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Internal Medicine / Hospital Medicine
Board Review Manual
Statement of
Editorial Purpose
The Internal Medicine/Hospital Medicine Board
Review Manual is a study guide for trainees
and practicing physicians preparing for board
examinations in internal medicine and hos­
pital medicine. Each manual reviews a topic
essential to the current practice of internal
medicine and hospital medicine.
PUBLISHING STAFF
PRESIDENT, Group PUBLISHER
Bruce M. White
Senior EDITOR
Robert Litchkofski
Myxedema Coma and Thyroid Storm: Diagnosis and Management
Contributors:
Maybelline V. Lezama, MD
Assistant Professor of Medicine, Texas A&M Health
Science Center College of Medicine, Temple, TX
Nnenna E. Oluigbo, MD
Saint Mary’s Hospital, New Haven, CT
Jason R. Ouellette, MD
Vice Chairman, Residency Program Director,
Department of Medicine, Saint Mary’s Hospital;
Assistant Clinical Professor, Yale University School of
Medicine, New Haven, CT
executive vice president
Barbara T. White
executive director
of operations
Jean M. Gaul
Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Myxedema Coma . . . . . . . . . . . . . . . . . . . . . . . . . 2
Thyroid Storm. . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
NOTE FROM THE PUBLISHER:
This publication has been developed with­
out involvement of or review by the Amer­
ican Board of Internal Medicine.
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Summary Points . . . . . . . . . . . . . . . . . . . . . . . . . 11
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Internal Medicine / Hospital Medicine Volume 14, Part 2 Myxedema Coma and Thyroid Storm
Internal Medicine/Hospital Medicine Board Review Manual
Myxedema Coma and Thyroid Storm: Diagnosis and Management
Maybelline V. Lezama, MD, Nnenna E. Oluigbo, MD, and Jason R. Ouellette, MD
INTRODUCTION
Thyroid storm and myxedema coma are disorders that fall within the spectrum of endocrine
emergencies. Considered true medical emergencies, these entities should be suspected in patients
with extreme manifestations of hypothyroidism or
hyperthyroidism. Although they have a low incidence, they must be promptly recognized and adequately treated in order to reduce associated morbidity and mortality. Aggressive treatment should
be initiated in the medical intensive care unit and
should not be delayed until the results of thyroid
function tests are available. With prompt recognition, morbidity and mortality related to myxedema
coma and thyroid storm may be diminished.
MYXEDEMA COMA
CASE PRESENTATION
A 65-year-old woman with no known past medical
history is brought to the emergency department with
altered mental status. On arrival, the patient is drowsy
but arousable. Vital signs include: oral temperature,
95°F; heart rate, 52 bpm; blood pressure, 110/50
mm Hg; respiratory rate, 15 breaths/min; and oxygen saturation, 92% on 4 L of oxygen. The physical
examination in the emergency department is unremarkable. Notable laboratory values include: white
blood cell count (WBC), 12,000 cells/µL; sodium, 128
mEq/L; potassium, 5 mEq/L; blood urea nitrogen,
8 mg/dL; and creatinine, 1.5 mg/dL. The arterial
blood gas reveals acute respiratory acidosis with pH
of 7.23; Paco2 of 63.7 mm Hg; and Pao2 of 71.2
mm Hg on room air. Chest radiograph and head
computed tomography are unremarkable. Diagnosis of hypercapnic respiratory failure is made, and
the patient is admitted to the medical intensive care
unit. The patient becomes more lethargic and her
respiratory acidosis worsens, requiring mechanical
ventilation. A more exhaustive examination reveals
generalized puffiness, periorbital edema, ptosis, and
macroglossia, and her extremities are dry and cool
with nonpitting edema. Myxedema coma is highly
suspected, and the patient is started on intravenous
levothyroxine. Her thyroxine (T4) level is below 0.35
ng/dL and her thyroid-stimulating hormone level is
above 200 µIU/mL.
