Gynecomastia pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{Gynecomastia}}
{{Gynecomastia}}
{{CMG}}; {{AE}}Husnain Shaukat
{{CMG}}; {{AE}} {{HS}}
==Overview==
==Overview==
The main pathophysiology behind gynecomastia is the result of increased estrogen to androgen ratio which can occur through multiple mechanisms that can be physiological, pathological or use of certain medications.
The main pathophysiology behind gynecomastia is increased estrogen to androgen ratio which can occur through multiple mechanisms. These mechanisms can be physiological, pathological or pharmacological.


==Pathophysiology==
==Pathophysiology==


===Hormones involved in breast development===
===Hormones involved in breast development===
*Estrogen and Progesterone act in a coordinated manner to support breast development. Estrogen helps duct growth and progesterone promotes alveolar development.<ref name="pmid10935020">{{cite journal |vauthors=Bocchinfuso WP, Korach KS |title=Mammary gland development and tumorigenesis in estrogen receptor knockout mice |journal=J Mammary Gland Biol Neoplasia |volume=2 |issue=4 |pages=323–34 |year=1997 |pmid=10935020 |doi= |url=}}</ref> <ref name="pmid8248223">{{cite journal |vauthors=Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O |title=Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue=23 |pages=11162–6 |year=1993 |pmid=8248223 |pmc=47942 |doi= |url=}}</ref>
*[[Estrogen]] and [[Progesterone|progesteron]]<nowiki/>e act in a coordinated manner to support breast development. [[Estrogen]] helps duct growth and [[progesterone]] promotes [[alveolar]] development which only occurs in female as gynecomastia doesn't have [[alveolar]] development. <ref name="pmid10935020">{{cite journal |vauthors=Bocchinfuso WP, Korach KS |title=Mammary gland development and tumorigenesis in estrogen receptor knockout mice |journal=J Mammary Gland Biol Neoplasia |volume=2 |issue=4 |pages=323–34 |year=1997 |pmid=10935020 |doi= |url=}}</ref><ref name="pmid8248223">{{cite journal |vauthors=Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O |title=Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue=23 |pages=11162–6 |year=1993 |pmid=8248223 |pmc=47942 |doi= |url=}}</ref>
*Growth hormone which acts through IGF-1 acts as a mediator in the presence of estrogen and progesterone for ductal breast duct development.<ref name="pmid10791764">{{cite journal |vauthors=Kleinberg DL, Feldman M, Ruan W |title=IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis |journal=J Mammary Gland Biol Neoplasia |volume=5 |issue=1 |pages=7–17 |year=2000 |pmid=10791764 |doi= |url=}}</ref> In a population based study of adolescent school boys, IGH-1 levels were higher in boys with pubertal gynecomastia suggesting the involvement of GH and IGF-1 in the pathogenesis of gynecomastia.<ref name="pmid24033660">{{cite journal |vauthors=Mieritz MG, Sorensen K, Aksglaede L, Mouritsen A, Hagen CP, Hilsted L, Andersson AM, Juul A |title=Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia |journal=Clin. Endocrinol. (Oxf) |volume=80 |issue=5 |pages=691–8 |year=2014 |pmid=24033660 |doi=10.1111/cen.12323 |url=}}</ref>
*[[Growth hormone]] which acts through [[IGF-1]] acts as a mediator in the presence of [[estrogen]] and [[progesterone]] for ductal [[Breast|breast duct development]].<ref name="pmid10791764">{{cite journal |vauthors=Kleinberg DL, Feldman M, Ruan W |title=IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis |journal=J Mammary Gland Biol Neoplasia |volume=5 |issue=1 |pages=7–17 |year=2000 |pmid=10791764 |doi= |url=}}</ref> The [[IGF-1]] levels have been found higher in boys with [[Gynecomastia|pubertal gynecomastia]] which shows the role of GH and IGF-1 in the [[pathogenesis]] of [[gynecomastia]].<ref name="pmid24033660">{{cite journal |vauthors=Mieritz MG, Sorensen K, Aksglaede L, Mouritsen A, Hagen CP, Hilsted L, Andersson AM, Juul A |title=Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia |journal=Clin. Endocrinol. (Oxf) |volume=80 |issue=5 |pages=691–8 |year=2014 |pmid=24033660 |doi=10.1111/cen.12323 |url=}}</ref>
*Prolactin in the presence of estrogen and progesterone also supports breast development. It also plays an indirect role as it causes central hypogonadism which alters the androgen/estrogen balance.<ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref> <ref name="pmid22790552">{{cite journal| author=Barros AC, Sampaio Mde C| title=Gynecomastia: physiopathology, evaluation and treatment. | journal=Sao Paulo Med J | year= 2012 | volume= 130 | issue= 3 | pages= 187-97 | pmid=22790552 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22790552  }} </ref>
*[[Prolactin]] in the presence of [[estrogen]] and [[progesterone]] also supports [[breast]] development. It also plays an indirect role as it causes [[central hypogonadism]] which alters the [[androgen]]/[[estrogen]] balance.<ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref> <ref name="pmid22790552">{{cite journal| author=Barros AC, Sampaio Mde C| title=Gynecomastia: physiopathology, evaluation and treatment. | journal=Sao Paulo Med J | year= 2012 | volume= 130 | issue= 3 | pages= 187-97 | pmid=22790552 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22790552  }} </ref>
*Aromatase catalyzes the conversion of androgens to estrogen and so initiate the cascade to breast development. So, gynecomastia can result from overexpression of aromatase.<ref name="pmid12239119">{{cite journal| author=Li X, Wärri A, Mäkelä S, Ahonen T, Streng T, Santti R et al.| title=Mammary gland development in transgenic male mice expressing human P450 aromatase. | journal=Endocrinology | year= 2002 | volume= 143 | issue= 10 | pages= 4074-83 | pmid=12239119 | doi=10.1210/en.2002-220181 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12239119  }} </ref> <ref name="pmid12736278">{{cite journal| author=Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K et al.| title=Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 19 | pages= 1855-65 | pmid=12736278 | doi=10.1056/NEJMoa021559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12736278  }} </ref>
*[[Aromatase]] [[catalyzes]] the conversion of [[androgens]] to [[estrogen]] and promotes the [[breast]] development. So, gynecomastia can also result from overexpression of [[aromatase]].<ref name="pmid12239119">{{cite journal| author=Li X, Wärri A, Mäkelä S, Ahonen T, Streng T, Santti R et al.| title=Mammary gland development in transgenic male mice expressing human P450 aromatase. | journal=Endocrinology | year= 2002 | volume= 143 | issue= 10 | pages= 4074-83 | pmid=12239119 | doi=10.1210/en.2002-220181 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12239119  }} </ref><ref name="pmid12736278">{{cite journal| author=Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K et al.| title=Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 19 | pages= 1855-65 | pmid=12736278 | doi=10.1056/NEJMoa021559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12736278  }} </ref>
{{familytree/start}}{{familytree | | | | | | | | | | | | | | | | | | | | | | |H02| |H02=Breast Tissue}}
 
{{familytree | | | | | | | | | | | | | | | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|-|.}}
 
{{familytree | | | | | | | | | | | | | | | |I01| | | | | | | | | | | | |I02|I01=Stimulatory Action|I02=Inhibitory Action}}
{{familytree/start}}
{{familytree | | | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | |!}}
{{familytree | | | | | | | | | | |H02| |H02=Breast Tissue}}
{{familytree | | | | | | | | | | | | | | | |J01| | | | | | | | | | | | | |J02|J01=Estrogen|J02= Androgens}}
{{familytree | | | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|-|.}}
{{familytree | | | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | }}
{{familytree | | | |I01| | | | | | | | | | | | | |I02|I01=Stimulatory Action|I02=Inhibitory Action}}
{{familytree | | | | | | | | | | | | | | | |J01| | | | | | | | | | | | | | |J01=GH & IGF-1|}}
{{familytree | | | | |!| | | | | | | | | | | | | | |!}}
{{familytree | | | |J01| | | | | | | | | | | | | |J02|J01=Estrogen|J02= Androgens}}
{{familytree | | | | |!| | | | | | | | | | | | | | | }}
{{familytree | | | |J01| | | | | | | | | | | | | | |J01=GH & IGF-1|}}
{{familytree/end}}
{{familytree/end}}


