Myxedema coma pathophysiology: Difference between revisions

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==Overview==
==Overview==
Myxedema coma occurs as a result of long-standing, undiagnosed, or undertreated hypothyroidism. Myxedema coma is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cell metabolism. Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems. Reduced metabolism and decreased oxygen results in hypothermia and decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents and can precipitate myxedema coma.
Myxedema coma occurs as a result of long-standing, un-diagnosed, or untreated [[hypothyroidism]] and is usually precipitated by a systemic illness. [[Thyroid hormone]] plays an important role in cellular [[metabolism]]. Long-standing [[hypothyroidism]] results in reduced [[metabolic rate]] and decreased [[oxygen]] consumption, which affects all [[organ systems]]. Reduced [[metabolism]] and decreased [[oxygen]] results in [[hypothermia]] and decreased drug [[metabolism]] leading to overdosing of medications particularly [[sedatives]], [[hypnotics]], and anesthetic agents and can precipitate myxedema coma.


==Pathophysiology==
==Pathophysiology==
*Myxedema coma occurs as a result of long-standing, undiagnosed, or undertreated hypothyroidism.
*Myxedema coma occurs as a result of long-standing, undiagnosed, or untreated [[hypothyroidism]].<ref name="pmid28825577">{{cite journal |vauthors=Rizzo LFL, Mana DL, Bruno OD, Wartofsky L |title=[Myxedema coma] |language=Spanish; Castilian |journal=Medicina (B Aires) |volume=77 |issue=4 |pages=321–328 |year=2017 |pmid=28825577 |doi= |url=}}</ref><ref name="pmid11130234">{{cite journal |vauthors=Wall CR |title=Myxedema coma: diagnosis and treatment |journal=Am Fam Physician |volume=62 |issue=11 |pages=2485–90 |year=2000 |pmid=11130234 |doi= |url=}}</ref><ref name="pmid21941682">{{cite journal |vauthors=Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S |title=Myxedema coma: a new look into an old crisis |journal=J Thyroid Res |volume=2011 |issue= |pages=493462 |year=2011 |pmid=21941682 |pmc=3175396 |doi=10.4061/2011/493462 |url=}}</ref><ref name="pmid17127141">{{cite journal |vauthors=Wartofsky L |title=Myxedema coma |journal=Endocrinol. Metab. Clin. North Am. |volume=35 |issue=4 |pages=687–98, vii–viii |year=2006 |pmid=17127141 |doi=10.1016/j.ecl.2006.09.003 |url=}}</ref>
*Myxedema coma is usually precipitated by a systemic illness.
*Myxedema coma is usually precipitated by a systemic [[Illnesses|illness]].
===Pathogenesis===
*[[Thyroid hormone]] plays an important role in cellular [[metabolism]].
*Long-standing [[hypothyroidism]] is associated with reduced [[metabolic rate]] and decreased [[oxygen]] consumption, which affects all [[organ systems]].
*Reduced [[metabolism]] results in [[hypothermia]].
*Reduced [[metabolism]] and decreased [[oxygen]] also result in decreased drug metabolism leading to overdosing of [[medications]] particularly [[sedatives]], [[hypnotics]], and [[anesthetic agents]]; this can precipitate myxedema coma.
*Even in severe [[hypothyroidism]], a balance of metabolic homeostasis is achieved through adaptive neurovascular mechanisms. However, in conditions such as [[respiratory]] or [[urinary tract infections]], [[cardiac]], [[acute myocardial infarction]] or [[stroke]] interfere with this adaptive mechanisms by decreasing the [[blood volume]] and [[ventilation]] triggering myxedema coma.
===Triggers===
===Triggers===
*Myxedema coma can result from any of the causes of hypothyroidism, most commonly chronic autoimmune thyroiditis.
*Myxedema coma can result from any of the causes of [[hypothyroidism]], most commonly chronic [[autoimmune thyroiditis]].
*Myxedema coma can also occur in patients who had thyroidectomy or underwent radioactive iodine therapy for hyperthyroidism.
*Myxedema coma can also occur in patients who had [[thyroidectomy]] or underwent [[Radioactive iodine|radioactive iodine therapy]] for [[hyperthyroidism]].
*Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone.
*Rare causes may include secondary [[hypothyroidism]] and medications such as [[lithium]] and [[amiodarone]].
===Pathogenesis===
{{familytree/start}}{{familytree | | | | | | | | | A01 | | | | | |A01=[[Hypothyroidism]]}}
*Thyroid hormone plays an important role in cell metabolism.
*Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems. [5]
*Reduced metabolism results in hypothermia.
*Reduced metabolism and decreased oxygen also results in decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents; this can precipitate myxedema coma.
*Even in severe hypothyroidism a balance of metabolic homeostasis is achieved through adaptive neurovascular mechanisms. However in conditions such as respiratory or urinary tract infections, cardiac, acute myocardial infarction or stroke interfere with this adaptive mechanisms by decreasing the blood volume and ventilation triggering myxedema coma.
{{familytree/start}}{{familytree | | | | | | | | | A01 | | | | | |A01=Hypothyroidism}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | B01 | | | | | |B01=Precipitating Factor}}
{{familytree | | | | | | | | | B01 | | | | | |B01=Precipitating Factor}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | Z01 | | | | | |Z01= '''↓'''T4}}
{{familytree | | | | | | | | | Z01 | | | | | |Z01= '''↓'''[[T4]]}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | X01 | | | | | |X01=↓ Intracellular T3}}
{{familytree | | | | | | | | | X01 | | | | | |X01=↓ Intracellular[[T3]]}}
{{familytree | | |,|-|-|-|v|-|-|^|-|-|v|-|-|-|.| }}
{{familytree | | |,|-|-|-|v|-|-|^|-|-|v|-|-|-|.| }}
{{familytree | | C01 | | C02 | | | | C03 | | C04 |C01=Hypothalamus|C02=Respiratory|C03=Cardiovascluar|C04=Renal}}
{{familytree | | C01 | | C02 | | | | C03 | | C04 |C01=[[Hypothalamus]]|C02=[[Respiratory]]|C03=[[Cardiovascluar]]|C04=[[Renal]]}}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=↓ thermogenesis|D02=Hypercapnia<br>Hypoxia|D03=↓ inotropic <br> bradycardia|D04=↓ Volume status}}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=↓ [[Thermogenesis]]|D02=[[Hypercapnia]]<br>[[Hypoxia]]|D03=↓ [[Inotropic]] <br> [[Bradycardia]]|D04=↓ Volume status}}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=Hypothermia|D02=Hypoventilation|D03=↓ Cardiac output<br>↓ blood volume|D04=↓ GFR <br>↑ ADH}}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=[[Hypothermia]]|D02=[[Hypoventilation]]|D03=↓ [[Cardiac output]]<br>↓ [[Blood volume]]|D04=↓ [[GFR]] <br>↑ ADH}}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=Alteration of mental state|D02=Cerebral anoxia|D03=↓arterial pressure/shock|D04=Hyponatremia<br> Edema}}
{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=[[LOC|Alteration of mental state]]|D02=Cerebral anoxia|D03=↓Arterial pressure/[[shock]]|D04=[[Hyponatremia]]<br> Edema}}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
{{familytree | | |`|-|-|-|^|-|-|v|-|-|^|-|-|-|'| }}
{{familytree | | |`|-|-|-|^|-|-|v|-|-|^|-|-|-|'| }}
Line 40: Line 40:
{{familytree/end}}
{{familytree/end}}


