Prolactinoma pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
*Prolactinoma are monoclonal in nature. This suggests that somatic cell mutation occurs before clonal expansion of 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>
*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>
** [[MEN1]] [[gene]] is located on 11q13.
** [[MEN1]] [[gene]] is located on 11q13.
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**Affected individuals carries one altered copy of [[MEN1]] [[gene]] and the other copy is lost due to [[somatic]] [[mutation]].
**Affected individuals carries one altered copy of [[MEN1]] [[gene]] and the other copy is lost due to [[somatic]] [[mutation]].
==Associated Diseases==
==Associated Diseases==
[[Prolactinoma]] may occur as part of a [[Genetic disorder|hereditary disorder]] called [[multiple endocrine neoplasia type 1]] ([[Multiple endocrine neoplasia type 1|MEN 1]]). A minority of [[prolactinoma]] are 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>
* [[Multiple endocrine neoplasia type 1]] ([[Multiple endocrine neoplasia type 1|MEN 1]])
 
*[[Carney complex]]
*[[Carney complex]]
*[[McCune-Albright Syndrome]]
*[[McCune-Albright Syndrome]]
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| ''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]]
|-
|-
| MEN1-like syndrome
| MEN1-like syndrome
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| ''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]])
|-
|-
| [[Familial]] isolated [[pituitary adenoma]]
| [[Familial]] isolated [[pituitary adenoma]]
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| 11q13
| 11q13
|
|
*classically growth hormone-producing adenoma - leads to [[acromegaly]]
*Classically growth hormone-producing adenoma - leads to [[acromegaly]]
*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>
*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>
|}
|}



Revision as of 20:53, 19 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]

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]

Pathophysiology

Associated Diseases

Prolactinoma may be associated with:[1]

Genetics

Familial pituitary adenomas

A pituitary adenoma may be part of a familial syndrome:[4]

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
  • Classically growth hormone-producing adenoma - leads to acromegaly
  • May also be associated with prolactinomas.[5]

Gross Pathology.[6]

  • 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

  1. sparsely granulated variant
  2. densely granulated variant


References

  1. 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. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.

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