===Pathogenesis===
===Pathogenesis===
*It is thought that Gynecomastia can result from any condition, drugs or disease state that causes an increase in circulating estrogen, decrease in androgen or the sensitivity of the breast tissue to the circulating estrogen.<ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref>
*It is thought that [[gynecomastia]] can result from any condition, [[drug]] or disease state that causes an increase in circulating [[estrogen]], a decrease in [[androgen]] or the sensitivity of the [[breast]] tissue to the circulating [[estrogen]].<ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref>
*The imbalance of estrogen/androgen can be due to increased levels of free estrogen secreted by the adrenals or testes, decreased estrogen breakdown, increased availability of estrogen precursors, exposure to estrogen like products or use of drugs that displaces more estrogen than androgen from sex hormone-binding globulin (SHBG).  
*The imbalance of [[estrogen]]/[[androgen]] can be due to increased levels of free [[estrogen]] secreted by the [[Adrenal|adrenals]] or [[testes]], decreased [[estrogen]] breakdown, increased availability of [[estrogen]] precursors, exposure to [[estrogen]] like products or use of drugs that displaces more [[estrogen]] than [[androgen]] from [[sex hormone-binding globulin]] [[Sex hormone binding globulin|(SHBG).]]
*On the other hand, the imbalance can result from altered androgen metabolism, decreased androgen production, increased androgen binding (relative to estrogen) by SHBG, or androgen receptor defects.<ref name="pmid19880691">{{cite journal| author=Johnson RE, Murad MH| title=Gynecomastia: pathophysiology, evaluation, and management. | journal=Mayo Clin Proc | year= 2009 | volume= 84 | issue= 11 | pages= 1010-5 | pmid=19880691 | doi=10.1016/S0025-6196(11)60671-X | pmc=2770912 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19880691  }} </ref> <ref name="pmid11546925">{{cite journal| author=Mathur R, Braunstein GD| title=Gynecomastia: pathomechanisms and treatment strategies. | journal=Horm Res | year= 1997 | volume= 48 | issue= 3 | pages= 95-102 | pmid=11546925 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11546925  }} </ref> <ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref>
*On the other hand, the imbalance can result from altered [[androgen]] metabolism, decreased [[androgen]] production, increased [[androgen]] binding (relative to [[estrogen]]) by [[SHBG]], or [[androgen]] receptor defects.<ref name="pmid19880691">{{cite journal| author=Johnson RE, Murad MH| title=Gynecomastia: pathophysiology, evaluation, and management. | journal=Mayo Clin Proc | year= 2009 | volume= 84 | issue= 11 | pages= 1010-5 | pmid=19880691 | doi=10.1016/S0025-6196(11)60671-X | pmc=2770912 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19880691  }} </ref> <ref name="pmid11546925">{{cite journal| author=Mathur R, Braunstein GD| title=Gynecomastia: pathomechanisms and treatment strategies. | journal=Horm Res | year= 1997 | volume= 48 | issue= 3 | pages= 95-102 | pmid=11546925 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11546925  }} </ref> <ref name="pmid25905330">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng JCM |title= |journal= |volume= |issue= |pages= |year= |pmid=25905330 |doi= |url=}}</ref>
====Examples ====
[[image:Gynecomastia pathophysiology.jpeg|400px|center]]
 
