Myxedema coma

Background

• Myxedema coma is a rare, life-threatening form of decompensated hypothyroidism with a high mortality rate (up to 40% despite treatment). Early detection and prompt, appropriate therapy is critical to avoid a fatal outcome.
• It is most commonly seen in women > 60 years old, especially those with untreated or inadequately treated hypothyroidism.
• The condition is usually triggered by an acute precipitating event in a patient with hypothyroidism, such as:
  • infection
  • myocardial infarction
  • intense cold exposure, especially if resulting in hypothermia
  • overdose of diuretics and/or sedatives, especially opioids
  • major surgery
  • gastrointestinal bleeding

Evaluation

• The diagnosis of myxedema coma is based on clinical presentation and exclusion of other causes of coma, as no set of laboratory test results definitively establishes the diagnosis.
• In precomatose patients, which is much more common than comatose patients, suspect myxedema coma in older adults (especially women aged 60-85 years) with:
  • profound hypothermia (< 95 degrees F [35 degrees C])
  • decreased mentation (may initially present as confusion, obtundation, and lethargy)
  • generalized edema
  • typical signs and symptoms of severe hypothyroidism
• Blood tests in patients with clinically suspected myxedema coma should include:
  • complete blood count
  • full chemistry profile
  • assessment of adrenocorticotropic hormone (ACTH) and plasma cortisol to identify hypothyroidism secondary to pituitary dysfunction and rule out coincident primary adrenal insufficiency, known as Schmidt syndrome (polyglandular autoimmune syndrome type 2)
  • thyroid function tests to assess thyroid function
    • Most patients will have primary hypothyroidism with high serum thyroid-stimulating hormone (TSH) and low serum free thyroxine (T4), though TSH levels have been reported to vary widely in patients with myxedema coma.
    • Secondary or central hypothyroidism due to underlying pituitary disease is rare and usually presents with low or normal TSH and low free T4.
• Laboratory abnormalities in patients with myxedema coma may include:
  • hypoxemia
  • hyponatremia
  • normocytic or macrocytic anemia
  • hypercholesterolemia
  • low blood glucose
  • low sodium and chloride
  • high total and ionized calcium
  • elevated blood urea nitrogen and creatinine (associated with mild renal failure)
• Perform electrocardiography to assess for cardiovascular complications. Findings may include:
  • sinus bradycardia
  • low voltage complexes
  • bundle branch blocks
  • complete heart blocks
  • nonspecific ST segment and T wave changes
• Chest x-ray may be used to assess for precipitating infection (such as pneumonia) or pleural effusion.

Management

• Initiate treatment based on clinical suspicion alone, without delaying for laboratory test results.
• Admit the patient to the intensive care unit for continuous pulmonary and cardiovascular monitoring and support.
  • Urgent supportive care is necessary to manage hypoventilation and hypothermia.
  • Provide fluid replacement as needed for patients with hyponatremia and/or hypoglycemia.
• Begin immediate empiric glucocorticoid treatment with hydrocortisone 50-100 mg IV (Strong recommendation).
• Once glucocorticoid coverage has started, administer thyroid hormone therapy with levothyroxine (LT4) (Strong recommendation).
  • A loading dose is 200-400 mcg IV, followed by a replacement dose of 75% of 1.6 mcg/kg/day IV.
  • Use lower doses for smaller or older patients and those with a history of coronary artery disease or arrhythmia.
• Consider adding liothyronine (LT3) to LT4 (Weak recommendation).
  • A loading dose is 5-20 mcg IV, followed by a maintenance dose of 2.5-10 mcg every 8 hours until the patient is clearly improving.
  • Use lower doses for smaller or older patients and those with a history of coronary artery disease or arrhythmia.
  • Avoid high doses due to a reported association of high serum triiodothyronine (T3) with mortality.
• It is necessary to treat underlying conditions precipitating myxedema coma, such as severe hyponatremia, heart failure, diabetes, and sepsis.
• Following thyroid hormone therapy, consider follow-up evaluations to determine if a therapeutic endpoint has been reached (Weak recommendation).
  • Look for improvement in clinical parameters (typically observed within first week) such as improved:
    • mental status
    • cardiovascular status
    • respiratory function
    • temperature
    • thyroid hormone status
    • electrolytes
  • Measure thyroid hormones every 1-2 days.
    • Optimal serum thyroid-stimulating hormone (TSH) and thyroid hormone levels are not well defined for this patient population.
    • Failure of thyroid hormone levels to improve or TSH to decrease may be an indication to increase LT4 therapy and/or add LT3 therapy.
    • High serum T3 may be an indication to decrease therapy due to safety concerns.
• Glucocorticoids can be discontinued once the patient is clinically stable if the patient's cortisol level comes back normal.