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Hospital Physician Board Review Manual
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Myxedema Coma and Thyroid Storm
Table 1. Common Precipitating Factors of Myxedema Coma
Stroke
Congestive heart failure
Surgery
Trauma
Gastrointestinal bleeding
Infections
Drugs
Anesthetics
Amiodarone
Lithium
Sedatives
Metabolic disturbances
Hypoglycemia
Hypoxemia
Acidosis
Hypercapnia
ETIOLOGY
Overview
Myxedema coma is an extreme manifestation of
hypothyroidism. It presents as central nervous system dysfunction, defective thermoregulation, and
cardiopulmonary decompensation. While most
believe that patients must be comatose for myxedema coma to be considered, deterioration in the
patient’s mental status in the appropriate clinical
setting is enough to consider this entity.1
EPIDEMIOLOGY
Myxedema coma was first reported by Ord in
1879 in London. It is a rare disorder, with only approximately 300 cases described in the literature.
Patients are typically elderly females and often
have longstanding, undiagnosed hypothyroidism.­­2
More than 90% of cases occur during winter
months, suggesting that low temperatures are a
potential contributing factor. Age-related loss of
temperature regulation, in addition to a decrease in
heat production secondary to hypothyroidism, may
also contribute.1
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Mortality had once been estimated to range from
50% to 60%.3 ­­However, a high level of clinical suspicion with earlier recognition, as well as advances
in intensive care and overall management, have decreased mortality to approximately 20% to 25%.4
Myxedema most commonly develops in patients
with neglected, inadequately treated, or undiagnosed hypothyroidism. Multiple factors appear to
precipitate myxedema coma, including the following: gastrointestinal bleeding; infection; metabolic
disturbances such as acidosis, hypoxemia, and
hypercapnia; stroke; and cardiovascular compromise (Table 1).5
Many patients who develop myxedema coma
are initially hospitalized with an unrelated medical
condition. During hospitalization, the patient slowly
develops a change in mental status. The diagnosis may not be suspected initially, especially when
narcotics or sedatives are being used.3
Drugs such as amiodarone and lithium are
also reported as precipitants of myxedema coma,
especially in patients with a history of lithium- or
amiodarone-induced hypothyroidism. This is due
in part to the effects of these drugs on thyroid
hormone metabolism.6,7 Lithium increases intrathyroidal iodine content, inhibits the coupling of
iodotyrosine residues to form T4 and triiodothyronine (T3), and inhibits their secretion.8 Amiodarone
has a high iodine content, and hypothyroidism can
occur due to the antithyroid effects of iodine. It
also has an effect on thyroid hormone synthesis
and release, especially in patients with underlying
thyroid disease.6
Clinical presentations
The diagnosis of myxedema coma is a clinical
one, and virtually every organ system can be af-
Internal Medicine / Hospital Medicine Volume 14, Part 2 Myxedema Coma and Thyroid Storm
fected. Patients often present with symptoms of
hypothyroidism, including excessive fatigue, weight
gain (despite a decrease in appetite), constipation,
and cold intolerance. Atypical presentations can
occur in elderly patients, who may simply exhibit
decreased mobility.9
Central Nervous System
Altered mental status may range from mild confusion, apathy, and lethargy to obtundation and coma.
While all patients with myxedema coma present with
some degree of altered mental status, only a few
present with true coma.10 Cognitive impairment (eg,
decreased attention, motor speed, memory, and
visual/spatial organization) and psychiatric disorders
(eg, depression, dementia) are other manifestations.
