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==Overview== | ==Overview== | ||
[[Prolactinoma]] is the most common type of [[ | [[Prolactinoma]] is the most common type of [[pituitary adenoma]]. [[Prolactinoma]] may occur in approximately 30% of [[multiple endocrine neoplasia type 1]] patients. It may also occur with [[Carney complex]] or [[McCune-Albright syndrome]]. There are a few reports of [[familial]] cases of [[prolactinoma]] unrelated to [[Multiple endocrine neoplasia type 1|MEN 1 syndrome]].<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062 }} </ref> | ||
[[Prolactinoma]] is also associated with various [[familial]] syndromes.<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue= | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551 }} </ref> On gross pathology, [[prolactinoma]] is divided on the basis of size into microprolactinoma and macroprolactinoma. On microscopic histological analysis, [[prolactinoma]] has two types: sparsely granulated and densely granulated. | |||
==Pathophysiology== | ==Pathophysiology== | ||
*[[Prolactinoma]] are [[monoclonal]] in nature. This suggests that [[somatic]] [[Cell (biology)|cell]] [[mutation]] occurs before clonal expansion of [[Lactotroph|lactotrophs]].<ref name="pmid1977759">{{cite journal| author=Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S| title=Clonal origin of pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1990 | volume= 71 | issue= 6 | pages= 1427-33 | pmid=1977759 | doi=10.1210/jcem-71-6-1427 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977759 }} </ref> | *[[Prolactinoma]] are [[monoclonal]] in nature. This suggests that [[somatic]] [[Cell (biology)|cell]] [[mutation]] occurs before clonal expansion of [[Lactotroph|lactotrophs]].<ref name="pmid1977759">{{cite journal| author=Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S| title=Clonal origin of pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1990 | volume= 71 | issue= 6 | pages= 1427-33 | pmid=1977759 | doi=10.1210/jcem-71-6-1427 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1977759 }} </ref> | ||
* | *One [[gene]] involved in the pathogenesis of [[prolactinoma]] is the [[PTTG1|pituitary tumor transforming gene-1]] ([[PTTG1|PTTG-1]]).<ref name="pmid17325339">{{cite journal| author=Vlotides G, Eigler T, Melmed S| title=Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. | journal=Endocr Rev | year= 2007 | volume= 28 | issue= 2 | pages= 165-86 | pmid=17325339 | doi=10.1210/er.2006-0042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17325339 }} </ref><ref name="pmid10022450">{{cite journal| author=Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD et al.| title=Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. | journal=J Clin Endocrinol Metab | year= 1999 | volume= 84 | issue= 2 | pages= 761-7 | pmid=10022450 | doi=10.1210/jcem.84.2.5432 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022450 }} </ref> | ||
**PTTG-1 gene is related to various endocrine and non-endocrine tumors such as: | **The [[PTTG1|PTTG-1 gene]] is related to various endocrine and non-endocrine tumors such as: | ||
***Endocrine related tumors: [[pituitary]], [[thyroid]], [[breast]], [[ovarian]], and [[uterine]] tumors. | ***Endocrine related tumors: [[pituitary]], [[thyroid]], [[breast]], [[ovarian]], and [[uterine]] tumors. | ||
***Non-endocrine related | ***Non-endocrine related tumors: [[central nervous system]], [[pulmonary]], and [[gastrointestinal]] tumors. | ||
**[[ | **[[Prolactinomas]] with a higher expression of the [[PTTG1|PTTG-1 gene]] tend to be more [[invasive]]. | ||
*Many [[ | *Many [[prolactinomas]] are related to [[multiple endocrine neoplasia type 1]].<ref name="pmid15153434">{{cite journal| author=Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB et al.| title=Molecular pathology of the MEN1 gene. | journal=Ann N Y Acad Sci | year= 2004 | volume= 1014 | issue= | pages= 189-98 | pmid=15153434 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15153434 }} </ref> | ||
** [[MEN1]] [[gene]] is located on 11q13. | ** The [[MEN1]] [[gene]] is located on 11q13. | ||
** [[MEN1]] [[gene]] is a [[tumor suppressor gene]] | ** The [[MEN1]] [[gene]] is a [[tumor suppressor gene]] that follows the '[[Tumor suppressor gene|two-hit hypothesis]],' which implies that both [[Allele|alleles]] that code for a particular [[gene]] must be affected before an effect manifests. | ||
**This is due to the fact that if only one [[allele]] for the [[gene]] is damaged, the second can still produce the correct [[protein]]. | **This is due to the fact that if only one [[allele]] for the [[gene]] is damaged, the second can still produce the correct [[protein]]. | ||
**Affected individuals | **Affected individuals carry one altered copy of the [[MEN1]] [[gene]] and the other copy is lost due to [[somatic]] [[mutation]]. | ||
==Associated Diseases== | ==Associated Diseases== | ||
[[Prolactinoma]] may be associated with:<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062 }} </ref> | [[Prolactinoma]] may be associated with:<ref name="pmid16411062">{{cite journal| author=Ciccarelli A, Daly AF, Beckers A| title=The epidemiology of prolactinomas. | journal=Pituitary | year= 2005 | volume= 8 | issue= 1 | pages= 3-6 | pmid=16411062 | doi=10.1007/s11102-005-5079-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16411062 }} </ref> | ||