====Some examples regarding gynecomastia development based on the pathophysiology include: ====
{| class="wikitable"
{| class="wikitable"
!Conditions causing increased estrogen
!Conditions causing increased estrogen
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|-
|
|
* Chronic liver disease
* [[Liver disease|Chronic liver disease]]
|
|
* [[Androgen-insensitivity syndrome]]
* [[Androgen-insensitivity syndrome]]
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|-
|-
|
|
* Large cell carcinoma of the lung
* [[Large cell carcinoma of the lung]]
|
|
* [[Kallman Syndrome]]
* [[Kallman Syndrome]]
|-
|-
|
|
* Chronic kidney disease
* [[Chronic kidney disease]]
|
|
* [[Klinefelter Syndrome]]
* [[Klinefelter Syndrome]]
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|
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* Testicular trauma
* [[Testicular trauma]]
|}
|}


==Genetics==
==Genetics==
*Genes involved in the pathogenesis of aromatase overexpression form of gynecomastia is encoded by a chromosome 15q21.2.<ref name="pmid12736278">{{cite journal| author=Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K et al.| title=Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 19 | pages= 1855-65 | pmid=12736278 | doi=10.1056/NEJMoa021559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12736278  }} </ref>
Genes involved in the pathogenesis of [[Aromatase|aromatase overexpression]] form of gynecomastia is encoded by a [[chromosome]] 15q21.2.<ref name="pmid12736278">{{cite journal| author=Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K et al.| title=Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 19 | pages= 1855-65 | pmid=12736278 | doi=10.1056/NEJMoa021559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12736278  }} </ref> As a result, any [[mutation]] in the mentioned loci result in [[Aromatase|aromatase overexpression]].
==Associated Conditions==
==Associated Conditions==
Gynecomastia is associated with psychological stresses.<ref name="WassersugOliffe2009">{{cite journal|last1=Wassersug|first1=Richard J.|last2=Oliffe|first2=John L.|title=The Social Context for Psychological Distress from Iatrogenic Gynecomastia with Suggestions for Its Management|journal=The Journal of Sexual Medicine|volume=6|issue=4|year=2009|pages=989–1000|issn=17436095|doi=10.1111/j.1743-6109.2008.01053.x}}</ref>
Gynecomastia is associated with [[psychological]] [[stress]] such as:<ref name="WassersugOliffe2009">{{cite journal|last1=Wassersug|first1=Richard J.|last2=Oliffe|first2=John L.|title=The Social Context for Psychological Distress from Iatrogenic Gynecomastia with Suggestions for Its Management|journal=The Journal of Sexual Medicine|volume=6|issue=4|year=2009|pages=989–1000|issn=17436095|doi=10.1111/j.1743-6109.2008.01053.x}}</ref><ref name="StrømsvikRåheim2010">{{cite journal|last1=Strømsvik|first1=Nina|last2=Råheim|first2=Målfrid|last3=Øyen|first3=Nina|last4=Engebretsen|first4=Lars Fredrik|last5=Gjengedal|first5=Eva|title=Stigmatization and Male Identity: Norwegian Males’ Experience after Identification as BRCA1/2 Mutation Carriers|journal=Journal of Genetic Counseling|volume=19|issue=4|year=2010|pages=360–370|issn=1059-7700|doi=10.1007/s10897-010-9293-1}}</ref><ref name="HackSawatzky2010">{{cite journal|last1=Hack|first1=Thomas F.|last2=Sawatzky|first2=Jo-Ann|last3=Pedersen|first3=Allison E.|title=The Sequelae of Anxiety in Breast Cancer: A Human Response to Illness Model|journal=Oncology Nursing Forum|volume=37|issue=4|year=2010|pages=469–475|issn=0190-535X|doi=10.1188/10.ONF.469-475}}</ref><ref name="Senín-CalderónRodríguez-Testal2017">{{cite journal|last1=Senín-Calderón|first1=Cristina|last2=Rodríguez-Testal|first2=Juan F.|last3=Perona-Garcelán|first3=Salvador|last4=Perpiñá|first4=Conxa|title=Body image and adolescence: A behavioral impairment model|journal=Psychiatry Research|volume=248|year=2017|pages=121–126|issn=01651781|doi=10.1016/j.psychres.2016.12.003}}</ref>
*[[Depression]]
*Decreased [[self-esteem]]
*Body dissatisfaction
==Gross Pathology==
On gross [[pathology]], characteristic findings of gynecomastia include:
*Excessive [[breast tissue]] and [[Areolar tissue|subareolar]] mass 
*Well circumscribed borders
*Firm surfaces


