Myxedema coma: Difference between revisions
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==Background==
==Background==
*Hypothyroidism + 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>
*Extreme, decompensated [[hypothyroidism]] with end-organ dysfunction
*Majority of the patients will be > 60yo<ref>Davis PJ, Davis FB. Hypothyroidism in the elderly. Compr Ther. 1984;10:17–23.</ref>
*'''True endocrine emergency''' with mortality '''30-60%''' even with treatment<ref>Ono Y, et al. Clinical characteristics and outcomes of myxedema coma: analysis of a national inpatient database in Japan. ''J Epidemiol''. 2017;27(3):117-122. PMID 28142035</ref>
*Occurs in 0.1% of patients with hypothyroidism
*Misnomer: patients are not always comatose and myxedema is not always present
*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>
*Most common in elderly women with undiagnosed or undertreated hypothyroidism
*Coma does not need to be present but there will be a decline in the patient's mental status.  Sever hypothyroidism may present with severe decompensated hypothyroidism as the first presentation of undiagnosed hypothyroidism<ref>Nicoloff JT et al.  A form of decompensated hypothyroidism. Endocrinol Metab Clin North Am. 1993;22:279–90.</ref>
*Precipitants:
*The classic myxedematous face, which is characterized by generalized puffiness, macroglossia, ptosis, periorbital edema may not be present, but other signs such as a palpaple goiter and thyroid medication use will help in suspecting the diagnosis.
**Infection/[[sepsis]] (most common trigger)
 
**Cold exposure, [[hypothermia]]
===Precipitants===
**Medication non-compliance with levothyroxine
*Bradycardia and hypothermia
**Surgery, trauma, [[MI]], [[stroke]]
*Burns
**Medications: amiodarone, lithium, sedatives, opioids, anesthetics
*[[CHF]]
**Adrenal crisis (concurrent [[adrenal insufficiency]])
*[[CVA]]
*Cold exposure
*[[GI bleed]]
*Metabolic abnormalities ([[hypoxia]], [[hypercapnia]], [[hyponatremia]], [[hypoglycemia]])
*Medications: B-blockers, sedatives, narcotics, phenothiazine, amiodarone<ref>Mazonson PD et al. Myxedema coma during long-term amiodarone therapy. Am J Med. 1984;77:751–4.</ref>
*Medication non-compliance (thyroid meds)
*[[MI]]
*[[Sepsis]]
*Trauma


==Clinical Features==
==Clinical Features==
===Hypothermia===
*'''Classic triad''': altered mental status + hypothermia + precipitating event
*Temperature <35.5°C (95.9°F).
*'''Altered mental status''': confusion, lethargy, obtundation → '''coma'''
===Cardiovascular===
*Hypothermia (may be severe, <32C; absence of fever despite infection is classic)
*[[Bradycardia]]
*Bradycardia and hypotension (refractory to vasopressors until thyroid hormone replaced)
*[[Hypotension]]
*Hypoventilation with [[hypercapnia]] and [[hypoxia]] (respiratory failure)
===Pulmonary===
*Hyponatremia (due to decreased free water excretion — [[SIADH]]-like)
*Hypoventilation
*Hypoglycemia (concurrent [[adrenal insufficiency]] or hepatic dysfunction)
**Early respiratory support with intubation is necessary to prevent respiratory collapse
*Non-pitting edema (myxedema), periorbital swelling
*[[Hypercapnia]]
*Delayed deep tendon reflexes (hung-up reflexes)
**There is often diaphragmatic dysfunction that causes worsening hypoventilation.  The dysfunction is reversed after thryroid hormone administration<ref>Martinez FJ et al. Hypothyroidism. A reversible cause of diaphragmatic dysfunction. Chest. 1989;96:1059–63.</ref>
*Ileus, urinary retention, [[hypothermia]]
*[[Pleural Effusion]]
*Pericardial effusion (may rarely cause tamponade)
*Upper airway obstruction from glottic edema, vocal cord edema, and macroglossia can complicate intubation.
===Neurologic===
*[[AMS]]/[[Coma]]


==Differential Diagnosis==
==Differential Diagnosis==
*[[Sepsis]] (most common precipitant AND mimic)
*[[Hypothermia]] (primary environmental)
*[[Adrenal crisis]]
*[[Adrenal crisis]]
*[[CHF]]
*[[Stroke]] / intracranial pathology
*[[CVA]]
*Drug overdose (opioids, sedatives)
*[[Depression]]
*[[Drug overdose]]
*[[Hypoglycemia]]
*[[Hypoglycemia]]
*[[Hypothermia]]
*[[Heart failure]]
*[[Meningitis]]
*[[Sepsis]]


