Practice Essentials
Myxedema is a term generally used to denote severe hypothyroidism. Myxedema is also used to describe the dermatologic changes that occur in hypothyroidism and occasionally hyperthyroidism. In this setting, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. When skin changes occur in hyperthyroidism, mostly Graves disease, it is called pretibial myxedema. [1, 2]
Myxedema coma, occasionally called myxedema crisis, is a rare, life-threatening clinical condition that represents severe hypothyroidism with physiologic decompensation. [3, 4] The condition usually occurs in patients with long-standing, undiagnosed hypothyroidism and is most often precipitated by infection, cerebrovascular disease, heart failure, trauma, or drug therapy. Patients with myxedema coma are generally severely ill, with significant hypothermia and depressed mental status.
A medical emergency, myxedema coma requires immediate attention. If the diagnosis is suspected, immediate management is necessary before confirming the diagnosis due to the high associated mortality rate. Patients with myxedema coma should be treated in an intensive care unit with continuous cardiac monitoring. Initial steps in therapy include airway management, thyroid hormone replacement, glucocorticoid therapy, and supportive measures.
Signs and symptoms of myxedema coma
Physical findings may include the following:
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Hypothermia
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Hypotension
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Bradycardia
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Decreased pulse pressure, normal systolic pressure, elevated diastolic pressure
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Decreased respiratory rate
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Periorbital puffiness
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Macroglossia
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Coarse or thinning hair
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Thyroid is commonly small
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Slow respiratory rate
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Signs of pleural effusion
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Soft or distant heart sounds, diminished apical impulse, pericardial effusion
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Abdominal distention due to ascites
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Diminished or absent bowel sounds due to ileus
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Bladder distension
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Cold extremities, nonpitting edema of the upper and lower extremities
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Cool, pale, dry, scaly, and thickened skin
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Dry, brittle nails
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Ecchymoses, purpura
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Confusion, stupor, slow speech, delayed reflexes, seizures, coma
Workup in myxedema coma
Laboratory studies are important to confirm the diagnosis of myxedema coma. Results include the following:
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Thyroid-stimulating hormone (TSH) is elevated in most patients, indicating a primary thyroid disorder
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Free thyroxine (T4) and free triiodothyronine (T3) levels are low
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Hyponatremia with low serum osmolality
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Because of decreased renal perfusion, serum creatinine levels are usually elevated
Assessment of adrenal function should be performed, as should a complete blood count (CBC). Leukocytosis may not be seen because of hypothermia. A white blood cell differential may be one of the few clues to the presence of infection.
Chest radiography may show signs of cardiomegaly, pericardial effusion, congestive heart failure, or pleural effusion.
Electrocardiography may reveal sinus bradycardia, low-amplitude QRS complexes, a prolonged QT interval, flattened or inverted T waves, or arrhythmias.
Management of myxedema coma
Medical care in myxedema coma includes the following:
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Airway management
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Thyroid hormone replacement - The ideal mode of therapy and doses of thyroid hormone therapy in myxedema coma remain controversial due to the rarity of the condition and lack of clinical trials
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Glucocorticoid therapy - Patients with primary hypothyroidism may have concomitant primary adrenal insufficiency, while patients with secondary hypothyroidism may have associated hypopituitarism and secondary adrenal insufficiency; the other rationale for treatment with corticosteroids is the potential risk of precipitating acute adrenal insufficiency caused by the accelerated metabolism of cortisol that follows T4 therapy [4]
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Supportive measures - Treat hypothermia with passive rewarming; treat associated infection; correct severe hyponatremia with saline and free water restriction; correct hypoglycemia with intravenous dextrose; hypotension is usually corrected with thyroid hormone therapy
Pathophysiology
Myxedema coma occurs as a result of long-standing, undiagnosed, or undertreated hypothyroidism and is usually precipitated by a systemic illness. Myxedema coma can result from any of the causes of hypothyroidism, most commonly chronic autoimmune thyroiditis. It can also occur in patients who had thyroidectomy or underwent radioactive iodine therapy for hyperthyroidism. Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone. [5, 6]
Given the importance of thyroid hormones in cell metabolism, long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems. [7] This results in hypothermia, which is a strong predictor of mortality. Another consequence is decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents; this can precipitate myxedema coma.
Cardiovascular
Cardiac contractility is impaired, leading to reduced stroke volume, low cardiac output, bradycardia and sometimes hypotension. [8] Reduced stroke volume in severe cases may also be due to pericardial effusions caused by the accumulation of fluid rich in mucopolysaccharides within the pericardial sac. Congestive heart failure is rarely seen in the absence of preexisting cardiac disease.
