Editing Myxedema

{{Short description|Extreme hypothyroidism}}
{{Hatnote|This article is about skin changes that occur in hypothyroidism. The word myxedema was historically used to refer [[hypothyroidism]] in general. For the related medical emergency, see [[myxedema coma]].}}
{{Infobox medical condition (new)
| name            = Myxedema
| synonyms        = '''Myxoedema'''
| image           = Hyaluronan.svg
| width           = 250
| caption         = [[Hyaluronan]], an example of a [[mucopolysaccharide]]
| pronounce       =
| field           = [[Endocrinology]]
| symptoms        =
| complications   =
| onset           =
| duration        =
| types           =
| causes          =
| risks           =
| diagnosis       =
| differential    =
| prevention      =
| treatment       =
| medication      =
| prognosis       =
| frequency       =
| deaths          =
}}

'''Myxedema''' ({{langx|en-GB|'''myxoedema'''}}) is a term used synonymously with severe [[hypothyroidism]], but also to describe a [[dermatology|dermatological]] change that can occur in hypothyroidism and (rare) [[paradoxical reaction|paradoxical]] cases of [[hyperthyroidism]]. In this latter sense, myxedema refers to deposition of [[mucopolysaccharide]]s in the [[dermis]], which results in [[Edema|swelling]] of the affected area. One manifestation of myxedema occurring in the lower limb is [[pretibial myxedema]], a hallmark of [[Graves disease]], an autoimmune form of [[hyperthyroidism]]. Myxedema can also occur in [[Hashimoto thyroiditis]] and other long-standing forms of [[hypothyroidism]].

==Signs and symptoms==
{{Multiple image
<!-- Essential parameters -->
| align = right
| direction = horizontal
| width = 175
<!-- Image 1 -->
| image1 = Myxedema face.png
| caption1 = Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor
<!-- Image 2 -->
| image2 = Myxedema standing.png
| caption2 = Additional findings include swelling of the arms and legs and significant [[ascites]].}}
[[File:BASA-3K-7-529-35(7)-Myxedema.jpg|thumb|Woman with myxedema, Bulgaria, 1930s.]]
Myxedema's characteristic physical sign is [[non-pitting edema]], in contrast to [[pitting edema]].<ref>{{Cite journal |last1=Bhutada |first1=Abhishek S. |last2=Kodankandath |first2=Thomas V. |date=July 2022 |title=Clinical Manifestations of Severe Untreated Hypothyroidism |journal=Cureus |volume=14 |issue=7 |pages=e26595 |doi=10.7759/cureus.26595 |doi-access=free |issn=2168-8184 |pmc=9354917 |pmid=35936163}}</ref>

Myxedema can also occur in the lower leg ([[pretibial myxedema]]) and behind the eyes ([[exophthalmos]]).{{cn|date=December 2024}}

Severe cases, requiring hospitalization can exhibit signs of hypothermia, hypoglycemia, hypotension, respiratory depression, and coma.{{cn|date=December 2024}}

==Causes==
Myxedema is known to occur in various forms of [[hypothyroidism]], as well as hyperthyroidism, including [[Graves disease]]. One of the hallmarks of Grave's disease is pretibial myxedema, myxedema of the lower limb.<ref name="Berger">{{cite book|last=Berger|first=William D. James, Dirk M. Elston, Timothy G.|title=Andrews' Diseases of the skin : clinical dermatology|publisher=Saunders/ Elsevier|location=[London]|isbn=978-1-4377-0314-6|edition=11th|year=2011}}</ref>

Myxedema is more common in women than in men.<ref>{{cite book|last=Schneider|first=Arthur S.|title=Pathology|url=https://archive.org/details/brspathologyboar00schn|url-access=limited|year=2009|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1451109061|pages=[https://archive.org/details/brspathologyboar00schn/page/n331 314]|edition=4th|author2=Kim, Philip A. Szanto  |author3=with special contributions by Sandra I. |author4= Swanson, Todd A. }}</ref>

