Myxedema Coma

Aka: Myxedema Coma, Hypothyroid Coma

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II. Epidemiology

  1. Incidence: Rare (0.22 per Million persons in U.S.)

III. Pathophysiology

  1. Severe Hypothyroidism

IV. Risk Factors: Predisposing Events

  1. Cold exposure
  2. Trauma or Burn Injury
  3. Hypoglycemia
  4. Infection (e.g. Pneumonia, Urinary Tract Infection, Sepsis, Influenza)
  5. Levothyroxine withdrawal
  6. Carbon Dioxide retention (e.g. COPD)
  7. Cerebrovascular Accident
  8. Medications
    1. Amiodarone
    2. Anesthesia
    3. Barbiturates
    4. Beta Blockers
    5. Diuretics
    6. Lithium
    7. Opioids
    8. Phenothiazines
    9. Phenytoin
    10. Rifampin
    11. Sedative-Hypnotics (Benzodiazepines)

V. Symptoms

  1. Confusion
  2. Generalized weakness
  3. Apathy
  4. Major Depression
  5. Dyspnea
  6. Weight gain
  7. Abdominal Pain
  8. Constipation
  9. Hoarse Voice (related to laryngeal edema)

VI. Signs

  1. See Hypothyroidism
  2. Constitutional
    1. Hypothermia
  3. Head and Neck
    1. Macroglossia (related to mucin and albumin deposits)
    2. Facial Edema (possible airway edema)
      1. May appear similar to Angioedema
      2. Generalized Facial Edema and periorbital edema
    3. Observe for Thyroid Goiter or anterior neck surgical scar
  4. Respiratory
    1. Hypoventilation
    2. Respiratory depression with hypercarbia
    3. Pleural Effusion
    4. Pulmonary Edema
  5. Cardiovascular
    1. Percardial effusion
    2. Congestive Heart Failure
    3. Hemodynamic instability
      1. Diastolic pressure increased
      2. Hypotension (late finding)
      3. Bradycardia
    4. Pretibial edema and lower extremity nonpitting edema
  6. Neurolologic and Psychiatric
    1. Altered Level of Consciousness (Stupor, lethargy, confusion or coma)
    2. Proximal Muscle Weakness
    3. Prolonged Deep Tendon Reflexes
    4. Psychosis
  7. Gastrointestinal
    1. Myxedema Megacolon (late finding)
    2. Ascites

VII. Labs

  1. See Hypothyroidism
  2. Bedside Glucose
    1. Hypoglycemia
  3. Thyroid Function Tests
    1. Normal Thyroid Function Tests may not exclude Myxedema Coma depending on timing of onset
    2. Thyroid Stimulating Hormone (TSH) increased (unless central Hypothyroidism)
    3. Free T4 (Thyroxine) significantly decreased
  4. Serum Cortisol
    1. Decreased if associated Adrenal Insufficiency
  5. Complete Blood Count
  6. Comprehensive Metabolic Panel
    1. Hyponatremia
    2. Hypoglycemia
    3. Acute Kidney Injury with increased Serum Creatinine
    4. Liver transaminases increased
  7. Venous Blood Gas
    1. Hypoxia
    2. Hypercapnea
  8. Creatinine Phosphokinase (CPK) increased
  9. Pregnancy Test in women of childbearing age (bHCG)
  10. Consider Lactic Acid and Blood Cultures and infection evaluation (e.g. Urinalysis, Chest XRay)

VIII. Differential Diagnosis

  1. See Hypothermia Causes
  2. See Altered Level of Consciousness Causes
  3. See Bradycardia
  4. See Muscle Weakness Causes

IX. Diagnostics

  1. Electrocardiogram
    1. Sinus Bradycardia is typical

X. Imaging

  1. Chest XRay
    1. Consider if pursuing suspected infection source

XI. Precautions

  1. Consider infection even in the absence of fever
    1. Even in Sepsis, severe Hypothyroidism may prevent fever response