==Diagnosis==
==Evaluation==
===Work-Up===
*TSH: markedly elevated in primary hypothyroidism (most common)
*Chemistry
**May be low/normal in central (pituitary/hypothalamic) hypothyroidism
*CBC
*Free T4: very low or undetectable
*TSH, FT4, FT3
*Free T3: low (but less reliable)
*Cultures
*BMP: [[hyponatremia]] (present in ~50%), [[hypoglycemia]]
*LFT
*CBC: may show anemia, leukopenia
*Cortisol level  
*ABG/VBG: respiratory acidosis, hypercapnia, hypoxemia
*VBG
*Cortisol level (before starting steroids) — rule out concurrent adrenal insufficiency
*CXR  
*Lactate: if concern for sepsis
*EKG
*ECG: [[bradycardia]], low voltage, prolonged QT, possible J (Osborn) waves
*CXR: cardiomegaly (pericardial effusion), pleural effusion
*Infectious workup: blood/urine cultures, CXR (infection is most common precipitant)


===Lab Abnormalities===
==Management==
*Abnormal Thyroid Hormone Levels
===Immediate===
**In primary hypothyroidism then TSH will be elevated and T4 and T3 will be low
*'''Airway management''': intubation for respiratory failure or severe AMS
**If the patient has secondary hypothroidism (Pituitary dysfunction) the TSH can be low or normal and T4 and T3 will be low
*Passive rewarming (avoid active external rewarming which can cause vasodilation and cardiovascular collapse)
*[[Anemia]]
*IV access, cardiac monitoring
*[[Rhabdomyolysis|Elevated CPK]]
*Treat precipitant (antibiotics for suspected infection, dextrose for hypoglycemia)
*[[Renal Failure|Elevated creatinine]]
 
*Elevated transaminases
===Thyroid Hormone Replacement===
*[[Hypercapnia]]
*IV levothyroxine (T4) is the mainstay:
*Hyperlipidemia
**Loading dose: 200-400 mcg IV (or 4 mcg/kg lean body weight)
*[[Hypoglycemia]]
**Then 50-100 mcg IV daily
*[[Hyponatremia]]
*IV liothyronine (T3) may be added for severe cases:
*[[Hypoxia]]
**5-20 mcg IV loading dose, then 2.5-10 mcg IV q8h
*Leukopenia
**T3 has faster onset of action (~4 hours vs 24 hours for T4)
*Respiratory acidosis
**Use with caution in elderly / cardiac patients (arrhythmia risk)
*'''Route must be IV''' — GI absorption unreliable due to ileus and mucosal edema


==Management==
===Stress-Dose Steroids===
===Respiratory Support===
*Hydrocortisone 100 mg IV q8h — give BEFORE or concurrent with thyroid hormone<ref>Jonklaas J, et al. Guidelines for the treatment of hypothyroidism. ''Thyroid''. 2014;24(12):1670-1751. PMID 25266247</ref>
*Early mechanical ventilation will prevent resipatory collapse and severe respiratory acidosis.
*Rationale: thyroid hormone replacement increases cortisol metabolism; if concurrent adrenal insufficiency exists, this can precipitate [[adrenal crisis]]
===Fluid Resuscitation===
*Discontinue steroids once adrenal insufficiency ruled out
*Patients are often intravsascularly depleted and have an underlying infection mandating agressive fluid resususcitation
*In patients who are hyponatremia, be cautious with rapid correction of hyponatremia and choose an appropriate fluid
*Hypoglycemic patients will require intravenous dextrose added into the fluids
===Hypotension===
*[[Vasopressors]] will be ineffective without concomitant thyroid hormone replacement
===Hormone Replacment===
*'''Hydrocortisone''' 100mg q8hr IV since there is also adrenal insufficiency present
*'''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 and potentially safer in patients with coronary artery disease (CAD).
*'''T3'''
**Dose: 20mcg IV followed by 2.5-10mcg q8hr<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>(Start with 10mcg if elderly or has CAD)
**Does not require extrathyroidal conversion
**More rapid onset but may be harmful in patients with CAD
*American Thyroid Association recommends combination therapy T4 with T3


===Hypothermia===
===Supportive Care===
*Treat with passive rewarming
*Fluid restriction if severe [[hyponatremia]] (dilutional)
*Hypothermia will also reverse with thryoid hormone administration
*Avoid hypotonic fluids (worsens hyponatremia)
*Cautious IV NS for hypotension
*Vasopressors may be needed but often refractory until thyroid hormone takes effect
*Avoid sedatives and opioids (impair respiratory drive)
*Electrolyte correction (hyponatremia, hypoglycemia)


==Disposition==
==Disposition==
*Admit to ICU
*ICU admission for all patients
*Serial monitoring: TSH, free T4, electrolytes, glucose, cortisol
*Improvement in vital signs expected within 24-48 hours
*Mental status may take '''days to weeks''' to normalize
*Long-term oral levothyroxine replacement once stabilized


==See Also==
==See Also==
*[[Hypothyroidism]]
*[[Hypothyroidism]]
*[[Thyroid (Main)]]
*[[Thyroid storm]]
*[[Adrenal insufficiency]]
*[[Hypothermia]]
*[[Hyponatremia]]


==References==
==References==
<references/>
<references/>
*Mathew V, et al. Myxedema coma: a new look into an old crisis. ''J Thyroid Res''. 2011;2011:493462. PMID 22028977
*Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. ''Med Clin North Am''. 2012;96(2):385-403. PMID 22443982
*Wall CR. Myxedema coma: diagnosis and treatment. ''Am Fam Physician''. 2000;62(11):2485-2490. PMID 11130234


