Gynecomastia
Gynecomastia: Excerpt from The 5-Minute Pediatric Consult
Julie A. Boom, MD
Gynecomastia - BASICS
Gynecomastia - description
Any visible or palpable proliferation of breast glandular tissue, unilateral or bilateral, owing to an increase in estrogen action in relation to androgen action at the level of the breast
Gynecomastia - epidemiology
2 peaks in age distribution occur in the pediatric population:
Gynecomastia - incidence
Peak incidence for pubertal gynecomastia in males is at 14 years (range, 10–16 years).
Gynecomastia - prevalence
- Neonatal gynecomastia occurs in 60–90% of all newborns.
- ~40% of boys develop transient gynecomastia (measuring ≥0.5 cm) during puberty.
Gynecomastia - risk factors
Any situation that leads to an increase in the net effect of estrogen action relative to androgen action at the level of the breast may lead to gynecomastia. These situations could include:
- Increased estrogen concentration (endogenous or exogenous)
- Normal estrogen levels with decreased androgen concentrations
- Congenital reduction in estrogen receptors
- Pharmacologic blockade of androgen receptors
- Increased breast or peripheral tissue aromatase, which converts androgens to estrogens
- Elevated leptin levels may increase aromatase enzyme acticity, stimulate growth of mammary cells or increase breast receptor sensitivity to estrogen
- Testicular dysfunction
- High levels of 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.
Gynecomastia - etiology
- Physiologic:
- Neonatal: Transient palpable breast tissue developing in newborns owing to elevated estrogen levels in the fetoplacental unit. This condition resolves as estrogen levels decline.
- Pubertal: Benign transient gynecomastia occurring in otherwise healthy adolescent males. Breast tissue in pubertal gynecomastia measuring <4 cm in diameter has a high likelihood of spontaneous regression.
- Involutional: Breast enlargement occurs in old men.
- Pathologic:
- Drug-induced:
- Hormones: Estrogen, androgens, gonadotropins, anabolic steroids, growth hormone, antiandrogens, and cosmetics, foods, hair products, and herbal remedies that contain estrogen
- Anti-infective agents: Ethionamide, isoniazid, ketoconazole, metronidazole
- Antiulcer drugs: Cimetidine, ranitidine, omeprazole
- Chemotherapeutic agents: Alkylating agents, methotrexate, vinca alkaloids
- Cardiovascular agents: Amiodarone, captopril, digitoxin, diltiazem, enalapril, methyl-dopa, nifedipine, reserpine, spironolactone, verapamil
- Psychotropic agents: Diazepam, haloperidol, phenothiazines, tricyclic antidepressants
- Drugs of abuse: Alcohol, amphetamines, heroin, marijuana, methadone
- Miscellaneous: Metoclopramide, phenytoin, penicillamine, theophylline, gabapentin, clonidine and pregabalin
- Hypogonadism: Primary or secondary
- Tumors: Testicular, adrenal, ectopic tumors that produce human chorionic gonadotropin
- Chronic disease: Hyperthyroidism, renal failure, liver disease, malnutrition with refeeding, HIV infection
- Congenital disorders: Klinefelter syndrome, vanishing testes syndrome (also known as anorchism, gonadal agenesis, or testicular regression), androgen resistance syndromes, true hermaphroditism, excessive peripheral tissue aromatase
- Acquired testicular failure: Viral orchitis, trauma, granulomatous disease, or castration
- Chest wall trauma or intercostal nerve damage following surgery or herpes zoster
- Psychologic stress
- Spinal cord injury
Gynecomastia - DIAGNOSIS
- Do not mistake pseudogynecomastia (i.e., fatty enlargement of the breasts) for true gynecomastia.
- Do not overlook a potentially drug-related cause. Drug-related gynecomastia is usually reversible if diagnosed within 1 year of onset.
Gynecomastia - signs & symptoms
Gynecomastia - history
- Time of onset relative to puberty:
- Genitalia maturation develops at least 6 months before onset of breast development.
- Rate of progression:
- Rapidly enlarging, painful gynecomastia with acute onset is of more concern than long-standing enlargement.
- Drug exposures, including alcohol and substance abuse:
- Marijuana and heroin addiction may cause gynecomastia.
- Exposure to exogenous estrogen
- Symptoms suggestive of hyperthyroidism
- Symptoms suggestive of liver disease, such as cirrhosis:
- Liver disease may alter the estrogen:androgen ratio and thus cause gynecomastia. Damaged hepatic cells may lose the ability to inactivate estrogens. Impaired hepatic removal of androstenedione from the bloodstream provides more androstenedione for the peripheral conversion to estrogen. Liver disease may result in the elevation of sex-steroid binding globulin, which reduces circulating free testosterone.
- Symptoms suggestive of renal failure:
- Renal disease may alter the estrogen:androgen ratio and thus cause gynecomastia. Chronic uremia can cause direct testicular damage resulting in decreased plasma testosterone levels. Renal disease may also result in an increased luteinizing hormone level.
- Symptoms suggestive of neoplastic disease:
- In patients <10 years of age, consider pituitary, adrenal, or testicular tumor. Liver tumors may cause gynecomastia owing to increased aromatization of circulating adrenal androgens or by secretion of chorionic gonadotropins.
- Symptoms suggestive of hypogonadism, such as decreased libido, decreased erectile function, or infertility, may indicate an abnormal estrogen:androgen ratio.
Gynecomastia - physical exam
- Assess height, weight, growth velocity, and BP.
- Assess for malnourishment. Malnourishment may result in hepatic dysfunction causing higher estrogen-to-androgen ratio.
- Perform a complete breast examination:
- 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, discoid mound of tissue arising concentrically below the nipple and areola. Measure the diameter of the disc of glandular tissue. Asymmetry and tenderness are common.