==Gross Pathology==
*On gross pathology, excessive breast tissue and subaerolar mass are characteristic findings of gynecomastia.
[[Image:Gynecomastia_1.jpg|left|300px|'''Gynecomastia''', source:https://librepathology.org]]
<br style="clear:left">
==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, ductal hyperplasia, increase in periductal connective tissue, are characteristic findings of gynecomastia.<ref name="pmid5539033">{{cite journal| author=Nicolis GL, Modlinger RS, Gabrilove JL| title=A study of the histopathology of human gynecomastia. | journal=J Clin Endocrinol Metab | year= 1971 | volume= 32 | issue= 2 | pages= 173-8 | pmid=5539033 | doi=10.1210/jcem-32-2-173 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5539033  }} </ref>
On microscopic inspection, gynecomastia histology shows:<ref name="pmid5539033">{{cite journal| author=Nicolis GL, Modlinger RS, Gabrilove JL| title=A study of the histopathology of human gynecomastia. | journal=J Clin Endocrinol Metab | year= 1971 | volume= 32 | issue= 2 | pages= 173-8 | pmid=5539033 | doi=10.1210/jcem-32-2-173 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5539033  }} </ref>
*[[Hyperplasia|Ductal hyperplasia]]
*Lengthening of the [[ducts]]
*[[inflammation]] surrounding the ducts
*Increase in periductal [[connective tissue]]


[[Image:Gynecomastia 2 (2).jpg|200px|left|frame|'''Ductal hyperplasia''', source:https://librepathology.org]]
[[Image:Gynecomastia 2 (2).jpg|200px|left|frame|'''Ductal hyperplasia''', source:https://librepathology.org]]
<br style="clear:left">
<br style="clear:left">
[[Image:1200px-Gynecomastoid hyperplasia - very high mag.jpg|thumb|400px|left|frame|'''Gynecomastoid hyperplasia''', source:https://librepathology.org]]
<br style="clear:left">
==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Endocrinology]]

Latest revision as of 14:51, 15 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Overview

The main pathophysiology behind gynecomastia is increased estrogen to androgen ratio which can occur through multiple mechanisms. These mechanisms can be physiological, pathological or pharmacological.

Pathophysiology

Hormones involved in breast development


 
 
 
 
 
 
 
 
 
 
Breast Tissue
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stimulatory Action
 
 
 
 
 
 
 
 
 
 
 
 
 
Inhibitory Action
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Estrogen
 
 
 
 
 
 
 
 
 
 
 
 
 
Androgens
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GH & IGF-1
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pathogenesis

Some examples regarding gynecomastia development based on the pathophysiology include:

Conditions causing increased estrogen Conditions causing decreased testosterone

Genetics

Genes involved in the pathogenesis of aromatase overexpression form of gynecomastia is encoded by a chromosome 15q21.2.[8] As a result, any mutation in the mentioned loci result in aromatase overexpression.

