Also known as: Myxedema coma

Related conditions: Hypothyroid crisis, myxedema crisis

1. Description of the problem

What every clinician needs to know

Myxedema coma is a rare syndrome that represents the extreme expression of severe, long-standing hypothyroidism. It is a medical emergency and, even with early diagnosis and treatment, the mortality can be as high as 60%. The name is somewhat a misnomer, as actual coma is rare. The syndrome includes decompensated hypothyroidism, central nervous system impairment and cardiovascular compromise.

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Clinical features

Myxedema coma occurs most often in the elderly and during the winter months; in one series, 9 of 11 cases of myxedema coma were admitted in late fall or winter. Myxedema coma is usually caused by a precipitating event in the untreated, or partially treated, hypothyroid patient. The clinical course of lethargy proceeding to stupor and then coma is often hastened by drugs, especially sedatives, narcotics, antidepressants, and tranquilizers. Indeed, many cases of myxedema coma have occurred in the undiagnosed hypothyroid patient who has been hospitalized for other medical problems. See Table I.

Table I.
Cold stress
Infection     Pneumonia     Urinary tract     Other
Congestive heart failure
Intravascular volume contraction     Gastrointestinal blood loss     Diuretic use
CNS-active drugs     Analgesics/narcotics     Sedatives/hypnotics     Tranquilizers     Anesthetic agents

Myxedema coma is primarily a clinical diagnosis with features of uncomplicated hypothyroidism but more exaggerated. Thyroid hormone levels are similar to those found in uncomplicated hypothyroidism. There is little correlation between the decrease in thyroid hormone and the presentation of myxedema coma. Indeed a recent case report described myxedema coma in the setting of subclinical hypothyroidism,

The cardinal features of myxedema coma are 1) hypothermia, which can be profound, 2) altered mental status and 3) cardiovascular depression. See Table II.

Table II.
*Hypothermia *Mental obtundation*Bradycardia HypotensionCoarse, dry skinMyxedema faciesHypoglycemiaAtonic GI tractAtonic bladderPleural, pericardial, and peritoneal effusions

*Cardinal features of myxedema coma

GI, gastrointestinal

Key management points

Myxedema coma is a medical emergency and should be treated in an intensive care unit. The mainstays of therapy are 1) supportive care with ventilatory and hemodynamic support, rewarming; 2) correction of hyponatremia and hypoglycemia; and treatment of the precipitating incident and 3) administration of thyroid hormone. Sedatives, hypnotics, narcotics and anesthetics must be minimized or avoided altogether due to their extended duration of action and exacerbation of obtundation in the hypothyroid patient.

2. Emergency management

Myxedema coma is a medical emergency and should be treated in an intensive care unit (Table III).

Table III.
SupportiveAssisted ventilation Hemodynamic support Passive rewarming for hypothermiaIV glucose for hypoglycemiaWater restriction or hypertonic saline for severe hyponatremiaHydrocortisone IV (100mg q 8 h) Treatment of precipitating factor(s)Avoidance of all CNS-acting medications
Thyroid hormone replacement L-T4 200–300mcg loading dose IV, up to 500mcg IV in the first 24 h and/orL-T3 12.5 mcg IV q 6 h

CNS, central nervous system; IV,intravenous.


Its severity may be underestimated if the thermometer used does not register below 30°C. The patient should be kept in a warm room and covered with blankets. Active heating should be avoided since it increases oxygen consumption and promotes peripheral vasodilation and circulatory collapse. Active heating is recommended only for situations of severe hypothermia where ventricular fibrillation is an immediate threat. In these cases, the rate of rewarming should not exceed 0.5 degrees C per hour.

Adrenal insufficiency

Because of a five to ten percent incidence of coexisting adrenal insufficiency, IV steroids (i.e., hydrocortisone 100 mg intravenously every 8 hours are indicated before initiating L-T4 therapy. When possible, a cortrosyn
®stimulation test should be performed to document the underlying adrenal function.

