Myxedema Coma: Diagnosis and Treatment

CRISTEN RHODES WALL, M.D.,

University of Texas Southwestern Medical Center, Dallas, Texas

Myxedema coma, the extreme manifestation of hypothyroidism, is an uncommon but potentially lethal
condition. Patients with hypothyroidism may exhibit a number of physiologic alterations to compensate for
the lack of thyroid hormone. If these homeostatic mechanisms are overwhelmed by factors such as
infection, the patient may decompensate into myxedema coma. Patients with hypothyroidism typically
have a history of fatigue, weight gain, constipation and cold intolerance. Physicians should include
hypothyroidism in the differential diagnosis of every patient with hyponatremia. Patients with suspected
myxedema coma should be admitted to an intensive care unit for vigorous pulmonary and cardiovascular
support. Most authorities recommend treatment with intravenous levothyroxine (T 4) as opposed to
intravenous liothyronine (T3). Hydrocortisone should be administered until coexisting adrenal insufficiency
is ruled out. Family physicians are in an important position to prevent myxedema coma by maintaining a
high level of suspicion for hypothyroidism. (Am Fam Physician 2000;62:2485-90.)

Myxedema coma is an extreme complication of hypothyroidism in which patients exhibit

multiple organ abnormalities and progressive mental deterioration. The term myxedema is often
used interchangeably with hypothyroidism and myxedema coma. Myxedema also refers to the
swelling of the skin and soft tissue that occurs in patients who are hypothyroid. Myxedema coma
occurs when the body's compensatory responses to hypothyroidism are overwhelmed by a
precipitating factor such as infection.

Patients with myxedema coma A common misconception is that a patient must be

are typically elderly women who comatose to be diagnosed with myxedema coma.
present during the winter months. However, myxedema coma is a misnomer because most
patients exhibit neither the nonpitting edema known as
myxedema nor coma.1,2 Instead, the cardinal manifestation of myxedema coma is a deterioration
of the patient's mental status.

When only comatose patients are considered, myxedema coma is exceedingly rare: one study
reports 200 cases between 1953 and 1996.3 Applying a broader definition results in a
significantly higher number of cases. While the actual prevalence of myxedema coma is
unknown, its lethal nature demands recognition. Even with early detection and appropriate
treatment, mortality ranges from 30 to 60 percent. 3,4 Family physicians must be alert to the
possibility of undiagnosed hypothyroidism in their patients.

Epidemiology
 TABLE 1
Factors Known to Precipitate Myxedema
Coma

Hypothyroidism is four times Burns Medications

more common in women than in Carbon dioxide retention Amiodarone
men; 80 percent of cases of Gastrointestinal (Cordarone)
myxedema coma occur in hemorrhage Anesthesia
females.5,6 Myxedema coma Hypoglycemia Barbiturates
Hypothermia Beta blockers
occurs almost exclusively in Infection Diuretics
persons 60 years and older.5 More Pneumonia Lithium
than 90 percent of cases occur Influenza Narcotics
during the winter months.6 This Urinary tract Phenothiazines
seasonal presentation is probably infection/urosepsis Phenytoin (Dilantin)
Sepsis Rifampin (Rifadin,
due to age-related loss of the Rimactane)
ability to sense temperature and Tranquilizers
lower heat production secondary Stroke
to hypothyroidism.7 Surgery
Trauma

Historical Features
Information from references 1 through 3 and 10 through 14.
Patients with myxedema coma
usually have longstanding hypothyroidism, although it may not have been previously diagnosed.
They often demonstrate classic symptoms of hypothyroidism: fatigue; constipation; weight gain;
cold intolerance; a deep voice; coarse hair; and dry, pale, cool skin. However, elderly patients
with hypothyroidism often have atypical presentations, such as decreased mobility, 8 and some
patients with compensated hypothyroidism are asymptomatic.9

Precipitating Event
Decompensation into myxedema coma occurs when the hypothyroid patient's homeostatic
mechanisms are disrupted. Multiple factors can precipitate myxedema coma (Table 1).1-3,10-14 Some
of the more common precipitating factors include infections, particularly pneumonia and
urosepsis, and certain medications. Another potential risk factor is failure to reinstate thyroid
replacement therapy during hospitalization.

Physical Findings

Physical findings in myxedema coma (Table 2) may include the classic myxedematous face,
which is characterized by generalized puffiness, macroglossia, ptosis, periorbital edema, and
coarse, sparse hair. Nonpitting edema of the lower extremities is sometimes present. The findings
from a thyroid examination are usually normal, but a goiter may be present in some patients. The
presence of a scar on the neck might suggest postsurgical hypothyroidism and may be an
important clue in the diagnosis of a patient who is comatose. A neurologic examination may
reveal decreased reflex tendon relaxation and will invariably reveal altered mentation.

Altered Mentation

All patients with myxedema coma display deterioration

All patients with myxedema coma
of their mental status. This decline may be subtle,
present with altered mentation,
manifesting as apathy, neglect or a decrease in
but this change may be subtle.
intellectual function; more obvious changes include
confusion, psychosis and, rarely, coma. While all patients with myxedema coma present with
some degree of mental status change, few progress to coma. When there is doubt about a change
in mental status, formal mental status testing should be performed.

