Gynecomastia

Etiology

The cause of most cases of gynecomastia is idiopathic. However, it has been proven to be associated with imbalances in the hormones estrogen and testosterone.[3][4]

This condition can appear transient at birth; this is thought to be due to an increased level of circulating maternal estrogens. Adolescent boys may also suffer from this condition due to an imbalance of estradiol and testosterone. In men older than 65 years, hypertrophy is thought to be due to a decline in testosterone levels and a shift in the ratio of testosterone to estrogen. In addition, older men are more likely to be taking medications that cause gynecomastia.

Underlying medical conditions such as breast cancer, obesity, hypogonadism, adrenal disease, thyroid disease, cirrhosis, renal failure, and malnutrition may contribute to this condition. Tumors of the adrenal glands, pituitary, lungs, and testes can impact hormonal changes resulting in imbalances and ultimately gynecomastia. Medications that have been shown to contribute to this condition include digoxin, thiazides, estrogens, phenothiazines, and theophylline. Use of certain recreational drugs including marijuana has also been associated with this disease. Chemotherapeutic drugs known to cause gynecomastia include methotrexate, alkylating agent, imatinib and vinca alkaloids. The most common drugs, however, have estrogen-like activity and include cimetidine, spironolactone, ketoconazole, and finasteride.

Epidemiology

Gynecomastia appears more within certain age groups of the male population. Newborns can suffer from this condition until their hormonal imbalances normalize. 

Adolescence hypertrophy occurs in boys beginning around age 13 and can last into early adulthood. The incidence of this condition again increases in men 65 years of age and older.

Pathophysiology

Gynecomastia is a result of enlargement of glandular breast tissue and adipose tissue. The hormone estrogen is responsible for the growth of glandular tissue, as well as the suppression of testosterone secretion. Estrogen suppresses luteinizing hormone, the hormone that is responsible for testicular secretion of testosterone. This process of hormonal imbalance leads to gynecomastia.

Pubertal gynecomastia is thought to be caused by a faster rise in estradiol than the rise of testosterone, causing an imbalance that normally regresses with time as testosterone increases.  

Medical conditions such as tumors of the adrenal, pituitary, and testes can cause increases in estrogen and decrease testosterone. These imbalances lead to hormonal imbalances resulting in gynecomastia in some males.[5][6][7]

Diseases of the liver, adrenal, thyroid, and testes can produce imbalances, along with the above-listed medications.  

Three types of gynecomastia, florid, fibrous and intermediate, have been identified. The type seen is usually related to the length of the condition. Florid gynecomastia is usually seen in early stages of the condition, four months or less. This type is characterized by an increase in ductal tissue and vascularity. Fibrous gynecomastia is seen after a year duration and is noted to have more stromal fibrosis and few ducts. After one year, intermediate gynecomastia is present which is thought to be a progression from florid to fibrous.

Histopathology

Typical features include

• Proliferation of the stroma and ductules
• Loose stroma seen in acute cases and dense stroma with few ductules seen in chronic cases

History and Physical

Important factors in the history from the patient include onset and duration of gynecomastia, associated symptoms, problems with certain organ systems such as liver, renal, adrenal, prostate, pulmonary, testicular or thyroid.

In some cases, the patient is found to have gynecomastia after undergoing an MRI or CT scan of the chest.

A careful review of family history, genetic history, medications, and recreational drug use should also be taken into consideration. A complete and thorough physical exam should be done. The head and neck exam should evaluate for any abnormal masses or thyroid abnormalities. Assess breasts for the nature of the tissue, masses, skin changes, nipple discharge, asymmetries, and tenderness, along with an axillary examination. The testes should be examined to look for asymmetry, masses, enlargement, or atrophy. Those males with feminizing characteristics should have endocrine testing and genetic testing. Any other positive findings on physical examination should be treated in an appropriate manner.

A condition called pseudogynecomastia has to be differentiated from gynecomastia. In the former, there is only circumferential fat in the subareolar area. The condition is often bilateral and in most cases, the deposit of fat remain of the same size for many years. Observation is prudent in such cases.

Evaluation

The history and physical will guide the remainder of the workup. Healthy males with no associated symptoms or physical abnormalities other than long-standing gynecomastia (more than 12 months) need no further workup. However, if symptoms are present, or if there are positive physical exam findings, these should be investigated first.

• Testicular masses require the following: testicular ultrasound, serum testosterone, luteinizing hormone (LH), estradiol, and DHEAS. If a thyroid mass is present the following are required: thyroid function tests, thyroid ultrasound (US), and endocrine evaluation.
• If a breast mass is palpated, the patient needs the following: mammography or US, biopsy, and possible surgical consultation.
• If hypogonadism is present, order the following: serum LH/follicle-stimulating hormone (FSH), estradiol, testosterone, DHEAS + karyotype +/- adrenal scan with the endocrine consult.
• If abdominal masses or hepatomegaly are present order the following: liver function tests, serum LH/FSH, estradiol, testosterone, DHEAS +/- abdominal CT, and an endocrine consultation.
• Renal and liver function tests should be ordered
• If hyperthyroidism is suspected, thyroid studies are in order.

Treatment / Management

Gynecomastia is classified into three grades depending on the amount of breast enlargement, skin excess, and ptosis. The treatment for each Grade differs depending on the amount of skin excess and ptosis.

• Grade I: Small enlargement, no skin excess
• Grade II: Moderate enlargement, no skin excess
• Grade IIb: Moderate enlargement with extra skin
• Grade III: Marked enlargement with extra skin

Treatment of this condition consists first of treating any underlying condition if this is contributing to the condition. If the condition has been present less than one year, and the history and physical are within normal limits, observation can be done with close follow-up. If an underlying medication is noted within history, this should be discontinued. If anything abnormal is found on physical exam, treatment depends on this finding.  If the underlying condition is treated, and the condition persists longer than a year, surgical treatment is suggested.[8][9][10](A1)

Medical therapy usually does not work in long-standing cases. Drugs like clomiphene, danazol and tamoxifen have been used in acute cases with varying success. However, these drugs also have adverse effects that are not well tolerated.

Patients with grade I or grade IIa can be treated with liposuction and surgical excision.

If the patient presents with grade IIb gynecomastia, open surgical excision with possible skin resection is indicated if a large amount of ptosis is present.[11]

Differential Diagnosis

Breast cancer

Lymphoma

Dermoid cyst

Prognosis

Gynecomastia is not life-threatening but it can cause significant emotional distress. Most cases take months or years to resolve. Further, men with Klinefelter syndrome also have a risk of developing male breast cancer. Young people with gynecomastia become depressed, isolated, refuse to participate in any activity that involves removing the shirt and have low self-esteem.