aj gynecomastia 15 aug 2011
TRANSCRIPT
Gynecomastia
PROF:AKMAL JAMALFCPS;FRCSEd:
13 AUG 2011
Definition of Gynecomastia True Gynecomastia:
Rubbery or firm mass Extending concentrically Symmetrically from the nippleUsually bilateral but can be unilateral
Pseudogynecomastia: Fat deposition without glandular proliferationOn exam fingers will not meet any resistance the nipple
Breast cancer: Hard or firm eccentric in location from the nippleMay be associated with skin dimpling Nipple retraction or dischargeAxillary lymphadenopathy
Hormonal control of breast development
estradiol stimulates glandular cells testosterone inhibits growth & differentiation GH,cortisol,IGF1,insulin act permissively thyroid hormones increase SHBG level cortisol & prolactin lower T levels
(hypothalamic & testicular effects)
Physiological vs pathological gynecomastia challenging common association with obesity psedogynecomastia pathological arbitrarily defined : palpable tissue > 4cm >2cm & tender >2cm & increasing
diagnosis of gynecomastia may be made
In the nonobese male, breast tissue measuring at least 2 cm in diameter must be present before a diagnosis of gynecomastia may be madedoes not predispose the male breast to cancer
Gynecomastia .
Physiologic gynecomastia: neonatal period, adolescence, and senescence. (excess of circulating estrogens in relation to circulating testosterone) .
The pathophysiologic mechanisms:
I. Estrogen excess states
A. Gonadal origin
B. Nontesticular tumors
C. Endocrine disorders
D. Diseases of the liver—nonalcoholic and alcoholic cirrhosis
E. Nutrition alteration states
II. Androgen deficiency states
A. Senescence
B. Hypoandrogen states (hypogonadism)
C. Renal failure
III. Drug-related
IV. Systemic diseases with idiopathic mechanisms Therapy.
Simon classification of gynecomastia
Grade Enlargement Skin excess
I small absent
IIA moderate absent
IIB moderate present
III large present
Prevalence
Gynecomastia has three peaks. 1. Infancy: 60-90%
Transient maternal E2,regresses over 2-3 week
2. Adolescence: 4-69% (variation due to examiner) Onset 10-12y Peaks 13-14. Normally regresses w/in 18mo Persistence uncommon after 17y
3. Older men: 24-65% Highest prevalence in the 50-80y
Glandular Proliferation
Androgen ExposureEstrogen Exposure
Balance T &E2 =T/E2
Physiopathology of Gynecomastia
Glandular Proliferation
Androgen Exposure
1-Deficiency:
Genetic
Tumors
Drugs
2-Resistance:
AR mutation
Anti-androgens
Estrogen Exposure:
1- Excess of Production:
Tumors
Aromatization(age,obesity)
2-Exogenous E2:
E2
Aromatizable E2
3- Excess of Free E2
Thyrotoxicosis-Drugs(SHBG)
Physiopathology of Gynecomastia
Absolute increase in free estrogen
Direct secretion from: Maternal-placental-fetal unit Testes Adrenal glands
Extraglandular aromatization: Adipose, liver, skin, muscle, kidney and bone
Displacement from SHBG : SHBG higher affinity for andro.than estrogens
Enhanced sensitivity of breast tissue to circulating E2: via increased aromatization
Exogenous estrogen admininstration: drugs
Decreased endogenous free androgens
Decreased secretion by testes and adrenals Increased metabolism via aromatization Increased binding to SHBG Congenital defects in A.R. structure or function Displacement of androgens from receptor
Aromatization
Inhibitory
Estrogens
5 α -
androgens
Androgens
5 α - reduction
N
Aromatization of Androgens
Etiologies of Gynecomastia
Drugs: No detectable abnormality Persistent pubertal gynecomastia Cirrhosis or malnutrition Primary hypogonadism Testicular tumors Secondary Hypogonadism Hyperthyroidism Chronic renal insufficiency
10-25%
25%
25%
8%
8%
3%
2%
1.5%
1%
Gynecomastia and Thyrotoxicosis
Presenting manifestation (unusual) Occurs in 0-83% of patients* Onset during thyrotoxicosis Disappearance after euthyroidism occurs
* wide range probably indicates differences in examining technique
Drugs associated with Gynecomastia
Androgen Exposure1-Deficiency:
Gn-GH analogs
Spirolactone
Ketodanazole
Anti-androgens
Tumors,Drugs
2-Resistance:
Cimetidine
Siprolactone
Finesteride
Bicalutamide
Estrogen Exposure:1- Excess of Production:
HCG
Aromatizable Androgens
2-Exogenous E2:
E2
Digoxin
Marijuana
3- Excess of Free E2
Spirolactone
Aromatizable E2
ACE,CCB ??
Specific Pathogeneses
Puberty During puberty, E2 rise to adult levels before the T. Transient increase in E2 at onset of puberty T.-E2-Estrone- Gonadotropins: No difference
Adult men ;Multifactorial Increase body fat Decrease in T. By testes Increase in LH Polypharmacy.