The mechanism for this change in mental status is
largely unknown; however, it has been reported that
there is decreased cerebral blood flow and cerebral
glucose metabolism in hypothyroid patients.11 Focal
and generalized seizures may also occur, possibly
related to concomitant hyponatremia, and hypoglycemia is seen in up to 25% of patients.12 There is
also a delay in deep tendon reflexes.13
Respiratory
Alveolar hypoventilation also occurs in myxedema as a result of depressed hypoxic ventilatory drive and hypercapnic ventilatory response.14,15
The respiratory depression seen in these patients
is related to both a reduced central nervous system drive to breathe and decreased respiratory
muscle activity.14,16 Increased alveolar-arterial oxygen gradient and ventilation-perfusion mismatch
are common and contribute to hypercapnia seen in
these patients. Pleural effusions as a result of fluid
accumulation may also occur. Myxedematous infiltration of the pharynx and tongue may significantly
contribute to the need for mechanical ventilation.17
Hospital Physician Board Review Manual
Respiratory dysfunction may also lead to obstructive sleep apnea,17 and this may be associated with
weight gain and obesity.
Cardiovascular
Cardiovascular manifestations include bradycardia and low cardiac output due to decreased cardiac contractility; however, frank congestive heart
failure is rare.3 Narrow pulse pressure and diastolic
hypertension is often seen in the early stages. Hypotension may be seen in the later stages, and it is
frequently exacerbated by bradycardia, low cardiac
output, and decreased blood volume. Increased
systemic peripheral resistance occurs and is thought
to be due to decreased T3 levels. Pericardial effusions may occur as a result of increased capillary
permeability, leading to fluid accumulation. Cardiac
tamponade, however, is rare.16
Renal
Renal impairment may be severe in patients with
myxedema and is attributed to decreased renal
blood flow and increased vascular resistance in the
afferent and efferent arterioles, which leads to a low
glomerular filtration rate.18,19 There is also decreased
free water clearance and reduced levels of Na+/K+
ATPase with concomitant reduction in sodium reabsorption; these changes lead to hyponatremia,
which is commonly seen in these patients.18
Gastrointestinal
The most common gastrointestinal presentation is constipation, which occurs as a result of
decreased intestinal motility.18 This may progress
to gastric atony, megacolon, and paralytic ileus,
mimicking an acute abdomen, as these patients
may present with anorexia, nausea, abdominal
pain, and distension.20 Ascites may be present but
is uncommon.
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Myxedema Coma and Thyroid Storm
Skin and Facial Appearance
Patients may present with classic myxedematous
facies, characterized by generalized puffiness, ptosis, macroglossia, coarse and sparse hair, and periorbital edema. The skin is dry, pale, and thickened
with nonpitting edema (myxedema); edema occurs
due to increased dermal glycosaminoglycan content, which traps water. The hair is dry, brittle, and
falls out easily, and the voice may be hoarse.13
Metabolic
Hypothermia is usually present, with a body
temperature that may fall as low as 24°C (75°F);
increased severity is associated with worse prognosis.3 Hypothermia is frequently not recognized
as many thermometers do not register extremely
low temperatures. It is important to be aware of the
presence of complicating factors, such as underlying infection, as fever may be masked by coexistent hypothermia.5
Laboratory Testing and Other Studies
Thyroid function tests in patients with myxedema
coma always demonstrate reduced free T4 and T3.
The thyroid-stimulating hormone level may be elevated, suggesting a primary thyroid disorder, but
it also may be low or normal in central/secondary
hypothyroidism. Arterial blood gases may reveal
hypoxia and hypercapnia with respiratory acidosis.
Electrolyte abnormalities include hyponatremia, due
to impairment in free water secretion and increased
vasopressin secretion. Hypoglycemia may be present as a result of down-regulation of metabolism,3 or
it may indicate coexisting adrenal insufficiency. Elevated creatinine may occur due to decreased renal
perfusion and glomerular filtration rate. Complete
blood count may show normocytic anemia and mild
leukopenia. Creatine kinase and serum transaminases are often elevated, and the lipid profile often
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reveals hyperlipidemia. Serum cortisol level should
be checked to evaluate for coexisting adrenal insufficiency. Electrocardiogram abnormalities include
bradycardia, decreased voltage, prolonged QT interval, nonspecific ST-T changes, and Osborn waves in
cases of hypothermia. Chest radiograph may reveal
pleural effusions and cardiomegaly.
