topic review Gynecomastia,Brian Lee, MD, 2nd Yr Internal Medicine Resident, Siriraj Hospital,Definition of Gynecomastia,True gynecomastia:,Pseudogynecomastia / lipomastia:,benign enlargement of male breast due to proliferation glandular components Rubbery or firm mound of tissue that is concentric with the nipple-areolar complex is felt,fat deposition without glandular proliferation,Braunstein G. N Engl J Med 2007;357:1229-1237,Differentiation of Gynecomastia from Pseudogynecomastia and Other Disorders by Physical Examination,Prevalence,Three peaks Infancy: 60-90% . Due to high maternal estrogen. Normally regresses over 2-3 week period. Adolescence: 48-64% . Peak at 13-14 yr. Normally regresses in 18 mo. Older men: 24-65%. Highest prevalence in 50-80 yr.,Etiologies,Drugs: 10-25% Idiopathic: 25% Persistent pubertal gynecomastia: 25% Cirrhosis or malnutrition: 8% Primary hypogonadism: 8% Testicular tumors: 3% Secondary Hypogonadism: 2% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1%,Harrisons Principles of Internal Medicine, 17th Ed.,Kronenberg: Williams Textbook of Endocrinology, 11th ed.,Kronenberg: Williams Textbook of Endocrinology, 11th ed.,Kronenberg: Williams Textbook of Endocrinology, 11th ed.,Braunstein G. N Engl J Med 1993;328:490-495,Glandular and Peripheral Origins and Interrelations of Testosterone, Androstenedione, Estrone, and Estradiol,Gynecomastia,How to approach,Braunstein G. N Engl J Med 2007;357:1229-1237,Interpretation of Serum Hormone Levels and Recommendations for Further Evaluation of Patients with Gynecomastia,Specific pathogeneses,Drug-induced gyncomastia,Spironolactone: inc. aromatization of T to E2, decrease T production by testes, displace T from SHBG inc. clearance rate, bind to androgen rct, displace or prevent binding of T or DHT to rct. Low dose 25-50 mg/d: 10% compared with 3% in placebo group Almost all pts using =100 mg/d CCB: nifedipine highest frequency; diltiazem lowest. H2RA or PPI: Cimetidine ranitidine omeprazole,Drug-induced gynecomastia,AIDS patients using HAART Usually due to increase in adipose tissue (pseudomgynecomastia), part of fat redistribution syndrome (lipodystrophy) Efavirenz: estrogen-like effect Co-existing hypogonadism,Specific Pathogeneses,Puberty Boys who develop gynecomastia have an transient increase in estradiol concentration at onset of puberty During puberty, the serum estradiol concentrations rise to adult levels before the testosterone concentration. Adult men Multifactorial including increase in body fat, decrease in testosterone by testes and increase in LH, and likely polypharmacy.,Specific Pathogeneses,Cirrhosis Increase androstenedione and its conversion to estrone and estradiol. Elevated SHBG levels, reducing free testosterone Malnutrition Decrease androgen with normal estrogen production. Refeeding mimics normal puberty hormone pattern.,Specific Pathogeneses,Male hypogonadism Primary hypogonadism can be associated with Klinefelters or enzymatic defect in the testosterone biosynthetic pathway, or testicular trauma, infection, infiltrative disorders, vascular insufficiency or aging. Net effect is decrease in testosterone with increase in estradiol. Secondary hypogonadism due to hypothalamic or pituitary abnormality result in low testosterone and increase in estrogen precursors. Testicular neoplasm Germ cell tumor may present with gynecomastia (2.5-6% of patients) which is a poor prognosis. Leydig cell tumor may present with gynecomastia (20-30%) These neoplasms produce estrogen/androgen inbalances.,Specific Pathogeneses,Hyperthyroidism due to Graves disease As many as 25-40% have gynecomastia due to increase of SHBG and enhanced aromatization Chronic renal failure and dialysis 50% develop gynecomastia due to Leydig cell dysfunction resulting in low testosterone Feminizing adrenocortical tumors Rare malignant tumors that have gynecomastia (98%), palpable tumor(58%), and testicular atrophy(50%),Treatment Options,Watchful Waiting Medications Surgery,Treatments,Watchful waiting In healthy adolescent with normal physical exam, including genitalia, reevaluate in 6 months Gynecomastia attributed to a medication should be stopped and patient reassessed after stopping medication Regression will occur in 85% of patients with gynecomastia due to various causes,Treatments,Medications May be indicated in patients with persistent gynecomastia, eg. Later puberty with severe pain, tenderness, psychosocial issues of embarrasment. Three types of medications Androgens, SERMS, aromatase inhibitors Limited clinical data None are FDA approved for gynecomastia,Androgens,Testosterone Improves gynecomastia in hypogonadism No use in eugonadal men May worsen gynecomastia due to aromatization of testosterone to estradiol Dihydrotestosterone (nonaromatizable androgen) Idiopathic gynecomastia: decrease in breast volume in 75% of patients, resolution in 25%. No noted side effects; decrease in tenderness within 1-2 weeks. Danazol Significantly reduced breast tenderness and size Use limted by side effects: edema, weight gain, acne, nausea and muscle cramps,