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==
-Risk factors
+*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>
-Common risk factors that can trigger myxedema coma in patients with hypothyroidism include:
+*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}}
-Hypothermia
+==== The following table summarizes the various effects of reduced thyroid hormone on different organ systems ====
-CVA
+{| class="wikitable"
-CHF
+!Organ System
-Infections ( pneumonia, influenza, UTI, sepsis)
+!Effect due to Decreased Thyroid Hormone
-Drugs ( Anesthestics, narcotics, amidirone, Lithium carbonate) 6486153
+!Manifestation
-GI bleeding
+|-
-Metabolic disturbances(Hypoglycemia, hyponatremia, acidosis, hypercalcemia, hypoxemia, hypercapneia)
+!Cardiovascular
-History
+|
-History of antecedent thyroid disease
+*Cardiac contractility impaired:
-History of radioiodine therapy or thyroidectomy
+**Leading to reduced [[stroke volume]]
-Discontinuation of medications.
+**Low [[cardiac output]]
-Historical Perspective
+**[[Bradycardia]]
-In 874, Gull was the first physician to describe hypothyroidism under the name myxedema due to its characteristics of swollen skin and its mucin content.
+**[[Hypotension]]
-In 1883, Semon was the first to establish a relationship between patients undergoing thyroidectomy and later developing symptoms of myxedema.
+*Reduced [[stroke volume]]
-In 1888, Clinical Society of London presented a paper describing that extreme loss of thyroid harmone can lead to cretinism and myxedema.
+**Accumulation of fluid rich in [[mucopolysaccharides]] within the [[pericardial sac]]
-In 1891, Murray was the first physician to discover cure for myxedema by using hypodermic injections of sheep thyroid extract.
+|
-Pathophysiology
+*[[Hypotension]]
-Myxedema coma occurs as a result of long-standing, undiagnosed, or undertreated hypothyroidism.
+*Narrowed [[pulse pressure]]
-Myxedema coma is usually precipitated by a systemic illness.
+*[[Edema]]
-Causes
+*[[Pericardial effusions]]
-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.
+!Neurologic
-Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone.
+|
-Pathogenesis
+*Altered [[brain function]] due to:
-Thyroid hormone plays an important role in cell metabolism.
+**Reduced [[oxygen]] delivery and consumption
-Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems. [5]
+**Decreased [[glucose]] utilization
-Reduced metabolism results in hypothermia.
+**Reduced [[cerebral blood flow]]
-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.
+|
-The following table summarizes the various effects of reduced thyroid hormone on different organ systems
+*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]]
+|}
-Organ System	Effect due to Decreased Thyroid Hormone	Manifestation
+==Associated Conditions==
-Cardiovascular
+Common conditions associated with myxedema coma include:
-Cardiac contractility is impaired
+*[[Type 1 diabetes]]
-Leading to reduced stroke volume
+*[[Addison's disease]]
+*[[Pernicious anemia]]
-Low cardiac output
+*[[Vitiligo]]
+*[[Rheumatoid arthritis]]
-Bradycardia
+*[[Premature ovarian failure]]
-Sometimes hypotension
-Reduced stroke volume in severe cases may also be due to pericardial effusions
-caused by the accumulation of fluid rich in mucopolysaccharides within the pericardial sac
-Hypotension
-Narrowed pulse pressure
-Fluid accumulation in tissue
-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
-Decreased responsiveness to hypoxia and hypercapnia
-Hypoventilation
-Renal
-Reduced glomerular filtration rate because of
-Low cardiac output
-Peripheral vasoconstriction
-Rhabdomyolysis
-Electrolyte abnormalities
-Low volume stimulates
-Antidiuretic hormone impairs water excretion leading to hyponatremia
-Gastrointestinal
-mucopolysaccharide infiltration and edema
-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
-Treatment
-Myxedema coma is a medical emergency and requires a prompt treatment. All patients must be shifted to ICU.
-Supportive Therapy
-Prevention of further heat loss by covering the patient with blankets but avoid external rewarming because it may produce vascular collapse.
-Consider warmed IV fluids.
-Cardiac monitoring of the patient.
-Acute Mecial Therapy
-Preffered regimen (1):- Levothyroxine 5 to 8 mcg/kg (200 to 500 mcg) IV infused over 15 min, then 50 to 100 mcg IV q24h until transition to an oral formulation is possible.
-Glucocorticoids should also be empirically administered until coexistent adrenal insufficiency can be ruled out. Hydrocortisone hemisuccinate 100 mg IV bolus is initially given, followed by 100 mg IV q8h until initial plasma cortisol level is confirmed normal.
-• IV hydration with D 5 NS is used to correct hypotension and hypoglycemia (if present); avoid overhydration and possible water intoxication because clearance of free water is impaired in these patients. • Rule out and treat precipitating factors (e.g., antibiotics in suspected sepsis).
-ECG
-Electrocardiographic findings may include bradycardia, varying degrees of block, low voltage, nonspecific ST-segment changes, flattened or inverted T waves, prolonged Q-T interval, and ventricular or atrial arrhythmias
-==Associated Conditions==
-==Gross Pathology==
-==Microscopic Pathology==
 ==References==
 {{reflist|2}}