Myxedema can occur in:
* ''[[Hyperthyroidism]]'', associated with pretibial myxedema and exophthalmos. Pretibial myxedema can occur in 1–4% of patients with [[Graves' disease]], a cause of hyperthyroidism.<ref name="thedoctorsdoctor pretibial myxedema">{{Cite web | url=http://www.thedoctorsdoctor.com/diseases/pretibial_myxedema.htm | title=Pretibial Myxedema | access-date=2009-03-27 | archive-url=https://web.archive.org/web/20160304051625/http://www.thedoctorsdoctor.com/diseases/pretibial_myxedema.htm | archive-date=2016-03-04 | url-status=dead }}</ref>
* ''[[Hypothyroidism]]'', including Hashimoto's thyroiditis.<ref>{{cite web |url=https://www.lecturio.com/concepts/hypothyroidism/| title=Hypothyroidism|website=The Lecturio Medical Concept Library |access-date= 27 July 2021}}</ref>

==Pathophysiology==
Myxedema describes a specific form of [[cutaneous]] and [[dermal]] [[edema]] secondary to increased deposition of [[connective tissue]] components. The connective fibres are separated by an increased amount of protein and mucopolysaccharides. This protein-mucopolysaccharide complex binds water, producing non-pitting boggy edema, in particular around eyes, hands, feet and in the supraclavicular fossae. This deposition involves not only the skin but also the tongue, myocardium, kidney medulla, lung, intestine and most other organs of the body (apart from the stomach).<ref> {{cite web | title = ACID GLYCOSAMINOGLYCANS IN MYXOEDEMA | URL = https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.1982.tb03166.x | date = February 1982}}</ref> Myxoedema is also responsible for the thickening of the laryngeal and pharyngeal mucous membranes, which results in thick slurred speech and hoarseness, both of which are seen commonly in hypothyroidism.{{cn|date=December 2024}}

The accumulation of [[glycosaminoglycans]] (GAGs) in the dermal tissues consists characteristically of [[hyaluronic acid]] with very little change in the dermatan sulfate abundance and perhaps a decrease in chondroitin sulfate.<ref name="Berger"/> The tissue change in myxedema can be related directly to the physicochemical properties of hyaluronate. Its hygroscopic nature allows it to swell to one thousand times its dry weight when hydrated.<ref>{{cite web | title = Thyroid hormone action on skin  | URL = https://pubmed.ncbi.nlm.nih.gov/22110782/ | date = July 2011}}</ref>

The pathogenesis of generalized myxedema is thought to be fairly well understood and related to the deficiency of thyroid hormone,<ref>{{cite web | title = Connective Tissue, Glycosaminoglycans, and Diseases the Thyroid | URL = https://academic.oup.com/edrv/article-abstract/10/3/366/2548557 | date = 1 August 1989}}</ref> but the
pathogenesis of pretibial and orbital myxedema due to Grave's disease is not fully understood, however, two mechanisms predominate:
* [[Fibroblast]] stimulation. It is thought that fibroblast stimulation by the [[thyroid stimulating hormone]] (TSH) receptor increases the deposition of glycosaminoglycan, which results in an osmotic [[edema]] and fluid retention. It is thought that many cells responsible for forming connective tissue react to increases in TSH levels.<ref>{{cite web  | title       = Fibroblast  | url         = http://ghr.nlm.nih.gov/glossary=fibroblast  | work        = Genetics Home Reference  | publisher   = U.S. National Library of Medicine  | date        = 2014-05-05  | access-date  = 2014-05-10}}</ref><ref>{{cite web|title=Fibroblasts|url=http://www.fibroblast.org/|access-date=16 August 2018}}</ref>
* [[Lymphocyte]] stimulation. In Graves' thyroid disease, lymphocytes react against the TSH receptor by inappropriately producing thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity). Lymphocytes react not only against thyroid receptors, but also any tissue with cells expressing the receptor. This can lead to tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans.<ref>{{cite web |url=https://www.lecturio.com/concepts/lymphocytes/| title=Lymphocytes|website=The Lecturio Medical Concept Library |access-date= 27 July 2021}}</ref>

==Diagnosis==
It is often possible to diagnose myxedema on clinical grounds alone. Characteristic symptoms are weakness, cold intolerance, mental and physical slowness, dry skin, typical facies, and hoarse voice. Results of the total serum thyroxine and free thyroxine index tests usually will confirm the diagnosis.<ref name="McConahey 61–66">{{Cite journal|last=McConahey|first=W. M.|date=March 1978|title=Diagnosing and treating myxedema and myxedema coma|journal=Geriatrics|volume=33|issue=3|pages=61–66|issn=0016-867X|pmid=624451}}</ref>

