Gynecomastia pathophysiology: Difference between revisions
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*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 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> | ||
*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 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> | ||
*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> | |||
==Genetics== | ==Genetics== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
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.[1]
- 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). 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.[2] [3] [1]
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.[4] [5]
- Growth hormone which acts through IGF-1 acts as a mediator in the presence of estrogen and progesterone for ductal breast duct development.[6] 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.[7]
- 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.[1] [8]
Genetics
- [Disease name] is transmitted in [mode of genetic transmission] pattern.
- Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
- The development of [disease name] is the result of multiple genetic mutations.
Associated Conditions
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
The condition can occur physiologically in neonates, in adolescents,adults and in the elderly. In adolescent boys the condition is a source of distress, but for the large majority of boys whose pubertal gynecomastia is not due to obesity, the breast development shrinks or disappears within a couple of years [9]. The common type of gynecomastia in males undergoing pueberty is idiopathic in nature.One should be aware that several causes of gynecomastia have significant sequela and need to be ruled out ethier by history and or laboratory examinations prior to treatment of the disorder. The most common presentation of gynecomastia is idiopathic in nature. It is important to note that pituitary and adrenal tumors can result in gynecomastia. In addition several other endocrinological disorders such as klinefelters syndrome can be associated with gynecomastia and should be ruled out in pre pubertal individuals.Male breast cancer although rare needs to be considered in the differential diagnosis, particularly in cases that are of rapid onset and are unilateral in nature. Several types of exogenously injested substances , most notably steroids, can result in gynecomastia. Breast prominence can result from hypertrophy of breast tissue, chest adipose tissue and skin, and is typically in combination. Two types of tissue : glandular ,breast tissue , and fat ,adipose cells,compose the tissue in the breast. Optimal treatment needs to be directed at correction of the glandular and fatty tissue along with the skin envelope in each patient. As the relative volumes of the aforementioned components of the breast differ from individual to individual a patient specific treament plan needs to be established in all cases.The treatment plan in addition to correction of the obvious physical manifestations of the disease may need to be combined with an appropriate medical workup to establish and if necessary treat any concomitant disorder. [10] [11].
Physiologic gynecomastia occurs in neonates, at or before puberty and with aging. Many cases of gynecomastia are idiopathic, meaning they have no clear cause. Potential pathologic causes of gynecomastia are: medications including hormones, increased serum estrogen, decreased testosterone production, androgen receptor defects, chronic kidney disease, chronic liver disease, HIV,[12] and other chronic illness. Gynecomastia as a result of spinal cord injury and refeeding after starvation has been reported.[13] In 25% of cases, the cause of the gynecomastia is not known.
Medications cause 10-20% of cases of gynecomastia in post-adolescent adults. These include cimetidine, omeprazole, spironolactone, imatinib mesylate, finasteride and certain antipsychotics. Some act directly on the breast tissue, while others lead to increased secretion of prolactin from the pituitary by blocking the actions of dopamine (prolactin-inhibiting factor/PIF) on the lactotrope cell groups in the anterior pituitary. Androstenedione, used as a performance enhancing food supplement, can lead to breast enlargement by excess estrogen activity. Medications used in the treatment of prostate cancer, such as antiandrogens and GnRH analogs can also cause gynecomastia. Marijuana use is also thought by some to be a possible cause; however, published data is contradictory.[14]
Increased estrogen levels can also occur in certain testicular tumors, and in hyperthyroidism. Certain adrenal tumors cause elevated levels of androstenedione which is converted by the enzyme aromatase into estrone, a form of estrogen. Other tumors that secrete hCG can increase estrogen. A decrease in estrogen clearance can occur in liver disease, and this may be the mechanism of gynecomastia in liver cirrhosis. Obesity tends to increase estrogen levels.[15][16]
Decreased testosterone production can occur in congenital or acquired testicular failure, for example in genetic disorders such as Klinefelter Syndrome. Diseases of the hypothalamus or pituitary can also lead to low testosterone. Abuse of anabolic androgenic steroids (AAS) has a similar effect. Mutations to androgen receptors, such as those found in Kennedy disease can also cause gynecomastia.
Although stopping these medications can lead to regression of the gynecomastia, surgery is sometimes necessary to eliminate the condition.
Repeated topical application of products containing lavender and tea tree oils among other unidentified ingredients to three prepubescent males coincided with gynecomastia; it has been theorised that this could be due to their estrogenic and antiandrogenic activity. However, other circumstances around the study are not clear, and the sample size was insignificant so serious scientific conclusions cannot be drawn.[17]
References
- ↑ 1.0 1.1 1.2 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) - ↑ 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.
- ↑ Mathur R, Braunstein GD (1997). "Gynecomastia: pathomechanisms and treatment strategies". Horm Res. 48 (3): 95–102. PMID 11546925.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Barros AC, Sampaio Mde C (2012). "Gynecomastia: physiopathology, evaluation and treatment". Sao Paulo Med J. 130 (3): 187–97. PMID 22790552.
- ↑ Adolescent gynecomastia
- ↑ Braunstein, GD (1993). "Gynecomastia". N Engl J Med. 328 (7): 490–5. PMID 8421478. Unknown parameter
|month=ignored (help) - ↑ Allee, Mark R (2006-11-15). "Gynecomastia". WebMD, Inc. (emedicine.com). Retrieved 2007-05-20.
- ↑ Peyriere, H (1999). "Report of gynecomastia in five male patients during antiretroviral therapy for HIV infection". AIDS. 13 (15): 2167–9. PMID 10546872. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Heruti, RJ (1997). "Gynecomastia following spinal cord disorder". Arch Phys Med Rehabil. 78 (5): 534–7. PMID 9161376. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Thompson D, Carter J. "Drug-induced gynecomastia". Pharmacotherapy. 13 (1): 37–45. PMID 8094898.
- ↑ Glass, AR (1994). "Gynecomastia". Endocrinol Metab Clin North Am. 23 (4): 825–37. PMID 7705322. Unknown parameter
|month=ignored (help) - ↑ Braunstein, GD (1999). "Aromatase and Gynecomastia". Endocr Relat Cancer. 6 (2): 315–24. PMID 10731125. Unknown parameter
|month=ignored (help) - ↑ Henley D, Lipson N, Korach K, Bloch C (2007). "Prepubertal gynecomastia linked to lavender and tea tree oils". N Engl J Med. 356 (5): 479–85. PMID 17267908.