Myxedema coma: Difference between revisions

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==Background==
==Background==
#Hypothyroidism + mental status changes/coma + hypothermia + precipitating stressor
*[[Hypothyroidism]] + [[AMS|mental status changes]]/[[coma]] + [[hypothermia]] + precipitating stressor<ref>Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician. Dec 1 2000;62(11):2485-90.</ref>
##80% mortality
*Majority of the patients > 60yo<ref>Davis PJ, Davis FB. Hypothyroidism in the elderly. Compr Ther. 1984;10:17–23.</ref>
#Occurs in 0.1% of patients with hypothyroidism
*Occurs in 0.1% of patients with hypothyroidism
**Usually occurs after precipitating incident in patient with untreated hypothyroidism <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*Mortality may be as high as 60%<ref>Arlot S et al. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med. 1991;17:16–8.</ref>
*Untreated mortality approaches 100% <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*~50% of cases become evident '''''after''''' admission
*Severe hypothyroidism may be first time presentation of hypothyroid<ref>Nicoloff JT et al.  A form of decompensated hypothyroidism. Endocrinol Metab Clin North Am. 1993;22:279–90.</ref>


==Precipitants==
===Precipitants===
#Infection
*[[Bradycardia]] and [[hypothermia]]
##Bradycardia and hypothermia may mask usual signs of fever
*[[Burns]]
#Cold exposure
*[[CHF]]
#Trauma
*[[CVA]]
#MI
*Cold exposure
#CHF
*[[GI bleed]]
#CVA
*Metabolic abnormalities ([[hypoxia]], [[hypercapnia]], [[hyponatremia]], [[hypoglycemia]])
#GI bleed
*Medications: [[Beta blockers]], [[sedatives]], [[opioids]], [[phenothiazines]], [[amiodarone]]<ref>Mazonson PD et al. Myxedema coma during long-term amiodarone therapy. Am J Med. 1984;77:751–4.</ref>
#Metabolic conditions (hypoxia, hypercapnia, hyponatremia, hypoglycemia)
**Especially medications with CNS depressant effect <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
#Burns
*Medication non-adherence (thyroid meds)
#Meds: B-blockers, sedatives, narcotics, phenothiazine, amiodarone
*[[MI]]
#Medication non-compliance (thyroid meds)
*[[Sepsis]]
*[[Trauma]]
*[[PE]]


==Diagnosis==
{{Thyroid gen background}}
#Hypothermia
##So common in myxedema that a normal temperature should suggest an underlying infection
##Absence of shivering distinguishes from accidental hypothermia
#Cardio
##Bradycardia
##Hypotension
#Pulm
##Hypoventilation -> respiratory collapse
###CO2 narcosis
##Pleural effusions
##Upper airway obstruction from glottic edema, vocal cord edema, and macroglossia
#Neuro
##AMS/coma


==Work-Up==
==Clinical Features==
#Chemistry
[[File:Myxedema face.png|thumb|Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor.]]
#CBC
[[File:Myxedema standing.png|thumb|Additional symptoms include swelling of the arms and legs and ascites.]]
#TSH, FT4, FT3
[[File:PMC3371544 IJD-57-247-g001.png|thumb|Pretibial "woody" (i.e. non-pitting) myxedema]]
#Cultures
[[File:PMC2923795 jkms-25-1394-g001.png|thumb|A case of myxedema coma presenting as a brain stem infarct in a 74-year-old Korean woman. (A, B) Severe periorbital edema and thinned eyebrow. (C, D) Non-pitting edema and desquamation of the hands and feet.]]
#LFT
===[[Hypothermia]]===
#Cortisol level
*Temperature <35.5°C (95.9°F).
#VBG
*Degree of hypothermia is proportional to mortality<ref>Thiessen, MEW. Thyroid and Adrenal Disorders. In Walls RM, Hockberger RS, Gausche-Hill M, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 9. Philadelphia, Elsevier 2018, (Ch) 120:p 1557-1571.</ref>
#CXR
#EKG
==DDx==
#Sepsis
#Depression
#Adrenal crisis
#CHF
#Hypoglycemia
#CVA
#Hypothermia
#Drug overdose
#Meningitis


