Myxedema is severe thyroid hormone deficiency, which can lead to a decreased level of consciousness, even coma. It has a reported fatality rate as high as 80%. The incidence of myxedema is three times higher in females than males; elderly females seem most susceptible to myxedema coma.
Pathophysiology
1. Thyroid hormone is essential for normal metabolism of all cells
2. Thyroid-stimulating hormone (TSH) secreted by the pituitary (under regulation of the hypothalamus) stimulates the thyroid to secrete thyroxine (T4) and smaller amounts of triiodothyronine (T3), which is the active form of thyroid hormone.
3. Most T3 is produced in the peripheral tissues by monodeiodination of circulating T4.
4. T3 and T4 circulate bound to serum proteins; the free T3 and T4 are metabolically active.
5. T3 feeds back on the pituitary gland to inhibit production of TSH.
6. In myxedema coma, the cause of coma is multifactorial (decreased cerebral perfusion associated with low cardiac output from bradycardia and reduced stroke volume, decreased circulating levels of thyroid hormones resulting in decreased mental responsiveness).
7. Hypothermia may result from decreased T3 or T4, leading to reduced metabolic rate in addition to an inability to shiver.
8. Hypoventilation (alveolar) is secondary to respiratory center depression (exacerbated by use of analgesics, sedatives, and anesthesia), defective respiratory muscle function, and occasionally airway obstruction (enlarged tongue).
9. Hyponatremia often accompanies myxedema and may have associated hypochloremia (may contribute to altered mental status).
10. Decreased plasma volume and intense peripheral vasoconstriction are typical.
Risk Factors
1. Infection
2. Surgery
3. Anesthesia
4. Myocardial infarction
5. Sedating drugs
6. Cerebrovascular accidents
7. Bleeding
8. Cold exposure
9. Trauma
10. Hyponatremia
Symptoms & Sign
Symptoms :
1. Decreased mental acuity
2. Hoarseness
3. Increased somnolence
4. Cold intolerance
5. Dry skin
6. Brittle hair
Signs :
1. Hypothermia
2. Bradycardia
3. Hypotension
4. Physical features consistent with long-standing hypothyroidism:
- Thick & doughy-appearing skin
- Periorbital edema
- Large tongue
- Alopecia
5. Disorders of muscular function (paralytic ileus, urinary retention, atonic bowel with fecal impaction)
Investigation
1. Confirmation of diagnosis relies on thyroid function tests to document hypothyroidism (measure TSH, T4, free T4, reverse T3 , T3RU).
- TSH level is elevated in primary hypothyroidism.
- In secondary and tertiary hypothyroidism, TSH is not elevated, and diagnosis will rely on other laboratory parameters and clinical judgment.
2. Serum cortisol level should be drawn initially to evaluate for concomitant adrenal insufficiency.
3. CBC, UA, blood, and urine cultures should be sent.
4. Serum cholesterol is usually elevated.
5. Chest x-ray may reveal signs of pleural or pericardial effusion or of infection.
6. ECG is often abnormal (sinus bradycardia, small voltage QRS complexes, prolonged Q-T intervals, isoelectric T-wave changes, supraventricular tachycardia).
7. ABG may reveal hypoxemia, hypercarbia, and respiratory acidosis.
8. Serum glucose or sodium may be low.
Differential Diagnosis
- Stroke
- Electrolyte disturbance
- Sepsis
- Hypothermia
- Hypopituitarism
- Hypoglycemia
- Renal Failure
Treatment
Myxedema is most often addressed by treating the underlying cause of hypothyroidism that led to the thickening and coarseness of the skin. Medication to replace the reduced thyroid hormones is the most common treatment, and when dosed appropriately, may halt the progression of myxedema.
1. Treatment of hypothyroidism underlying myxedema
- Thyroid hormone replacement therapy is required in most cases of hypothyroidism.