DIAGNOSIS
A thorough past medical history should be elicited
in all patients, especially if there is a prior history of
thyroid disease, thyroidectomy, radioiodine therapy,
or noncompliance with thyroid therapy. Given a reasonable index of suspicion in a patient presenting as
previously described, initiation of treatment should not
be delayed until the results of thyroid function tests are
available. Furthermore, because of concurrent illness,
thyroid-stimulating hormone values may not be elevated in proportion to the severity of hypothyroidism.
Thyroid-stimulating hormone is elevated in most patients. An exception is patients in whom hypothyroidism is attributed to hypothalamic or pituitary disease
(< 5% cases of myxedema coma), in which case
the thyroid-stimulating hormone is low or normal.
Independent of whether the underlying cause of
hypothyroidism is primary or secondary, all patients
with myxedema coma have low total and free T4 and
T3 concentrations.3
TREATMENT
Myxedema coma is an acute medical emergency and should be treated in the intensive care
unit. Continuous monitoring of the patient’s cardiovascular and pulmonary status is required, and
ventilatory support is often needed (Table 2).
Thyroid Hormone
The optimal mode of thyroid hormone therapy
in patients with myxedema coma is controversial.
Internal Medicine / Hospital Medicine Volume 14, Part 2 Myxedema Coma and Thyroid Storm
Table 2. Summary of Myxedema Coma Management
Admit to intensive care unit for continuous monitoring of cardiovascular and pulmonary status
Supportive care
ABC measures
Treat hypothermia with passive rewarming
Treat hyponatremia with normal saline and free-water restriction
Thyroid hormone treatment
Levothyroxine (T4)
Loading dose: 300 to 400 µg IV then 50 to 100 µg IV daily
until oral medication can be given
If suboptimal response consider concurrent liothyronine (T3): 5
µg IV every 8 hr
Corticosteroid therapy
First draw baseline cortisol level and start hydrocortisone 100
mg IV, followed by 50 mg IV every 6 to 8 hr
Follow-up steroid therapy:
If initial cortisol level > 25 µg/dL, discontinue
If initial cortisol level is < 25 µg/dL, continue and send
corticotropin-stimulation testing
IV = intravenously.
As the incidence of the condition is low, no adequate trials have been conducted to compare
different regimens. Some of the arguments for
T4 (levothyroxine) over T3 (liothyronine) therapy
are based on the fact that levothyroxine therapy,
despite its slow onset of action, maintains steadier
hormone levels with less risk of adverse events.
Because T4 → T3 conversion is impaired in sick,
hypothyroid patients, some experts prefer the fasteracting liothyronine. Liothyronine has the disadvantage of higher cost and low availability. In addition, its
serum concentration fluctuates between doses.22
Patients with myxedema coma may absorb
drugs poorly, and for this reason, it is important
that levothyroxine be administered intravenously.
An initial loading dose of 300 to 400 µg of levothyroxine intravenously is indicated (due to marked
total body depletion) followed by 80% of the calculated full replacement dose intravenously daily.
If after a few days the clinical response has been
Hospital Physician Board Review Manual
suboptimal, some experts recommend adding intravenous liothyronine to the regimen at a dose of
5 µg IV every 8 hours. A rise in body temperature
and the return of normal cerebral and respiratory
function often indicate that therapy is adequate.2
In older patients, especially those with underlying cardiovascular disease, treatment should be
started slowly as there could be a risk of precipitating angina, heart failure, and arrhythmia.
