CATASRTOPHE OF ALPHA CHEST:

SURGERY IS THE ULTIMATE

WEAPON

NAME : MUHAMMAD IQBAL BIN ALIAS

MATRICS NO. : 1142253
SUPERVISOR : ASSOCIATE PROFESSOR DR.
ZAIRINA A. RAHMAN
UNIVERSITY : UNIVERSITI SAINS ISLAM MALAYSIA
1. Introduction

Enlargement of male breast also known as ‘man boobs’ is usually benign in nature and do not
disrupt the functionality of an individual if left untreated. Many come seeking for physician
consultation due to cosmetic effect that will lead to low self-esteem as a man having a female
breast is not consider as a masculine alpha male. Gynecomastia is one of the most common
cause of male breast enlargement. This paper will cover most aspect of gynecomastia starting
from the definition of gynecomastia itself until the management of this condition. The options of
treatments available for these condition and which one of them has the better efficacy above
another will also be emphasized. Gynaecomastia has a high prevalence in various population
involving different range of ages. According to researches done in multi population, 60-90
percent of infants has a mild gynaecomastia associated with the oestrogen from the mother.
During the phase of puberty, about 69 percent of adolescents are affected by gynaecomastia
and 20 percent of them have persisted until adulthood. In 24 – 65 percent of middle age and
older men have been affected. (1) Patients are usually more concern about the aesthetic part of
the disease which lead to emotional distress and low self-confidence. Based on a study done by
Department of Plastic and Reconstructive Surgery of St Georges' Hospital, 80 percent of them
had their surgeries done due to aesthetic reasons and only minority of them have the surgery
due to pain and tenderness. (2)

2. Definition
Gynecomastia is the enlargement of male breast due to over proliferation of the breast glandular
tissues which is benign in nature. This condition is commonly occur during adolescence, infancy
and aging. This condition can be painful however patients usually complains of cosmetic defect
caused by it or fear of development of any malignancy. (3)

3. Causes of Gynecomastia

Causes of gynecomastia can be classified into two groups which are physiological and
pathological causes. (4)

3.1 Physiological

Physiological gynecomastia occurs during infancy and puberty.

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 a. Infancy.
During placental phase the androgen is continuously being transferred into oestrogen
which then enter the foetal circulation and thus stimulate the glandular proliferation of the
breast. However this condition usually resolved by itself during the first year of life. (5)

b. Puberty
During puberty, it is common for the androgen/oestrogen ratio to be in an imbalance
state which explain the occurrence of enlarging of male breast or gynecomastia. This
condition will dissipate by itself when the androgen/oestrogen comes to the correct ratio
for male which is usually happens when male reach 18 years old. (6)

3.2 Pathological gynecomastia can occurs due to numerous causes such as listed below:

a. Drugs. Children and adolescence might be exposed to drugs that are necessary for
them to take it despite having the side effect of having gynecomastia.

i.
Oestrogens or the substances that have the same mechanism of action as
oestrogens. For example: medications such as oral contraceptive pills and
digitalis, cosmetics such as lavender oil and tea tree oil or food that is
phytoestrogens such as soy. (7)
ii.
Drugs that increase the production of oestrogens. For example gonadotropins
and clomiphene. (8)
iii.
Drugs with testosterone inhibitor properties. For example ketoconazole,
metronidazole and cimetidine. (8)
iv.
Antiretroviral drugs. For example non-nucleoside reverse transcriptase inhibitor.
(8)

v. Alcohol and illicit drugs. For example marijuana and anabolic steroids. (9)

b. Hypogonadism. Primary hypogonadism is the cause of gynecomastia in 10% of the

cases. (4) Klinefelter syndrome, polysomy X; is the commonest congenital cause of
hypogonadism during adolescence. 70% of patients with Klinefelter syndrome have a
slowly progressive gynecomastia. (10) Rapidly progressive gynecomastia in patients with
Klinefelter syndrome indicate the presence extragonadal human chorionic gonadotropin
(hCG)-secreting tumour in the mediastinum; however these malignant germ cell tumours

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 only occur in approximately 1% of patients with Klinefelter syndrome. (11) (12)

c. Acquired causes
i. Infection: mumps, echovirus, group B arboviruses, leprosy
ii. Trauma: testicular torsion
iii. Radiation

d. Chronic liver or kidney diseases (13)

