Case Of the Month 10 – Answer

Thyroid dysfunction can present in many unusual ways, and the extremes on the spectrum of thyroid disease are particularly deadly. Given that this patient has not taken his levothyroxine in two months, you should always consider whether he is experiencing significant hypothyroidism or even myxedema crisis. Considering his bradycardia, cold and clammy skin, non-pitting edema, and progressive lethargy, myxedema crisis should be clinically suspected prior to obtaining thyroid function tests.

Myxedema crisis can have a mortality of up to 60%, even in treated cases; however, it is a rare entity without a precise incidence in the US. It occurs mostly in patients with a known diagnosis of hypothyroidism after an inciting factor. The two most common triggers are infection and non-adherence to medication. Patients will typically present with bradycardia, hypothermia, hypotension, confusion or lethargy, non-pitting lower extremity edema, abdominal pain, and even cardiogenic shock. The classic term “myxedema coma” is an inaccurate description as most patients will present with confusion or lethargy as opposed to coma.

Confirmation of this diagnosis is made with laboratory studies, but treatment should not be delayed for the results of blood tests given the high mortality associated with myxedema crisis. TSH will be elevated, and free T₄ and free T₃ will be low. Assessment of adrenal function should be performed prior to initiating thyroid hormone replacement, as the clinical features of cortisol deficiency frequently overlap with those of myxedema crisis. Additionally, T₄ repletion may increase the metabolism of cortisol and precipitate acute adrenal insufficiency. Therefore, a random serum cortisol level should be obtained in all cases. This test will only provide diagnostic clarity if the values are markedly low, so an ACTH stimulation test may need to be performed later to definitively rule out adrenal insufficiency.

As mentioned, treatment revolves around thyroid hormone repletion. Current guidelines recommend administration of both T₄ and T₃ as patients in myxedema crisis may have impaired conversion of T₄ to T₃:

T4:  Loading dose of 300-600 micrograms IV followed by a daily IV dose of 50-100 micrograms.

T3_: 5-20 micrograms intravenous bolus and continue at a dosage of 2.5-10 micrograms every 8 hours.

There is a risk of dysrhythmias and myocardial infarction with a rapidly increase in thyroid hormone levels; however, it is a risk that may be accepted given the high mortality associated with myxedema crisis. American Thyroid Association guidelines recommend dosing these medications in the lower range for patients at risk for arrhythmias or ischemic heart disease. Oral dosing can be considered in mild cases of myxedema; however, if absorption of oral medication during a crisis is an issue, IV formulations are preferred. Treatment can be converted to oral medications once the patient is tolerant. Stress-dose steroids should be administered until adrenal insufficiency is ruled out. Hydrocortisone 100mg q8hrs or dexamethasone 2-4mg q12hrs should be administered until the results of laboratory testing have returned; however, the use of hydrocortisone will alter the results of an ACTH-stimulation test. All other abnormalities and findings should be managed with supportive care until the patient’s clinical status improves.

In summary: Suspect myxedema crisis in any patient with a past history of hypothyroidism presenting with altered sensorium and depressed vital signs. Then, search for an inciting factor and aggressively treat and correct these factors. Remember to first treat adrenal insufficiency in all cases of myxedema and then rule it out with random cortisol or ACTH-stimulation test.