Diff-Dx | Lab |
A benign glandular enlargement of the male breast that is generally bilateral
(may be asymmetric, or rarely, unilateral)
Gynecomastia is affected by increased estrogen/androgen
Types of Gynecomastia:
Type I: Benign adolescent hypertrophy
Physiologic discoid subacute mass
Type II: Physiologic gynecomastia - Generalized enlargement
to greater degree
Type III: Obesity simulates gynecomastia
Type IV: Pectoral muscle hypertrophy
Marshall & Tanner Stages of breast
[Adapted from Marshall WA, Tanner JM. Variations in pattern of pubertal
changes in girls. Arch Dis Child 1969: 44:2291-303.]
Stage 1: Preadolescent; only papillae are elevated.
Stage 2: Breast bud and papilla are elevated and a small mount is present;
areola diameter is enlarged.
Stage 3: Further enlargement of breast mound; increased palpable glandular
Stage 4: Areola and papilla are elevated to form a second mound above the
level of the rest of the breast.
Stage 5: Adult mature breast; recession of areola to the mound of breast
tissue, rounding of the breast mound,
and projection of only the
papilla are evident.
Physiologic cause - transient in neonatal boys, at puberty, aging;
and idiopathic cause.
1. Decreased production or action of
Klinefelter syndrome: XXY chromosomes. Common features are small testes,
minimal spermatogenesis, low testosterone, infertility. If the buccal smear
is chromatin positive, the testosterone level is reduced, & FSH level
is high, a definitive diagnosis can be made.
Androgen resistance (testicular feminization & Reifenstein syndrome),
Androgen production deficiency,
Defects in testosterone synthesis; Testicular failure
Secondary testicular failure: trauma castration, viral hepatitis, renal
failure, neurological & granulomatous disease.
2. Increased estrogen production
(1) True hermaphroditism
(2) Testicular tumors: germinal cell testicular tumors.
(3) Ca of lung: gonadotropin producing bronchogenic Ca
(4) Tumors - estrogen secreting, gonadotropin secreting and prolactin secreting
Increased substrate for peripheral aromatase
(1) Adrenal tumors
(2) Liver cirrhosis
3. Drug-induced gynecomastia :
Inhibitors of testosterone synthesis +/or actions:
ketoconazole, metrodazole, alkylating agents, cisplatin,
spironolactone(Aldactone), cimetidine(Tagament), metoclopramide, flutamide,
Estrogens, DES, Birth control pill, digoxin, phytoestrogens
Drugs that enhance endogenous estrogen secretion as: Gonadotropins,
Unknown mechanism: heroin, marijuana, sedatives as diazepam, amphetamine,
busulphan, cytotoxic drugs, INH, BP meds as: methyldopa, ACE inhibitors,
Ca-blockers; tricyclic antidepressant, ethionamide, ?Flexeril, etc. primary
hyperparathyroidism; Amphotericin B toxicity
4. Idiopathic pathologic gynecomastia
In all published series half or more of subjects evaluated for
gynecomastia do not have an underlying endocrinopathy that is diagnosable
at autopsy or by careful endocrine work-up. If one adds those instances in
all large series in which the designated cause is tenuous, the idiopathic
category accounts for approximately three fourths of cases.
Physiological: newborn, adolescence, aging
Obesity with increase in adipose tissue, lipomas
Breast Carcinoma of the male; adrenal, testicular, or other tumors
(lung Ca, hepatoblastoma, etc.) especially with recent progressive, painful
Cirrhosis, Thyrotoxicosis, Renal failure, etc.
Plasma testosterone, LH & FSH measurements -
help diagnose hypogonadism
Serum estradiol E2, serum prolactin, Liver function
, Thyroid function test, BUN, Creat,
24-hour urine 17 KS (Ketosteroids) level.
Human chorionic gonadotropin HCG levels - high levels may lead to finding
a choriocarcinoma or other hCG-secreting malignant tumor
Others if clinically indicated e.g., thyroid function, chromosomal analysis
Full endocrine investigations may be indicated
CT, ultrasonography (rarely indicated)
Biopsy, if suspicious for cancer
An elevated estrogen level indicates the need for testicular ultrasonography
and adrenal CT or MRI.
Estradiol, however, is so potent that significant gynecomastia can develop
without elevation of the plasma estradiol level. Progressive gynecomastia
without a known explanation (e.g., puberty, cirrhosis, hyperthyroidism) should
therefore be evaluated by imaging of the adrenals and testes.
The combination of recent gynecomastia with elevated estrogen and hCG titers
should prompt a search for a primary tumor. Although the finding of hCG in
the plasma of normal people has thickened the plot, high hCG titers and dynamic
studies can be used to identify a tumor as the probable cause.
Correct underlying disorder
Withdrawal of causative drug if feasible
Observation with reassurance that problem is transient
Subcutaneous mastectomy for severe, persistent cases or those with psychological
Tamoxifen (Norvadex), estrogen antagonist , has
been used and anastrozole (Arimidex), a potent and selective
fourth-generation aromatase inhibitor, is also known to be effective in Tanner
stage III or less gynecomastia. (Suggested by YC
Various drug regimens have been tried for gynecomastia with varying degrees
of success, including the antiestrogens tamoxifen and
clomiphene, the aromatase inhibitor testolactone, and
danazol, a weak androgen that acts by inhibiting gonadotropin
secretion and causing a fall in plasma testosterone. Treatment with
dihydrotestosterone (which cannot be aromatized to estrogen) is also reported
to cause significant symptomatic improvement in gynecomastia. However, no
prospective controlled studies have been performed with any of these regimens,
and their clinical usefulness is not established.
[Serels S; Melman A: J Urol 1998 Apr;159(4):1309 Tamoxifen use in
Staiman VR; Lowe FC: Urology 1997 Dec;50(6):929-33 - tamoxifen 10-30 mg/day
for 1 month
McDermott MT, et al Tamoxifen therapy for painful idiopathic gynecomastia.
South Med J 83: 1283, 1990
Anastrozole, an aromatase inhibitor Tx for gynecomastia reported by groups
from Southwestern Med Ctr in Dallas and also from Harbor-UCLA in Torrence
at Endo Society mtg at San Diego Jun. of 1999.
Plourde PV, et al.:Breast Cancer Res Treat. 1994;30(1):103-11 - Arimedex
Lonning PE, et al.: "anastrozole" -Breast Cancer Res Treat. 1998;49 Suppl
1:S53-7; discussion S73-7. Review..]
Dambro: Griffith's 5-Minute Clinical Consult, 1999 ed.- Timothy L. Black
Scientific American Medicine 10-1999