[[Category:Endo]]
[[Category:Endocrinology]]
[[Category:Critical Care]]

Latest revision as of 09:28, 22 March 2026

Background

  • Extreme, decompensated hypothyroidism with end-organ dysfunction
  • True endocrine emergency with mortality 30-60% even with treatment[1]
  • Misnomer: patients are not always comatose and myxedema is not always present
  • Most common in elderly women with undiagnosed or undertreated hypothyroidism
  • Precipitants:
    • Infection/sepsis (most common trigger)
    • Cold exposure, hypothermia
    • Medication non-compliance with levothyroxine
    • Surgery, trauma, MI, stroke
    • Medications: amiodarone, lithium, sedatives, opioids, anesthetics
    • Adrenal crisis (concurrent adrenal insufficiency)

Clinical Features

  • Classic triad: altered mental status + hypothermia + precipitating event
  • Altered mental status: confusion, lethargy, obtundation → coma
  • Hypothermia (may be severe, <32C; absence of fever despite infection is classic)
  • Bradycardia and hypotension (refractory to vasopressors until thyroid hormone replaced)
  • Hypoventilation with hypercapnia and hypoxia (respiratory failure)
  • Hyponatremia (due to decreased free water excretion — SIADH-like)
  • Hypoglycemia (concurrent adrenal insufficiency or hepatic dysfunction)
  • Non-pitting edema (myxedema), periorbital swelling
  • Delayed deep tendon reflexes (hung-up reflexes)
  • Ileus, urinary retention, hypothermia
  • Pericardial effusion (may rarely cause tamponade)

Differential Diagnosis

Evaluation

  • TSH: markedly elevated in primary hypothyroidism (most common)
    • May be low/normal in central (pituitary/hypothalamic) hypothyroidism
  • Free T4: very low or undetectable
  • Free T3: low (but less reliable)
  • BMP: hyponatremia (present in ~50%), hypoglycemia
  • CBC: may show anemia, leukopenia
  • ABG/VBG: respiratory acidosis, hypercapnia, hypoxemia
  • Cortisol level (before starting steroids) — rule out concurrent adrenal insufficiency
  • Lactate: if concern for sepsis
  • ECG: bradycardia, low voltage, prolonged QT, possible J (Osborn) waves
  • CXR: cardiomegaly (pericardial effusion), pleural effusion
  • Infectious workup: blood/urine cultures, CXR (infection is most common precipitant)

Management

Immediate

  • Airway management: intubation for respiratory failure or severe AMS
  • Passive rewarming (avoid active external rewarming which can cause vasodilation and cardiovascular collapse)
  • IV access, cardiac monitoring
  • Treat precipitant (antibiotics for suspected infection, dextrose for hypoglycemia)

Thyroid Hormone Replacement

  • IV levothyroxine (T4) is the mainstay:
    • Loading dose: 200-400 mcg IV (or 4 mcg/kg lean body weight)
    • Then 50-100 mcg IV daily
  • IV liothyronine (T3) may be added for severe cases:
    • 5-20 mcg IV loading dose, then 2.5-10 mcg IV q8h
    • T3 has faster onset of action (~4 hours vs 24 hours for T4)
    • Use with caution in elderly / cardiac patients (arrhythmia risk)
  • Route must be IV — GI absorption unreliable due to ileus and mucosal edema

Stress-Dose Steroids

  • Hydrocortisone 100 mg IV q8h — give BEFORE or concurrent with thyroid hormone[2]
  • Rationale: thyroid hormone replacement increases cortisol metabolism; if concurrent adrenal insufficiency exists, this can precipitate adrenal crisis
  • Discontinue steroids once adrenal insufficiency ruled out

Supportive Care

  • Fluid restriction if severe hyponatremia (dilutional)
  • Avoid hypotonic fluids (worsens hyponatremia)
  • Cautious IV NS for hypotension
  • Vasopressors may be needed but often refractory until thyroid hormone takes effect
  • Avoid sedatives and opioids (impair respiratory drive)
  • Electrolyte correction (hyponatremia, hypoglycemia)

Disposition

  • ICU admission for all patients
  • Serial monitoring: TSH, free T4, electrolytes, glucose, cortisol
  • Improvement in vital signs expected within 24-48 hours
  • Mental status may take days to weeks to normalize
  • Long-term oral levothyroxine replacement once stabilized

See Also

References

  1. ↑ Ono Y, et al. Clinical characteristics and outcomes of myxedema coma: analysis of a national inpatient database in Japan. J Epidemiol. 2017;27(3):117-122. PMID 28142035
  2. ↑ Jonklaas J, et al. Guidelines for the treatment of hypothyroidism. Thyroid. 2014;24(12):1670-1751. PMID 25266247
  • Mathew V, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res. 2011;2011:493462. PMID 22028977
  • Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am. 2012;96(2):385-403. PMID 22443982
  • Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician. 2000;62(11):2485-2490. PMID 11130234
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