Thyroid hormone treatment

Parenteral administration of thyroid hormone is necessary initially because of uncertain absorption through the gut. A reasonable approach is an initial IV loading dose of 200 to 300 mcg L-T4. If there is inadequate improvement in the state of consciousness, the blood pressure or the core temperature during the first 6 to 12 hours after administration, another dose of L-T4 should be given to bring the total dose during the first 24 hours to 0.5 mg. This should be followed by 50 to 100mcg intravenously every 24 hours until the patient is stabilized.

Alternatively, one can use L-T3 at a dosage of 12.5 to 25mcg intravenously every 6 hours until the patient is stable and conscious. Once the patient is stable, the patient should be switched to L-T4.

3. Diagnosis

Diagnostic criteria and tests

The cardinal features of myxedema coma are: 1) hypothermia, which can be profound, 2) altered mental status and 3) cardiovascular depression. The severely hypothyroid patient essentially becomes poikilothermic due to disordered thermoregulation. This is the reason many cases occur in the winter months. Body temperatures as low as 23.3°C have been reported; thus, rectal temperatures are essential to making the diagnosis.

Excessive lethargy and sleepiness may have been present for weeks to months, often interfering with meals. Rarely, psychosis and delirium have been reported. Bradycardia and hypotension may be profound and the respiratory rate is often depressed. Since intrinsic hypothyroidism by itself is insufficient to produce the clinical syndrome of myxedema coma, a precipitating cause must be assumed to be present.

Most patients have the physical features of severe hypothyroidism including macroglossia; delayed reflexes; dry, rough skin and myxedematous facies, which results from the periorbital edema; pallor, hypercarotenemia, periorbital edema, and patchy hair loss. Hypotonia of the GI 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. Pleural, pericardial and peritoneal effusions may be present. Severe airway obstruction has been reported.

Thyroid function tests

There are no distinct laboratory abnormalities and thyroid hormone levels are similar to those found in uncomplicated overt hypothyroidism; there is little correlation between the degree of decrease of thyroid hormone and the presentation of myxedema coma. Indeed a recent case report described myxedema coma in the setting of subclinical hypothyroidism. Since more than 95% of cases of myxedema coma are due to primary hypothyroidism, the laboratory findings include an elevated serum thyroid stimulating hormone (TSH) and low or undetectable total and free serum T4 concentrations.

In the patient with central hypothyroidism, the diagnosis of myxedema coma may be very difficult, as serum TSH concentrations will be normal or low. However, other symptoms of pituitary dysfunction are usually present in these rare patients.

How do I know this is what the patient has?

Dilutional hyponatremia is common and may be severe. Elevated creatine kinase concentrations, sometimes markedly so, are encountered frequently and may misdirect the clinical picture toward cardiac ischemia. However, the MB fraction in most of these cases is normal, and an electrocardiogram (ECG) often demonstrates low voltage and loss of T waves that is characteristic of severe hypothyroidism. Elevated lactate dehydrogenase concentrations, acidosis, and anemia are common findings. Lumbar puncture reveals increased opening pressure and high protein content.

Confirming the diagnosis

Myxedema coma is a clinical diagnosis, so the clinician requires a high index of suspicion. Elderly patients may present with particularly subtle findings. Even though rare, the diagnosis of myxedema coma should be considered in any hypothermic, obtunded patient. Medical history in these patients, including a prior history of hypothyroidism, may only be able to be confirmed from other sources. Friends, relatives and acquaintances might have noted increasing lethargy, complaints of cold intolerance, and changes in the voice.

Clues to the diagnosis include an outdated container of L-T4 discovered with the patient’s belongings. In the medical record, a report of prior thyroid hormone use, previous referral to treatment with radioactive iodine, or a history of a thyroidectomy all can raise suspicion. On the physical examination, the finding of a thyroidectomy scar or a goiter should raise suspicion as to the diagnosis.

Differential diagnosis

Myxedema coma must be differentiated from any illness that can cause coma, including sepsis, CNS events and drugs (sedatives, tranquilizers). Also hypoglycemia, hypothermia and protein-calorie malnutrition can contribute to a similar clinical picture. All of these conditions can also precipitate myxedema coma.

