What is the pathophysiology of myxedema coma?

Pathophysiology of Myxedema Coma

Myxedema coma is a rare, life-threatening complication of severe hypothyroidism characterized by altered mental status, hypothermia, bradycardia, hypotension, hyponatremia, and respiratory failure that can lead to multisystem organ failure if not promptly treated.1

Definition and Clinical Presentation

• Myxedema coma represents the extreme end of the hypothyroidism spectrum, typically presenting with decompensation of previously untreated or undertreated hypothyroidism 2
• Clinical manifestations include decreased consciousness, hypothermia, bradycardia, hypotension, hypoventilation with CO2 retention, and non-pitting edema 3, 2
• This condition is considered a true endocrine emergency with high mortality despite appropriate intervention 1, 4

Underlying Pathophysiological Mechanisms

• Severe thyroid hormone deficiency leads to profound metabolic derangements affecting multiple organ systems 2
• The primary pathophysiological changes include:
  • Decreased cardiac output due to impaired myocardial contractility 1
  • Reduced respiratory drive leading to hypoventilation and CO2 retention 3
  • Impaired thermoregulation resulting in hypothermia 2
  • Decreased metabolic rate and oxygen consumption 2
  • Water retention and dilutional hyponatremia 1, 2

Cardiovascular Effects

• Severe hypothyroidism causes decreased cardiac contractility and reduced cardiac output 1
• This can progress to cardiogenic shock in advanced cases 1
• Bradycardia is a hallmark finding due to decreased sympathetic activity 2
• Pericardial effusions may develop, further compromising cardiac function 4

Neurological Effects

• Altered mental status ranging from confusion to coma is characteristic 1, 4
• The mechanism involves decreased cerebral blood flow and metabolism 2
• Hyponatremia and hypoglycemia contribute to neurological symptoms 4

Respiratory Effects

• Decreased respiratory drive leads to hypoventilation 3
• CO2 retention (hypercapnia) and hypoxemia are common 2
• Respiratory muscle weakness further compromises ventilation 3

Metabolic and Electrolyte Abnormalities

• Hypoglycemia is common due to impaired gluconeogenesis and decreased insulin clearance 4
• Hyponatremia results from impaired free water excretion 2
• Decreased metabolic rate leads to hypothermia 2

Precipitating Factors

• Myxedema coma is often precipitated by:
  • Infections, particularly pneumonia 2
  • Medications (sedatives, anesthetics) 1
  • Cold exposure 2
  • Trauma or surgery 2
  • Discontinuation of thyroid replacement therapy 3

Adrenal Involvement

• Severe hypothyroidism can lead to decreased adrenocortical activity 5
• When thyroid replacement therapy is initiated, metabolism increases faster than adrenocortical activity, potentially precipitating adrenocortical insufficiency 5
• This explains why glucocorticoid administration is recommended during initial treatment 6

Pathophysiological Basis for Treatment

• Treatment focuses on addressing the underlying thyroid hormone deficiency with thyroid hormone replacement 7
• Intravenous administration of thyroid hormones provides rapid correction of the deficiency 7
• Supportive care addressing hypothermia, hypotension, and respiratory compromise is essential 6
• Glucocorticoid administration is recommended to prevent adrenal crisis 6, 5

Mortality and Prognosis

• Myxedema coma carries a high mortality rate despite appropriate treatment 1, 4
• Factors associated with poor prognosis include advanced age, delayed diagnosis, and presence of multiple comorbidities 2
• Early recognition and aggressive management are crucial for improving outcomes 1, 4