Dosage should be adjusted accordingly and
thyroid-stimulating hormone should be measured
frequently.2,3
Glucocorticoid Therapy
Due to the possibility of concomitant adrenal
insufficiency, it is prudent to initiate hydrocortisone
100 mg intravenously, followed by 50 mg intravenously every 6 hours. In addition, thyroid hormone
therapy may increase cortisol clearance and precipitate adrenal insufficiency.5 Glucocorticoid therapy
can be withdrawn if the pretreatment plasma cortisol
is 25 µg/dL or greater, or if results of a corticotropin
(ACTH)-stimulation test are within normal limits.
Supportive Measures
Associated illnesses, such as infection or heart
failure, must be evaluated and appropriately treated. Hypotonic fluids should be avoided as they
may worsen hyponatremia. Passive rewarming is
preferred. Active rewarming is not recommended
as it increases the risk of vasodilatation, which may
lead to hypotension and cardiovascular collapse.23
THYROID STORM
CASE PRESENTATION
A 45-year-old woman with no significant past medical history and who has not seen a physician in
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Myxedema Coma and Thyroid Storm
several years is admitted with a 2-day history of flulike symptoms, worsening shortness of breath, fever,
nausea/vomiting, and diarrhea. In the month prior to
admission, she developed increased shortness of
breath (especially on exertion), palpitations, fatigue,
and 8-lb weight loss despite an increased appetite.
She is not on any medications at home. Her family history is significant for Graves’ disease in her mother and
sister. She is a nonsmoker and denies any history of
alcohol or illicit drug use. Her vital signs on admission
include: temperature, 103oF (39.4oC); heart rate 145 to
160 bpm; blood pressure, 120/60 mm Hg; respiratory
rate, 22 breaths/min; and oxygen saturation, 96% on
room air.
On physical exam, she is alert and oriented to
person but not to place or time. She appears restless and anxious. She has no exophthalmos, lid lag,
or stare. Her thyroid gland is diffusely enlarged with
a bruit. Her cardiovascular exam reveals a laterally
displaced apical beat with irregular tachycardia. She
has a fine resting tremor of her upper extremities
and a nonpitting pretibial edema in both lower extremities. Her deep tendon reflexes are hyperactive.
The rest of her exam is unremarkable.
Her electrocardiogram shows atrial fibrillation with
rapid ventricular response. Her chest radiograph
reveals cardiomegaly. Results of her laboratory
studies include: WBC, 15,000 cells/μL; hemoglobin,
9 g/dL; platelet count, 250,000 cells/μL; sodium,
136 mEq/L; potassium, 3.2 mEq/L; and creatinine,
1.0 mg/dL. Urinalysis is negative. Blood cultures are
taken.
A diagnosis of a viral illness is made and underlying hyperthyroidism is suspected. Intravenous fluid
is initiated and a stat dose of oral metoprolol and potassium chloride is given. Six hours after admission,
she has worsening dyspnea and is hypotensive as
well as increasingly irritable and agitated. She is
transferred to the intensive care unit for close moniwww.turner-white.com
toring and treatment with vasopressors. A presumed
diagnosis of thyroid storm is made and propylthiouracil and propranolol are started. She is also given
a stat dose of hydrocortisone. Her thyroid-stimulating hormone level and free T4 level are reported at <
0.01 µIU/mL and 8 ng/dL, respectively.
Overview
Thyroid storm is a syndrome characterized by
excess thyroid concentration and is considered the
most extreme manifestation of thyrotoxicosis.24 The
diagnosis is clinical, bearing no direct relation to the
absolute levels of thyroid hormones in the serum.
Although some authors have proposed a point system for determining whether a patient’s condition
represents true storm or severe thyrotoxicosis, the
distinction between these 2 entities is not useful
clinically.24,25
EPIDEMIOLOGY
Thyroid storm is relatively rare, with a frequency of
less than 10% in hospitalized patients with thyrotoxicosis. Mortality associated with this disorder ranges
from 20% to 30%.24,26 Thyroid storm typically occurs
in untreated or partially treated thyrotoxic patients.