==Treatment==
===Cardiovascular===
#Supportive care
*[[Bradycardia]]
##Respiratory distress
*[[Hypotension]]
###Mechanical ventilation if needed
*[[Pericardial effusion]]
##Hypoglycemia
 
###IV dextrose
===Pulmonary===
##Hyponatremia
*Hypoventilation, [[hypercapnia]]
###Water restriction
**There is often diaphragmatic dysfunction that causes worsening hypoventilation.  The dysfunction is reversed after thyroid hormone administration<ref>Martinez FJ et al. Hypothyroidism. A reversible cause of diaphragmatic dysfunction. Chest. 1989;96:1059–63.</ref>
##Hypotension
**Early respiratory support with intubation may be necessary to prevent respiratory collapse
###Vasopressors (ineffective w/o thyroid hormone replacement)
*[[Hypoxia]]
###Hydrocortisone 100mg q8hr IV (adrenal insufficiency may also be present)
*[[Pleural Effusion]]
####Give first dose before starting thyroid replacement therapy
*Upper airway obstruction from glottic edema, vocal cord edema, and macroglossia can complicate intubation.
##Hypothermia
 
###Treat w/ passive rewarming (active rewarming may cause hypotension)
===Neurologic===
#Thyroid replacement therapy
*[[Altered mental status]]/[[Coma]] due to CO2 narcosis
##Optimal regimen is controversial
*[[Coma]] is very rare
##Can give T3 or T4 or both
*Pseudomyotonic "hung up" deep tendon reflexes
##T4
**Particularly Achilles reflex
###Advantages
**Relaxation phase of DTR twice as long as contraction phase
####Smooth, slow steady onset of action
*Neuropsychiatric symptoms <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
####May be safer in pts with CAD
**[[Depression]]
###Disadvantages
**[[Psychosis]]
####Requires extrathyroidal conversion of T4 -> T3 to work (may be reduced in myxedema)
 
###Dose: Start 4mcg/kg IV followed by 100mcg IV in 24hr
==Differential Diagnosis==
##T3
*[[Adrenal crisis]]
###Advantages
*[[CHF]]
####Does not require extrathyroidal action to work
*[[CVA]]
####Rapid onset of action
*[[Depression]]
###Disadvantages
*[[Drug overdose]]
####Rapid onset of action (may not be desirable in pts w/ CAD)
*[[Hypoglycemia]]
###Dose: 20mcg IV followed by 10mcg q8hr until pt is conscious
*[[Hypothermia]]
####Start with 10mcg if elderly or has CAD
*[[Meningitis]]
#Treat precipitating factors
*[[Sepsis]]
 
==Evaluation==
[[File:PMC2923795 jkms-25-1394-g002.png|thumb|ECG showing sinus bradycardia, low QRS voltage, and a prolonged QT interval.]]
===Work-Up===
*TSH, FT4, FT3
**In primary hypothyroidism TSH will be elevated and T4 and T3 will be low
**If the patient has secondary hypothyroidism (Pituitary dysfunction) the TSH may be low or normal and T4 and T3 will be low
*Chemistry
**[[Hyponatremia]]
**[[Hypoglycemia]]
**+/- [[renal failure|Elevated creatinine]]
*CBC
**Mild [[anemia]], [[leukopenia]]
*[[Blood cultures]]
*[[LFTs]]
**Elevated transaminases
*[[Rhabdomyolysis|Elevated CPK]]
*Cortisol level
*[[VBG]]/ABG
**[[Hypercapnia]]
**Hypoxia
*Lipid levels
**Hypercholesterolemia
*[[CXR]]
*[[ECG]]
**Sinus bradycardia
**Non-specific ST-T wave changes
**Prolonged QTc
**Ventricular dysrhythmias
*Bedside [[cardiac US]] for [[pericardial effusion]]
 
