Pathophysiology of Myxedema Coma
Myxedema coma represents a catastrophic failure of cellular metabolism when critically low thyroid hormone levels prevent the brain from meeting its metabolic demands, resulting in altered mental status and coma as the defining clinical feature. 1
Core Metabolic Derangements
The fundamental pathophysiology centers on severe thyroid hormone deficiency causing a collapse of basal metabolism across all organ systems 2. This creates a cascade of life-threatening complications:
Neurological Dysfunction
- The brain's metabolic requirements cannot be sustained with critically depleted thyroid hormone levels, leading to progressive mental status changes culminating in coma 1
- Altered consciousness ranges from confusion to frank coma, though the term "myxedema coma" is somewhat misleading as patients may present with less severe symptoms 3
Cardiovascular Collapse
- Hypothyroidism causes cardiac dysfunction including delayed relaxation, decreased cardiac contractility, bradycardia, and abnormal cardiac output 4
- Decreased ventricular filling and increased systemic vascular resistance further compromise hemodynamic stability 4
- Pericardial effusions may develop as part of the systemic manifestations 5
Metabolic and Electrolyte Abnormalities
- Hyponatremia develops due to impaired free water clearance 6
- Hypoglycemia must be identified and corrected immediately 7
- Metabolic acidosis and renal failure can occur 5
- Elevated creatinine phosphokinase reflects muscle involvement 5
Thermoregulatory Failure
- Hypothermia is a cardinal feature, reflecting the profound reduction in metabolic heat production 6, 8
- Temperature may drop to dangerously low levels (e.g., 33.2°C) 5
Precipitating Factors
Myxedema coma typically occurs when acute physiologic stressors overwhelm the already compromised homeostatic mechanisms in patients with severe, longstanding hypothyroidism 1, 8:
- Surgery represents a major physiologic stressor that can precipitate myxedema coma 7, 1
- Trauma or injury can trigger decompensation 7, 1
- Infection/sepsis is a common precipitant 6, 8
- Cold exposure 8
- Myocardial infarction 8
- Malnutrition (in at least one reported case) 3
Critical Clinical Context
While myxedema coma classically occurs in patients with severe biochemical hypothyroidism, it has been reported even in subclinical hypothyroidism 5. In one remarkable case, a patient with elevated TSH but normal free T4 and T3 levels developed full myxedema coma with hypothermia, circulatory collapse, and coma 5. This highlights that clinical evaluation must take precedence when laboratory findings and clinical presentation are discordant 5.
The condition carries extremely high mortality and represents a true medical emergency requiring immediate treatment initiation even before laboratory confirmation 8. The multisystem nature of the metabolic collapse—affecting brain, heart, kidneys, and thermoregulation simultaneously—explains why this condition is so rapidly fatal without aggressive intervention 6, 8, 3.