ETIOLOGY
Graves’ disease is the most common underlying cause of thyrotoxicosis and is a common cause
of hyperthyroidism in middle-aged patients. It is an
autoimmune disease in which the presence of anti–
thyroid-stimulating-hormone antibodies cause hyperstimulation of thyroid hormone along with uncontrolled
thyroidal synthesis and secretion of T4 and T3.27
Thyroid storm may also occur in patients with
a solitary toxic adenoma and toxic multinodular
goiter.28 Rare causes of thyrotoxicosis leading to
thyroid storm include hypersecretory thyroid carcinoma, thyrotropin-secreting pituitary adenoma,
Internal Medicine / Hospital Medicine Volume 14, Part 2 Myxedema Coma and Thyroid Storm
Table 3. Precipitating Factors in Thyroid Storm
Infection
Stress
Trauma
Non-thyroidal surgery
Diabetic ketoacidosis
Psychosis
Labor
Myocardial infarction/heart diseases
Pulmonary thromboembolism
Drugs
Salicylates
Pseudoephedrine
Thyroid-related factors
Excessive ingestion or intravenous administration of iodine
(radio-contrast dye, amiodarone)
Discontinuation of antithyroid drugs
Thyroid surgery
Thyroid injury (palpation, infarction of adenoma)
Radioiodine treatment
struma ovarii/teratoma, and human chorionic
gonadotropin–secreting hydatidiform mole.28,29
Historically, thyroid surgery in patients with uncontrolled hyperthyroidism was the most common
precipitant of thyroid storm. Currently, infections
appear to be the most common culprit.24 Other
precipitating factors associated with thyrotoxic crisis
include stress, trauma, thyroidal or nonthyroidal
surgery, diabetic ketoacidosis, labor, heart disease,
discontinuation of antithyroid drugs, and rarely, radioactive iodine treatment (Table 3).30
PATHOPHYSIOLOGY
The effects of thyroid storm are due to an increased
concentration of free thyroid hormone.31 Another
suggested mechanism of thyroid storm is alteration
of tissue responsiveness to cathecolamines by thyroid hormone via modulation of adrenergic receptor
expression or post-receptor modifications in the
submembranic signaling pathways. This mecha Hospital Physician Board Review Manual
nism may explain why features of thyroid storm are
similar to those seen in catecholamine excess.32,33
Clinical Presentation
Thyroid storm is characterized by an exaggeration of the clinical manifestations of hyperthyroidism; however, fever, tachycardia, central nervous
system dysfunction, and gastrointestinal symptoms
predominate.33
General
Patients may present with weight loss (despite
unchanged caloric intake), generalized weakness,
and fatigue. These patients also have a hypermetabolic state, which leads to increased heat
production and loss, resulting in increased sweating and heat intolerance. Fever associated with
inappropriately excessive diaphoresis is common
and can easily progress to frank hyperpyrexia.33
Central Nervous System
Neuropsychiatric symptoms, including anxiety,
emotional lability, agitation, confusion, psychosis,
and even coma may be seen in patients with
thyroid storm.33 Neurologic findings may include
muscle wasting, hyperreflexia, fine tremors, and
periodic paralysis.28
Gastrointestinal
Gastrointestinal symptoms typically manifest as
diarrhea or hyperdefecation due to increased motor
contraction of the small bowel.28 Patients may also
present with nausea/vomiting and rarely jaundice.34
Cardiovascular
Cardiorespiratory symptoms include palpitations
and dyspnea on exertion due to decreased lung
compliance or left ventricular failure.28 Congestive
heart failure may occur, especially in the elderly,
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Myxedema Coma and Thyroid Storm
and most patients have systolic hypertension.
Cardiovascular findings include a hyperdynamic precordium with tachycardia, increased pulse
pressure, and a strong apical impulse. Sinus
tachycardia and atrial fibrillation occur in approximately 40% and 10% to 20% of patients with thyrotoxicosis, respectively.28
Genitourinary
Oligomenorrhea and anovulation can be seen
in females, while symptoms in males may include
decreased libido and gynecomastia.
