What is the diagnosis of myxedema coma (hypothyroidism-induced coma)?

From the Guidelines

Myxedema coma is a life-threatening emergency that requires immediate diagnosis and treatment, and it should be suspected in any patient with altered mental status, hypothermia, bradycardia, and other severe symptoms, with laboratory confirmation including low serum free T4 and T3 levels with elevated TSH, as indicated in the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1. The diagnosis of myxedema coma is based on clinical presentation and laboratory findings, and it is crucial to identify the condition promptly to initiate treatment and reduce mortality rates.

• Clinical presentation includes altered mental status, hypothermia, bradycardia, hypotension, hyponatremia, and hypoglycemia, especially with a history of thyroid disease or thyroidectomy.
• Laboratory confirmation includes low serum free T4 and T3 levels with elevated TSH (except in secondary hypothyroidism where TSH may be low), as well as other tests such as complete blood count, comprehensive metabolic panel, cortisol level, and blood cultures to rule out infection.
• Additional tests, such as arterial blood gases and ECG, may show respiratory acidosis due to hypoventilation, bradycardia, low voltage, and prolonged QT interval.
• The management of myxedema coma involves holding immune checkpoint inhibitor therapy until symptoms resolve to baseline, with endocrine consultation to assist with rapid hormone replacement, and hospital admission for supportive care, including IV levothyroxine dosing, steroids, and other necessary interventions, as outlined in the guideline update 1.
• It is essential to identify and address precipitating factors, such as infection, medication non-compliance, stroke, or exposure to cold, simultaneously with the treatment of myxedema coma.
• The diagnosis should not be delayed waiting for laboratory confirmation if clinical suspicion is high, as treatment should begin immediately to reduce mortality rates, which remain high (30-60%) even with treatment, emphasizing the need for prompt and aggressive management of this condition 1.

From the FDA Drug Label

The clinical features of myxedema coma include depression of the cardiovascular, respiratory, gastrointestinal and central nervous systems, impaired diuresis, and hypothermia. The diagnosis of myxedema coma is based on clinical features such as:

• Depression of the cardiovascular system
• Depression of the respiratory system
• Depression of the gastrointestinal system
• Depression of the central nervous system
• Impaired diuresis
• Hypothermia No specific laboratory test is mentioned in the drug label for the diagnosis of myxedema coma, but thyroid status can be assessed by means of appropriate laboratory tests, including serum T3 and TSH levels 2.

From the Research

Diagnosis of Myxedema Coma

• Myxedema coma is a rare endocrine emergency resulting from the decompensation of severe hypothyroidism, characterized by deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation 3.
• The clinical triad of myxedema coma is altered mental status, hypothermia, and the presence of a precipitating factor 4.
• Typical patients with myxedema coma are over age 60 years, female, and have clinical features associated with hypothyroidism, including dry skin, coarse hair, and non-pitting edema 4.
• Myxedema coma has a temporal association with most cases occurring in the winter months 4.

Diagnostic Criteria

• The diagnosis of myxedema coma can be based on the diagnostic scoring system for myxedema coma proposed by Popoveniuc et al. 5.
• Laboratory findings, such as severe hypothyroidism, elevated thyroid-stimulating hormone (TSH), and acute kidney injury, can also aid in diagnosis 6.

Importance of Early Diagnosis

• Early disease diagnosis and advancements in intensive supportive care have reduced the mortality rate of myxedema coma 3.
• Prompt recognition and aggressive management of myxedema coma are crucial to prevent multisystem organ failure and high mortality risk 6.
• A high degree of suspicion is necessary to make the diagnosis in the emergency department, as recognition can be challenging and delayed treatment can be fatal 4.

Treatment Options

• Appropriate management of the underlying thyroid hormone deficiency is essential, and treatment options include intravenous levothyroxine, oral levothyroxine, and combination therapy with levothyroxine and liothyronine 3, 6, 5, 7.
• Oral levothyroxine can be an effective treatment option for myxedema coma when intravenous levothyroxine is unavailable 5, 7.
• Intensive supportive care, including fluid therapy, empirical antibiotics, mechanical ventilation, and inotropic agents, is also necessary to manage myxedema coma 6, 7.