- Pseudogynecomastia:
- If pseudogynecomastia (fatty enlargement of breasts) is present, no glandular disc will be palpable.
- Check for galactorrhea:
- Seen in association with drug ingestion and pituitary tumor
- Determine whether macrogynecomastia (disc diameter >5 cm with a secondary mound above the level of the breast) is present:
- Macrogynecomastia may be physiologic or pathologic and is unlikely to regress.
- Examine the thyroid gland for the presence of a goiter:
- Gynecomastia may be seen in hyperthyroidism.
- Determine the level of growth using Tanner staging:
- Gynecomastia is a physiologic process found in many males during early puberty. Perform a careful testicular examination with measurement of size. Consider Klinefelter syndrome if testes <3 cm in length or 8 mL in volume.
Gynecomastia - tests
Gynecomastia - lab
- None indicated for pubertal and neonatal gynecomastia
- Karyotype: To rule out Klinefelter syndrome.
- Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone (DHEA), and human chorionic gonadotropin (hCG):
- To determine whether hypogonadism, precocious puberty, testicular tumor, or adrenal tumor could be present. An isolated elevated estradiol level in an otherwise normal prepubertal boy may suggest direct or indirect exogenous estrogen exposure.
- Prolactin level
Gynecomastia - imaging
- None indicated for pubertal and neonatal gynecomastia
- Bone age (radiograph of the left hand and wrist):
- Elevated estrogen levels may accelerate skeletal maturation.
- Testicular ultrasound:
- To rule out testicular tumor, or elevated levels of human chorionic gonadotropin and estradiol, or finding of asymmetric testes on physical examination
- Chest radiograph with abdominal CT
- Adrenal CT or MRI:
- To rule out adrenal neoplasm, if estradiol elevated, dehydroepiandrosterone elevated, luteinizing hormone level decreased or normal, and testicular ultrasound normal
- Skull radiograph, brain MRI or CT:
- If pituitary tumor is suspected
Gynecomastia - differencial diagnosis
- Infectious:
- Neoplastic:
- Breast neoplasm
- Neurofibroma
- Lymphangioma
- Lipoma
- Neuroblastoma metastasis
- Trauma:
- Miscellaneous:
- Pseudogynecomastia: Excessive adipose tissue only; no discrete subareolar tissue
- Dermoid cyst
Gynecomastia - TREATMENT
Gynecomastia - special therapy
- Reassurance for patients with pubertal gynecomastia measuring <4 cm. Treatment guidelines are variable for gynecomastia measuring 4–5 cm. Surgical 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.
Gynecomastia - medication
- Generally, drug therapy should proceed under the guidance of an endocrinologist.
- Ralloxifene and tamoxifen (as unlabeled or investigational use) and testolactone (an aromatase inhibitor for which safety and efficacy in pediatric patients has not been established) have shown some benefit in adolescents with benign pubertal gynecomastia.
- If gynecomastia has been present for >1 year, pharmacologic therapy is of little benefit. After 1 year, regardless of the cause of gynecomastia, epithelial growth becomes less prominent whereas periductal fibrosis and hyalinization are more evident. Because of the increase in fibrosis, gynecomastia of longer duration is less amenable to medical treatment.
Gynecomastia - surgery
- Surgery is the therapy of choice for macrogynecomastia or persistent gynecomastia refractory to medical therapy.
- Surgical options include periareolar incision with adjunctive liposuction or glandular tissue removal through 2 incisions in the anterior axillary regions.
- Ultrasound-assisted liposuction has emerged as a new alternative surgical option.
Gynecomastia - FOLLOW UP
- Watch for signs of psychologic stress.
- Watch for symptoms of chronic disease and abnormal physical changes.
Gynecomastia - disposition
Gynecomastia - issues for referral
Consider surgical consultation in patients with >4 cm diameter of glandular tissue.
Gynecomastia - prognosis
- Overall, good
- Pubertal gynecomastia: 75% disappears spontaneously within 2 years, and 90% within 3 years.
- Neonatal gynecomastia usually resolves within the 1st year of life.
Gynecomastia - complications
- Physical pain, which may interfere with sports
- Psychologic stress
- Embarrassment
- Skin erosion of the nipple owing 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.
Gynecomastia - bibliography
- Felner EI, White PC. Prepubertal gynecomastia: Indirect exposure to estrogen cream. Pediatrics. 2000;105:e55.
- Glass AR. Gynecomastia. Endocrinol Metab Clin North Am. 1994;23:825–837.
- Lawrence SE, Faught KA, Vethamuthu J, et al. Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomasta. J Pediatr. 2004;145;71–76.
- McKiernan JF, Hull D. Breast development in the newborn. Arch Dis Child. 1981;56:525–529.
Gynecomastia - CODES
Gynecomastia - icd9
611.1 Hypertrophy of breast
Gynecomastia - FAQ
- Q: When should a patient with gynecomastia be referred to a specialist?
- A: If macrogynecomastia is present, if there is an abnormal hormonal workup 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 1st 2 weeks of life. The breast tissue then decreases to an average diameter of 10 mm until about 4–6 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 1st 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 5th to 7th day of life. Witch’s milk may persist for 1–7 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. <0.1% of all breast cancers occur in patients <20 years of age. Benign tumors, such as fibroadenomas, are much more common than malignant breast tumors.
- Q: Has the incidence of gynecomastia increased?
- A: As the prevalence of childhood and adolescent obesity has increased, the presence of pseudogynecomastia has also increased. If glandular tissue is not present, pseudogynecomastia should be treated with diet and exercise.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Gynecomastia
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Medical Books Excerpts
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- "Professional Guide to Signs & Symptoms (Fifth Edition)" (2006)
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- "The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter" (2000)
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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