Physicians should also be alert to the possibility of depression in the seemingly demented patient
and perform depression screening in any patient with mental status changes. Lumbar puncture
may also be clinically appropriate.

Hypothermia
TABLE 2 Another common clinical feature of myxedema
Physical Findings in Myxedema coma is hypothermia. The patient's temperature
Coma is usually less than 35.5°C (95.9°F). 13
Conditions that may precipitate myxedema
Altered mentation coma such as hypoglycemia and cold exposure
Alopecia may exacerbate the hypothermia. However, the
Bladder dystonia and distention patient's temperature is not always an accurate
Cardiovascular diagnostic aid because some patients present
Elevated diastolic blood pressure--
early
with a normal temperature.
Hypotension--late
Bradycardia Blood Pressure Changes
Delayed reflex relaxation Patients with compensated hypothyroidism
Dry, cool, doughy skin often exhibit diastolic hypertension. Decreased
Gastrointestinal
Decreased motility
oxygen consumption and lowered body
Abdominal distension temperature result in peripheral
Paralytic ileus vasoconstriction and central shunting.2 Only
Fecal impaction when the patient has begun to decompensate do
Myxedema megacolon--late these neurovascular mechanisms fail. The
Hyperventilation
Hypothermia
patient may then display the hypotension
Myxedematous face characteristically associated with myxedema
Generalized swelling coma. Bradycardia, low cardiac output and
Macroglossia overall blood volume deficit frequently
Ptosis exacerbate the hypotension.
Periorbital edema
Coarse, sparse hair
Nonpitting edema
Hypoventilation
Hypoventilation in myxedema coma results
from the body's decreased ventilatory response
to hypoxia and hypercapnia.15 Respiratory dysfunction may lead to sleep apnea, 16 and respiratory
difficulties may be exacerbated by myxedematous infiltration of the tongue and pharynx. 15,17 The
diaphragmatic weakness induced by hypothyroidism is reversed by thyroid hormone
replacement. 16,18

Diagnostic Testing
 Multiple diagnostic findings are reported in patients with myxedema coma. This disorder impacts
thyroid hormone levels, electrolyte levels, creatine kinase (CPK) levels and other laboratory
values (Table 3).

Thyroid Hormone

Primary hypothyroidism results from the inability of the thyroid gland to produce adequate
amounts of thyroid hormone. Typically, patients with myxedema coma have primary
hypothyroidism manifested by low serum levels of thyroxine (T4) and triiodothyronine (T3) and a
high thyroid stimulating hormone (TSH) level. However, primary hypothyroidism should be
differentiated from secondary hypothyroidism, tertiary hypothyroidism and the low T 4 level/low
T3 level syndrome (euthyroid sick syndrome).

Secondary hypothyroidism is a result of pituitary

dysfunction; tertiary hypothyroidism is caused by a Typically, patients with myxedema
hypothalamic abnormality. If the patient has have primary hypothyroidism
hypopituitarism, the level of TSH is not increased. The manifested by low T4 levels and
findings of a low T4 level and low-normal or decreased elevated TSH levels.
TSH level mandate a search for pituitary abnormalities.
However, a low level of serum T4 (and T3) with a normal TSH level may simply indicate that the
patient's thyroid function tests have been altered as a result of illness unrelated to the thyroid
(euthyroid sick syndrome).

Electrolyte Abnormalities
The hyponatremia seen in myxedema coma is a result of decreased free water clearance.
Elevated levels of antidiuretic hormone and/or diminished blood flow to the kidneys are believed
to be responsible for the inability to excrete free water. 19,20 Hyponatremia is classically associated
with a low serum osmolality. The level of serum creatinine is usually high, and while the level of
calcium is generally low, it may be elevated. 21
Hypoglycemia may be a result of the down-
TABLE 3 regulation of metabolism seen in hypothyroidism2;
Laboratory Abnormalities in it may also indicate the possibility of adrenal
Myxedema Coma insufficiency.

Elevated Creatine Kinase

Anemia Patients with myxedema coma may be
Elevated CPK misdiagnosed with myocardial infarction
Elevated creatinine based on elevated CPK levels in association
Elevated transaminases
Hypercapnia
with nonspecific electrocardiographic (ECG)
Hyperlipidemia findings. Increased CPK and other
Hypoglycemia transaminases are thought to result from
Hyponatremia altered membrane permeability.22
Hypoxia
Leukopenia
Respiratory acidosis

CPK = creatine kinase

Fractionation of the CPK reveals a skeletal block and a prolonged QT interval.
muscle source. ECG changes include Conversely, physicians should be alert to the
bradycardia, decreased voltages, non- possibility of myocardial infarction as a
specific ST and T changes, varying types of triggering event for myxedema coma.

