Gynaecomastia evaluation and management

Dr sumer yadav

Definition

Gynaecomastia is an enlargement of the male breast, secondary to proliferation of both epithelial and stromal components . Gynaecomastia term is derived from Greek words gynae (female) and mastos(breast). Enlargement of the male breast looking like women breast

Prevalence• Gynaecomestia is a common

condition . In various studies its prevalence is found to be about 36% in healthy young adult males , 57% in healthy old males.

• The neonatal period - In neonates it is estimated that 60 to 90% of infants have transient gynaecomastia due to transplacental transfer of maternal estrogens……...

........This stimulus for breast growth ceases as the estrogens are cleared from the neonatal circulation and the breast tissue gradually regresses over a 2 to 3 week period . It usually regresses completely by the end of first year.

Puberty• Transient gynaecomastia may occur

in up to 60% boys. It may first appear at as early as 10 years of age, with a peak onset between 13 to 14 years, followed by an involution that is generally complete by 16 to 17 years

In old age

• The incidence of gynaecomastia increase in advancing age , with the highest prevalence found at the age of 50 to 80 years range. Ageing is associated with progressive testicular dysfunction with reduction in serum testosterone level and, in some cases, elevated Luteinising hormone (LH).

Pathophysiology• Gynaecomastia results from an

altered estrogen – androgen balance , in favor of estrogen, or increase breast sensitivity to a normal circulating estrogen level. The imbalance is between the stimulatory effect of estrogen and the inhibitory effect of androgen.

Estrogens induced ductal epithelial hyperplasia , ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity . The histologic picture is similar in male and female breast tissue after exposure to estrogen.

• Estrogen production in males is mainly from the peripheral conversion of androgens ( testosterone and androstenedione ) through the action of the enzyme aromatase, mainly in muscles, skin and adipose tissue in the form of estrone and estradiol.

• The normal production ratio of testosterone to estrogen in males is approximately 100:1. But in ciculation it is 300:1.

Histopathology• Characteristic findings include

proliferation of ductules and stroma (consisting of connective tissue elements such as fibroblasts, collagen and myofibroblasts) and occasional acini. Gynaecomastia of short duration consists of a prominent ductular component with loose stroma. Long standing gynaecomastia consists of dense stroma with few ductules.

Causes Physiological Gynaecomastia • New born• Adolescence• Aging

Pathological Gynaecomastia Deficient production or action of

testosterone • Congenital anorchia• Androgen resistance (testicular

feminization and reifenstein syndrome

• Defect of testosterone synthesis …….

…..

• Klinefeltar syndrome

• Viral orchitis

• Trauma

• Castration

• Neurological and granulomatous diseases

• Renal failure

….

Increase estrogen production

Increased estrogen secretion

• Testicular tumor

• True hermaphroditism

• Carcinoma of the lungs and other tumor producing HCG

……….

….... Increase substrate for extra glandular

aromatase

• Adrenal disease • Liver disease (cirrhosis of the liver)• Malnutrition• Hyperthyroidism

Increase in extra glandular aromatase ………

Drugs• Estrogens

• Drugs that enhances estrogen secretions ( gonadotropins , clomiphen )

• Inhibitors of testosterone synthesis or action

I. Ketoconazole

II. Metronidazole

III. Alkylating agent

IV. Cisplatin

V. Spironolactone

VI. Cimetidine

VII. Flutamide

• Unknown mechanism

Busulfan Isoniazide Methyldopa Tricyclic antidepressant Penicillamine Diazepam Omeprazole Growth hormone

Calcium channel blocker Metoclopramide Angiotensin converting

enzyme inhibitors Heroin Marijuana

• Idiopathic

• Most patients of gynaecomastia are asymptomatic

• It may be an incidental finding during routine physical examination

• The main presenting symptom in patient with recent onset of gynaecomastia is usually breast or nipple pain and tenderness and those who present late usually complain of breast enlargement

Clinical features and diagnostic evaluation

Physical examination

• Perform a thorough examination of breast , noting their size and consistency. Also determine the presence of any nipple discharge or axillary lymphadinopathy.

• Differentiate between the true gynaecomastia and pseudo gynaecomastia / lipomastia.

• Gynaecomastia can be detected when the size of glandular tissue exceeds 0.5 cm in diameter. ………..

……

• Examination of the testicles , noting there size and consistency. Carefully look for any nodules or asymmetry

• Note signs of feminization, including typical body hair distribution and eunuchoid habitus

• Check for any stigmata of chronic liver diseases , thyroid disease or renal disease

Simon’s classification of gynaecomastia

Group 1• Minor but visible breast enlargement without

skin redundancy Group 2A• Moderate breast enlargement without skin

redundancyGroup 2B• Moderate breast enlargement with minor skin

redundancy Group 3• Gross breast enlargement with skin redundancy

that looks like a pendulous female breast

Investigations• Patients with physiological

gynaecomastia do not require further evaluation

• Further evaluation is necessary in patients with the following

I. Breast size greater then 5 cm (macromastia)

II. A lump that is tender , of recent onset , progressive or of unknown duration

III. Sign of malignancy

Serum chemistry

LFT Thyroid function test Renal function test Total or free testosterone level ,

serum prolactine , LH , oestradiol , dehydroepiandrostenone sulphate levels to evaluate a patient with possible feminization syndrome

