Updated: October 20th 2021

Thyroid Storm and

Hyperthyroidism
Author Nicole Cimino-Fiallos, MD

Section Editors George Willis, MD , Bennett Myers, MD

Associate Editor Dale Woolridge, MD, PhD

Editors in Chief Amal Mattu, MD , Stuart Swadron, MD

Rapid Access

Approach to the Critical Patient

AIRWAY/BREATHING

Ensure airway protection in cases of altered level of consciousness.

A large goiter may compress or even obstruct the airway.

CIRCULATION

Administer medications in order.

Beta blockers

Propranolol 0.5-1 mg IV bolus q10min, titrate to heart rate <100

bpm OR

Esmolol IV bolus 100-500 μg/kg over 1 min, followed by a

continuous IV infusion: Initial rate, 25-100 μg/kg/min,
subsequently, titrate in 25-50 μg/kg/min increments.
 Alternatives for patients with contraindications: cardioselective
beta blockers, calcium channel blockers, intramuscular Reserpine
or oral (PO) Guanethidine.

Anti-thyroid medications

Propylthiouracil (PTU) 500 mg PO load, 250 mg PO q4h OR

Methimazole 40 mg PO load, 25 mg PO q6h

Iodine

Saturated solution of potassium iodide 5 drops PO q6h OR

Lugol’s solution, 4-8 drops PO q6-8h

Administer AT LEAST 60 min after giving the anti-thyroid

medications

Hydrocortisone 100 mg IV q8h

DISABILITY/EXPOSURE

Treat hyperthermia with passive cooling and acetaminophen.

Non-steroidal anti-inflammatory drugs (NSAIDs) are

contraindicated.

Identify and treat the stressor.

EM:RAP Links
Hyperthyroidism and Thyroid Storm: 2019 audio

Thyroid Storm audio

Thyroid Storm Treatment emrap-video

Key Concepts
Hyperthyroidism is a clinical syndrome caused by an excessive amount of
thyroid hormone. Thyroid storm is the severe, life-threatening extreme of
 hyperthyroidism.

The main differences between hyperthyroidism and thyroid storm relate to

hyperthermia, cardiac effects such as dysrhythmias and heart failure,
central nervous system excitation, and gastrointestinal disruptions.

Thyroid storm is an uncommon but potentially fatal condition caused by an

excessive release of thyroid hormone.

Hemodynamic instability is expected in this disease process. Tachycardia,

hypertension, and hyperpyrexia must be treated aggressively.

There are no defined thyroid-stimulating hormone (TSH) or free T4 values

that indicate or exclude the possibility of thyroid storm.

PITFALLS

Thyroid storm is almost always associated with a trigger, such as sepsis,

pregnancy, recent surgery, discontinuation of anti-thyroid medication, etc. It
is important to look for and treat an inciting event in addition to treating the
hyperthyroidism.

The order of medication administration in the treatment algorithm of

hyperthyroidism is important. Giving the appropriate medications in the
wrong order could increase the release of thyroid hormone into circulation
and worsen the patient’s condition.

Many of the medications used to treat thyroid storm are oral medications. A
nasogastric tube can be used in patients whose mental status precludes
them from oral intake. PR preparations are also available.

Diagnosis
Textbook presentation: A 53-y-old female presents to the ED with a 3-mo
history of palpitations and vomiting. Review of systems demonstrates a
recent unintentional 30-lb weight loss and heat intolerance. On exam, the
patient is diaphoretic, confused, and tachycardic.

Early symptoms include fever, diaphoresis, emotional lability, and anxiety.

Gastrointestinal symptoms are present in 69% of patients. These

symptoms can include nausea, excessive vomiting, profuse diarrhea, and
 diffuse abdominal pain.

Among these patients, 84% exhibit central nervous system signs such as
agitation, delirium, or frank coma.

Among these patients, 50% exhibit cardiovascular manifestations. Among

these cases, 75% of patients have tachycardia greater than 130 bpm, and
40% of patients experience heart failure.

Exophthalmos is present in 20% of patients with Graves’ disease.

PEARLS

Elderly patients are at risk for developing apathetic thyroid storm, which
presents with apathy, depression, weakness, and fatigue.

Scoring systems exist but lack specificity and external validation.

There is no defined TSH, T4, or T3 serum level that distinguishes

hyperthyroidism from thyroid storm, as the diagnosis is strictly clinical.

TSH screening is very sensitive but not specific. Free T4 levels are more
specific.

Treatment
Manage the ABCs.