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==Genetics== | ==Genetics== | ||
====Familial | ====Familial Pituitary adenoma|pituitary adenomas==== | ||
*A pituitary adenoma may be part of a familial syndrome:<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue= | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551 }} </ref> | *A [[pituitary adenoma]] may be part of a familial syndrome:<ref name="pmid17613551">{{cite journal| author=Karhu A, Aaltonen LA| title=Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. | journal=Hum Mol Genet | year= 2007 | volume= 16 Spec No 1 | issue= | pages= R73-9 | pmid=17613551 | doi=10.1093/hmg/ddm036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17613551 }} </ref> | ||
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto" | {| class="wikitable sortable" style="margin-left:auto;margin-right:auto" | ||
! Syndrome | ! Syndrome | ||
| Line 36: | Line 37: | ||
|- | |- | ||
| [[Multiple endocrine neoplasia type 1|Multiple endocrine neoplasia I]] | | [[Multiple endocrine neoplasia type 1|Multiple endocrine neoplasia I]] | ||
| MEN1 | | [[MEN1]] | ||
| 11q13 | | 11q13 | ||
| Characterized by the 3 Ps: [[Pituitary adenoma|'''p'''ituitary adenoma]], [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[Pancreatic neuroendocrine tumor|'''p'''ancreatic neuroendocrine tumor]] | | Characterized by the 3 Ps: [[Pituitary adenoma|'''p'''ituitary adenoma]], [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[Pancreatic neuroendocrine tumor|'''p'''ancreatic neuroendocrine tumor]] | ||
| Line 43: | Line 44: | ||
| CDKN1B | | CDKN1B | ||
| 12q13 | | 12q13 | ||
| Associated with pituitary adenoma, parathyroid adenoma, neuroendocrine tumor | | Associated with [[pituitary adenoma]], [[parathyroid adenoma]], [[neuroendocrine tumor]] | ||
|- | |- | ||
| [[Carney complex]] | | [[Carney complex]] | ||
| PRKAR1A | | [[PRKAR1A]] | ||
| 17q24 | | 17q24 | ||
| Other findings (mnemonic ''NAME''): [[Nevus|nevi]], [[atrial myxoma]], myxoid [[neurofibroma]], ephelides ([[freckles]]) | | Other findings (mnemonic ''NAME''): [[Nevus|nevi]], [[atrial myxoma]], myxoid [[neurofibroma]], ephelides ([[freckles]]) | ||
| Line 54: | Line 55: | ||
| 11q13 | | 11q13 | ||
| | | | ||
*Classically growth hormone-producing adenoma | *Classically [[growth hormone]]-producing [[adenoma]], leads to [[acromegaly]] | ||
*May also be associated with prolactinomas | *May also be associated with prolactinomas<ref name="pmid22612670">{{cite journal| author=Korbonits M, Storr H, Kumar AV| title=Familial pituitary adenomas - who should be tested for AIP mutations? | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 3 | pages= 351-6 | pmid=22612670 | doi=10.1111/j.1365-2265.2012.04445.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22612670 }} </ref> | ||
|} | |} | ||
==Gross Pathology== | ==Gross Pathology== | ||
Gross pathology of [[prolactinoma]] is as follows:<ref>{{cite book | last = Bigner | first = D. D. | title = Russell and Rubinstein's pathology of tumors of the nervous system | publisher = Hodder Arnold Distributed in the United States of America by Oxford University Press | location = London New York, NY | year = 2006 | isbn = 978-0340810071 }}</ref> | Gross pathology of [[prolactinoma]] is as follows:<ref>{{cite book | last = Bigner | first = D. D. | title = Russell and Rubinstein's pathology of tumors of the nervous system | publisher = Hodder Arnold Distributed in the United States of America by Oxford University Press | location = London New York, NY | year = 2006 | isbn = 978-0340810071 }}</ref> | ||
* | *Microprolactinomas (<10mm size) are usually found in the [[lateral]] wing of [[pituitary gland]]. They are most often surrounded by well defined pseudocapsules composed of [[reticulin]]. | ||
* | *Macroprolactinomas (>10mm size) differ substantially in size and behavior. Some cause [[Sella turcica|sellar]] expansion while others invade the [[skull]] base. | ||
*About 50% of all [[prolactinoma]] grossly invade surrounding | *About 50% of all [[prolactinoma]] grossly invade surrounding structures. | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
*[[Prolactinoma]] are | *[[Prolactinoma]] are divded into two types based on microscopy: | ||
# Sparsely granulated variant | # Sparsely granulated variant | ||
# Densely granulated variant | # Densely granulated variant | ||
Revision as of 18:44, 8 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2], Faizan Sheraz, M.D. [3]
Overview
Prolactinoma is the most common type of pituitary adenoma. Prolactinoma may occur in approximately 30% of multiple endocrine neoplasia type 1 patients. It may also occur with Carney complex or McCune-Albright syndrome. There are a few reports of familial cases of prolactinoma unrelated to MEN 1 syndrome.[1]
Prolactinoma is also associated with various familial syndromes.[2] On gross pathology, prolactinoma is divided on the basis of size into microprolactinoma and macroprolactinoma. On microscopic histological analysis, prolactinoma has two types: sparsely granulated and densely granulated.
