Editing Carpal tunnel syndrome (section)

=== Discrete pathophysiology and CTS ===

Hereditary neuropathy with susceptibility to pressure palsies is a genetic condition that appears to increase the probability of developing CTS. Heterozygous mutations in the gene [[SH3TC2]], associated with [[Charcot-Marie-Tooth]], may confer susceptibility to [[neuropathy]], including CTS.<ref>{{cite journal | vauthors = Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA | title = Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy | journal = The New England Journal of Medicine | volume = 362 | issue = 13 | pages = 1181–1191 | date = April 2010 | pmid = 20220177 | pmc = 4036802 | doi = 10.1056/NEJMoa0908094 }}</ref>

Association between common benign tumors such as [[lipomas]], [[ganglion]], and [[vascular malformation]] should be handled with care. Such tumors are very common and are more likely to cause  pressure on the median nerve.<ref name="Tiong_2005">{{cite journal | vauthors = Kellett J, McKeown P, Deane B | title = Differences between self-referred and physician-referred hospital admissions | journal = Irish Journal of Medical Science | volume = 174 | issue = 3 | pages = 70–78 | year = 2005 | pmid = 16285343 | doi = 10.1007/BF03170208 | s2cid = 71606479 }}</ref> Similarly, the association between [[Familial amyloid polyneuropathy|transthyretin amyloidosis]]-associated [[polyneuropathy]] and carpal tunnel syndrome is under investigation. Prior carpal tunnel release is often noted in individuals who later present with [[transthyretin]] amyloid-associated [[cardiomyopathy]].<ref>{{cite journal | vauthors = Conceição I, González-Duarte A, Obici L, Schmidt HH, Simoneau D, Ong ML, Amass L | title = "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy | journal = Journal of the Peripheral Nervous System | volume = 21 | issue = 1 | pages = 5–9 | date = March 2016 | pmid = 26663427 | pmc = 4788142 | doi = 10.1111/jns.12153 }}</ref> There is consideration that bilateral carpal tunnel syndrome could be a reason to consider amyloidosis, timely diagnosis of which could improve heart health.<ref>{{cite journal | vauthors = Donnelly JP, Hanna M, Sperry BW, Seitz WH | title = Carpal Tunnel Syndrome: A Potential Early, Red-Flag Sign of Amyloidosis | journal = The Journal of Hand Surgery | volume = 44 | issue = 10 | pages = 868–876 | date = October 2019 | pmid = 31400950 | doi = 10.1016/j.jhsa.2019.06.016 | s2cid = 199540407 | doi-access = free }}</ref> Amyloidosis is rare, even among people with carpal tunnel syndrome (0.55% incidence within 10 years of carpal tunnel release).<ref name="Sood 1284–1294">{{cite journal | vauthors = Sood RF, Kamenko S, McCreary E, Sather BK, Schmitt M, Peterson SL, Lipira AB | title = Diagnosing Systemic Amyloidosis Presenting as Carpal Tunnel Syndrome: A Risk Nomogram to Guide Biopsy at Time of Carpal Tunnel Release | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 103 | issue = 14 | pages = 1284–1294 | date = July 2021 | pmid = 34097669 | doi = 10.2106/JBJS.20.02093 | s2cid = 235370526 }}</ref> In the absence of other factors associated with a notable probability of amyloidosis, it is not clear that biopsy at the time of carpal tunnel release has a suitable balance between potential harms and potential benefits.<ref name="Sood 1284–1294" />

Other specific pathophysiologies that can cause CTS via pressure include:
* Rheumatoid arthritis and other diseases that cause inflammation of the flexor tendons.
* With severe untreated [[hypothyroidism]], generalized [[myxedema]] causes deposition of [[mucopolysaccharides]] within both the perineurium of the [[median nerve]], as well as the tendons passing through the carpal tunnel. Association of CTS with lesser degrees of [[hypothyroidism]] is questioned.
* [[Pregnancy]] may bring out symptoms in genetically predisposed individuals, which may be caused by the temporary changes in hormones and fluid increase pressure in the carpal tunnel.<ref name="Padua 1273–1284" /> High [[progesterone]] levels and water retention may increase the size of  the [[synovium]].
* Bleeding and swelling from a fracture or dislocation. This is referred to as acute carpal tunnel syndrome.<ref>{{cite journal | vauthors = Dyer G, Lozano-Calderon S, Gannon C, Baratz M, Ring D | title = Predictors of acute carpal tunnel syndrome associated with fracture of the distal radius | journal = The Journal of Hand Surgery | volume = 33 | issue = 8 | pages = 1309–1313 | date = October 2008 | pmid = 18929193 | doi = 10.1016/j.jhsa.2008.04.012 }}</ref>
* [[Acromegaly]] causes excessive secretion of [[growth hormone]]s. This causes the soft tissues and bones around the carpal tunnel to grow and compress the median nerve.<ref>{{Cite web|title=Carpel Tunnel Syndrome in Acromegaly|url=http://www.treatmentandsymptoms.com/endocrine/acromegaly/|url-status=dead|archive-url=https://web.archive.org/web/20160126014823/http://www.treatmentandsymptoms.com/endocrine/acromegaly/|archive-date=2016-01-26|access-date=2011-10-05|publisher=Treatmentandsymptoms.com}}</ref>

====Other considerations====
* [[Pathophysiology of nerve entrapment#Double crush syndrome|Double crush syndrome]] is a debated hypothesis that [[Nerve compression syndrome|nerve compression]] or irritation of nerve branches contributing to the median nerve in the neck, or anywhere above the wrist, increases sensitivity of the nerve to compression in the wrist. There is little evidence to support this theory and some concern that it may be used to justify more surgery.<ref name=":0">{{cite journal | vauthors = Molinari WJ, Elfar JC | title = The double crush syndrome | journal = The Journal of Hand Surgery | volume = 38 | issue = 4 | pages = 799–801; quiz 801 | date = April 2013 | pmid = 23466128 | pmc = 5823245 | doi = 10.1016/j.jhsa.2012.12.038 }}</ref><ref>{{cite journal | vauthors = Kane PM, Daniels AH, Akelman E | title = Double Crush Syndrome | journal = The Journal of the American Academy of Orthopaedic Surgeons | volume = 23 | issue = 9 | pages = 558–562 | date = September 2015 | pmid = 26306807 | doi = 10.5435/JAAOS-D-14-00176 | s2cid = 207531472 | doi-access = free }}</ref>