What is the diagnosis and treatment of myxedema coma?

Myxedema Coma: Diagnosis and Treatment

Diagnosis

Myxedema coma is a clinical diagnosis that must be made immediately based on the characteristic presentation, without waiting for laboratory confirmation, as it is a life-threatening endocrine emergency requiring immediate treatment. 1, 2

Clinical Presentation

The diagnosis relies primarily on recognizing the classic clinical features:

• Altered mental status progressing to coma (Glasgow Coma Score ≤8 warrants intubation) 1
• Hypothermia (often <35°C or 95°F) - a cardinal feature that distinguishes this from other causes of coma 3, 2
• Bradycardia and hypotension leading to circulatory collapse 3, 4
• Hypoventilation with CO₂ retention (hypercarbia and hypoxemia) 3, 5
• Hyporeflexia or delayed deep tendon reflexes 3

Laboratory Findings

While treatment should not be delayed for laboratory results, supportive biochemical evidence includes:

• Elevated TSH with low free T4 and T3 in primary hypothyroidism 3, 2
• Hyponatremia (should prompt consideration of hypothyroidism in any patient) 2
• Elevated creatinine phosphokinase 4
• Hypoglycemia (must be corrected immediately) 1
• Metabolic acidosis and renal failure 4

Important Diagnostic Caveat

Myxedema coma can rarely occur even with subclinical hypothyroidism (elevated TSH but normal T4/T3), so do not exclude the diagnosis based solely on borderline thyroid function tests if the clinical picture is compelling. 4

Precipitating Factors to Identify

Look for triggering events in the history:

• Infections (especially pneumonia) 2, 5
• Sedatives, anesthetics, or other CNS depressants 6, 5
• Cold exposure (more common in winter months) 5, 7
• Inadequate thyroid hormone replacement or discontinuation 3
• Systemic illness or physiologic stress 5

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Treatment

Immediate Stabilization (First Priority)

Admit to intensive care unit immediately for aggressive supportive care. 1

• Secure airway with intubation and mechanical ventilation if Glasgow Coma Score ≤8 or significant hypercarbia 1
• Correct hypoglycemia immediately if present 1
• Passive rewarming only (avoid active external rewarming which can cause vasodilation and cardiovascular collapse) 5, 7
• Hemodynamic support with pressors if needed for hypotension 5

Thyroid Hormone Replacement (Second Priority)

Administer intravenous levothyroxine (T4) as the preferred agent, though IV liothyronine (T3) is also used by some authorities. 6, 2

The FDA-approved approach for myxedema coma specifically states: "Myxedema coma is usually precipitated in the hypothyroid patient of long standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. An intravenous preparation of liothyronine sodium is marketed under the trade name Triostat® for use in myxedema coma/precoma." 6

However, most authorities recommend IV levothyroxine (T4) over liothyronine (T3) due to more stable serum levels and fewer cardiovascular side effects. 2

For elderly patients or those with cardiac disease, use lower initial doses (25-50 μg) to avoid precipitating cardiovascular complications. 1

Glucocorticoid Administration (Critical Third Step)

Give hydrocortisone 100 mg IV every 8 hours immediately, before or concurrent with thyroid hormone, until adrenal insufficiency is ruled out. 1, 6

This is essential because:

• Thyroid hormone replacement can precipitate adrenal crisis in patients with concurrent adrenal insufficiency 1, 6
• The therapy of myxedema coma requires simultaneous administration of glucocorticoids 6

Additional Supportive Measures

• Treat underlying infections with antibiotics 5, 7
• Correct electrolyte disturbances, particularly hyponatremia (but avoid overly rapid correction) 4, 7
• Provide respiratory support for hypoventilation 5, 7
• Monitor for pericardial effusion which may be present 4

Transition to Maintenance Therapy

Once stabilized:

• Typical maintenance dose is 1.6 μg/kg/day for patients without risk factors 1
• For elderly or cardiac patients, start with 25-50 μg daily and titrate gradually 1
• Monitor TSH every 6-8 weeks while titrating to goal of TSH within reference range 1

Critical Pitfall to Avoid

Monitor closely for adrenal crisis, which can be precipitated by thyroid hormone replacement in patients with concurrent adrenal insufficiency - this is why glucocorticoids must be given prophylactically. 1, 6