In patient with chronic liver disease, sex hormone binding globulin levels in the blood is
affected which alter the circulating levels of estradiol and testosterone. Different from
kidney disease which lead to alteration of testosterone production from Leydig cells
which is associated in the increase of estradiol and luteinizing hormone (LH). In addition,
gynecomastia might be the result of the effects of chronic disease on the hypothalamic-
pituitary-testicular (HPT) axis, medications used in the management of the disease, and
declining nutrition. (14) It is estimated that chronic disease is the culprit for approximately
8% of cases of gynecomastia in adult patients (4) . However it is not known how
frequently the chronic disease causes gynecomastia in children and adolescents.

e. Malnutrition suppresses the HPT axis which lead to the decrease of testosterone
production. The HPT axis re-engages when refeeding is done. This increases production
of testosterone and estradiol is similar to the one during the physiologic puberty.

f. Hyperthyroidism is an uncommon cause of gynecomastia but it may be the first

manifestation of hyperthyroidism (15).

4. Clinical Presentation of Gynecomastia (16)

Patient with gynecomastia is commonly presented with bilateral swelling which are
symmetrical in shape around the nipple-areolar complex. The swelling is usually tender upon
palpation during the earlier course. However patients might also presented with bilateral breast
enlargement but one is bigger than the other. The presentation also varies according to age.

Adolescents usually came seeking for treatment due to painful tender breast. Whereas adults
with gynecomastia usually presented with enlargement of breast which is painless and

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asymptomatic in nature. They commonly experience increase in nipple sensitivity towards
rubbing against the shirt. However severe symptoms in men should be taken into account for
earlier therapeutic intervention as the fibrotic changes will start to take place at 6 to 12 months.

5. Differential Diagnosis (17)

There are diseases that can be falsely diagnosed as gynecomastia. The most common
diseases are pseudogynecomastia and breast cancer. Breast cancer is rare among male
therefore gynecomastia would be the first differential diagnosis. However patient with breast
cancer presented with unilateral non-painful mass. The mass is also eccentric to nipple - areolar
complex and can’t be mobilized. Pseudogynecomastia in the other hand differed from
gynecomastia as it is caused by increased in breast fatty tissue. This can be differentiated as
patient’s breast will be diffusely enlarged and there would be no well-defined border of the
mass.

6. Investigations

6.1. Patients with physiologic gynecomastia do not need further evaluation as it will not
change the management and re-evaluation need to be done after six month.

6.2. However when the patient has a breast with size larger than 5 cm or presence of tender
lumps which of recent onset, progressive and of unknown duration or the lump shows
the sign of malignancy which are hard, fixated and positive lymph nodes findings further
evaluations need to be done. (18)

6.3. There are several modalities that can be used to evaluate the non-physiological
gynaecomastia. Below I will include several modalities that are being used to find the
cause of the abnormalities.

6.3.1. Mammography, a commonly used imaging modality for detection of breast

pathologies in women due to its high sensitivity. However it is less commonly used
in male patients due to rare occurrence of breast cancer among males.
Gynecomastia in mammography can appeared as diffused, nodular and dendritic in

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 appearance. (19) Below are pictures of different types of gynaecomastia based on
radiological image.

Figure 1 shows dendritic gynecomastia; Mediolateral oblique (A) and craniocaudal (B) views of dendritic gynecomastia.
Dendritic gynecomastia occurs due to fibrosis of the glandular tissue which make it no longer reversible. This can be
seen in patient with long standing gynecomastia for more than a year . (20)

Figure 2 shows the appearance of nodular gynecomastia in mammogram. A is mediolateral view and B is
(20)
craniocaudal view. This finding is common in those with early phase gynecomastia which is less than a year.

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 Figure 3 shows mediolateral view of a male breast which shows enlargement with no sub areolar opacities which
indicates the accumulation of fats with no ductal or glandular involvements. This finding indicate
pseudogynaecomastia. (19)

6.3.2. Mammogram is more sensitive to detect breast malignancy and abnormalities.

However studies have shown that ultrasonography is more specific. (21) Below are
pictures showing results or ultrasonography on different breast anomalies. As it is
important to differentiate between benign and malignant causes of gynecomastia I
will include the benign and malignant findings of male breast enlargement.

Figure 4 shows the appearance of nodular gynaecomastia in ultrasonography. The lesion appear to be hypoechoic
(22)
and its margin is well defined and homogenous in nature.

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Figure 5 shows the appearance of dendritic gynaecomastia in ultrasonography. The lesion appear as triangular in
(22)
shape and hypoechoic which branches extended into peripheral adipose tissue.