Electrocardiographic findings may include bradycardia, varying degrees of block, low voltage, nonspecific ST-segment changes, flattened or inverted T waves, prolonged Q-T interval, and ventricular or atrial arrhythmias. [9]
The reduction of the effect of beta-adrenergic receptors leads to prevalence of the effect of alpha-adrenergic receptors, increased catecholamines, and increased systemic vascular resistance, causing some patients to have diastolic hypertension and a narrowed pulse pressure.
Plasma volume is decreased, and capillary permeability is increased, leading to fluid accumulation in tissue and spaces and pericardial effusions. [10]
Neurologic
Despite the term myxedema coma, many patients do not present in coma, but manifest variable degrees of altered consciousness. [3] Brain function is affected by reduction in oxygen delivery and subsequent consumption, decreased glucose utilization and reduced cerebral blood flow. Hyponatremia can also contribute to altered mental function.
Pulmonary
The main pulmonary effect of myxedema coma is hypoventilation, which results from central depression of ventilatory drive with decreased responsiveness to hypoxia and hypercapnia. [11, 12] Other contributing factors to hypoventilation include respiratory muscle weakness, mechanical obstruction by a large tongue, and obesity-hypoventilation syndrome. Fluid accumulation may cause pleural effusions and decreased diffusing capacity.
Renal
Kidney function may be compromised with reduced glomerular filtration rate because of low cardiac output and peripheral vasoconstriction or because of rhabdomyolysis. [13, 14] Hyponatremia is common in patients with myxedema coma and is caused by increased serum antidiuretic hormone and impaired water excretion. [15, 16]
Gastrointestinal
The gastrointestinal tract in myxedema coma can be marked by mucopolysaccharide infiltration and edema. In addition, neuropathic changes can cause malabsorption, gastric atony, impaired peristalsis, paralytic ileus, and megacolon. [17] Ascites may occur due to increased capillary permeability, heart failure, or other mechanisms. [18] Gastrointestinal bleeding secondary to an associated coagulopathy may occur. [19]
Hematologic
Myxedema coma is associated with a higher risk of bleeding caused by coagulopathy related to an acquired von Willebrand syndrome (type 1) and decreases in factors V, VII, VIII, IX, and X. [20, 21] Patients may also have microcytic anemia secondary to hemorrhage, or macrocytic anemia caused by vitamin B12 deficiency, or normocytic normochromic anemia, which may be secondary to decreased oxygen requirement and reduced erythropoietin. [10]
Epidemiology
United States
Myxedema coma is a rare consequence of untreated hypothyroidism, and the exact prevalence in the United States is not known.
International
A report from Spain showed that the incidence rate of myxedema coma is 0.22 per million per year. [22] A study by Ono et al estimated the annual incidence of myxedema coma in Japan to be 1.08 per million people. [23]
Prognosis
Myxedema coma is a medical emergency. If the condition is not promptly diagnosed and treated, the mortality rate can be more than 50%. Even with immediate recognition and timely medical intervention, mortality rates are as high as 25%. [10]
A retrospective study by Bourcier et al of adults admitted to intensive care units (ICUs) with severe hypothyroidism found the overall ICU and the 6-month post-admission mortality rates to be 26% and 39%, respectively. [24]
The most common causes of death in myxedema coma are respiratory failure, sepsis, and gastrointestinal bleeding.
Because myxedema coma carries a high mortality and morbidity rate, timely recognition and proper management is critical. Factors suggesting a poor prognosis are older age, persistent hypothermia, bradycardia, lower degree of consciousness by Glasgow Coma Scale, and multiorgan impairment indicated by high APACHE (Acute Physiology and Chronic Health Evaluation) II score. [25, 26, 27, 28] The aforementioned study by Ono et al reported that, as revealed through multivariable logistic regression, a higher inhospital mortality rate was associated with older age and catecholamine use (with or without steroids). [23]
The above-mentioned Bourcier report found mortality in severe hypothyroidism to be strongly associated with older age and hemodynamic and respiratory failure but not with neurologic failure. [24]
Patient Education
Patients who are diagnosed with hypothyroidism should be counseled regarding the necessity of taking daily thyroid hormone replacement and monitoring of thyroid tests on a regular basis.
Patients with a history of thyroiditis or who have undergone thyroid irradiation or thyroid surgery should be counseled that hypothyroidism might occur in the future. They should be educated about the symptoms of hypothyroidism and should understand the importance of seeking timely medical advice for examination and testing.
