What is the treatment for myxedema coma (a severe form of hypothyroidism)?

From the Guidelines

Myxedema coma is a life-threatening emergency requiring admission and a high level of care, with treatment involving intravenous levothyroxine and supportive care. According to the guidelines for managing immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, myxedema coma is a severe manifestation of hypothyroidism that requires immediate attention 1. The condition is characterized by altered mental status, hypothermia, and multiple organ dysfunction, and its management involves a multidisciplinary approach.

Key Considerations

• Treatment should begin with intravenous levothyroxine (T4) and concurrent administration of intravenous hydrocortisone until adrenal insufficiency is ruled out, as indicated in the guidelines for grade 3-4 hypothyroidism 1.
• Supportive care includes passive warming, mechanical ventilation if needed, careful fluid management, and treatment of precipitating factors such as infections or medications.
• Blood glucose, electrolytes, and vital signs require close monitoring, and the underlying pathophysiology involves profound thyroid hormone deficiency leading to decreased metabolic rate, impaired thermoregulation, reduced cardiac output, hypoventilation, and impaired renal function.

Management Approach

• The guidelines suggest holding immune checkpoint inhibitor therapy until symptoms resolve to baseline with appropriate supplementation, and endocrine consultation to assist with rapid hormone replacement 1.
• Inpatient endocrinology consultation can assist with IV levothyroxine dosing, steroids, and supportive care, and if there is uncertainty about whether primary or central hypothyroidism is present, hydrocortisone should be given before thyroid hormone is initiated 1.
• The mortality rate remains high (20-40%) despite appropriate treatment, with advanced age, persistent hypothermia, and delayed treatment being poor prognostic factors, highlighting the need for prompt and aggressive management of myxedema coma.

From the FDA Drug Label

The therapy of myxedema coma requires simultaneous administration of glucocorticoids. Many investigators recommend that corticosteroids be administered routinely in the initial emergency treatment of all patients with myxedema coma. Patients with pituitary myxedema should receive adrenocortical hormone replacement therapy at or before the start of liothyronine sodium injection (T 3) therapy Patients with primary myxedema may also require adrenocortical hormone replacement therapy since a rapid return to normal body metabolism from a severely hypothyroid state may result in acute adrenocortical insufficiency and shock

The treatment of myxedema coma requires the administration of thyroid hormones and glucocorticoids.

• Liothyronine sodium (T 3) is used to treat myxedema coma.
• Glucocorticoids should be administered simultaneously with thyroid hormones.
• Adrenocortical hormone replacement therapy may be required in patients with pituitary or primary myxedema. The clinical features of myxedema coma include depression of the cardiovascular, respiratory, gastrointestinal and central nervous systems, impaired diuresis, and hypothermia. Administration of thyroid hormones reverses or attenuates these conditions 2. Thyroid hormones increase heart rate, ventricular contractility and cardiac output, as well as decrease total systemic vascular resistance 2. Thyroid hormones correct hypothermia by markedly increasing the basal metabolic rate, as well as the number and activity of mitochondria in almost all cells of the body 2. Liothyronine sodium has a rapid onset of action and a short half-life, which allows for quick dosage adjustment and control of the effects of overdosage 2. Concomitant use of liothyronine sodium injection (T 3) and artificial rewarming of patients is contraindicated 2.

From the Research

Definition and Characteristics of Myxedema Coma

• Myxedema coma is a life-threatening manifestation of hypothyroidism associated with altered mental status, hypothermia, and symptoms related to the slowing of other organ systems 3.
• It can occur as a culmination of severe, longstanding hypothyroidism or be precipitated by acute stressors such as infection, myocardial infarction, cold exposure, and surgery in patients with poorly controlled hypothyroidism 3.
• Myxedema coma is characterized by the deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation 4.

Diagnosis and Treatment

• The diagnosis of myxedema coma should be suspected based on the clinical presentation, and treatment should not be delayed while awaiting confirmatory laboratory data 3, 5.
• Treatment consists of correction of electrolyte abnormalities, passive rewarming, treatment of infections, respiratory and hemodynamic support, administration of stress-dose glucocorticoids, and thyroid hormone replacement 5.
• Intravenous thyroxine, between 200 and 500 micrograms as the initial dose followed by 50 to 100 micrograms/day, is recommended 5.
• Concurrent therapy with triiodothyronine can also be considered 5.
• Oral levothyroxine is an effective option for myxedema coma when intravenous levothyroxine is unavailable 6.

Management and Outcome

• Patients with suspected myxedema coma should be admitted to an intensive care unit for vigorous pulmonary and cardiovascular support 7.
• Hydrocortisone should be administered until coexisting adrenal insufficiency is ruled out 3, 7.
• Early disease diagnosis and advancements in intensive supportive care have reduced the mortality rate of myxedema coma 4.
• With appropriate treatment, patients with myxedema coma can survive and recover, as demonstrated by the improvement of symptoms and mild change in thyroid hormone levels during hospitalization in a case report 3.