Other Abnormalities
Arterial blood gases often reveal respiratory acidosis, hypoxia and hypercapnia. Mild leukopenia
and a normocytic anemia are also frequently present. However, macrocytic anemia and
pernicious anemia caused by associated immune dysfunction are sometimes present. 13,23 A chest
radiograph may show cardiomegaly and pleural effusions. If cardiomegaly is present, an
echocardiogram should be obtained to rule out a pericardial effusion. When performed, lumbar
puncture typically reveals elevated protein levels 13,15,24 and a high opening pressure. Results of
electroencephalography are nonspecific.13

Treatment

The patient with myxedema coma should be admitted to the intensive care unit, and hypovolemia
and electrolyte abnormalities corrected. Mechanical ventilation may be necessary.
Cardiovascular status should be monitored carefully, especially after intravenous thyroid
hormone replacement. Myocardial infarction must be ruled out and blood pressure stabilized. If
possible, pressors and ionotropes should be avoided because of their tendency to provoke
arrhythmias in the setting of intravenous thyroid replacement. Patients with hypothermia should
be covered with regular blankets; the use of warming blankets should be avoided because the
resulting peripheral dilatation may lead to hypotension and cardiovascular collapse.

Thyroid Hormone Replacement

Any patient with suspected myxedema coma should be treated presumptively with thyroid
hormone. While there is concern regarding the precipitation of arrhythmias or myocardial
infarction by administering large doses of intravenous levothyroxine, this concern must be
balanced against T4's potentially life-saving and usually nondetrimental effect.25
Myxedema coma is treated with
an initial IV T4 dose of 100 to 500
While the necessity of intravenous thyroid hormone
µg followed by 75 to 100 µg IV
replacement is apparent, some controversy exists
daily until the patient is able to
regarding the use and dosages of levothyroxine (T 4) and
take oral therapy.
liothyronine (T3). Because of the relatively small number
of patients with myxedema coma, controlled studies comparing various dosages of T 4 and T3 are
lacking. Because T3 is more biologically active than T4, and because the conversion of T4 to T3 is
suppressed in myxedema coma,26,27 some have advocated T3 replacement. However, parental T3 is
not only expensive and difficult to obtain, it may also contribute to increased mortality.27

Most authorities therefore recommend use of T4 alone.2,7,13,14,27 An initial levothyroxine dose of 100
to 500 µg administered intravenously should be followed by 75 to 100 µg administered
intravenously daily until the patient is able to take oral replacement. The lower initial dose
should be administered to patients who are frail or have other comorbidities, particularly
cardiovascular disease. Elderly patients typically require 100 to 170 µg of oral levothyroxine
daily.13

Antibiotics
Infection is often the cause of the patient's decompensation; therefore, an infectious etiology
should be sought with blood and urine cultures as well as a chest radiograph. Some authorities
advocate empiric therapy with broad-spectrum intravenous antibiotics.2

Steroids
Because of the possibility of secondary hypothyroidism and associated hypopituitarism,
hydrocortisone should be administered until adrenal insufficiency has been ruled out.
Hydrocortisone should be administered intravenously at a dosage of 100 mg every eight hours.
Failure to treat with hydrocortisone in the face of adrenal insufficiency may result in the
precipitation of adrenal crisis. A random cortisol level should be drawn prior to therapy, and if
not depressed, the hydrocortisone can be discontinued without tapering. An adrenocorticotropic
hormone stimulation test can be administered if clinically warranted.

Prognosis

The prognosis for patients with myxedema coma is Factors associated with a poor
difficult to define because of the small number of cases prognosis in patients with
reported in the literature. The severity of the condition, myxedema coma include
however, is clear. One study reported a mortality rate of advanced age, bradycardia and
about 30 percent, while another suggests the mortality persistent hypothermia.
rate may be as high as 60 percent.3,4 Factors associated
with a poor prognosis include advanced age, bradycardia and persistent hypothermia.27

Final Comment

Family physicians should be alert for myxedema coma, particularly in elderly women with
mental status changes who present during the winter months. An accurate diagnosis generally
follows a careful history, physical examination and laboratory evaluation. The most important
elements in treatment of myxedema coma are early recognition, presumptive thyroid hormone
replacement, hydrocortisone and appropriate supportive care. While myxedema coma carries a
significant mortality rate even with appropriate testing and treatment, an early diagnosis of
hypothyroidism may well save a patient's life.

nfluenza is a significant public health burden. In 1997, influenza and pneumonia were the sixth
leading causes of death in the United States.1 Over the past 25 years, approximately 20,000
deaths per year have been attributed to influenza in this country alone. The economic cost of
influenza is estimated at $3 to $5 billion annually.2,3

The author thanks the Baylor-Garland Family Practice Residency, Garland, Tex., the Faculty
Development Center in Waco, Tex., and the University of Texas Southwestern Medical Center at Dallas
for assistance with the manuscript, and Teresa Hanson for her research support.

The Author

CRISTEN RHODES WALL, M.D., is an assistant professor in the Department of Family

Practice and Community Medicine at the University of Texas Southwestern Medical Center at
Dallas, where she received her medical degree. Dr. Wall is a recent graduate of the Baylor-
Garland Family Practice Residency Program, Garland, Tex.
Address correspondence to Cristen R. Wall, M.D., University of Texas Southwestern Medical Center at
Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9067. Reprints are not available from the author.

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