==Management==
Primary treatment is prompted by the administration of adequate doses of either the thyroid hormone [[L-thyroxine]] given intravenously or by giving [[liothyronine]] via a nasogastric tube. It is essential to identify and treat the condition precipitating the coma.<ref name="McConahey 61–66"/>

Myxedema coma is rare but often fatal. It occurs most often in elderly women and may be mistaken for one of the chronic debilitating diseases common to this age group.<ref name="McConahey 61–66"/>

Gabrilove et al demonstrated that histological skin changes can be observed within 3-4 weeks after initiating thyroid hormone replacement therapy with desiccated thyroid extract.<ref>{{Cite web | title=THE HISTOGENESIS OF MYXEDEMA| url=https://academic.oup.com/jcem/article-abstract/17/8/925/2717225 | date= August 1957 }}</ref> This was documented through skin biopsies performed on individuals with hypothyroidism both before and after treatment. The magnitude of these effects was related to the dose of thyroid hormone administered, and the rate at which this occurred depended on the amounts of material present at the outset.

Though the exact cause of myxedema is still unclear, a wealth of research has demonstrated the importance of [[Iodine in biology|iodine]].<ref name="Lindholm 2011 1–10">{{Cite journal|last1=Lindholm|first1=J.|last2=Laurberg|first2=P.|date=2011|title=Hypothyroidism and Thyroid Substitution: Historical Aspects|journal=Journal of Thyroid Research|language=en|volume=2011|pages=809341|doi=10.4061/2011/809341|pmid=21760981|pmc=3134382 |doi-access=free }}</ref> In an important study<ref>{{Cite journal|last1=Vanderpas|first1=Jean B.|last2=Rivera-Vanderpas|first2=Maria T.|last3=Bourdoux|first3=Pierre|last4=Luvivila|first4=Kapata|last5=Lagasse|first5=Raphael|last6=Perlmutter-Cremer|first6=Noémi|last7=Delange|first7=François|last8=Lanoie|first8=Leo|last9=Ermans|first9=André M.|date=1986-09-25|title=Reversibility of Severe Hypothyroidism with Supplementary Iodine in Patients with Endemic Cretinism|journal=New England Journal of Medicine|volume=315|issue=13|pages=791–795|doi=10.1056/NEJM198609253151302|issn=0028-4793|pmid=3018564}}</ref> the researchers showed that in the myxedematous type of cretinism treatment with iodine normalizes thyroid function provided that the treatment is begun early in the postnatal period. If not, the prognosis remains dismal.<ref name="Lindholm 2011 1–10"/>

==History==
Myxedema was first treated successfully in 1891 when [[George Redmayne Murray]] diagnosed a 46-year-old woman with the disease. He prescribed an extract from sheep thyroid. The patient improved significantly within a few weeks and lived another 28 years while taking the sheep thyroid extract.<ref>{{cite web|title=Eating Organs to Cure Disease|url=https://tacomed.com/chapter-3-prelude-to-a-discovery/eating-organs-to-cure-a-disease/|website=Tacomed.com|access-date=15 June 2017|archive-url=https://web.archive.org/web/20170906224450/https://tacomed.com/chapter-3-prelude-to-a-discovery/eating-organs-to-cure-a-disease/|archive-date=6 September 2017|url-status=dead}}</ref>

==Etymology==
The word myxedema originates from {{lang|grc|μύξᾰ}}, meaning "mucus" or "slimy substance", and {{lang|grc|οἴδημα}} for "swelling".{{cn|date=December 2024}}

== References ==
{{reflist}}

== External links ==
{{Medical resources
|  ICD10 = {{ICD10|E|03|9|e|00}} 
|  ICD9 = {{ICD9|244.9}} 
|  DiseasesDB = 6558 
|  ICDO = 
|  OMIM = 
|  MedlinePlus = 000353 
|  eMedicineSubj = med 
|  eMedicineTopic = 1581 
|  eMedicine_mult = {{eMedicine2|derm|347}} 
|  MeshID = D009230
}}

{{Thyroid disease}}
{{Authority control}}

[[Category:Endocrine-related cutaneous conditions]]
[[Category:Skin conditions resulting from errors in metabolism]]