​Kembara Xtra - Medicine - Gynecomastia

Gynecomastia on the left picture. Right picture is normal breast in male.

​Kembara Xtra - Medicine - Gynecomastia 
Introduction 

Gynecomastia develops as a result of increased estrogen activity compared to androgen. Benign glandular expansion of male breast tissue. Gynecomastia may be temporary and signify the typical physiological changes that take place in utero or during puberty. Gynecomastia that manifests or persists in maturity, however, is often pathogenic in origin.
Lipomastia, also known as pseudogynecomastia (subareolar fat),


Up to 70% of men between the ages of 50 and 69 report having gynecomastia, which affects 60 to 90% of babies and 50 to 60% of pubertal boys.
Incidence
According to a 2007 study from Bulgaria, the prevalence of pubertal gynecomastia in Caucasian boys aged 10 to 19 was 3.9%.
Prevalence
Between 22% and 69% of adolescents and 36% to 57% of adult males are affected.


Pathophysiology and Etiology 

Gynecomastia can be triggered by a variety of causes that change the estrogen to androgen ratio, including:
Inhibition of the androgen receptor; a rise in the level of sex hormone-binding globulin (SHBG) or the affinity of androgens to SHBG (which lowers free or bioavailable testosterone); displacement of estrogen relative to testosterone from SHBG due to medication; and/or a decrease in the production of androgens.

Risk Elements 

Gynecomastia may be either pathologic or physiological in origin.
Boys in their early years and adolescents might develop physiological gynecomastia, which resolves on its own.
- Neonatal gynecomastia: Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulfate (DHEA-S) are converted by the placenta to estrone and estradiol, causing temporary gynecomastia.
- Adolescent gynecomastia: Gynecomastia is caused by brief rises in estradiol levels at the start of puberty.

Pathologic gynecomastia includes persistent and adult-onset forms. Idiopathic conditions account for 25% of instances, most of which are brought on by aging-related declines in free testosterone and adipose tissue-mediated aromatase activity.

Alert
Illegal substances: alcohol, amphetamines, methadone, marijuana, heroin, and over-the-counter bodybuilding supplements.
Androgens, anabolic steroids, estrogens, estrogen agonists, and human chorionic gonadotropin (hCG) are among the hormones.
Bicalutamide, flutamide, nilutamide, cyproterone, and GnRH agonists (leuprolide and goserelin) are antiandrogens or inhibitors of androgen production.

Cimetidine, ranitidine, metoclopramide, and proton pump inhibitors are antiulcer medications. Methotrexate, alkylating agents, and vinca alkaloids are cytotoxic agents. Digoxin, spironolactone, calcium channel blockers, ACE inhibitors, amiodarone, methyldopa, reserpine, minoxidil, and recently statins can be added to this list of cardiovascular medications.
Benzodiazepines, phenothiazines, haloperidol, and risperidone are examples of psychoactive drugs. HIV treatments like efavirenz, phenytoin, penicillamine, sulindac, or theophylline are examples of medications.
Reasons to exclude:
- Androgen insensitivity syndromes (androgen receptor defects), Klinefelter syndrome, and primary hypogonadism
- Testicular tumor: Sertoli cell (excessive aromatization to estrogens), Leydig cell (secretes estrogen), and germ cell (secretes hCG).
- Adrenal tumors (release estrogens and DHEA-S)
- Ectopic hCG cancers (renal cell carcinomas, stomach tumors, and hepatoblastoma)
Cirrhosis and secondary hypogonadism can also be caused by prolactinemia or Kallmann syndrome, which can also increase milk production in breast tissue.
- Overactive thyroid
- Dialysis or renal disease
Rare (true hermaphroditism [both testicular and ovarian tissue present]) malnutrition/starvation
Child Safety Considerations
Boys in their pubertal years may experience transient gynecomastia, which normally disappears between six to twenty-four months.
Aspects of Geriatrics
Low free testosterone levels are caused by medications, age-related declines in testosterone synthesis, and increases in SHBG production. Adipose tissue-mediated peripheral testosterone to estrogen conversion is caused by an increase in the ratio of fat mass to lean mass.


Accompanying Conditions 

 Gynecomastia develops in 50–75% of patients receiving estrogen and antiandrogen therapy for prostate cancer.
Breast cancer risk factors include cirrhosis and primary hypogonadism, particularly Klinefelter syndrome.
Testicular cancers, particularly those that are Leydig or Sertoli cell tumors and are linked to the Peutz-Jeghers syndrome or the Carney complex

Diagnosis 
Ask about muscle mass, decreased shaving frequency, libido, and erectile dysfunction if you have any reason to suspect hypogonadism.
Discover any Carney complex or Peutz-Jeghers syndrome in the family history.

