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[[Prolactinoma]] is the most common type of [[Pituitary adenoma|Pituitary adenomas]]. [[Prolactinoma]] may occur in approximately 30% of [[Multiple endocrine neoplasia type 1]].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 the most common type of [[Pituitary adenoma|Pituitary adenomas]]. [[Prolactinoma]] may occur in approximately 30% of [[Multiple endocrine neoplasia type 1]].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: microprolactinoma and macroprolactinoma. On microscopic histological analysis,[[prolactinoma]] has two types: sparsely granulated variant and densely granulated variant. | [[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: microprolactinoma and macroprolactinoma. On microscopic histological analysis, [[prolactinoma]] has two types: sparsely granulated variant and densely granulated variant. | ||
==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> | ||
*Gene involved in the pathogenesis of [[prolactinoma]] include Pituitary tumor transforming gene-1(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> | *Gene involved in the pathogenesis of [[prolactinoma]] include Pituitary tumor transforming gene-1(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 | **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 tumor: Tumors involving the central nervous, [[pulmonary]], and [[gastrointestinal]] systems. | ||
*** | |||
**[[Prolactinoma]] with higher expression of PTTG-1 gene tend to be more [[invasive]]. | **[[Prolactinoma]] with higher expression of PTTG-1 gene tend to be more [[invasive]]. | ||
*Many [[prolactinoma]] 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> | *Many [[prolactinoma]] 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> | ||
Revision as of 18:57, 28 July 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 adenomas. Prolactinoma may occur in approximately 30% of Multiple endocrine neoplasia type 1.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: microprolactinoma and macroprolactinoma. On microscopic histological analysis, prolactinoma has two types: sparsely granulated variant and densely granulated variant.
Pathophysiology
- Prolactinoma are monoclonal in nature. This suggests that somatic cell mutation occurs before clonal expansion of lactotrophs.[3]
- Gene involved in the pathogenesis of prolactinoma include Pituitary tumor transforming gene-1(PTTG-1).[4][5]
- PTTG-1 gene is related to various endocrine and non-endocrine tumors such as:
- Prolactinoma with higher expression of PTTG-1 gene tend to be more invasive.
- Many prolactinoma are related to multiple endocrine neoplasia type 1.[6]
- MEN1 gene is located on 11q13.
- MEN1 gene is a tumor suppressor gene which follows the 'two-hit hypothesis', which implies that both alleles that code for a particular gene must be affected before an effect is manifested.
- 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 carries one altered copy of MEN1 gene and the other copy is lost due to somatic mutation.
Associated Diseases
Prolactinoma may be associated with:[1]
Genetics
Familial 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]
- Microprolactinoma (<10mm size) are usually found in the lateral wing of pituitary gland. They are most often surrounded by well defined pseudocapsule composed of reticulin.
- Macroprolactinoma (>10mm size) differ substantially in size and behavior. Some causes sellar expansion while others invade the skull base.
- About 50% of all prolactinoma grossly invade surrounding structure.
Microscopic Pathology
- Prolactinoma are of 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.