Urinary 17 ketosteroid Beta HCG

Imaging Studies USG breast

Mammography

Testicular ultra sonography and thermography

CT Scan for adrenal gland

MRI for pituitary gland

Differential Diagnosis

• Pseudo gynaecomastia

• Breast cancer

• Dermoid cyst

• Haematoma

• Lipoma

• Lymphangioma

• Neurofibroma

Treatment• Generally no treatment is required for

physiological gynaecomastia

• A major factor that should influence the initial choice of therapy is the duration of gynaecomastia

• If the patient is at the pubertal age, and has an otherwise normal general physical and testicular examination , he probably has transient or persistent gynaecomastia

….….…

Reexamination at six month intervals should determine whether the condition is transient or persistent . At this time , medical or surgical therapy should be considered. If the patient is on a drug causing gynaecomastia , this should be stopped or changed to another medication if possible , and reexamine the patient after one month .

If the drug was the cause , then reduction in breast pain and tenderness should occur during that time . Similarly , breast enlargement following cytotoxic chemotherapy may also resolve spontaneously.

Treatment of hyperthyroidism and surgical removal of testicular , adrenal , or other causative tumor may lead to regression in patients with hypogonadism , treatment with testosterone may produce regression by providing androgen and suppressing LH stimulated oestradiol secretion.

Medical treatment • As gynaecomastia has high frequency

of spontaneous regression , the decision of when to treat is often difficult. Trials of medical therapy should be limited to only six months , due to limited experience and unknown long term side effects of the drugs . When gynaecomastia has been present for more then 2 years , medical therapy is unlikely to be effective , and surgery may be the only useful treatment

• Options include androgens (testosterone , danazole) , anti estrogen( clomiphene , tamoxifen) and aromatase inhibitors

• Androgen

Testosterone – it is a male sex hormone given in dose of 200 to 300 mg IM

Danazole – it is synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action doses are 200 mg bd for 3 months. It is the only drug liscenced for the treatment of gynaecomastia in UK.

• Antiestrogen Clomiphene citrate – it stimulates

release of pitutory gonadotropin 50 to 100 mg QID for 6 months.

Tamoxifen – compititive binds to estrogen receptor , producing a nuclear complex that inhibits estrogen effects. Dose 10 to 20 mg BD

• Aromatase inhibitors

Testolactone – it is synthetic peripheral aromatase inhibitors . It blocks production of estradiol and estrone from testosterone. Dose 150 mg TDS for 6 months

Surgery Surgical treatment is indicated in patients

in whom the gynaecomastia causes distress and psychological trauma , when there is no underlying treatable condition and when hormonal treatment is failed, then operative treatment is indicated

Surgical treatment includes • Open subcutaneous mastectomy • Endoscopic assisted subcutaneous

mastectomy• Liposuction assisted mastectomy• Ultra sound assisted liposuction

• Open subcutaneous mastectomy – this is most commonly performed procedure in gynaecomastia. This is carried out through circumareolarincision between 3 and 9 o clock position. The length of incision varies

• Endoscopic assisted subcutaneous mastectomy – with this technique it is possible to excise the glandular breast tissue through very small distant incision. Thus avoiding breast and areolar scar

• Liposuction assisted mastectomy

– this is most popular method used to correct pseudo gynaecomastia. Advantage compared to the open subcutaneous mastectomy includes reduced risk of nipple / aerioral ischemia , reduced chance of nipple distortion , lower risk of saucer deformity and reduced risk of hemorrhage and hematoma.

• This technique is not recommended for glandular gynaecomastia. The Incesion is 3 to 4 mm in length, it can be made in axillary folds or inframammary fold or periareolar . Post operative compression garments are applied for at least two weeks .

• Ultrasound assisted liposuction – this permits emulsification and cavitations of glandular tissue which can then be followed by standard liposuction to remove excess fat in liquefied tissue

Complication of surgery • Bleeding and hematoma • Seroma• Nipple , areola related complications –

inversions, distortion and alteration of symmetry and necrosis

• Scar related complications includes painful hypertrophid or keloid scar

• Breast asymmetry • Contour irregularity• Infection

PreventionTwo situations exist in which

gynaecomastia can be prevented. The first is by avoiding drugs that can cause gynaecomastia.

The second area of prevention applies to patients with prostate cancer who are about to receive estrogen or anti androgen therapy.

Studies have shown that prophylactic breast irradiation (with low dose of 900 red) is effective in preventing gynaecomastia in patients with prostate cancer.

PrognosisRegardless of he etiology of

gynaecomastia the pronosis is excellent. Studies have shown that 90% of physiological gynaecomastia involutes spontaneously within 2 years.

In drug induced gynaecomastia, withdrawal of the medication leads to regression in 60% of the patient

• If the gynaecomastia is of long duration it is unlikely to regress spontaneously.

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