Eye and Skin/Thyroid
Typical eye findings include exophthalmos, ophthalmoplegia, diplopia, and conjunctival injection/
chemosis. Thyroid gland findings will depend on the
etiology of thyrotoxicosis and can vary. Myxedema
associated with Graves’ disease typically occurs in
pretibial areas as asymmetric, raised, firm, and pink
to purple plaques of nonpitting edema.28 Hair loss,
palmar erythema, and warm moist skin may also be
seen in these patients.
In the Elderly
Elderly patients typically display few of the sympathomimetic features characteristic of the thyrotoxic state. The term apathetic thyrotoxicosis has
been applied to these patients. They often present
atypically with depression, lethargy, weakness,
and cachexia. Agitation and confusion can mimic
dementia, and unexplained weight loss occurs in
up to 80%.35 Elderly patients may also present with
atrial fibrillation, with a slow ventricular response in
up to 20% of patients.36
Laboratory Testing and Other Studies
Serum total and free T4 and T3 levels are elevated and thyroid-stimulating hormone is undewww.turner-white.com
tectable. Mild hyperglycemia can be seen due to
catecholamine-mediated inhibition of insulin release
and increased glycogenolysis. Serum electrolytes
are usually normal, although mild hypercalcemia can
be observed secondary to both hemoconcentration
and thyroid hormone–stimulated acute bone resorption. Nonspecific elevations in liver enzymes as well
as lactate dehydrogenase and creatine kinase may
be observed. A leukocytosis with a left shift may be
seen, even in the absence of infection. Conversely,
leukopenia can occur in cases of Graves’ disease.33
Radioactive iodine uptake, although not necessary for diagnosis, may reveal increased uptake of
radioiodine as early as 1 to 2 hours after isotope
administration, indicating rapid intraglandular turnover of iodine.33
DIAGNOSIS
The diagnosis of thyroid storm remains a clinical
one. The results of laboratory tests can be indistinguishable from those seen in uncomplicated thyrotoxicosis. A very small study by Brooks and colleagues
comparing the hormone levels in patients with thyroid
storm and mild thyrotoxicosis found that total T4 was
similar in both groups but free T4 was higher in the
thyroid storm group.31 If the clinical suspicion is strong,
initiation of treatment should not be delayed until laboratory confirmation becomes available.
TREATMENT
Initial treatment of thyroid storm involves stabilization, airway protection, oxygenation, intravenous
fluids, and continuous monitoring in an ICU setting
(Table 4).
Inhibition of New Hormone Synthesis and
Prevention of T4→T3 Conversion
Antithyroid medications are the first-line therapy
in the management of thyroid storm. They in-
Internal Medicine / Hospital Medicine Volume 14, Part 2 Myxedema Coma and Thyroid Storm
Table 4. Summary of Thyroid Storm Management
Admit to intensive care unit for continuous monitoring of cardiovascular and pulmonary status
Administer drugs that cause inhibition of thyroid hormone synthesis and prevent T4 T3 conversion:
Propylthiouracil: 800–1200 mg orally, given as 200–300 mg orally every 4 to 6 hr
Methimazole: 80–100 mg orally daily, given as 20 to 25 mg orally every 6 to 8 hr
Lithium carbonate: 1200 mg/daily, orally every 6 to 8 hr
Administer drugs that stop the release of stored thyroid hormone:
Inorganic iodine:
Saturated solution of potassium iodide: 5 drops (250 mg) orally every 6 to 12 hr
Lugol’s solution: 4 to 8 drops orally every 6 hr
Reverse systemic disturbances:
Intravenous fluids if volume depletion
Antipyretics or cooling blankets to treat hyperpyrexia (avoid aspirin—can decrease thyroid protein binding, causing increase in free
thyroid levels)
β-blockers:
Propanolol: 60–80 mg orally every 4 hr
Propanolol IV: 0.5–1 mg bolus over 10 min followed by 1–3 mg over 10 min
Esmolol IV: 50–100 µg/kg/min
Identify and treat underlying cause
Definitive therapy
Radioactive iodine
Surgical thyroidectomy