Specific Pathogeneses Drugs
Increase E2 Act as Antiandrogens by binding receptors and displacing
androgens. Increase aromatization of T. To E2 Decrease T. Production Displace T. From SHBGincreasing its metabolic clearance
Cirrhosis Increase Androstenedione and its conversion to Estrone & E2 Elevated SHBG levels, reducing free T.
Malnutrition Decrease androgen with normal Estrogen production. Refeeding mimics normal puberty hormone pattern.
Specific Pathogeneses Male hypogonadism
Primary hypogonadism: Klinefelter’s enzymatic defect in the T. testicular trauma infection infiltrative disorders vascular insufficiency aging: decrease in T. with increase in E2 Secondary hypogonadism : low T.- increase in E2 precursors
Testicular neoplasm Germ cell tumor (2.5-6%) =poor prognosis Leydig cell tumor (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 dysfxn resulting
in low testosterone
Feminizing adrenocortical tumors Rare malignant tumors that have gynecomastia( 98%), palpable
tumor(58%), and testicular atrophy(50%).
Specific Pathogeneses Ectopic production hCG
Precocious puberty in boys with hepatoblastomas In adults, large cell CA of lung, gastric CA, renal cell Ca, and
occasionally hepatomas.
True Hermaphroditism Harbor both testicular and ovarian tissue. Increased estrogen activity
can suppress testosterone production by testes.
Androgen Insensitivity Syndromes Defects or absence of androgen receptors in target tissue
Excessive extraglandular aromatase activity X-linked recessive or sex-limited autosomal trait have many fold
increase in extraglandular conversion of plasma androstenedione to estrone.
Anabolic abuse
Evaluation whom to evaluate
how to evaluate
Candidates needing evaluation breast tenderness
rapid enlargement
eccentric, hard or irregular mass
lesion >4cm in diameter
Candidates not requiring evaluation
asymptomatic
stable
obese
<5cm
Work-up History
Onset Bilateral/unilateral Pain Change in size Nipple discharge Drugs/medications Family history
Work-up Complete Physical Exam
Look for signs of liver and kidney disease Evaluate for hyperthyroidism Seek for signs hypogonadism: eg. Impotence, decreased
libido, strenght, and change in testicular size Check for abdominal mass and testicular mass Careful breast exam
Examination : local presence or absence of breast disc diameter of breast disc to pinch the tissue between thumb &
forefinger lateral to nipple; ability to flip an edge of tissue at the interface of normal & glandular tissue signifies gynecomastia
comparison of consistency with abdominal fat or fat in the axillary line
tenderness
Physiologic gynecomastia :no further evaluation Further evaluation is necessary in the following:
Breast size greater than 5 cm (macromastia) A lump that is tender, of recent onset, progressive,
unknown duration Signs of malignancy (eg, hard or fixed lymph nodes or
positive lymph node findings)
Evaluation for renal or liver disease Free or totalT.,LH,E2,DHAS :patient with possible
feminization syndrome TSH and FT4 if hyperthyroidism is suspected
Laboratory Studies
Work-up Labs if gynecomastia of recent onset, persistent,
or painful/tender and has no clear physiologic etiology. TSH, LH, FSH, hCG, Prolactin, Estradiol,
Testosterone, Androstenedione
Imaging? US and mammogram for any eccentric or discrete mass.
Biochemical investigations testosterone 17β estradiol DHEAS LH β hCG thyroid function test liver function test
proceed further according to lead
Treatment Options Watchful Waiting Medications Surgery
A major factor that should influence the initial choice of therapy
Pubertal gynecomastia :resolves spontaneously within several weeks to 3 years in approximately 90%
Breasts greater than 4 cm in diameter may not completely regress.
the duration of 12 mo or longer(late fibrotic stage): unlikely that any medical therapy will result in significant regression
Treatments Watchful waiting
In healthy adolescent ; normal genital exam, 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 gynecomast.; Later puberty with severe pain tenderness, psychosocial issues of embarrasment
Consider that current medications have only been studied in small sizes that have been unblinded and uncontrolled
Three types of medical therapy Androgens, antiestrogens and aromatase inhibitors None are FDA approved for gynecomastia
Androgens Testosterone
Not more effective than placebo and can be aromatized exogenously Reduce the prevalence of gyne. in patients with cirrhosis
Dihydrotestosterone (nonaromatizable androgen) Decrease in breast volume in 75% Resolution in 25%. No noted side effects
Danazol Complete resolution , in 23%(12% in placebo ) well tolerated S.E: edema, weight gain, acne, nausea , muscle cramps.
Antiestrogens Clomiphen
Dose=50-100 mg 6 mo ;Response rates of 36-95%
Tamoxifen significant reduction in pain and breast size , none had complete
remission. S.E. :no major side effects, except for occassional epigastric distress
and nausea.
Surgery Should be considered in patients who do not
respond to medical therapy or who have long standing gynecomastia.
Options Include Liposuction Direct surgical excision, or both
Complications Permanent numbness, compromise of blood supply,
irregular contour, hematoma, seroma, wound infection.