The following table summarizes the various effects of reduced thyroid hormone on different organ systems
==== The following table summarizes the various effects of reduced thyroid hormone on different organ systems ====
{| class="wikitable"
{| class="wikitable"
!Organ System
!Organ System
Line 46: Line 46:
!Manifestation
!Manifestation
|-
|-
|Cardiovascular
!Cardiovascular
|
|
*Cardiac contractility is impaired
*Cardiac contractility impaired:
**Leading to reduced stroke volume
**Leading to reduced [[stroke volume]]
**Low cardiac output
**Low [[cardiac output]]
**Bradycardia
**[[Bradycardia]]
**Hypotension
**[[Hypotension]]
*Reduced stroke volume  
*Reduced [[stroke volume]]
**Accumulation of fluid rich in mucopolysaccharides within the pericardial sac
**Accumulation of fluid rich in [[mucopolysaccharides]] within the [[pericardial sac]]
|
|
*Hypotension
*[[Hypotension]]
*Narrowed pulse pressure
*Narrowed [[pulse pressure]]
*Edema
*[[Edema]]
*Pericardial effusions
*[[Pericardial effusions]]
|-
|-
|Neurologic
!Neurologic
|
|
*Altered brain function due to
*Altered [[brain function]] due to:
**Reduced oxygen delivery and consumption
**Reduced [[oxygen]] delivery and consumption
**Decreased glucose utilization
**Decreased [[glucose]] utilization
**Reduced cerebral blood flow.
**Reduced [[cerebral blood flow]]
|
|
*Altered consciousness
*Altered [[consciousness]]
|-
|-
|Pulmonary
!Pulmonary
|
|
*Central depression of ventilatory drive
*Central depression of ventilatory drive:
**Hypoxia  
**[[Hypoxia]]
**Hypercapnia
**[[Hypercapnia]]
|
|
*Hypoventilation
*[[Hypoventilation]]
|-
|-
|Renal
!Renal
|
|
*Reduced glomerular filtration rate because of
*Reduced [[glomerular filtration rate]] because of:
**Low cardiac output
**Low [[cardiac output]]
**Peripheral vasoconstriction
**Peripheral [[vasoconstriction]]
**Rhabdomyolysis
**[[Rhabdomyolysis]]
*Low volume stimulates
*Low volume stimulates
**Antidiuretic hormone impairs water excretion leading to hyponatremia
**[[Antidiuretic hormone]] impairs water excretion leading to [[hyponatremia]]
|
|
* [[Dysuria]]
* [[Urinary frequency]]
* [[Nocturia]]
|-
|-
|Gastrointestinal
!Gastrointestinal
|
|
*Mucopolysaccharide infiltration and edema results in
*[[Mucopolysaccharide]] infiltration and [[edema]] results in:
**Malabsorption
**[[Malabsorption]]
**Gastric atony
**Gastric atony
**Impaired peristalsis
**Impaired [[peristalsis]]
**Paralytic ileus
**[[Paralytic ileus]]
**Megacolon
**[[Megacolon]]
|
|
*GI bleeding
*[[Gastrointestinal bleeding|GI bleeding]]
*Ascites
*[[Ascites]]
*Constipation
*[[Constipation]]
|-
|-
|Hematologic
!Hematologic
|
|
*Coagulopathy
*[[Coagulopathy]]
**due to decrease in production of factors V, VII, VIII, IX, and X
**Due to decrease in production of [[Factor V|factors V]], [[Factor 7|VII]], [[Factor VIII|VIII]], [[Factor 9|IX]], and [[Factor X|X]]
*Hemorrhage and vitamin B12 deficiency
*[[Hemorrhage]] and [[vitamin B12 deficiency]]
|
|
*Bleeding
*[[Bleeding]]
*Anemia
*[[Anemia]]
|}
|}