Figure 6 shows diffuse glandular gynecomastia which resembles the female breast. The hypoechoic glandular
tissues are distributed evenly within the adipose tissues . (22)

Figure 7 show the features of pseudogynaecomastia in ultrasonography. As you can see there are lobular
hypoechoic region of adipose tissues which are homogenous and surrounded by thin fibrous tissues. (22)

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 Figure 8 shows the finding in ultrasonography of a male breast with malignancy. The hypoechoic mass appear as
solid nodule with well-defined margin and large central nucleus which is irregular and centrally located. (22)

Figure 9 shows the ultrasonography of a male breast with pseudogynaecomastia. Figure shows abundant of adipose
tissues containing anechoic structure with well-defined margins which is a cyst. Usually there will be posterior
acoustic enhancement but in this picture the enhancement are hardly to be seen. (22)

Figure 10 shows anechoic structures (cysts) adhering to one another in the male with nodular gynecomastia. The
lesion has well-defined margins with subtle posterior acoustic enhancement. (22)

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 Figure 11 shows a simple cyst appearance in ultrasonography which appears to be anechoic structure with well-
defined margins. This ultrasonography is taken from a patient with dendritic gynecomastia. (22)

Figure 12 shows a lipoma under ultrasonography. The mass is well circumscribed and hyperechoic. The mass lies
(22)
parallel to the subcutaneous tissues. It is surrounded by thin capsules which appears hyperechoic.

6.3.3. As most of gynecomastia are caused by the imbalance of hormones in the body.
Therefore biochemical testing might will help to find the underlying causes which
lead to occurrence of gynaecomastia. (23)

Below are the tests that can be done to investigate the underlying causes of
hormonal imbalance. Hypogonadism, a medical condition where the gonads which
are testes and ovaries produce insufficient amount of hormones. It can be divided
into two which are primary hypogonadism and secondary hypogonadism. (24)
Patient with primary hypogonadism shows decrease in testosterone level but
increase in luteinizing or follicle stimulating hormone different from those with
secondary hypogonadism which has all of the mentioned hormones decreased in
concentration. (25)

Testicular germ cell tumours, the commonest among all types of testicular cancer
which accounted for 95 percent of them (26) is also one of the causes of

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gynaecomastia. There are three serum tumour markers which usually increase in
patient with germ cell tumour; alpha-fetoprotein, the beta subunit of human
chorionic gonadotropin and lactate dehydrogenase (LDH). However neither one nor
all three of them together have sufficient sensitivity and selectivity to diagnose germ
cell tumour. It is helpful for initial diagnosis and future prognosis. These tumour
markers are actually used to monitor the effectivity of the treatment done on the
patient. (27) Although, among these tumour markers only one causes gynaecomastia
which is human chorionic gonadotropin. (28)

In liver cirrhosis, oestrogen can’t be catabolized leading to excessive accumulation.

When serum oestrogen concentration in man increases, oestrogen will dominate
the action on the breast tissue over androgen which lead to excessive proliferation
of glandular tissue. (29) Findings in liver function tests are increase in level of
aspartate aminotransferase (AST) and alanine aminotransferase (ALT). AST is
commonly more elevated then ALT. Serum bilirubin will progressively increase in
patient with liver cirrhosis but in the early onset of cirrhosis bilirubin level might
appeared to be normal as it is still well-compensated. Albumin, a protein that is
exclusively synthesized in the liver will decrease in serum concentration also known
as hypoalbuminemia. This will lead to other manifestation such as ascites. (30)

In hyperthyroidism it also found that there is a significant increase of free oestrogen

in the blood. This circumstance is the result of hepatic overstimulation directly by
the thyroid hormones leading to increase production of sex hormone binding
globulin (SHBG). SHBG bind to both oestrogen and testosterone. However, it has
higher affinity towards testosterone forming strong testosterone-globulin complex
leading the action of testosterone towards other receptor in the body can’t be
initiated and making the free oestrogen concentration in the blood relatively higher
compared to concentration of free testosterone. Responding to this hormonal
changes in the body, pituitary gland increase the secretion of luteinizing hormone
which stimulate leydig cells to secrete testosterone and estradiol until the
concentration of unbound testosterone in the blood returns to normal. Estradiol will
then being converted into oestrogen which will lead to increase oestrogen
concentration in the blood leading to over-proliferation of glandular breast tissue.
To confirm hyperthyroidism as the underlying cause of gynaecomastia thyroid

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 function test can be done. Patient with gynaecomastia secondary to
hyperthyroidism can be treated by anti-thyroid treatment without requiring
unnecessary surgical intervention. (31)

7. Treatments (32)

As there are so many causes of gynaecomastia, the choice of treatments are also varied.
The non-invasive ones are usually put on trials to observe the responds towards the
management.

