Are you sure the patient has myxedema coma?
Clinical Features of Myxedema Coma
Myxedema coma is a rare syndrome that represents the extreme expression of severe, longstanding 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. 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.
Table I summarizes potential precipitating factors of myxedema coma.
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.
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.
What else could the patient have?
Myxedema coma must be differentiated from any illness that can cause coma, including sepsis, central nervous system 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.
Key laboratory and imaging tests
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 exam, the finding of a thyroidectomy scar or a goiter should raise suspicion as to the diagnosis.
Myxedema coma is primarily a clinical diagnosis with features of uncomplicated hypothyroidism that are 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. In fact, a recent case report described myxedema coma in the setting of subclinical hypothyroidism. See Table II.
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 >95% of cases of myxedema coma are due to primary hypothyroidism, the laboratory findings include an elevated serum TSH and low or undetectable total and free serum T4 concentrations.
In the patient with central hypothyroidism, the diagnosis of myxedema coma maybe very difficult, as serum TSH concentrations will be normal or low. However, other symptoms of pituitary dysfunction are usually present in these rare patients.
Other tests that may prove helpful diagnostically
Dilutional hyponatremia is common and may be severe. Elevated creatine kinase concentrations, sometimes markedly so, are encountered frequently and may misdirect the clinical picture towards cardiac ischemia. However, the MB fraction in most of these cases is normal, and an electrocardiogram (ECG) often demonstrates bradycardia, 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.
Management and treatment of the disease
Myxedema coma is a medical emergency and should be treated in an intensive care unit. The mainstays of therapy are:
supportive care with ventilatory and hemodynamic support, rewarming using a non-heated blanket
correction of hyponatremia and hypoglycemia; and treatment of the precipitating incident
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. See Table III.
Hypothermia – 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° C per hour.
Adrenal insufficiency – 5-10% incidence of coexisting adrenal insufficiency, intravenous steroids (i.e. hydrocortisone 100 mg intravenously every 8 h) are indicated before initiating L-T4 therapy. When possible, serum cortisol should be obtained and an ACTH stimulation test should be carried out, if necessary, to document the underlying adrenal function.
Thyroid hormone treatment – Parenteral administration of thyroid hormone is necessary initially due to uncertain absorption through the gut. A reasonable approach is an initial intravenous loading dose of 200-400 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 50-100 mcg intravenously every 24 hours until the patient is stabilized.
Alternatively, one can use L-T3 at a dosage of 12.5-25 mcg intravenously every 6 hours until the patient is stable and conscious. Once the patient is stable, the patient should be switched to L-T4. Follow serum levels of FT4 or FTI daily until patient recovers, with goal levels in the mid- to upper half of the normal range. Once the patient is clinically stable on an oral dose of levothyroxine, a FT4 or FTI and TSH should be re-checked in 6-8 weeks and the oral dose adjusted as in routine hypothyroidism.
The expectation is medical stabilization and mental status clearing in 24-48 hours.
What’s the Evidence?/References
Wartofsky, L. “Myxedema coma”. Endocrinol Metab Clin North Am. Dec. vol. 35. 2006. pp. 687-698. (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. Dec. vol. 9. 1999. pp. 1167-1174. (Review of myxedema coma.)
Rodriguez, I, Fluiters, E, Perez-Mendez, LF, Luna, R, Paramo, C, Garcia-Mayor, RV. “Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution”. J Endocrinol. Feb. vol. 180. 2004. pp. 347-350. (In-depth review 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”. Intensive Care Medicine. vol. 17. 1991. pp. 16-18. (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. 622-624. (This study shows that creatine kinase elevations in myxedema coma are not due to myocardial ischemia.)
Wartofsky, L, Braverman, LE, Cooper, C. “Myxedema coma”. Werner & Ingbars' The Thyroid. (An excellent overview of myxedema coma.)
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