Hospital Medicine

Myxedema Coma

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I. What every physician needs to know.

Myxedema coma (or myxoedema coma) is defined as severe hypothyroidism that leads to altered mental status and hypothermia, as well as hypoglycemia, hyponatremia and hypoventilation. It can be the end-point of severe, long-standing, untreated (or under-treated) hypothyroidism or can be a hypothyroidism crisis precipitated by infection, infarction, cold exposure, or overdose. It can rapidly progress to death if not diagnosed and treated quickly.

II. Diagnostic Confirmation: Are you sure your patient has Myxedema Coma?

Myxedema coma can be mistaken for other life-threatening conditions, such as septic shock, myocardial infarction, stroke or overdose.

A. History Part I: Pattern Recognition:

  • Altered mental status such as disorientation, confusion or lethargy and, at it's most extreme, non-responsiveness requiring mechanical ventilation.

  • Dysthermoregulation (core temperature below 37 degrees Celsius).

  • Insidious onset.

  • Women more often than men (as women are more often afflicted with hypothyroidism, than men).

  • Presentation in winter.

  • Symptoms of severe hypothyroidism, including weakness, dry skin, complaints of feeling cold, hair loss, poor concentration, constipation, weight gain, dyspnea.

B. History Part 2: Prevalence:

Patients with poorly controlled hypothyroidism or poor med compliance are at risk for myxedema coma. Additionally, patients often have an acute stressor, such as infection, that brings them to medical attention.

C. History Part 3: Competing diagnoses that can mimic Myxedema Coma.

Septic shock can look like, or contribute to, myxedema coma, though myxedema coma will not improve with early goal directed therapy, in the same way that septic shock will.

Myocardial infarction can look like, or contribute to, myxedema coma but, just like septic shock, will not improve along the same trajectory that one would expect, with the appropriate treatment.

Stroke can look like myxedema coma, but with myxedema coma there will be no objective evidence for intracranial event on computed tomography (CT) or magnetic resonance imaging (MRI) of the head, nor will there be focal neurologic findings.

D. Physical Examination Findings.

  • Altered mental status such as disorientation, confusion or lethargy and, at it's most extreme, non-responsiveness requiring mechanical ventilation.

  • Core body temperature below 37 degrees Celsius.

  • Dry, coarse skin.

  • Facial or periorbital edema.

  • Non-pitting edema of the extremities.

  • Diffuse alopecia.

  • Bradycardia.

  • Delayed tendon reflex relaxation.

Interestingly, the presence or absence of a goiter does not contribute to the acute diagnosis, but it can be helpful information if thyroid dysfunction is a new diagnosis for the patient, in that it can help guide diagnostic testing plans after the acute phase has been managed.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

TSH (thyroid stimulating hormone); if very elevated (often greater than 30), the diagnosis is made. If TSH is very elevated, full thyroid function tests (free T4 and total T3) should then be added on to the original serum sample, if possible, or should be drawn.

Sodium, to look for concomitant hyponatremia.

Glucose (serum) to look for concomitant hypoglycemia.

ABG (arterial blood gas) to look for hypercarbia and/or hypoxia.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specifically required radiologic exams to order, in order to establish the diagnosis.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

There are no over-utilized or wasted diagnostic tests associated with the diagnosis of myxedema coma.

III. Default Management.

Until the TSH level is known and the diagnosis is made, default management will include managing the symptomology with which the patient presented. This may include mechanical ventilation and/or broad-spectrum antibiotic therapy. Care should be taken to address and correct metabolic derangements such as hyponatremia and hypoglycemia.

A. Immediate management.

Once the diagnosis of myxedema coma is made, the patient should be transferred to an ICU (intensive care unit) setting.

It is critical that thyroid replacement therapy begin immediately, but there are no large, prospective trials for myxedema coma, so dosing remains a question not answered by evidence-based medicine. Multiple sources promote the use of levothyroxine 500 micrograms IV once, followed by levothyroxine 50 to 100 micrograms IV daily. The thought is that a patient has the best prognosis when his or her entire extrathyroidal pool of T4 is replaced as quickly as possible.

Dosing adjustments should be based upon age and cardiac history, with care taken to reduce the dose in the setting of advanced age, or current or prior history of cardiac events. It should be noted that the onset of action is longer for T4 (levothyroxine) than T3, but there is concern that rapid administration of T3 alone can lead to cardiac events, thus it is not recommended.

Simultaneous steroid therapy is also recommended, as adrenal insufficiency may coexist and, additionally, thyroid replacement therapy can increase the clearance rate of cortisol. Therefore, the use of hydrocortisone 50 mg IV q6hrs, or similar regimen, is recommended and may already been in place if the patient is already being treated for septic shock. As per those guidelines, tapering the steroids to off, over the course of days to a week, is advisable and the taper is managed based upon clinical response.

