Myxedema coma pathophysiology: Difference between revisions

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Latest revision as of 00:30, 26 October 2017

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

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

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.
Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone.

Hypothyroidism

Precipitating Factor

↓T4

↓ IntracellularT3

↓ Thermogenesis

↓ 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	Cardiac contractility impaired: Leading to reduced stroke volume Low cardiac output Bradycardia Hypotension Reduced stroke volume Accumulation of fluid rich in mucopolysaccharides within the pericardial sac	Hypotension Narrowed pulse pressure Edema Pericardial effusions
Neurologic	Altered brain function due to: Reduced oxygen delivery and consumption Decreased glucose utilization Reduced cerebral blood flow	Altered consciousness
Pulmonary	Central depression of ventilatory drive: Hypoxia Hypercapnia	Hypoventilation
Renal	Reduced glomerular filtration rate because of: Low cardiac output Peripheral vasoconstriction Rhabdomyolysis Low volume stimulates Antidiuretic hormone impairs water excretion leading to hyponatremia	Dysuria Urinary frequency Nocturia
Gastrointestinal	Mucopolysaccharide infiltration and edema results in: Malabsorption Gastric atony Impaired peristalsis Paralytic ileus Megacolon	GI bleeding Ascites Constipation
Hematologic	Coagulopathy Due to decrease in production of factors V, VII, VIII, IX, and X Hemorrhage and vitamin B12 deficiency	Bleeding Anemia

Associated Conditions

Common conditions associated with myxedema coma include:

References

↑ 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)
↑ Wall CR (2000). "Myxedema coma: diagnosis and treatment". Am Fam Physician. 62 (11): 2485–90. PMID 11130234.
↑ 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.
↑ 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.

[pmid28825577-1] 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)

[pmid11130234-2] Wall CR (2000). "Myxedema coma: diagnosis and treatment". Am Fam Physician. 62 (11): 2485–90. PMID 11130234.

[pmid21941682-3] 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.

[pmid17127141-4] 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.

[1]

[2]

[3]

[4]

