What is Myxedema?
Myxedema is the severe, life-threatening manifestation of profound hypothyroidism characterized by altered mental status, hypothermia, cardiovascular collapse, and multiorgan dysfunction—representing a medical emergency with high mortality despite treatment. 1, 2
Clinical Definition and Pathophysiology
Myxedema represents the extreme end of the hypothyroidism spectrum where critically low thyroid hormone levels cause the brain's metabolic demands to go unmet, leading to altered consciousness and coma 3. The term "myxedema coma" is actually a misnomer—patients don't always present in frank coma but may show progressively worsening confusion or lethargy 4.
- Every patient with myxedema has hypothyroidism, but not every hypothyroid patient develops myxedema 5
- The condition occurs when homeostatic mechanisms compensating for chronic hypothyroidism become overwhelmed by physiologic stressors 1, 2
- Critically low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia, and coma 2
Cardinal Clinical Features
Neurological Manifestations
- Altered mental status ranging from confusion to frank coma is the defining feature 3, 6
- Mental and physical slowness progressing to lethargy 5
- The patient may present with less severe symptoms than true coma, making the diagnosis easily missed 4
Cardiovascular Dysfunction
- Cardiac dysfunction with delayed myocardial relaxation and reduced contractility 3
- Bradycardia and hypotension leading to cardiogenic shock 6, 2
- Decreased ventricular filling combined with increased systemic vascular resistance compromises hemodynamic stability 3
- Severely reduced left ventricular ejection fraction that may require vasopressor support 6
- Arrhythmias and potential cardiac arrest (pulseless electrical activity) 6, 2
Classic Hypothyroid Symptoms (Often Present in History)
- Weakness and fatigue 5, 1
- Cold intolerance 5, 1
- Weight gain and constipation 1
- Dry skin and typical myxedematous facies 5
- Hoarse voice 5
Additional Life-Threatening Features
- Hypothermia (though may not be prominent in tropical climates) 2
- Respiratory failure requiring mechanical ventilation 6, 2
- Hyponatremia (hypothyroidism should be in the differential of every patient with hyponatremia) 1
- Hypoglycemia requiring immediate correction 7
- Acute kidney injury 6
- Multisystem organ failure 6
Major Precipitating Factors
Myxedema coma rarely occurs spontaneously—it is typically triggered by physiologic stressors in patients with underlying severe hypothyroidism. 1, 2
- Infection is the most common precipitating factor 2
- Discontinuation of thyroid hormone replacement 2
- Surgery as a major physiologic stressor 3, 7
- Trauma or injury 3, 7
- History of radiation therapy to the neck region 7
- Sedative drug intake 2
- Malnutrition (rare but documented precipitant) 4
- Coexisting adrenal insufficiency 6, 1
Diagnostic Approach
Laboratory Confirmation
- Markedly elevated TSH (can exceed 400 µU/L in severe cases) 4
- Severely low or undetectable free T4 6, 4
- Total serum thyroxine and free thyroxine index confirm the diagnosis 5
Clinical Diagnosis
- It is often possible to diagnose myxedema on clinical grounds alone before laboratory confirmation 5
- Maintain a high index of suspicion in any patient with altered mental status and history of hypothyroidism 1, 2
- Look for history of thyroid disease, prior thyroid surgery, radioactive iodine therapy, or neck irradiation 7
Critical Management Principles
Immediate Interventions
- Admit to intensive care unit immediately for vigorous pulmonary and cardiovascular support 1
- Prompt administration of adequate thyroid hormone replacement is essential 5, 1
- Most authorities recommend intravenous levothyroxine (T4) over intravenous liothyronine (T3) 1
- Administer hydrocortisone until coexisting adrenal insufficiency is ruled out—never start thyroid hormone before addressing potential adrenal crisis 6, 1
- Identify and correct hypoglycemia immediately 7
- Provide vasopressor support for cardiogenic shock 6
- Mechanical ventilation for respiratory failure 6
Treatment Efficacy
- Oral thyroid hormone replacement through nasogastric tube with loading dose and maintenance therapy is as efficacious as intravenous therapy 2
- In countries where T3 is unavailable, oral T4 can be used effectively without significant difference in outcomes 2
- Neurological status and thyroid function typically return to normal over several days with appropriate treatment 6
Prognostic Indicators
Myxedema coma carries high mortality rates (historically 20-50%) despite appropriate intervention. 6, 2
Poor Prognostic Factors
- Hypotension and bradycardia at presentation 2
- Need for mechanical ventilation 2
- Hypothermia unresponsive to treatment 2
- Sepsis 2
- Intake of sedative drugs 2
- Lower Glasgow Coma Scale score 2
- High APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores >6 2
Prevention Strategies
Family physicians are in a critical position to prevent myxedema coma by maintaining high suspicion for hypothyroidism and ensuring treatment compliance. 1
- Early intervention in hypothyroid patients developing sepsis or other precipitating factors 2
- Ensuring continued intake of thyroid supplements prevents mortality and morbidity 2
- Patient education regarding medication adherence 6
- Regular endocrinology follow-up for thyroid hormone titration 6
- Careful thyroid hormone titration in elderly patients to avoid cardiac complications 5
Key Clinical Pearls
- The term "myxedema coma" is misleading—patients may present with confusion rather than frank coma 4
- Myxedema coma is rare but often fatal, occurring most commonly in elderly women 5
- The condition may be mistaken for chronic debilitating diseases common in elderly populations 5
- TSH levels can reach extraordinarily high values (>400 µU/L documented) 4
- Coagulation disorders are increasingly recognized complications 2
- The transition from hypothyroid to euthyroid state places added burden on the heart, requiring careful monitoring 5