B. Physical Examination Tips to Guide Management.

There are no specific physical exam findings to follow in these patients.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

As with thyroid replacement dosing, the time course over which to repeat the TSH measurement is not well agreed-upon. TSH is not, however, a lab value that is checked daily, even in these patients.

Daily labs should include electrolytes (and these labs should be checked more frequently until any derangements are stabilized).

D. Long-term management.

Long-term management includes determination of the etiology of the patient's hypothyroidism, if not already known, and continuation of thyroid replacement therapy via PO route, as dictated by the patient's thyroid function.

E. Common Pitfalls and Side-Effects of Management.

None

The most commonly quoted regimen is:

  • Levothyroxine 500 micrograms IV once (can be dose-adjusted down based upon the patient's age and cardiac function)

  • Levothyroxine 100 micrograms IV daily (can be dose-adjusted down based upon the patient's age and cardiac function)

  • Hydrocortisone 50 micrograms IV q6hrs (will be tapered to off, based upon clinical response)

IV. Management with Co-Morbidities.

Septic shock

Myxedema coma in the setting of septic shock: The patient should be managed for both of the disorders, in that the patient will receive thyroid replacement therapy and adjunctive corticosteroids for the myxedema coma, and will be treated appropriately for his or her septic shock via the tenets described in the Surviving Sepsis Campaign.

Overdose

Myxedema coma in the setting of overdose: The patient should be managed for both of the disorders, in that the patient will receive thyroid replacement therapy and adjunctive corticosteroids for the myxedema coma, and will be treated appropriately for any or all drug overdoses that are suspected or proven by laboratory studies (i.e. serum or urine toxicology screens). Use should be made of the appropriate Poison Control Center resources.

Mycocardial infarction

Myxedema coma in the setting of mycocardial infarction: The patient should be managed for both of the disorders, in that the patient will receive thyroid replacement therapy and adjunctive corticosteroids for the myxedema coma, and will be treated appropriately for his or her known or suspected myocardial infarction until such time that it is decided that there is no need for cardiac intervention, or until such intervention is completed. Dose adjustments (i.e. reductions) should be made, as needed, to reduce the patient's risk of tachyarrhythmia in the setting of thyroid replacement therapy.

A. Renal Insufficiency.

Hyponatremia may be found in myxedema coma and should be treated appropriately.

There are no dose adjustments needed for thyroid replacement, or corticosteroids, in the setting of renal insufficiency.

B. Liver Insufficiency.

There are no dose adjustments needed for thyroid replacement, or corticosteroids, in the setting of liver insufficiency.

C. Systolic and Diastolic Heart Failure.

Thyroid hormone can cause tachyarrhythmias and thyroid replacement doses should be decreased in the setting of current or prior heart failure diagnoses if the patient has a risk for tachyarrhythmias.

D. Coronary Artery Disease or Peripheral Vascular Disease.

Thyroid hormone can cause tachyarrhythmias and thyroid replacement doses should be decreased in the setting of current or prior diagnoses of coronary artery disease, if the patient has a risk for tachyarrhythmias.

E. Diabetes or other Endocrine issues.

Diabetes can be exacerbated by the administration of corticosteroids and close monitoring of blood glucose should be employed while the patient is being acutely managed. Hyperglycemia itself can result just from steroid administration, so close glucose monitoring of non-diabetics, in the acute setting, is prudent, as well.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

No unique considerations.

B. Anticipated Length of Stay.

Length of stay will be dictated by the patient's clinical course after the diagnosis of myxedema coma. Mechanical ventilation will increase length of stay.

C. When is the Patient Ready for Discharge.

Extubation and normalization of mental status and core temperature are key signs that the patient is improving toward discharge.

D. Arranging for Clinic Follow-up.

Patients treated for myxedema coma should be closely followed in an Endocrinology practice after discharge.

1. When should clinic follow up be arranged and with whom.

The first Endocrinology appointment should be 1-2 weeks after discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

At a minimum, TSH should be drawn on the day of, or just prior to, the first clinic visit.

E. Placement Considerations.

Hospitalizations that include mechanical ventilation often require placement of the patient in a rehabilitation facility for some length of time. The longer that the patient is intubated, and the greater the number of comorbidities, the longer that the patient is likely to need rehabilitation.

F. Prognosis and Patient Counseling.

Prognosis has improved with improvement of laboratory assays for TSH, but remains grim. In 2008, the most recent year that a review article was written on this topic, mortality was quoted at 20-40%.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

It is really important that these patients receive close follow-up with Endocrinology after discharge. Additionally, if the precipitating factors included social issues such as poor access to medications, poor adherence to medication regimens, or poor access to home heating, it is important that these issues be addressed prior to discharging the patient to a home environment.

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