC CAUSES

1. Medication-Induced

• Common: many drugs alter androgen/estrogen balance or act directly on breast tissue.
• Examples:
  • Antiandrogens (flutamide, spironolactone)
  • Antibiotics (isoniazid, ketoconazole)
  • Oncologic agents (alkylators, imatinib)
  • Anti-ulcer meds (cimetidine)
  • Cardiovascular (digoxin, methyldopa)
  • Illicit drugs (marijuana, heroin)
  • Hormonal (estrogens, androgens, anabolic steroids, hCG)
  • Psychoactive (haloperidol, phenothiazines)
• Mechanisms:
  • Block testosterone receptors (e.g., spironolactone).
  • Enhance peripheral conversion of testosterone → estradiol.
  • Increase testosterone clearance.
  • Decrease gonadotropin secretion → low testosterone.

2. Hypogonadism

• Primary (testicular failure):
  • e.g., Klinefelter syndrome (47,XXY), infection, trauma, radiation.
  • Low testosterone → unopposed estrogen action.
• Secondary (pituitary failure):
  • e.g., Nonfunctioning pituitary macroadenoma → LH/FSH deficiency.
  • Prolactinomas → decreased LH/FSH, low T → but prolactin itself does not directly cause gynecomastia.

3. Chronic Liver Disease (Cirrhosis)

• Mechanisms:
  • Increased adrenal androgens.
  • Enhanced aromatization → higher estrogens.
  • Many cirrhotic patients on spironolactone.

4. Malnutrition / Cachexia

• Secondary Hypogonadism occurs (low LH/FSH) while adrenal estrogen production persists → low androgen : estrogen ratio → gynecomastia.

5. Tumors Producing hCG

• Testicular germ cell tumors (choriocarcinoma, embryonal carcinoma) → hypersecrete hCG → ↑testosterone but also ↑aromatase activity → more estrogens.
• Extragonadal hCG tumors (lung, stomach, kidney, liver).

6. Hyperthyroidism

• ~25% men with hyperthyroidism have gynecomastia.
  • Mechanisms:
    • Increased LH secretion → more T → more peripheral aromatization → more E.
    • Increased SHBG → lowers free T.

7. Estrogen-Secreting Tumors

• Adrenal tumors (often adrenocortical carcinomas) rarely produce high estrogen → gynecomastia.

8. Idiopathic Gynecomastia

• No identifiable cause found; possibly slight hormonal imbalance or sensitivity at breast tissue.