XII. Management

  1. ABC Management
    1. Medical emergency with high mortality
    2. Address hypoventilation and airway management
    3. Ventilatory and hemodynamic support
    4. Exercise caution with Rapid Sequence Intubation
      1. Myxedema Coma patients will have little oxygen reserve and may desaturate quickly on intubation attempt
  2. Consider Stress Dose Corticosteroids (for concurrent suspected Adrenal Insufficiency)
    1. Give prior to T4 or T3 in the empiric management of Myxedema Coma
    2. Hydrocortisone 100 mg IV every 8 hours
  3. Intravenous Thyroxine (T4)
    1. Administer empirically if suspected (e.g. Hypothyroidism history)
      1. Normal TSH does not exclude Myxedema Coma (e.g. Amiodarone-induced Hypothyroidism)
    2. Standard Protocol (Thyroxine alone)
      1. Thyroxine (T4) 4 mcg/kg up to 200 to 500 mcg slow IV bolus over 5-10 minutes AND THEN
      2. Thyroxine (T4) 50 to 100 mcg (1.6 mcg/kg) orally daily
        1. Intravenous dose is reduced to 75% or oral dose
    3. Alternative Protocol: Combined T4 and T3
      1. Precautions
        1. T4 alone may not significantly modify Blood Pressure or Heart Rate
        2. Endogenous conversion of T4 to T3 is typically delayed in Myxedema Coma
        3. T3 is however associated with increased risk of precipitating Arrhythmia or coronary syndrome
      2. Dosing
        1. Thyroxine (T4) as above AND
        2. Triiodothyronine (T3) 10 mcg (range 5-20 mcg) IV over 5-10 minutes AND THEN
        3. Triiodothyronine (T3) 2.5 to 10 mcg IV every 8 hours until clinical improvement
    4. Monitoring
      1. Observe for Acute Coronary Syndrome and atrial Arrhythmias (e.g. Atrial Fibrillation)
      2. Expect stabilization of Hypotension and Heart Rate after Thyroxine administration
        1. Hypothermia and mental status are often slower to respond to Thyroxine
      3. Thyroid Function Tests
        1. Obtain Free T4 and T3 every 1-2 days (at least one hour after T3 dose)
        2. Obtain TSH weekly (expect TSH drop of 50% per week)
  4. Intravenous Fluids
    1. Administer isotonic crystalloid (NS or LR) as indicated for Hypovolemia
    2. Myxedema Coma patients may appear fluid up with third spacing, but they are typically intravascularly dry
      1. Consider monitoring with Inferior Vena Cava Ultrasound for Volume Status
    3. Anticipate reflex vasodilation and Hypotension with rewarming
  5. Rewarming
    1. May treat Hypothermia with Passive Rewarming
    2. However, monitor hemodynamic status carefully, maintain hydration and expect Hypotension
  6. Vasopressors
    1. Hypotension may be refractory to Vasopressors and fluids until Thyroxine has been administered
  7. Endocrinology Consultation
  8. ICU admission
  9. Anticipate Electrolyte abnormalities (e.g. Hyponatremia)
  10. Consider empiric Antibiotics if infection is considered trigger (even if no fever, esp. if hypothermic)

XIII. Prognosis

  1. Associated with high risk (30-60% of cases) of cardiovascular collapse or death

XIV. Complications

  1. Congestive Heart Failure

XV. References

  1. Mason and Swadron in Herbert (2019) EM:Rap-C3 3(11):1-10
  2. Swaminathan and Willis in Herbert (2020) EM:RAP 20(1): 9-10
  3. Matthew (2011) J Thyroid Res +PMID: 21941682 [PubMed]
  4. Rhodes Wall (2000) Am Fam Physician 62(11): 2485-90 [PubMed]
  5. Wartofsky (2006) Endocrinol Metab Clin North Am 35(4): 687-98 [PubMed]
  6. Wilson (2021) Am Fam Physician 103(10): 605-13 [PubMed]

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