2. Treatment of myxedema symptoms
- Compression stockings, which may help reduce the swelling associated with myxedema
- Topical corticosteroids, which may be used to decrease the inflammation associated with skin thickening in myxedema
Reference
1. Joseph Varon, Handbook of Critical and Intensive Care Medicine, 2nd edition (2010).
Pathophysiology
1. Thyroid hormone is essential for normal metabolism of all cells
2. Thyroid-stimulating hormone (TSH) secreted by the pituitary (under regulation of the hypothalamus) stimulates the thyroid to secrete thyroxine (T4) and smaller amounts of triiodothyronine (T3), which is the active form of thyroid hormone.
3. Most T3 is produced in the peripheral tissues by monodeiodination of circulating T4.
4. T3 and T4 circulate bound to serum proteins; the free T3 and T4 are metabolically active.
5. T3 feeds back on the pituitary gland to inhibit production of TSH.
6. In myxedema coma, the cause of coma is multifactorial (decreased cerebral perfusion associated with low cardiac output from bradycardia and reduced stroke volume, decreased circulating levels of thyroid hormones resulting in decreased mental responsiveness).
7. Hypothermia may result from decreased T3 or T4, leading to reduced metabolic rate in addition to an inability to shiver.
8. Hypoventilation (alveolar) is secondary to respiratory center depression (exacerbated by use of analgesics, sedatives, and anesthesia), defective respiratory muscle function, and occasionally airway obstruction (enlarged tongue).
9. Hyponatremia often accompanies myxedema and may have associated hypochloremia (may contribute to altered mental status).
10. Decreased plasma volume and intense peripheral vasoconstriction are typical.
Risk Factors
1. Infection
2. Surgery
3. Anesthesia
4. Myocardial infarction
5. Sedating drugs
6. Cerebrovascular accidents
7. Bleeding
8. Cold exposure
9. Trauma
10. Hyponatremia
Symptoms & Sign
Symptoms :
1. Decreased mental acuity
2. Hoarseness
3. Increased somnolence
4. Cold intolerance
5. Dry skin
6. Brittle hair
Signs :
1. Hypothermia
2. Bradycardia
3. Hypotension
4. Physical features consistent with long-standing hypothyroidism:
- Thick & doughy-appearing skin
- Periorbital edema
- Large tongue
- Alopecia
5. Disorders of muscular function (paralytic ileus, urinary retention, atonic bowel with fecal impaction)
Investigation
1. Confirmation of diagnosis relies on thyroid function tests to document hypothyroidism (measure TSH, T4, free T4, reverse T3 , T3RU).
- TSH level is elevated in primary hypothyroidism.
- In secondary and tertiary hypothyroidism, TSH is not elevated, and diagnosis will rely on other laboratory parameters and clinical judgment.
2. Serum cortisol level should be drawn initially to evaluate for concomitant adrenal insufficiency.
3. CBC, UA, blood, and urine cultures should be sent.
4. Serum cholesterol is usually elevated.
5. Chest x-ray may reveal signs of pleural or pericardial effusion or of infection.
6. ECG is often abnormal (sinus bradycardia, small voltage QRS complexes, prolonged Q-T intervals, isoelectric T-wave changes, supraventricular tachycardia).
7. ABG may reveal hypoxemia, hypercarbia, and respiratory acidosis.
8. Serum glucose or sodium may be low.
Differential Diagnosis
- Stroke
- Electrolyte disturbance
- Sepsis
- Hypothermia
- Hypopituitarism
- Hypoglycemia
- Renal Failure
Treatment
Myxedema is most often addressed by treating the underlying cause of hypothyroidism that led to the thickening and coarseness of the skin. Medication to replace the reduced thyroid hormones is the most common treatment, and when dosed appropriately, may halt the progression of myxedema.
1. Treatment of hypothyroidism underlying myxedema
- Thyroid hormone replacement therapy is required in most cases of hypothyroidism.
2. Treatment of myxedema symptoms
- Compression stockings, which may help reduce the swelling associated with myxedema
- Topical corticosteroids, which may be used to decrease the inflammation associated with skin thickening in myxedema
Reference
1. Joseph Varon, Handbook of Critical and Intensive Care Medicine, 2nd edition (2010).
2. Health Grades : http://www.healthgrades.com/conditions/myxedema
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