Specific confirmatory tests

Serum levels of thyroid hormones and TSH. A total T4 by itself is often misleading and unhelpful – an estimate of the free T4 concentration is needed. Serum free T4 is measured either by Free T4 by analog assay (FT4) or Free T4 index (FTI), which is a multiplication of the total T4 x T3 resin uptake. Serum T3 levels are unhelpful as they may be normal even in the face of severe hypothyroidism.

4. Specific Treatment

First-line and other therapies

Myxedema coma is a medical emergency that should be managed in an intensive care setting. The mainstays of therapy are as follows:

1) Supportive care with ventilatory and hemodynamic support. Re-warming should be passive rather than active unless the core temperature is less than 28 degrees C. Since ventricular fibrillation is a risk at these temperatures, the rate of re-warming should be no greater than 0.5 degrees C per hour until 31 degrees C is achieved.

2) Correction of hyponatremia and hypoglycemia and treatment of the precipitating incident

3) IV administration of thyroid hormone. IV administration of steroids should be given owing to a 5% to 10% incidence of co-existing adrenal insufficiency.

4) Sedatives, hypnotics, narcotics and anesthetics are to be avoided.

Drugs and dosages

Hydrocortisone 100mg IV q 8 h x 24 h, first dose prior to L-T4; continue steroids as clinically indicated.

Levothyroxine (L-T4) 200 to 300mcg IV as a loading dose, 500mcg in the first 24 hours, then 100 to 125mcg (or the outpatient dose, if known) IV or PO daily until stable.

Consider Liothyronine (L-T3) 12.5mcg IV q 6 h until awake in addition to L-T4.

What do I do about particularly refractory cases?

Continue L-T4 daily and supportive measures until patient recovers. Follow serum levels of FT4 or FTI daily until patient recovers; goal is a level in the mid- to upper half of the normal range.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

The expectation is medical stabilization and mental status clearing in 24 to 48 hours.

When should I suspect I've made the wrong diagnosis?

If there is no clinical improvement in 24 to 48 hours despite a significant increase in the serum levels of FT4/FTI.


Once the patient is clinically stable on an oral dose of levothyroxine, a FT4/FTI and TSH should be re-checked in 4 to 6 weeks and the oral dose adjusted as in routine hypothyroidism.


The pathophysiology is due to longstanding hypothyroidism and all of the concomitant changes associated with this. Myxedema coma ensues when a significant clinical stress occurs in this setting.

What's the evidence?

Myxedema Coma

Arlot, S, Debussche, X, Lalau, JD. “Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment”. Intens Care Med. vol. 17. 1991. pp. 16-8. (Classic article examining the use of oral vs intravenous L-T4 therapy.)

Wartofsky, L. “Myxedema in coma”. Endocrinol Metab Clin North Am. vol. 35. 2006. pp. 687-98. (Recent in-depth review of myxedema coma.)

Yamamoto, T, Fukuyama, J, Fujiyoshi, A. “Factors associated with mortality of myxedema coma: report of eight cases and literature survey”. Thyroid. vol. 9. 1999. pp. 1167-74. (Review of the mortality risk factors.)

Rodriguez, I, Fluiters, E, Perez-Mendez, LF, Luna, R, Paramo, C, Garcia-Mayor, RV. “Factors associated with mortality of patients with myxedema coma: prospective study in 11 cases treated in a single institution”. J Endocrinol. vol. 180. 2004. pp. 347-50. (In depth reviews on the pathophysiology, presentation and management of myxedema coma.)

Arlot, S, Debussche, X, Lalau, JD. “Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment”. Intens Care Med. vol. 17. 1991. pp. 16-8. (This study documents alternatives to oral administration of thyroid hormone and antithyroid drugs.)

Hickman, PE, Sylvester, W, Musk, AA, McLellan, GH, Harris, A. “Cardiac enzyme changes in myxedema coma”. Clin Chem. vol. 33. 1987. pp. 622-4. (This study shows that creatine kinase elevations in myxedema coma are not due to myocardial ischemia.)