A 94-year-old male resident of an extended care facility presents to

the emergency department (ED) with altered mental status and

confusion. He is unable to provide a medical history, so a collateral
history is obtained from EMS, available medical records, and the
patient's nephew. The patient has recently been hospitalized for
pneumonia, chronic kidney disease, congestive heart failure,
hypothyroidism, and a myocardial infarction. The patients
medications are amiodarone, amlodipine, clopidogrel, levothyroxine,
lisinopril, metoprolol, propafenone, and simvastatin. It is initially
unclear which of these he is currently taking. A review of systems is
unattainable because of the patients mental status changes. A chart
review reveals an iodine allergy and remote tobacco use. The EMS
report details that, according to the patients nephew, the patient is
generally alert and oriented to person and place; however, over the last
24 hours, he has become less responsive and increasingly confused.
EMS personnel confirm decreased responsiveness and document a
heart rate of 30s to 40s en route to the ED.

On presentation, the patients blood pressure is 109/76 mm Hg, heart

rate is 49 bpm, respiratory rate is 19 breaths/min, rectal temperature is
91.22F (32.9C), and oxygen saturation is 98%. The patient is
noncommunicative and in mild distress. His pupils are equal, round,
and sluggishly reactive to light. The cardiovascular examination is
notable for a bradycardic regular rhythm, without murmurs. The distal
pulses are faint but appreciable bilaterally. His respiratory rate and
effort are normal and the lungs are clear to auscultation bilaterally.
The abdomen is soft, nontender, nondistended, and with normal bowel
sounds. The rectal examination reveals guaiac-positive brown stool.
The patient's skin is cool, dry, and nonedematous. He is nonverbal, but
does turn his head in response to his name. The initial work-up
includes an electrocardiogram (ECG), chest radiograph, complete
blood cell count (CBC), basic metabolic panel (BMP), urinalysis, and
cardiac enzymes. The ECG (Figure 1) shows a bradycardic junctional
rhythm at a rate of 49 bpm (compared with previous ECGs showing a
normal sinus rhythm with a rate in the 80s) and a prolonged QT
interval. The CBC shows a normal white blood cell and platelet count,
but a hemoglobin of 8.5 g/dL (85 g/L; decreased approximately 2 g/dL
from a previous admission). The BMP shows stable stage 4 chronic
kidney disease and a blood glucose level of 102 mg/dL (5.7 mmol/L).
The cardiac enzyme examination and urinalysis are normal. Chest
radiography shows mild vascular congestion and no infiltrates.
Computerized tomography (CT) scanning of the head reveals no acute
disease.

The patient's heart rate throughout the initial ED evaluation ranges

from the high 40s to the low 60s. The patient receives a transfusion of
packed red blood cells (RBCs). His hypothermia is treated with the
application of warming blankets. The patient is re-evaluated and found
to have a Glasgow Coma Scale (GCS) rating of 9. His blood glucose
is rechecked and is 49 mg/dL (2.72 mmol/L). The low blood glucose
is treated but the patients mental status does not improve. He
continues to be hypothermic and bradycardic. He is endotracheally
intubated for airway protection and admitted to the medical intensive
care unit (MICU).
DISCUSION

After reviewing the patient's presenting findings, including the altered

mental status, hypothermia (rectal temperature, 91.2F [32.9C]),
bradycardia (junctional rhythm with a rate in the 40s), and
hypoglycemia (a blood sugar of 49 mg/dL [2.72 mmol/L]), and
correlating them with his past medical history, current medications,
and current laboratory studies, a working diagnosis of myxedema
coma was made. Thyroid function tests were ordered, and treatment
was begun with 4 mg dexamethasone intravenous and 250 mcg
levothyroxine intravenous prior to MICU admission. A chart check
revealed that the patient had started amiodarone for paroxysmal atrial
fibrillation 3 months previously. Also, although the patient was
reportedly asymptomatic, on a previous admission, his thyroid
stimulating hormone (TSH) was elevated and hed been started on
levothyroxine. The ECG (Figure 1) showed a bradycardic junctional
rhythm (with a rate of 49 bpm) and a prolonged QT interval. While
the ECG findings could have been caused by the patients
polypharmacy, they are also consistent with myxedema. The patient
returned to a sinus rhythm with a heart rate of 65 bpm shortly
following administration of intravenous levothyroxine. Other
information that reduced the likelihood of alternate diagnoses included
a normal white blood cell count, no obvious source of infection
(pneumonia, urinary tract, skin, or soft tissues) and a CT scan of the
brain showing no acute processes. Although the patients stool was
guaiac-positive and he was anemic, he had a normal blood pressure
and bradycardia, and no melena was found. As the patient was being
transported from the ED to the MICU, the thyroid function tests
returned, which provided laboratory evidence supporting our clinical
diagnosis of myxedema coma. His TSH level was elevated, at 83.37
U/mL, and free T3 and free T4 were low, at 1.0 pg/dL (0.0154
pmol/L) and 0.8 ng/dL (10.3 pmol/L), respectively.