===Diagnosis===
[[File:thyroid studies.JPG|px200]]
 
==Management==
===Respiratory Support===
*Early mechanical ventilation will prevent respiratory collapse and severe respiratory acidosis.
===Fluid Resuscitation===
*Often intravascularly depleted
**May have underlying illness causing dehydration
*In patients who are hyponatremic, be cautious with rapid correction of hyponatremia
**Consider fluid restriction
*Use D5NS if hypoglycemic
*Monitor for unmasking of CHF
 
===[[Hypotension]]===
*[[Vasopressors]] will be ineffective without concomitant thyroid hormone replacement
===Hormone Replacement===
*'''[[Levothyroxine]] (T4)''' (generally agreed upon first line therapy)
**Dose: 100 to 500 mcg (4mcg/kg IV) followed by 75 to 100 mcg administered IV daily until the patient takes oral replacement.<ref>Smallridge RC. Metabolic and anatomic thyroid emergencies: a review. Crit Care Med. 1992;20:276–91</ref>
**Does require extrathyroidal conversion which can be reduced in myxedema but will have a slow steady onset of action
**Potentially safer in patients with CAD
**American Thyroid Association recommends treatment with both T4 and T3<ref>Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014 Dec. 24 (12):1670-751.</ref>
*'''T3''' 5-20mcg IV followed by 2.5-10mcg q8hr <ref>Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267409/</ref><ref>Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350620/</ref>
**Start with 10mcg if elderly or has CAD
**Does not require extrathyroidal conversion
**More rapid onset but may be harmful in patients with CAD
 
===[[Adrenal Insufficiency]]===
*[[Hydrocortisone]] 100 mg IV q8h for possible concomitant adrenal insufficiency
**Alternative: [[dexamethasone]] 2-4mg q12hrs (will not affect cortisol level or ACTH stimulation test)
 
===[[Hypothermia]]===
*Treat with passive rewarming
*[[Hypothermia]] will also reverse with thyroid hormone administration
*Avoid mechanical stimulation
*Do not actively rewarm:
**Usually are volume depleted
**Rapid peripheral vasodilation may induce worsening hypotension


==Disposition==
==Disposition==
#Admit to ICU
*Admit to ICU
#Endocrine consult


==See Also==
==See Also==
*[[Hypothyroidism]]
*[[Hypothyroidism]]
*[[Thyroid (General)]]
*[[Thyroid (Main)]]
 
==External Links==
*[https://emcrit.org/ibcc/myxedema/ IBCC Decompensated Hypothyroidism (“Myxedema Coma”)]


==Source==
==References==
Tintinalli's
<references/>


[[Category:Endo]]
[[Category:Endocrinology]]

Latest revision as of 11:38, 5 January 2022

Background

  • Hypothyroidism + mental status changes/coma + hypothermia + precipitating stressor[1]
  • Majority of the patients > 60yo[2]
  • Occurs in 0.1% of patients with hypothyroidism
    • Usually occurs after precipitating incident in patient with untreated hypothyroidism [3]
  • Mortality may be as high as 60%[4]
  • Untreated mortality approaches 100% [5]
  • ~50% of cases become evident after admission
  • Severe hypothyroidism may be first time presentation of hypothyroid[6]

Precipitants

Spectrum of Thyroid Disease

Thyroid physiology: Hypothalamus (top) releases TRH; causing pituitary gland (second from top) to release TSH; causing thyroid gland (third from top) to make T3 and T4; inhibition loops also shown.

Clinical Features

Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor.
Additional symptoms include swelling of the arms and legs and ascites.
Pretibial "woody" (i.e. non-pitting) myxedema
A case of myxedema coma presenting as a brain stem infarct in a 74-year-old Korean woman. (A, B) Severe periorbital edema and thinned eyebrow. (C, D) Non-pitting edema and desquamation of the hands and feet.