clude propylthiouracil, methimazole, and carbimazole
(available in Europe only). These medications act
by interfering with the thyroperoxidase-catalyzed
coupling process by which iodotyrosine residues
are combined to form T4 and T3. Propylthiouracil is
a thiouracil bound to albumin (80%–90%), and it
remains the drug of choice. Its mechanism of action
includes inhibiting conversion of T4 to T3 outside the
thyroid gland. The recommended dose is 800 to
1200 mg orally daily in divided doses of 200 to 300
mg every 6 hours. Methimazole is an imidazole and
has a longer half-life than propylthiouracil. It does not
have any effect on T4 conversion to T3. The recommended dose is 80 to 100 mg orally daily, divided in
doses of 20 to 25 mg every 6 hours, which can be
decreased to once or twice daily.37 Both medications
are available in rectal preparations. Side effects of
both antithyroid drugs include pruritus, urticaria, and
10 Hospital Physician Board Review Manual
fever. Dose-related agranulocytosis occurs with methimazole (rare at doses < 40 mg daily) but not with
propylthiouracil.38
Halt the Release of Stored Thyroid Hormone
Iodine therapy blocks the release of pre-stored
hormone and decreases iodine transport and
oxidation in follicular cells. This decrease in organification due to increasing doses of inorganic
iodine is known as the Wolff–Chaikoff effect. Large
amounts of exogenous iodine actually inhibit hormone formation. It is important to consider that
despite maintenance of high doses of iodine, the
thyroid gland eventually escapes inhibition after
approximately 48 hours.39,40
Iodine therapy should be given 2 hours after antithyroid medications to allow organification blockade. The use of iodine is limited, and it is used
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Myxedema Coma and Thyroid Storm
only in severe thyrotoxicosis or thyroid storm in
combination with thionamide therapy.23,39,40
Reverse Systemic Disturbances
Hyperpyrexia should be managed aggressively,
preferably with acetaminophen. Passive measures
can also be used, including ice packs and cooling
blankets. Volume depletion should be managed
with fluid replacement.41
Beta-blockade is essential in controlling the peripheral action of thyroid hormone, having beneficial
effects on the associated fever, diaphoresis, agitation, psychosis, and gastrointestinal symptoms. In
thyroid storm, propranolol is dosed at 60 to 80 mg
every 4 hours, or 80 to 120 mg every 6 hours. The
onset of action after oral dosing is within 1 hour.
If oral propranolol is ineffective, intravenous propranolol and esmolol are reasonable options.42
Glucocorticoids may be used as an adjunctive
therapy and are effective in reducing T3 levels
as well as inhibiting the conversion of T4 to T3.29,43
It also may be used to treat possible relative adrenal insufficiency.26
with extreme manifestations of hypothyroidism or
hyperthyroidism.
• Aggressive treatment should be initiated in the
medical intensive unit, even in the absence of
known thyroid hormones levels at the time of
treatment initiation.
• The principles in management of these emergencies include: rapid initiation of therapy with
either thyroid hormone replacement or antithyroid
medications; treatment of any precipitating cause;
and supportive measures, including ventilation, if
needed.
BOARD REVIEW QUESTIONS
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References
1.
2. Assess the Precipitating Factor
The precipitating event should be recognized
promptly and managed appropriately, since treatment of the underlying pathology greatly increases
chances of a successful outcome. Once the patient
has been rendered euthyroid, definitive treatment
should be considered with radioiodine therapy or
surgery.26
3.
4.
5. 6. SUMMARY POINTS
• Myxedema coma and thyroid storm are considered true medical emergencies.
• These entities should be suspected in patients
www.turner-white.com
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