Pathophysiology
- Prolactinoma are monoclonal in nature. This suggests that somatic cell mutation occurs before clonal expansion of lactotrophs.[3]
- One gene involved in the pathogenesis of prolactinoma is the pituitary tumor transforming gene-1 (PTTG-1).[4][5]
- The PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Endocrine related tumors: pituitary, thyroid, breast, ovarian, and uterine tumors.
- Non-endocrine related tumors: central nervous system, pulmonary, and gastrointestinal tumors.
- Prolactinomas with a higher expression of the PTTG-1 gene tend to be more invasive.
- The PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Many prolactinomas are related to multiple endocrine neoplasia type 1.[6]
- The MEN1 gene is located on 11q13.
- The MEN1 gene is a tumor suppressor gene that follows the 'two-hit hypothesis,' which implies that both alleles that code for a particular gene must be affected before an effect manifests.
- This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein.
- Affected individuals carry one altered copy of the MEN1 gene and the other copy is lost due to somatic mutation.
Associated Diseases
Prolactinoma may be associated with:[1]
Genetics
Familial Pituitary adenoma|pituitary adenomas
- A pituitary adenoma may be part of a familial syndrome:[2]
| Syndrome | Gene | Gene locus | Notes |
|---|---|---|---|
| Multiple endocrine neoplasia I | MEN1 | 11q13 | Characterized by the 3 Ps: pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumor |
| MEN1-like syndrome | CDKN1B | 12q13 | Associated with pituitary adenoma, parathyroid adenoma, neuroendocrine tumor |
| Carney complex | PRKAR1A | 17q24 | Other findings (mnemonic NAME): nevi, atrial myxoma, myxoid neurofibroma, ephelides (freckles) |
| Familial isolated pituitary adenoma | AIP | 11q13 |
|
Gross Pathology
Gross pathology of prolactinoma is as follows:[8]
- Microprolactinomas (<10mm size) are usually found in the lateral wing of pituitary gland. They are most often surrounded by well defined pseudocapsules composed of reticulin.
- Macroprolactinomas (>10mm size) differ substantially in size and behavior. Some cause sellar expansion while others invade the skull base.
- About 50% of all prolactinoma grossly invade surrounding structures.
Microscopic Pathology
- Prolactinoma are divded into two types based on microscopy:
- Sparsely granulated variant
- Densely granulated variant
References
- ↑ 1.0 1.1 Ciccarelli A, Daly AF, Beckers A (2005). "The epidemiology of prolactinomas". Pituitary. 8 (1): 3–6. doi:10.1007/s11102-005-5079-0. PMID 16411062.
- ↑ 2.0 2.1 Karhu A, Aaltonen LA (2007). "Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update". Hum Mol Genet. 16 Spec No 1: R73–9. doi:10.1093/hmg/ddm036. PMID 17613551.
- ↑ Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S (1990). "Clonal origin of pituitary adenomas". J Clin Endocrinol Metab. 71 (6): 1427–33. doi:10.1210/jcem-71-6-1427. PMID 1977759.
- ↑ Vlotides G, Eigler T, Melmed S (2007). "Pituitary tumor-transforming gene: physiology and implications for tumorigenesis". Endocr Rev. 28 (2): 165–86. doi:10.1210/er.2006-0042. PMID 17325339.
- ↑ Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD; et al. (1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". J Clin Endocrinol Metab. 84 (2): 761–7. doi:10.1210/jcem.84.2.5432. PMID 10022450.
- ↑ Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB; et al. (2004). "Molecular pathology of the MEN1 gene". Ann N Y Acad Sci. 1014: 189–98. PMID 15153434.
- ↑ Korbonits M, Storr H, Kumar AV (2012). "Familial pituitary adenomas - who should be tested for AIP mutations?". Clin Endocrinol (Oxf). 77 (3): 351–6. doi:10.1111/j.1365-2265.2012.04445.x. PMID 22612670.
- ↑ Bigner, D. D. (2006). Russell and Rubinstein's pathology of tumors of the nervous system. London New York, NY: Hodder Arnold Distributed in the United States of America by Oxford University Press. ISBN 978-0340810071.