What are the clinical features and findings in a patient with myxedema (severe untreated hypothyroidism)?

Clinical Presentation of Myxedema

Cardinal Features of Severe Hypothyroidism

Myxedema represents the most extreme, life-threatening manifestation of severe hypothyroidism, characterized by deteriorating mental status, hypothermia, and multiple organ system dysfunction. 1

Neurological Manifestations

• Altered mental status progressing to coma is the defining feature, occurring when critically low thyroid hormone levels prevent the brain from meeting its metabolic demands 2
• Confusion, lethargy, and progressive obtundation leading to unresponsiveness 1, 3
• The term "myxedema coma" specifically refers to this profound neurological deterioration 1

Dermatologic and Physical Examination Findings

• Severe systemic non-pitting edema (myxedema) affecting the entire body, which does not indent with pressure—this distinguishes it from cardiac or renal edema 4, 5
• Puffy face with periorbital edema 5
• Thin or absent lateral eyebrows (madarosis) 5
• Bilateral leg swelling with characteristic nonpitting quality in severe, long-standing disease 4
• The nonpitting nature of the edema is pathognomonic for myxedema and results from mucopolysaccharide deposition in tissues 4

Cardiovascular Manifestations

• Bradycardia (slow heart rate) 2, 5, 3
• Hypotension and hemodynamic instability 5, 3
• Cardiac dysfunction characterized by delayed myocardial relaxation, reduced contractility, and decreased ventricular filling 2
• Abnormal cardiac output with increased systemic vascular resistance 2
• Low cardiac output state, though clinical heart failure is uncommon 4
• Pericardial effusions may occur in severe cases 4
• Risk of sudden cardiac arrest due to hemodynamic dysfunction 5

Metabolic and Laboratory Abnormalities

• Hypothermia (low body temperature) 1, 3
• Hypoglycemia (low blood sugar, e.g., glucose 59 mg/dL) 3
• Severely elevated TSH (e.g., >150 IU/mL) with profoundly low free T4 (e.g., 0.1 ng/dL) and free T3 3, 6
• Elevated creatine kinase (CK) and myoglobin levels indicating secondary rhabdomyolysis 6
• Atypical presentation: Rarely, myxedema coma may present with low or normal TSH levels in the setting of severe sepsis or central hypothyroidism, though this is uncommon 7

Respiratory Complications

• Respiratory decompensation with carbon dioxide narcosis is a common pathway leading to coma 1
• Hypoxia (low oxygen levels) 5
• May require intubation and mechanical ventilation 3

Precipitating Factors

• Surgery and trauma are major physiologic stressors that can precipitate myxedema coma in patients with chronic hypothyroidism 2
• Infection (severe sepsis) 7
• Non-compliance with thyroid hormone replacement therapy in patients with known hypothyroidism 6
• Cold exposure, medications (sedatives, anesthetics), and other acute illnesses 1

Diagnostic Approach

The diagnosis of myxedema coma is clinical—based on history and physical examination findings—not on any single objective thyroid laboratory test. 1

Key Diagnostic Steps

• Obtain TSH and free T4 levels to confirm severe hypothyroidism 4, 3
• Measure anti-thyroid peroxidase (anti-TPO) antibodies to identify autoimmune etiology (Hashimoto's thyroiditis) 3, 6
• Check for hypoglycemia, electrolyte abnormalities, and elevated CK/myoglobin 3, 6
• Perform echocardiography to assess for pericardial effusion and cardiac function 3
• Clinically based scoring systems have been proposed to aid in diagnosis, though treatment should not be delayed pending laboratory confirmation 1

Typical Patient Profile

• Elderly women are most commonly affected, as thyroid hypofunction is more prevalent in women 1
• May or may not have a history of previously diagnosed or treated thyroid dysfunction 1
• In children, the majority have Hashimoto's thyroiditis, thyroid hypoplasia, or thyroid aplasia 6

Critical Pitfalls to Avoid

• Do not wait for laboratory confirmation before initiating treatment—myxedema coma is a clinical diagnosis requiring immediate intervention 1
• Recognize that myxedema coma can be the first manifestation of primary hypothyroidism in patients with no prior diagnosis 3
• Be aware of atypical presentations with low TSH in the setting of severe sepsis or central hypothyroidism 7
• Distinguish nonpitting myxedema edema from cardiac or renal edema by its characteristic failure to indent with pressure 4, 5
• Exclude other causes of bilateral leg swelling including heart failure, renal disease, venous insufficiency, and medication effects 4

Treatment Urgency

Without early and appropriate therapy, the outcome is often fatal. 1 Therapy must be initiated immediately in a critical care setting with thyroid hormone replacement (levothyroxine) and glucocorticoid treatment 3. Following treatment, significant improvements occur in muscle strength, thyroid function, and clinical parameters, with high survival rates when diagnosed and treated promptly 6.