 Carefully review the medication list and enquire about the usage of illicit drugs.
The usage of herbal supplements, marijuana, and over-the-counter H2 antagonists such as cimetidine

clinical assessment 
A thorough breast exam to assess the following qualities:
The area beneath the nipple and areola is firm, concentric glandular tissue that may be felt by pressing the thumb and fingers together from either side of the breast toward the nipple. For diagnostic reasons, this tissue's diameter spans from >0.5 to >2.0 cm, but the most recent significant study suggested using 1.0 cm as the diagnostic threshold.
– Possibly affects one or both breasts
- Usually asymptomatic, but if it has just started, it may hurt or feel painful.
- Although probing of subareolar fat is more consistent with pseudogynecomastia, off-center, hard, fixed mass is alarming for malignancy.
– Breast discharge should prompt worry about prolactinemia or cancer. The discharge with the latter is often clear or milky.
Thyroid examination; abdominal examination (size of liver and assessment of tumors);

 Genitourinary examination (look for an ovary or uterus and assess testicular size and hair pattern).
Examining the visual field to check for peripheral field defects.

Differential Diagnosis Breast cancer is typically unilateral, firm, eccentric to the nipple, with skin dimpling, nipple retraction/discharge, and lymphadenopathy. Other diagnoses include lipomas, sebaceous cysts, dermoid cysts, mastitis, hematomas, and hamartomas.

Laboratory Results 
The results of laboratory and radiologic tests should be adjusted to the patient's history and physical exam results.
Initial examinations (lab, imaging)

Luteinizing hormone (LH) levels are increased in primary hypogonadism and decreased in secondary hypogonadism, morning total and free testosterone levels are decreased in hypogonadism, hCG levels are raised in germ cell tumors and ectopic hCG tumors, estradiol levels are raised in Leydig cell tumors, Sertoli cell tumors, adrenal tumors, and with increased aromatase activity, and DHEA-S levels may

Other/Diagnostic Procedures

To rule out malignancy (i.e., off center, hard, fixed, discharge), consider a biopsy.

Interpretation of Tests
Check testicular ultrasound if your hCG level is elevated. If a mass is seen, it is probably a testicular germ cell tumor. Consider extragonadal germ cell tumor or hCG-secreting neoplasm if the ultrasound results are negative, and request a CXR and CT abdomen.

Elevated LH: Primary hypogonadism is likely if it is associated with low testosterone. Check free thyroxine (FT4) and thyroid-stimulating hormone (TSH) if they are raised in connection with high testosterone. If FT4 is raised and TSH is suppressed, hyperthyroidism is probably present; if both are normal, androgen resistance is probably present.
Check prolactin levels if LH is normal or lowered in response to low testosterone. If prolactin levels are high, a prolactin-secreting pituitary tumor is probably to blame (MRI required); if they are normal, secondary hypogonadism is probably to blame.
Check testicular ultrasonography if LH is normal or lowered in response to elevated estradiol. If a mass is found, it is probably a Leydig or Sertoli cell tumor. If there is no lump, examine the adrenals with a CT scan of the abdomen. If a mass is seen, it may be an adrenal tumor as opposed to an adenoma; if none is found, it is probably attributable to increased aromatase activity in extraglandular tissue.


Management 

Gynecomastia typically goes away on its own six months after it first appears. For the first six months, observe.
Gynecomastia that is newborn or pubertal resolves on its own about six to twenty four months. 8% of pubertal boys have persistent pubertal gynecomastia (>24 months). Gynecomastia is secondary to persistent pubertal gynecomastia, medicines, and idiopathic disorders in 75% of adult males. Only 25% of the time is connected to an underlying medical issue.
● If necessary, all illegal drug use and prescription drugs should be stopped.
Treat underlying medical issues, such as prolactinoma with a dopamine agonist, hypogonadal men with testosterone replacement therapy, thyrotoxicosis with the proper medication, and tumor removal.

Medication 
There are no drugs for the treatment of gynecomastia that have been approved by the US Food and Drug Administration.
● SERMs: 90% of study participants experienced successful resolution of idiopathic gynecomastia after 3 to 9 months of treatment with raloxifene (60 mg/day) and tamoxifen (10 to 20 mg/day) in clinical trials. Aromatase inhibitors prevent peripheral androgen to estrogen conversion. Anastrozole, a drug used to treat prostate cancer, stopped the development of gynecomastia in individuals receiving androgen deprivation therapy.

Further Therapies 

In clinical trials, preventive radiation shielded patients with prostate cancer receiving androgen deprivation therapy from developing gynecomastia.

Surgical Techniques 

Gynecomastia may require surgery if it does not go away on its own or with medical treatment within a year, if it causes substantial discomfort (pain, tenderness), embarrassment, or worry, or if a biopsy reveals a cancer that is suspected.

Patient Follow-Up Monitoring
Every 3 to 6 months for 24 months; if severe, painful symptoms continue after 6 to 12 months, consider medication therapy (such as tamoxifen); after 12 to 24 months, consider surgery. Routine annual breast and physical exams are advised for people with asymptomatic or moderate illness.
Patients should be reassured that gynecomastia is typically benign in nature.

The majority of patients experience regression once the underlying disorder is treated or the offending agents are eliminated. The majority of patients who have surgery are happy with the postoperative cosmetic appearance. The prognosis is good in physiologic cases because they frequently regress spontaneously within 3 to 6 months.

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