Mira Sofia Torres
Charles H. Emerson
Myxedema coma is a syndrome that occurs in advanced untreated hypothyroidism [1,2,3,4,5]. It is defined by a group of characteristic clinical features and not by laboratory evidence of severe hypothyroidism (Table 103.1). Myxedema coma is generally preceded by increasingly severe signs and symptoms of thyroid insufficiency. Fortunately, it is quite rare. Hypothyroid patients who are neglectful or whose contact with family and friends is limited are most vulnerable. Despite early and intensive treatment, mortality from myxedema coma is still as high as 30% to 50% [2,4,6,7,8].
Etiology and Pathophysiology
By definition, myxedema coma does not occur in the absence of hypothyroidism. If hypothyroidism is due to hypothalamic or pituitary insufficiency, the condition is even more serious because it is also accompanied by adrenal failure. Pituitary tumors are the major cause of central hypothyroidism in the United States. In countries with poor access to health care, postpartum pituitary necrosis is quite prevalent and is therefore another important cause of secondary hypothyroidism.
More than 95% of patients with hypothyroidism have primary thyroid disease. Most patients with primary hypothyroidism have either autoimmune thyroid failure or hypothyroidism secondary to ablative procedures on the thyroid. These include radioactive iodine and surgery for hyperthyroidism, thyroid resection for thyroid cancer, and external thyroid irradiation for head and neck tumors. Certain drugs, such as lithium carbonate and amiodarone, can cause hypothyroidism but are only rarely associated with myxedema coma.
Myxedema coma is distinguished from uncomplicated hypothyroidism by a variety of features that relate to central nervous system (CNS) dysfunction. The pathophysiology of myxedema coma will become clearer when there is a better understanding of the effects of thyroid hormone on the brain. Narcotics and hypnotics should be used with caution in hypothyroid patients because these patients are very sensitive to their sedative effects. These agents, alone or in combination with other factors, may precipitate myxedema coma in hypothyroid patients. Other precipitating factors are trauma, surgery, and severe infection [1,2,3,4,5,6,7,8,9]. The most important factor in temperate climates, however, is cold stress. In one series, 9 of 11 patients with myxedema coma were admitted in the late fall or winter .
Table 103.1 Clinical Features of Myxedema Coma
Patients are partially or completely obtunded. Therefore, the history must often be obtained from other sources. Friends, relatives, and acquaintances might have noted increasing lethargy, complaints of cold intolerance, and changes in the voice. An outdated container of L-thyroxine discovered with the patient’s belongings suggests that he or she has been remiss in taking medication. The medical record may also indicate that the patient was taking thyroid hormone or may refer to previous treatment with radioactive iodine. A thyroidectomy scar suggests the possibility of hypothyroidism. Other than coma itself, the cardinal manifestations are hypothermia and hypotension. Hypotonia of the gastrointestinal tract is common and often so severe as to suggest an obstructive lesion. Urinary retention due to a hypotonic bladder is related but less frequent. Most patients have the physical features of severe hypothyroidism, including bradycardia and slow relaxation of the deep tendon reflexes. A myxedematous facies (Fig. 103.1) results from the dry puffy skin, pallor, hypercarotenemia, periorbital edema, and patchy hair loss.
Diagnosis and Differential Diagnosis
The diagnosis of myxedema coma is based on the presence of the characteristic clinical syndrome in a patient with hypothyroidism. The laboratory’s role is to confirm that the patient is hypothyroid and determine whether there are treatable complications of myxedema coma, such as hypoventilation, hypoglycemia, and hyponatremia. Because of the gravity of hypothyroidism, treatment must be instituted before laboratory tests confirm the diagnosis.
The diagnostic laboratory features of primary hypothyroidism are a subnormal serum-free thyroxine index or serum-free thyroxine (T4) concentration and an elevated serum thyroid-stimulating hormone (TSH) concentration. The serum-free thyroxine index is also low in severely ill patients with a wide variety of conditions. This is the so-called “sick euthyroid syndrome” or nonthyroidal illness. Unlike patients with myxedema coma, however, serum TSH concentrations are not elevated in patients with the sick euthyroid syndrome, except in a small percentage, and only as they are clearly recovering from their severe illness. Distinction between hypothyroidism secondary to pituitary or hypothalamic disease (i.e., central hypothyroidism) and the sick euthyroid syndrome is difficult because serum TSH concentrations are low or, when TSH bioactivity is reduced as in secondary hypothyroidism, only mildly elevated in patients with central hypothyroidism. It is important to measure TSH as well as the serum-free thyroxine or free thyroxine index in patients presenting with myxedema coma. In central hypothyroidism, the typical clinical presentation of the myxedematous patient would help establish the diagnosis. The sick euthyroid syndrome is discussed in Chapter 107. The measurement of the total serum triiodothyronine (T3) concentration is of no value in the diagnosis of hypothyroidism or myxedema coma. It lacks sensitivity in the diagnosis of hypothyroidism and is depressed not only by illness but also by fasting.
Alone, few of the signs and symptoms described in this chapter are unique to myxedema coma. For example, the differential diagnosis of hypothermia (see Chapter 65) includes numerous conditions, such as protein-calorie malnutrition, sepsis, hypoglycemia, and exposure to certain drugs and toxins . Hypotension and hypoventilation, other cardinal features of myxedema coma, occur in other disease states. What distinguishes myxedema coma from other disorders is laboratory evidence of hypothyroidism, characteristic myxedema facies with periorbital puffiness, skin changes, obtundation, and, frequently, a constellation of other physical signs characteristic of severe hypothyroidism.