7.1. The first step is to ensure that the patient is not under any medication such as
spironolactone, ketoconazole, metronidazole and other drug that may inhibit
testosterone action or enhance oestrogen effectivity as stated in the previous paragraph.
If the patient is not under any medication that is related to gynaecomastia, then the
patient is planned for another appointment in three months’ time to monitor the progress
of the disease. Usually gynaecomastia will regress spontaneously if there is no
underlying causes. However, if it does not resolve after three months’ time medical
intervention will be started.

7.2. Despite having hundreds or maybe thousands of aetiologies, gynaecomastia isn’t

actually that complicated. Its pathophysiology is the same even though the causes are
different; either it is caused by high concentration of oestrogen in the blood or low
concentration of testosterone.

7.3. Therefore, medical treatments are focused into preventing the action of oestrogen on
the glandular breast tissue or increasing the testosterone concentration in the blood.
There are two types of medical treatment which are androgen replacement therapy and
selective oestrogen receptor modulators. Two most common drugs used are
testosterone and tamoxifen respectively and are interchangeably used based on the
conditions of the patient.

7.4. In adolescent boys with severe breast enlargement due to glandular tissue over-
proliferation and experiencing pain and embarrassment tamoxifen is the drugs of choice.
If the breast enlargement is not severe enough put the patient under three month follow

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 up as adolescent gynaecomastia commonly regresses by itself.

7.5. Same goes to the adults with underlying medical diseases, tamoxifen is also the drug of
choice. Patient with prostate cancer with androgen deprivation therapy, this patient
medications can’t be stopped as it will deteriorate the underlying disease. This patient
can’t also be started on testosterone replacement because the testosterone level will
increase in the blood leading to poor prognosis of his prostate cancer. Therefore the
most effective and non-complicating way to deal with this patient condition is by using
tamoxifen which won’t disturbed the course of treatment he is on.

7.6. However in those who have low concentration of serum testosterone such as in
hypogonadism the treatment of choice wold be testosterone replacement therapy.

7.7. Therefore seeking early medical treatment is really important at the early stage of
gynaecomastia. When gynaecomastia if left untreated for a long time, tissue fibrosis will
take place. When tissue undergone fibrosis it is impossible for any drugs or hormonal
therapy to be effective. After 12 months of untreated gynaecomastia, most of the
patients will have permanent breast enlargement.

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 7.8. The medical treatment only works efficiently during in the first three month of the onset
of gynaecomastia or during the period breast tenderness. When gynaecomastia reached
it florid phase, the only way to get rid of the large flabby breast is through surgery. Below
is the histological changes of breast tissues in patient with gynaecomastia:

Figure 12 shows the normal male breast tissue which demonstrate a duct lined by single layer of epithelial cells
surrounded by loose stoma tissue with no evidence of inflammatory cells infiltration.

Figure 13 shows profound ductal lining epithelial proliferation and infiltration of inflammatory cells.

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 7.9. In adolescent breast reduction is not done until adult testicular size is attained. This is
because of possibility of regrowth in those whose puberty is not completed. In patient
with underlying diseases that cause increase in serum oestrogen concentration,
tamoxifen must be prescribed for three month to avoid regrowth then breast reduction
can be done. The treatment usually involved surgical incision of the glandular tissues
and liposuction of peripheral excess fatty tissue.

7.10. In patient with extreme breast enlargement skin excision is needed to avoid flabby and
ugly breast. A transverse eclipse of excess skin, fat and glandular tissue is excised and
the nipple-areolar complex is completely remove as a full graft. After the excision is
done, the complex is placed at the normal anatomical position. This procedure need an
experience plastic surgeon.

Summary

Gynaecomastia does have a great effect on psychological aspect of men’s life. Therefore it is
important to have a treatment that can resolve the cosmetic part of the disease as well. As
gynaecomastia has the same pathophysiology, it is not as complicated as it seems to tackle it.
As a conclusion the most effective treatment to cure gynaecomastia is through the combination
of medical and surgical intervention. Neither medical nor surgical intervention alone can bring
back the patient’s nice alpha chest that he used to have in florid stage of gynaecomastia and it
is important to detect any underlying diseases at the early stage of gynaecomastia as the
patient might not need to undergo any unnecessary surgical which might have a lot of
complication compared to medical treatment.

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