Myxedema coma is rare and establishing the diagnosis requires a high

index of suspicion. Myxedema coma represents the severest form of
hypothyroidism and has an associated mortality rate of 30%-40%.[1] It
can occur due to long-standing, untreated hypothyroidism, but is often
linked to a precipitant, such as acute infection, myocardial infarction,
congestive heart failure, cerebral vascular accident, trauma, or drug
toxicity.

The signs and symptoms of hypothyroidism are exaggerated as the

patient approaches myxedema coma. The manifestations include
metabolic derangements and neurologic and cardiovascular
disturbances. Decreased metabolic function leads to hypothermia,
hypoglycemia, hypoventilation, and hyponatremia. As metabolism
decreases, there is a concomitant decrease in thermogenesis, thereby
causing hypothermia.[1] While hypoglycemia is thought to occur from
multiple contributing factors, including hypothyroidism itself, it can
also result from adrenal insufficiency with decreased
gluconeogenesis. Patients with myxedema coma will often be
hypercapnic due to decreased muscle strength and diminished
ventilatory drive causing hypoventilation. Hyponatremia is seen in
approximately 50% of patients with myxedema coma. With decreased
metabolic function, patients often have decreased free water clearance
because of impaired renal function or vasopressin secretion, which
causes dilutional hyponatremia. Patients may be confused and
lethargic or frankly obtunded and comatose.

Cardiovascular findings in myxedema coma can be profound, with

bradycardia, decreased cardiac output, decreased myocardial
contractility, diastolic hypertension, and occasionally
hypotension. This is partly caused by an overall reduction of beta-
adrenergic responsiveness resulting in decreased chronotropic and
inotropic activity, and also by a relative increase in alpha-adrenergic
receptor responsiveness. All of these abnormalities can be corrected to
varying degrees with thyroid hormone replacement therapy.
Several medications can cause hypothyroidism, and patients taking
them must be carefully monitored. These medications include
amiodarone, lithium, and sedatives. Amiodarone can cause both
thyrotoxicosis and hypothyroidism. Roughly 37% of amiodarone by
weight is organic iodine; a maintenance dose of 200 mg/day yields a
daily iodine intake of approximately 75 mg. This is greater than 100
times the daily requirement of iodine. One proposed mechanism for
the pathogenesis of amiodarone-induced hypothyroidism is the Wolff-
Chaikoff effect. Amiodarone metabolism results in a large iodide
release, which inhibits TSH production. As iodide exposure continues,
TSH production resumes, possibly due to reduced iodide within the
thyroid, since iodide is not easily transported across the intrathyroidal
membrane. This TSH production rebound is called "escape from the
Wolff-Chaikoff effect," and persists because of an underlying defect
in thyroid hormonogenesis. Due to these interactions and other
feedback mechanisms, amiodarone has multiple significant effects on
thyroid physiology, and subsequently on other organ systems. When
amiodarone therapy is begun, baseline thyroid function values should
be established. They should be repeated after 3 months. If elevated
TSH and decreased T4 levels are detected, treat with levothyroxine.
The goal of treatment is not to normalize thyroid function studies, but
rather to increase thyroxine (T4) levels to a high-normal, or slightly
above normal range. This will result in a TSH reduction, although it
will likely remain elevated. An alternative approach is to avoid
amiodarone in patients with underlying thyroid disease, possibly using
antiarrhythmics which do not contain iodine, such as dronedarone.

In myxedema coma there is often a precipitating factor underlying the

patient's decline. It is crucial to identify and treat this underlying
cause, while simultaneously correcting the effects of profound
hypothyroidism. If a myxedematous patient is on amiodarone, it
should be stopped and other antiarrhythmics used as needed. Treat
sepsis or infection aggressively. Diagnose and manage congestive
heart failure or myocardial infarction.

No consensus exists on specific thyroid hormone replacement

regimens for myxedema coma. Most experts agree that a large
intravenous bolus of levothyroxine should be administered (200 - 400
mcg), followed by daily doses of 50 - 100 mcg, based on the patient's
weight and comorbidities. Other experts advocate the use of
triiodothyronine (T3) or a combination of both T3 and T4. In addition
to thyroid replacement therapy, it is important to detect coexisting
adrenal insufficiency and treat patients with stress-dose steroids to
avoid precipitating adrenal crisis.

Myxedema coma patients also require good supportive care in order to

ensure a favorable outcome. They often require mechanical ventilation
secondary to hypoventilation and hypercapnia, rewarming for
hypothermia, and careful fluid and electrolyte management to correct
hypoglycemia and hyponatremia.[1,2,3,4]Myxedema coma patients
should be admitted to the intensive care unit for close monitoring and
aggressive thyroid hormone replacement.

In this case, the patient had recently been started on amiodarone for
atrial fibrillation rate control. It was immediately discontinued once
the diagnosis of myxedema coma was established. Endotracheal
intubation and mechanical ventilation were quickly instituted, as was
passive rewarming with warming blankets (since active rewarming
risks vasodilation and hypotension).[1] Stress-dose steroid therapy and
levothyroxine administration continued during the patients MICU
course. He gradually became more alert and responsive. His heart rate
increased, his blood sugars stabilized, and his thyroid function studies
improved. He was extubated on hospital day five, with a return to his
baseline mental status, and was able to communicate with family and
caregivers.