Hypothermia

  • Temperature <35.5°C (95.9°F).
  • Degree of hypothermia is proportional to mortality[9]

Cardiovascular

Pulmonary

  • Hypoventilation, hypercapnia
    • There is often diaphragmatic dysfunction that causes worsening hypoventilation. The dysfunction is reversed after thyroid hormone administration[10]
    • Early respiratory support with intubation may be necessary to prevent respiratory collapse
  • Hypoxia
  • Pleural Effusion
  • Upper airway obstruction from glottic edema, vocal cord edema, and macroglossia can complicate intubation.

Neurologic

Differential Diagnosis

Evaluation

ECG showing sinus bradycardia, low QRS voltage, and a prolonged QT interval.

Work-Up

Diagnosis

px200

Management

Respiratory Support

  • Early mechanical ventilation will prevent respiratory collapse and severe respiratory acidosis.

Fluid Resuscitation

  • Often intravascularly depleted
    • May have underlying illness causing dehydration
  • In patients who are hyponatremic, be cautious with rapid correction of hyponatremia
    • Consider fluid restriction
  • Use D5NS if hypoglycemic
  • Monitor for unmasking of CHF

Hypotension

  • Vasopressors will be ineffective without concomitant thyroid hormone replacement

Hormone Replacement

  • Levothyroxine (T4) (generally agreed upon first line therapy)
    • Dose: 100 to 500 mcg (4mcg/kg IV) followed by 75 to 100 mcg administered IV daily until the patient takes oral replacement.[12]
    • Does require extrathyroidal conversion which can be reduced in myxedema but will have a slow steady onset of action
    • Potentially safer in patients with CAD
    • American Thyroid Association recommends treatment with both T4 and T3[13]
  • T3 5-20mcg IV followed by 2.5-10mcg q8hr [14][15]
    • Start with 10mcg if elderly or has CAD
    • Does not require extrathyroidal conversion
    • More rapid onset but may be harmful in patients with CAD

Adrenal Insufficiency

  • Hydrocortisone 100 mg IV q8h for possible concomitant adrenal insufficiency
    • Alternative: dexamethasone 2-4mg q12hrs (will not affect cortisol level or ACTH stimulation test)

Hypothermia

  • Treat with passive rewarming
  • Hypothermia will also reverse with thyroid hormone administration
  • Avoid mechanical stimulation
  • Do not actively rewarm:
    • Usually are volume depleted
    • Rapid peripheral vasodilation may induce worsening hypotension

Disposition

  • Admit to ICU

See Also

External Links

References

  1. ↑ Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician. Dec 1 2000;62(11):2485-90.
  2. ↑ Davis PJ, Davis FB. Hypothyroidism in the elderly. Compr Ther. 1984;10:17–23.
  3. ↑ Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.
  4. ↑ Arlot S et al. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med. 1991;17:16–8.
  5. ↑ Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.
  6. ↑ Nicoloff JT et al. A form of decompensated hypothyroidism. Endocrinol Metab Clin North Am. 1993;22:279–90.
  7. ↑ Mazonson PD et al. Myxedema coma during long-term amiodarone therapy. Am J Med. 1984;77:751–4.
  8. ↑ Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.
  9. ↑ Thiessen, MEW. Thyroid and Adrenal Disorders. In Walls RM, Hockberger RS, Gausche-Hill M, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 9. Philadelphia, Elsevier 2018, (Ch) 120:p 1557-1571.
  10. ↑ Martinez FJ et al. Hypothyroidism. A reversible cause of diaphragmatic dysfunction. Chest. 1989;96:1059–63.
  11. ↑ Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.
  12. ↑ Smallridge RC. Metabolic and anatomic thyroid emergencies: a review. Crit Care Med. 1992;20:276–91
  13. ↑ Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014 Dec. 24 (12):1670-751.
  14. ↑ Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267409/
  15. ↑ Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350620/
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