==Associated Conditions==
==Associated Conditions==
Common conditions associated with myxedema coma include:
*[[Type 1 diabetes]]
*[[Addison's disease]]
*[[Pernicious anemia]]
*[[Vitiligo]]
*[[Rheumatoid arthritis]]
*[[Premature ovarian failure]]
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 00:30, 26 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Myxedema coma occurs as a result of long-standing, un-diagnosed, or untreated hypothyroidism and is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cellular metabolism. Long-standing hypothyroidism results in reduced metabolic rate and decreased oxygen consumption, which affects all organ systems. Reduced metabolism and decreased oxygen results in hypothermia and decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents and can precipitate myxedema coma.

Pathophysiology

  • Myxedema coma occurs as a result of long-standing, undiagnosed, or untreated hypothyroidism.[1][2][3][4]
  • Myxedema coma is usually precipitated by a systemic illness.

Pathogenesis

Triggers

 
 
 
 
 
 
 
 
Hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Precipitating Factor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↓T4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↓ IntracellularT3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypothalamus
 
Respiratory
 
 
 
Cardiovascluar
 
Renal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↓ Thermogenesis
 
Hypercapnia
Hypoxia
 
 
 
↓ Inotropic
Bradycardia
 
↓ Volume status
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypothermia
 
Hypoventilation
 
 
 
↓ Cardiac output
↓ Blood volume
 
↓ GFR
↑ ADH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alteration of mental state
 
Cerebral anoxia
 
 
 
↓Arterial pressure/shock
 
Hyponatremia
Edema
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myxedema Coma
 
 
 
 
 
 

The following table summarizes the various effects of reduced thyroid hormone on different organ systems

Organ System Effect due to Decreased Thyroid Hormone Manifestation
Cardiovascular
Neurologic
Pulmonary
Renal
Gastrointestinal
Hematologic

Associated Conditions

Common conditions associated with myxedema coma include:

References

  1. ↑ Rizzo L, Mana DL, Bruno OD, Wartofsky L (2017). "[Myxedema coma]". Medicina (B Aires) (in Spanish; Castilian). 77 (4): 321–328. PMID 28825577. Vancouver style error: initials (help)
  2. ↑ Wall CR (2000). "Myxedema coma: diagnosis and treatment". Am Fam Physician. 62 (11): 2485–90. PMID 11130234.
  3. ↑ Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S (2011). "Myxedema coma: a new look into an old crisis". J Thyroid Res. 2011: 493462. doi:10.4061/2011/493462. PMC 3175396. PMID 21941682.
  4. ↑ Wartofsky L (2006). "Myxedema coma". Endocrinol. Metab. Clin. North Am. 35 (4): 687–98, vii–viii. doi:10.1016/j.ecl.2006.09.003. PMID 17127141.
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