@@ Line 4: / Line 4: @@
 ==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==
-A normal body core temperature is preserved in compensated hypothyroidism because of neurovascular adaptations, including chronic peripheral vasoconstriction, mild diastolic hypertension, and diminished blood volume. The hypothyroid heart also compensates by performing more work at a given amount of oxygen through better coupling of ATP to contractile events. These adaptations to thyroid hormone deficiency maintain homeostasis, albeit at a precarious balance. A further reduction in blood volume (e.g., secondary to gastrointestinal bleeding or the use of diuretics) may disrupt this precarious balance, which homeostatic mechanisms are no longer able to restore. Likewise, the already compromised ventilatory drive may progress to respiratory failure by intercurrent pulmonary infection. Impairment in central nervous system function can be provoked further by stroke, the use of sedatives, and hyponatremia (a common phenomenon in severe 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 [[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===
+*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|radioactive iodine therapy]] for [[hyperthyroidism]].
+*Rare causes may include secondary [[hypothyroidism]] and medications such as [[lithium]] and [[amiodarone]].
+{{familytree/start}}{{familytree | | | | | | | | | A01 | | | | | |A01=[[Hypothyroidism]]}}
+{{familytree | | | | | | | | | |!| | | | | | | | }}
+{{familytree | | | | | | | | | B01 | | | | | |B01=Precipitating Factor}}
+{{familytree | | | | | | | | | |!| | | | | | | | }}
+{{familytree | | | | | | | | | Z01 | | | | | |Z01= '''↓'''[[T4]]}}
+{{familytree | | | | | | | | | |!| | | | | | | | }}
+{{familytree | | | | | | | | | X01 | | | | | |X01=↓ Intracellular[[T3]]}}
+{{familytree | | |,|-|-|-|v|-|-|^|-|-|v|-|-|-|.| }}
+{{familytree | | C01 | | C02 | | | | C03 | | C04 |C01=[[Hypothalamus]]|C02=[[Respiratory]]|C03=[[Cardiovascluar]]|C04=[[Renal]]}}
+{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
+{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=↓ [[Thermogenesis]]|D02=[[Hypercapnia]]<br>[[Hypoxia]]|D03=↓ [[Inotropic]] <br> [[Bradycardia]]|D04=↓ Volume status}}
+{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
+{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=[[Hypothermia]]|D02=[[Hypoventilation]]|D03=↓ [[Cardiac output]]<br>↓ [[Blood volume]]|D04=↓ [[GFR]] <br>↑ ADH}}
+{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
+{{familytree | | D01 | | D02 | | | | D03 | | D04 |D01=[[LOC|Alteration of mental state]]|D02=Cerebral anoxia|D03=↓Arterial pressure/[[shock]]|D04=[[Hyponatremia]]<br> Edema}}
+{{familytree | | |!| | | |!| | | | | |!| | | |!| }}
+{{familytree | | |`|-|-|-|^|-|-|v|-|-|^|-|-|-|'| }}
+{{familytree | | | | | | | | | |!| | | | | | | | }}
+{{familytree | | | | | | | | | E01 | | | | | | |E01=Myxedema Coma }}
+{{familytree/end}}
+==== The following table summarizes the various effects of reduced thyroid hormone on different organ systems ====
+{| class="wikitable"
+!Organ System
+!Effect due to Decreased Thyroid Hormone
+!Manifestation
+|-
+!Cardiovascular
+|
+*Cardiac contractility impaired:
+**Leading to reduced [[stroke volume]]
+**Low [[cardiac output]]
+**[[Bradycardia]]
+**[[Hypotension]]
+*Reduced [[stroke volume]]
+**Accumulation of fluid rich in [[mucopolysaccharides]] within the [[pericardial sac]]
+|
+*[[Hypotension]]
+*Narrowed [[pulse pressure]]
+*[[Edema]]
+*[[Pericardial effusions]]
+|-
+!Neurologic
+|
+*Altered [[brain function]] due to:
+**Reduced [[oxygen]] delivery and consumption
+**Decreased [[glucose]] utilization
+**Reduced [[cerebral blood flow]]
+|
+*Altered [[consciousness]]
+|-
+!Pulmonary
+|
+*Central depression of ventilatory drive:
+**[[Hypoxia]]
+**[[Hypercapnia]]
+|
+*[[Hypoventilation]]
+|-
+!Renal
+|
+*Reduced [[glomerular filtration rate]] because of:
+**Low [[cardiac output]]
+**Peripheral [[vasoconstriction]]
+**[[Rhabdomyolysis]]
+*Low volume stimulates
+**[[Antidiuretic hormone]] impairs water excretion leading to [[hyponatremia]]
+|
+* [[Dysuria]]
+* [[Urinary frequency]]
+* [[Nocturia]]
+|-
+!Gastrointestinal
+|
+*[[Mucopolysaccharide]] infiltration and [[edema]] results in:
+**[[Malabsorption]]
+**Gastric atony
+**Impaired [[peristalsis]]
+**[[Paralytic ileus]]
+**[[Megacolon]]
+|
+*[[Gastrointestinal bleeding|GI bleeding]]
+*[[Ascites]]
+*[[Constipation]]
+|-
+!Hematologic
+|
+*[[Coagulopathy]]
+**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]]
+|
+*[[Bleeding]]
+*[[Anemia]]
+|}
 ==Associated Conditions==
-==Gross Pathology==
+Common conditions associated with myxedema coma include:
-==Microscopic Pathology==
+*[[Type 1 diabetes]]
+*[[Addison's disease]]
+*[[Pernicious anemia]]
+*[[Vitiligo]]
+*[[Rheumatoid arthritis]]
+*[[Premature ovarian failure]]
 ==References==
 {{reflist|2}}