In a case series of 8 people with myxedema coma, hyponatremia as low as 110 mEq/L was seen. It is attributed to a syndrome of inappropriate secretion of antidiuretic hormone and decreased renal blood flow.44 Only 5% to 10% of myxedema coma patients have an associated hypoglycemia.44 When present in myxedema coma, hypoglycemia should raise suspicions for an associated adrenal insufficiency and other causes of hypoglycemia.
Both hyper- and hyponatremia are related to hyperthyroid states and are typically not associated with clinical findings. Hyperglycemia is present in up to half of all patients with hyperthyroidism. Serum potassium levels are generally unchanged but may be severely low in the rare cases of thyrotoxic periodic paralysis. Asymptomatic hypercalcemia is present in hyperthyroid states.
TSH, T4, T3
TSH, T3, total T4, and FT4 levels are not affected during the acute phase of myxedema coma and thyroid storm. When drawn at the time of crisis, the laboratory test findings reflect the patient's chronic thyroid state. A study comparing patients with thyroid storm with patients with uncomplicated hyperthyroidism showed that thyroxine levels were the same in the 2 groups.45,46 Although these laboratory tests may be helpful to the consultant at a later date, they are generally not a part of the ED evaluation of patients with suspected thyroid crisis. An understanding of thyroid laboratory tests will give the emergency clinician insight into a patient's chronic thyroid state.
Normal TSH levels virtually exclude hyperthyroidism, except in the very rare case of a pituitary adenoma. A low value by itself, however, is not diagnostic of a hyperthyroid state. A number of conditions are associated with low TSH levels: chronic nonthyroid illnesses, such as liver disease or renal failure, and adverse drug effects, as seen with glucocorticoids and dopamine. The new generation of extremely sensitive TSH tests redefine the normal range of TSH to 0.3 to 0.5 mU/L.47 To confirm a diagnosis of hyperthyroidism, the TSH should be less than 0.1 mU/L.47 Concurrent evaluation with a FT4 and total T3 is recommended.48
A low TSH level with an elevated FT4 level is seen in 95% of patients with hyperthyroidism.49 Less than 5% of patients have normal FT4 levels with elevated T3 levels, which are diagnostic of a T3 thyrotoxicosis. Total T4 levels, although commonly available, are difficult to interpret because the level is affected by serum thyroid binding proteins. These protein leve s are altered by multiple conditions, including pregnancy, medications, and chronic liver disease.
The TSH and FT4 levels are central to the diagnosis of hypothyroidism. Expect to find elevated TSH levels with low levels of FT4 and T3 in primary hypothyroidism. In patients with secondary or tertiary causes of hypothyroidism, expect to find low TSH levels and low FT4 levels. An elevated TSH level is the most sensitive indicator of a hypothyroid state, and changes in its level will precede any changes in serum FT4. Early in the disease process, elevations in TSH levels may maintain normal FT4 and T3 levels. As with hyperthyroid cases, the total T4 level is difficult to interpret and may be elevated or depressed, depending on changes in serum thyroxine binding globulin levels.
Thyroid laboratory tests are affected by many physiologic states and medications. Importantly, acute illness can alter thyroid tests to give the impression of a hypothyroid state by altering T3 levels. Low T3 levels with low or normal TSH and T4 levels are typically seen in patients who are acutely ill. This is the sick euthyroid syndrome. In addition, dopamine in doses used for shock causes a low serum TSH.49 A multitude of factors can retard the peripheral conversion of T4 to T3, resulting in a low T3 level in patients who are physiologically euthyroid. These factors include glucocorticoids, high doses of propanolol, and radiocontrast agents amiodarone.48,50-55 T4 is decreased in patients treated with phenytoin, rifampin, and carbamazepine. Serum TSH levels remain normal in these patients.56,57
Other Diagnostic Tests
Given the broad differential associated with severe hyper- and hypothyroidism, consider a broad initial laboratory evaluation. Obtain cardiac markers and B-type natriuretic peptide levels to assess for cardiac ischemia or acute cardiac failure. Serum lactate levels assess perfusion status in the hypotensive patient. Consider drawing a random cortisol level if the possibility of adrenal insufficiency exists. Urinalysis is critical in assessing for an infectious source. A urine pregnancy test or b-hCG (human chorionic gonadotropin) in all women of childbearing age is mandatory as the management of thyroid storm and myxedema coma in the pregnant patient requires unique considerations. (See the Special Circumstances: Pregnancy section.)
An arterial blood gas is useful to quantify the level of hypercapnia and hypoxemia in severely hypothyroid patients and to identify acidosis in hypermetabolic patients with thyrotoxicosis. In a severely obtunded patient, expect to find a respiratory acidosis with hypoxemia and hypercapnia, both secondary to a decreased ventilatory drive in myxedema coma.58
See Table 7 for thyroid laboratory tests in thyroid disease.
The electrocardiogram (ECG) may reveal alternate diagnoses and concomitant illness as well as the cardiac effect of the thyroid crisis. The emergency clinician should assess for dysrhythmias and signs of cardiac ischemia. Acute cardiac ischemic events can precipitate thyroid emergencies, especially myxedema coma.
In hyperthyroidism, sinus tachycardia is the most common dysrhythmia, followed by atrial fibrillation. A retrospective review of 58 patients with thyrotoxicosis in an outpatient setting reported incident rates for sinus tachycardia and atrial fibrillation of 65.5% and 15.5%, respectively.20 Up to 15% of patients with hyperthyroidisms develop atrial fibrillation.59 The sinus tachycardia is typically out of proportion to the fever.60 Atrial fibrillation with rapid ventricular response due to hyperthyroidism is typically refractory to digitalis and reverts to sinus in 20% to 50% of patients after antithyroid therapy.60,61 Supraventricular tachycardia (defined as 10 supraventricular contractions in a row with a heart rate > 130 beats per minute) is also more common in patients with thyrotoxicosis than in matched controls.62 Ventricular tachycardia and ventricular fibrillation, however, are not typically associated with thyrotoxicosis and, if present, are usually r elated to heart failure due to ischemic disease.63
Sinus bradycardia is the most common dysrhythmia in the patient with hypothyroidism. ECG changes consistent with a pericardial effusion, low voltage, electrical alternans, and diffuse ST-segment and T-wave changes are present in 50% of patients with myxedema coma.32 These ECGs are nonspecific and poorly sensitive and should neither rule in nor rule out the diagnosis.
A chest X-ray (CXR) is best used to evaluate alternate and coexisting diagnoses in the severely ill patient. Assess for cardiomegaly, pleural effusions, and pericardial effusions. Assess for pneumonia, a common precipitating event in myxedema coma. CXR is an insensitive and nonspecific tool for assessing the presence of pericardial effusions. CXRs demonstrate a 30% false negative rate and a 40% false positive rate in detecting hypothyroid-related pericardial effusions.32,33
A rapid transthoracic echocardiogram gives vital information to the emergency clinician and should be performed if there is concern for significant pericardial effusion or cardiac dysfunction. All emergency clinicians should be provided 24-hour access to a bedside ultrasonography machine.
Computerized Tomography Head
Consider the need for computerized tomography of the head without contrast to assess for other potential causes of a depressed or altered mental status in the patient with severe hyper- or hypothyroidism.
Lumbar puncture may be necessary to evaluate the patient for an intracranial infectious process. However, this procedure is not always feasible in an acutely altered or unstable patient. The emergency clinician must weigh the risks and benefits of this procedure. Nonspecific cerebrospinal fluid findings associated with myxedema coma include an increased opening pressure and an elevated protein level.36