Myxedema and Myxedema Coma: Causes, Diagnosis, Treatment

Introduction to Myxedema

Myxedema is a potentially deadly endocrine regulation disease that usually arises in connection with pre-existing hypothyroidism, when the normal homeostatic mechanisms for responding to hypothyroidism are overwhelmed. It occurs most often in elderly women and is usually characterized by swelling of the skin and other soft tissues (Wall, 2000).

The thyroid gland is central to homeostatic metabolic functions and operates as part of a complex feedback loop involving both the pituitary gland and the hypothalamus to control essential elements of fluid and electrolyte balance and thermoregulation. Under normal conditions, the hypothalamus influences the pituitary gland's output of thyroid-stimulating hormone (TSH) via the secretion of thyrotropin-releasing hormone (TRH). Virtually any disruption of the precise functioning of these individual glands, or of their complex interrelationships, can precipitate conditions of hyperthyroidism and Graves' Disease or hypothyroidism and myxedema (MedicineNet, 2002).

Classic symptoms of myxedema include facial puffiness caused by subcutaneous accumulation of mucopolysaccharide, coarsening or roughening of facial features, and excess facial hirsutism. These changes often give patients a much older appearance—sometimes by two decades—than their chronological age. Other symptoms include a decline in mental processes and functioning, as well as impaired muscle stretch and relaxation reflexes. Because unexplained hoarseness sometimes occurs in conjunction with hypothyroidism, physicians must also be cautious about misdiagnosing its cause as a function of ordinary laryngeal disease (Schneiderman, 1993).

While more often related to chronic hypothyroidism, myxedema onset is sometimes much more sudden. In its most extreme manifestations, myxedema affects multiple organ systems, causing hypothermia (lowering the core body temperature by three degrees or more), diastolic hypertension, respiratory dysfunction, and sleep apnea, ultimately developing into myxedema coma. Myxedema coma is only treatable through near-toxic doses of thyroxine. Partly for this reason, mortality rates—which are 100% without treatment—may still approach 50% even with early diagnosis and aggressive intervention (Manifold, 2001).

Causes and Frequency

By far, the most common causes of myxedema and thyroid deficiency are primary hypothyroidism resulting from loss or atrophy of thyroid tissue, secondary hypothyroidism resulting from hypothalamic or pituitary malfunction, and goitrous hypothyroidism resulting from direct impingement by enlarged goitrous tissue. Surgical removal or radiological destruction of hypothalamic or pituitary tissue is also an obvious cause of myxedema and myxedema coma in the absence of chronic hypothyroidism (Wall, 2000).

Iodine deficiency-based endemic goiter is also implicated as a causal factor of myxedema, which is corroborated by surveys of iodine-deficient areas such as the mountainous regions of the Andes and Himalayas, where glacier activity may leach iodine from the soil. Worldwide, evidence derived primarily from neonatal screening programs suggests that myxedema affects as many as 200 million people and as many as one in every four thousand births. In the United States, myxedema affects women approximately five to ten times as frequently as it affects men, with 2% of adult women exhibiting symptoms of hypothyroid malfunction (Manifold, 2001).

Hyperthyroidism and myxedema are closely related to other metabolic diseases resulting from thyroid malfunction, such as Graves' Disease, even though the latter is a function of hyperthyroidism in which too much, rather than too little, thyroid hormone is produced. The two main thyroid hormones are thyroxine (T-4) and triiodothyronine (T-3). While T-4 constitutes 99.9% of production, T-3, which constitutes only 0.1%, is associated with the most metabolic control and biological activity (MedicineNet, 2002). Because hypothyroidism—and particularly myxedema coma—is treated with extreme doses of thyroid hormone, Graves' Disease is a possible complication of advanced hypothyroidism and the therapeutic intervention for myxedema.

Diagnosis

In the context of this disease, "coma" carries a different meaning than its usual connotation, since myxedema coma rarely includes any loss of consciousness. It is far more readily—and often—diagnosed by progressive mental decline in the absence of other causes (Wall, 2000). Fortunately, myxedema only progresses to the point of myxedema coma in approximately one out of every thousand cases of hypothyroidism (Manifold, 2001).

Since the most likely precipitating factors for the progression of hypothyroidism into myxedema coma include infections such as pneumonia and urosepsis, blood and urine cultures along with chest X-rays are required. One school of thought also recommends broad-spectrum antibiotic administration concurrent with initial treatment of myxedema (Wall, 2000).

Early diagnosis of myxedema coma is crucial to effective treatment, which requires immediate hospitalization, very high doses of thyroid hormone, hydrocortisone, and other appropriate intensive interventions. As a result, physicians are trained to order diagnostic testing whenever geriatric female patients present with symptoms of mental decline, particularly when those symptoms first manifest during the winter months. Likewise, hypothyroidism must be considered whenever female patients—especially those over the age of forty—experience fatigue, weight gain, constipation, and cold temperature intolerance (Wall, 2000).

Because one of the primary indications of myxedema is decline in mental function combined with facial tissue swelling, its symptoms are sometimes overlooked or misdiagnosed as other psychological or psychosocial issues, including chronic alcoholism (Schneiderman, 1993).