Associated Conditions

Gynecomastia is associated with psychological stress such as:[11][12][13][14]

Gross Pathology

On gross pathology, characteristic findings of gynecomastia include:

Microscopic Pathology

On microscopic inspection, gynecomastia histology shows:[15]

Ductal hyperplasia, source:https://librepathology.org


Gynecomastoid hyperplasia, source:https://librepathology.org


References

  1. ↑ Bocchinfuso WP, Korach KS (1997). "Mammary gland development and tumorigenesis in estrogen receptor knockout mice". J Mammary Gland Biol Neoplasia. 2 (4): 323–34. PMID 10935020.
  2. ↑ Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O (1993). "Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene". Proc. Natl. Acad. Sci. U.S.A. 90 (23): 11162–6. PMC 47942. PMID 8248223.
  3. ↑ Kleinberg DL, Feldman M, Ruan W (2000). "IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis". J Mammary Gland Biol Neoplasia. 5 (1): 7–17. PMID 10791764.
  4. ↑ Mieritz MG, Sorensen K, Aksglaede L, Mouritsen A, Hagen CP, Hilsted L, Andersson AM, Juul A (2014). "Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia". Clin. Endocrinol. (Oxf). 80 (5): 691–8. doi:10.1111/cen.12323. PMID 24033660.
  5. ↑ 5.0 5.1 5.2 De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng J. PMID 25905330. Vancouver style error: initials (help); Missing or empty |title= (help)
  6. ↑ Barros AC, Sampaio Mde C (2012). "Gynecomastia: physiopathology, evaluation and treatment". Sao Paulo Med J. 130 (3): 187–97. PMID 22790552.
  7. ↑ Li X, Wärri A, Mäkelä S, Ahonen T, Streng T, Santti R; et al. (2002). "Mammary gland development in transgenic male mice expressing human P450 aromatase". Endocrinology. 143 (10): 4074–83. doi:10.1210/en.2002-220181. PMID 12239119.
  8. ↑ 8.0 8.1 Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K; et al. (2003). "Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene". N Engl J Med. 348 (19): 1855–65. doi:10.1056/NEJMoa021559. PMID 12736278.
  9. ↑ Johnson RE, Murad MH (2009). "Gynecomastia: pathophysiology, evaluation, and management". Mayo Clin Proc. 84 (11): 1010–5. doi:10.1016/S0025-6196(11)60671-X. PMC 2770912. PMID 19880691.
  10. ↑ Mathur R, Braunstein GD (1997). "Gynecomastia: pathomechanisms and treatment strategies". Horm Res. 48 (3): 95–102. PMID 11546925.
  11. ↑ Wassersug, Richard J.; Oliffe, John L. (2009). "The Social Context for Psychological Distress from Iatrogenic Gynecomastia with Suggestions for Its Management". The Journal of Sexual Medicine. 6 (4): 989–1000. doi:10.1111/j.1743-6109.2008.01053.x. ISSN 1743-6095.
  12. ↑ Strømsvik, Nina; Råheim, Målfrid; Øyen, Nina; Engebretsen, Lars Fredrik; Gjengedal, Eva (2010). "Stigmatization and Male Identity: Norwegian Males' Experience after Identification as BRCA1/2 Mutation Carriers". Journal of Genetic Counseling. 19 (4): 360–370. doi:10.1007/s10897-010-9293-1. ISSN 1059-7700.
  13. ↑ Hack, Thomas F.; Sawatzky, Jo-Ann; Pedersen, Allison E. (2010). "The Sequelae of Anxiety in Breast Cancer: A Human Response to Illness Model". Oncology Nursing Forum. 37 (4): 469–475. doi:10.1188/10.ONF.469-475. ISSN 0190-535X.
  14. ↑ Senín-Calderón, Cristina; Rodríguez-Testal, Juan F.; Perona-Garcelán, Salvador; Perpiñá, Conxa (2017). "Body image and adolescence: A behavioral impairment model". Psychiatry Research. 248: 121–126. doi:10.1016/j.psychres.2016.12.003. ISSN 0165-1781.
  15. ↑ Nicolis GL, Modlinger RS, Gabrilove JL (1971). "A study of the histopathology of human gynecomastia". J Clin Endocrinol Metab. 32 (2): 173–8. doi:10.1210/jcem-32-2-173. PMID 5539033.
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