II. Epidemiology
- Incidence: Rare (0.22 per Million persons in U.S.)
III. Pathophysiology
- Severe Hypothyroidism
IV. Risk Factors: Predisposing Events
- Cold exposure
- Trauma or Burn Injury
- Hypoglycemia
- Infection (e.g. Pneumonia, Urinary Tract Infection, Sepsis, Influenza)
- Levothyroxine withdrawal
- Carbon Dioxide retention (e.g. COPD)
- Cerebrovascular Accident
- Medications
V. Symptoms
- Confusion
- Generalized weakness
- Apathy
- Major Depression
- Dyspnea
- Weight gain
- Abdominal Pain
- Constipation
- Hoarse Voice (related to laryngeal edema)
VI. Signs
- See Hypothyroidism
- Constitutional
- Head and Neck
- Macroglossia (related to mucin and albumin deposits)
- Facial Edema (possible airway edema)
- May appear similar to Angioedema
- Generalized Facial Edema and periorbital edema
- Observe for Thyroid Goiter or anterior neck surgical scar
- Respiratory
- Hypoventilation
- Respiratory depression with hypercarbia
- Pleural Effusion
- Pulmonary Edema
- Cardiovascular
- Percardial effusion
- Congestive Heart Failure
- Hemodynamic instability
- Diastolic pressure increased
- Hypotension (late finding)
- Bradycardia
- Pretibial edema and lower extremity nonpitting edema
- Neurolologic and Psychiatric
- Altered Level of Consciousness (Stupor, lethargy, confusion or coma)
- Proximal Muscle Weakness
- Prolonged Deep Tendon Reflexes
- Psychosis
- Gastrointestinal
VII. Labs
- See Hypothyroidism
- Bedside Glucose
-
Thyroid Function Tests
- Normal Thyroid Function Tests may not exclude Myxedema Coma depending on timing of onset
- Thyroid Stimulating Hormone (TSH) increased (unless central Hypothyroidism)
- Free T4 (Thyroxine) significantly decreased
-
Serum Cortisol
- Decreased if associated Adrenal Insufficiency
- Complete Blood Count
- Comprehensive Metabolic Panel
- Hyponatremia
- Hypoglycemia
- Acute Kidney Injury with increased Serum Creatinine
- Liver transaminases increased
-
Venous Blood Gas
- Hypoxia
- Hypercapnea
- Creatinine Phosphokinase (CPK) increased
- Pregnancy Test in women of childbearing age (bHCG)
- Consider Lactic Acid and Blood Cultures and infection evaluation (e.g. Urinalysis, Chest XRay)
VIII. Differential Diagnosis
IX. Diagnostics
-
Electrocardiogram
- Sinus Bradycardia is typical
X. Imaging
-
Chest XRay
- Consider if pursuing suspected infection source
XI. Precautions
- Consider infection even in the absence of fever
- Even in Sepsis, severe Hypothyroidism may prevent fever response
XII. Management
-
ABC Management
- Medical emergency with high mortality
- Address hypoventilation and airway management
- Ventilatory and hemodynamic support
-
Exercise caution with Rapid Sequence Intubation
- Myxedema Coma patients will have little oxygen reserve and may desaturate quickly on intubation attempt
- Consider Stress Dose Corticosteroids (for concurrent suspected Adrenal Insufficiency)
- Give prior to T4 or T3 in the empiric management of Myxedema Coma
- Hydrocortisone 100 mg IV every 8 hours
- Intravenous Thyroxine (T4)
- Administer empirically if suspected (e.g. Hypothyroidism history)
- Normal TSH does not exclude Myxedema Coma (e.g. Amiodarone-induced Hypothyroidism)
- Standard Protocol (Thyroxine alone)
- Alternative Protocol: Combined T4 and T3
- Precautions
- T4 alone may not significantly modify Blood Pressure or Heart Rate
- Endogenous conversion of T4 to T3 is typically delayed in Myxedema Coma
- T3 is however associated with increased risk of precipitating Arrhythmia or coronary syndrome
- Dosing
- Thyroxine (T4) as above AND
- Triiodothyronine (T3) 10 mcg (range 5-20 mcg) IV over 5-10 minutes AND THEN
- Triiodothyronine (T3) 2.5 to 10 mcg IV every 8 hours until clinical improvement
- Precautions
- Monitoring
- Observe for Acute Coronary Syndrome and atrial Arrhythmias (e.g. Atrial Fibrillation)
- Expect stabilization of Hypotension and Heart Rate after Thyroxine administration
- Hypothermia and mental status are often slower to respond to Thyroxine
- Thyroid Function Tests
- Obtain Free T4 and T3 every 1-2 days (at least one hour after T3 dose)
- Obtain TSH weekly (expect TSH drop of 50% per week)
- Administer empirically if suspected (e.g. Hypothyroidism history)
-
Intravenous Fluids
- Administer isotonic crystalloid (NS or LR) as indicated for Hypovolemia
- Myxedema Coma patients may appear fluid up with third spacing, but they are typically intravascularly dry
- Consider monitoring with Inferior Vena Cava Ultrasound for Volume Status
- Anticipate reflex vasodilation and Hypotension with rewarming
- Rewarming
- May treat Hypothermia with Passive Rewarming
- However, monitor hemodynamic status carefully, maintain hydration and expect Hypotension
-
Vasopressors
- Hypotension may be refractory to Vasopressors and fluids until Thyroxine has been administered
- Endocrinology Consultation
- ICU admission
- Anticipate Electrolyte abnormalities (e.g. Hyponatremia)
- Consider empiric Antibiotics if infection is considered trigger (even if no fever, esp. if hypothermic)
XIII. Prognosis
- Associated with high risk (30-60% of cases) of cardiovascular collapse or death
XIV. Complications
XV. References
- Mason and Swadron in Herbert (2019) EM:Rap-C3 3(11):1-10
- Swaminathan and Willis in Herbert (2020) EM:RAP 20(1): 9-10
- Matthew (2011) J Thyroid Res +PMID: 21941682 [PubMed]
- Rhodes Wall (2000) Am Fam Physician 62(11): 2485-90 [PubMed]
- Wartofsky (2006) Endocrinol Metab Clin North Am 35(4): 687-98 [PubMed]
- Wilson (2021) Am Fam Physician 103(10): 605-13 [PubMed]