Myxedema Coma or Crisis 

The term myxedema has been applied to several clinical entities and is often used interchangeably with severe hypothyroidism, the common clinical condition in which the thyroid gland produces abnormally low levels of hormones.

Myxedema also refers to 2 different dermatologic conditions. Pretibial myxedema, an uncommon skin disorder, occurs not in cases of hypothyroidism but in hyperthyroid states, including, most commonly, Graves disease. The term pretibial is somewhat misleading, because the condition can affect other areas of the body and could more accurately be called localized dermopathy.

The other skin condition, called myxedema, occurs in severe, long-standing hypothyroid states and is caused by the deposition of mucopolysaccharides within the dermis.

This article discusses myxedema coma, an uncommon but life-threatening form of untreated hypothyroidism with physiological decompensation.^{[1, 2, 3]} The condition occurs in patients with long-standing, untreated hypothyroidism and is usually precipitated by a secondary insult, such as climate-induced hypothermia, infection, or another systemic condition, or drug therapy. Patients with myxedema coma have changes in their mental status, including lethargy, stupor, delirium, or coma. A more appropriate term for myxedema coma is myxedema crisis; this article often uses the term myxedema coma/crisis.

Myxedema coma/crisis occurs most commonly in older women with long-standing, undiagnosed or undertreated hypothyroidism who experience an additional significant stress, such as infection, a systemic disease, certain medications, and exposure to a cold environment.

When hypothyroidism is long-standing, physiologic adaptations occur. Reduced metabolic rate and decreased oxygen consumption result in peripheral vasoconstriction, which maintains core temperature. The number of beta-adrenergic receptors is reduced, usually with preservation of alpha-adrenergic receptors and circulating catecholamines, causing beta/alpha-adrenergic imbalance, diastolic hypertension, and reduced total blood volume.

Myxedema coma/crisis is a form of decompensated hypothyroidism in which adaptations are no longer sufficient.^[4] Essentially, all organ systems are affected.

Metabolic

Thyroid hormones are critical for cell metabolism and organ function. With an inadequate supply, organ tissues do not grow or mature, energy production declines, and the action of other hormones is affected.

Although weight gain is common, severe obesity is rarely secondary to hypothyroidism alone. However, long-standing, untreated hypothyroidism may result in years of inactivity, eventually with a large increase in weight.

Because of decreased drug metabolism, overdoses of medications (eg, morphine, hypnotics, anesthetic agents, sedatives) can occur and can even precipitate myxedema crisis.

Neurologic

Although the condition is called myxedema coma, the absence of coma does not exclude the diagnosis of this disorder. The presenting mental status may be lethargy or stupor. The exact mechanisms causing changes in mental status are not known. Brain function is influenced by reductions in cerebral blood flow and oxygen delivery, a lack of thyroxine (T4) and triiodothyronine (T3), and reductions in oxygen and glucose consumption; all of these factors are probably involved. Hyponatremia brought on by renal dysfunction may be an additional cause of altered mental function.

Cardiovascular

The heart is profoundly depressed, with bradycardia and decreased contractility causing low stroke volume and cardiac output. These changes are caused by decreased production of myocyte contractile proteins and enzymes, including NA⁺/K⁺ adenosine triphosphatase (NA⁺/K⁺ ATPase), as a result of low levels of gene transcription in the absence of T3.

Increased systemic vascular resistance occurs; although the causes appear to be multifactorial, a study suggests that in many cases, the increase is secondary to decreased T3 levels.^[5] Nonspecific ST- and T-wave inversion changes, low voltage, and ventricular arrhythmias may be noted. Plasma volume is decreased, and capillary permeability is increased, leading to fluid accumulation in tissue and spaces and possibly causing pericardial effusions.

Pulmonary

Typically, the lungs are not severely affected. Respiratory muscle dysfunction may be compromised, and depressed ventilatory drive and increased alveolar-arterial oxygen gradient are common. Fluid accumulation may cause pleural effusions and decreased diffusing capacity. Ventilation-perfusion mismatch is common, contributing to hypercapnia. Dysfunction of other organ systems may have profound effects. Severe obesity, if present, causes decreased lung volumes, diffusion capacity, and flow rates and may be the primary cause of the hypoventilation, hypoxia, hypercarbia, and depressed respiratory drive that is often noted in these patients. However, hypothyroidism may also have a direct impact, because the condition can cause obstructive sleep apnea that resolves with thyroid replacement (even without weight loss).

Renal

Kidney function may be severely compromised, partly because of low cardiac output and vasoconstriction that causes a low glomerular filtration rate. Reduced levels of NA⁺/K⁺ ATPase decrease sodium reabsorption and impair free water excretion, resulting in hyponatremia, which is usually present in myxedema coma.

Gastrointestinal

Severe or even mild hypothyroidism decreases intestinal motility. Patients with myxedema coma can present with gastric atony, megacolon, or paralytic ileus. Malabsorption has also been reported. Ascites, while uncommon, may occur due to increased capillary permeability, congestive heart failure, or other mechanisms.

Frequency

United States

Hypothyroidism is a common disorder in the older population; in the United States, the condition is present in 8% of women and 2% of men older than 50 years. Myxedema coma is a rare consequence of untreated hypothyroidism.

International

In areas in which the population ingests sufficient iodine, the most common cause of hypothyroidism is autoimmune thyroid disease and thyroid ablation therapy, with a prevalence of approximately 8% of women aged 50 years or older.

In regions where not enough iodine is ingested, the most common cause of hypothyroidism is iodine deficiency, with the prevalence of hypothyroidism correlating with the iodine content of the diet. Severe hypothyroidism (neonatal thyrotropin [TSH] >5 mU/L in >40% of births) and cretinism are observed with severe iodine deficiency (< 20 mcg/dL). Iodine deficiency of this magnitude is generally observed only in isolated, mountainous regions of South America, Africa, and Asia. The prevalence of myxedema coma/crisis in the populations of these areas is unknown.

Mortality/Morbidity

Myxedema coma/crisis is a metabolic and cardiovascular emergency. If the condition is not promptly diagnosed and treated, the mortality rate is approximately 50% or more. Even with immediate recognition and appropriate medical intervention, mortality rates of up to 25% are observed.^[6] Factors suggesting a poor prognosis are a body temperature of less than 93° F, persistent hypothermia that is unresponsive to 72 hours of therapy, advanced age, bradycardia (< 44 beats per min), sepsis, myocardial infarction, and hypotension. In addition, a study found that the patient's admission level of consciousness, as well as his/her score on the Glasgow Coma Scale and on the Acute Physiology and Chronic Health Evaluation (APACHE) II, were most predictive of survival.^[7]

Race

No studies suggest a race or ethnic predilection to myxedema coma/crisis.

Sex

Myxedema coma/crisis is approximately 4-8 times more common in women than in men, corresponding to the increased incidence of hypothyroidism in women.

Age

The incidence of hypothyroidism increases with age; the physiological decompensation of severe hypothyroidism, myxedema coma/crisis, occurs primarily in the elderly.^[8] However, this condition should not be automatically ruled out in young adults.