Continuous cardiac monitoring.

IV access.

Administer medications in order.

Beta blockers

Propranolol 0.5-1 mg IV bolus q10min, titrate to heart rate <100 bpm

OR

Esmolol IV bolus 100-500 μg/kg over 1 min, followed by a continuous

IV infusion: Initial rate, 25-100 μg/kg/min, subsequently, titrate in 25-50
μg/kg/min increments.

If beta blockers are contraindicated, as in reactive airway disease,

 other options are available, including calcium channel blockers,
cardioselective beta blockers, intramuscular reserpine (an alkaloid
agent that depletes catecholamine stores), and PO guanethidine (an
agent that inhibits catecholamine release).

Anti-thyroid medications

Propylthiouracil (PTU) 500 mg PO load, 250 mg PO q4h OR

Methimazole 40 mg PO load, 25 mg PO q6h

Iodine should be administered 60 min after administration of the anti-

thyroid medications.

Saturated solution of potassium iodide 5 drops PO q6h OR

Lugol’s solution, 4-8 drops PO q6-8h

Administer AT LEAST 60 min after giving the anti-thyroid

medications

Hydrocortisone 100 mg IV q8h

Treat hyperthermia with passive cooling and acetaminophen 650 mg PO.

PITFALLS

NSAIDs are contraindicated.

Use passive cooling with fans, and lower the room temperature.

Active cooling can precipitate a hypertensive crisis and should be

avoided.

Heart failure

PITFALLS

Consider bedside echocardiogram to assess high-output vs. low-output

failure.

Avoid nitrates and afterload reducers in high-output heart failure and

focus on heart rate control.

Plasmapheresis can be used for patients refractory to typical therapies.

 Identify and treat the stressor.

Disposition
Admission
Patients with thyroid storm will require admission to the hospital and
should not be discharged.

Patients in thyroid storm often require continuous cardiac monitoring to

check for dysrhythmias and for the development of heart failure.

Most cases of thyroid storm will require care at the ICU level. Patients are
hemodynamically unstable and at high risk for decompensation, multi-
organ dysfunction, heart failure, coagulopathy, and death.

Operating room/surgery
Radioactive iodine ablation therapy or surgery may be used in the
treatment of some patients but is not appropriate as first-line treatment in
the ED.

Deep Dive
Background
Epidemiology
In the United States, the incidence of hyperthyroidism is estimated at <1.3%.

Among patients with hyperthyroidism, the incidence of thyroid storm is

approximately 2%.

The most common underlying cause of hyperthyroidism in thyroid storm is

Graves’ disease, accounting for 60-80% of all causes.

Other less-common causes of hyperthyroidism include

Toxic multinodular goiter (second most common cause)

 Painless thyroiditis

Postpartum thyroiditis

Rare causes: TSH-secreting pituitary adenoma, thyrotropin-releasing

hormone-secreting tumors in the hypothalamus, follicular thyroid cancer,
struma ovarii, hyperemesis gravidarum, and gestational trophoblastic
tumor.

Thyroid disease is 5 times more common in women than in men. The

typical age of initial presentation ranges between 20 and 50 y.

Even with early recognition and appropriate treatment, the mortality of

thyroid storm can approach 50%.

Multi-organ failure is the most common cause of death.

Other causes of death include heart failure, respiratory failure,

disseminated intravascular coagulopathy (DIC), sepsis, and brain injury.

Pathophysiology
A hyperthyroid state produces excess T4 and T3. The T4 is taken into cells
in peripheral tissues and converted to the active hormone, T3. Excess T3
can over-activate gene transcription, resulting in the symptoms of
hyperthyroidism. Excess thyroid hormone subsequently feeds back to the
pituitary gland to suppress TSH production, but depending on the cause of
the thyrotoxicosis, thyroid hormone may still be produced despite the lack
of TSH stimulation.

During thyroid storm, the amount of free or unbound thyroid hormone

increases as the hormone is released from its binding sites. Additionally,
thyroid hormone receptors appear to develop an increased sensitivity to
thyroid hormone during thyroid storm.

It is not yet understood what escalates a patient from uncomplicated

hyperthyroidism to thyroid storm. The combination of increased sensitivity
to thyroid hormone, increased circulating free thyroid hormone, and
enhanced binding to thyroid hormone receptors appears to contribute to
the development of thyroid storm.

Thyroid storm causes an adrenergic activation leading to increased

 catecholamine release. Additionally, the body increases the expression of
adrenergic receptors, causing an elevated responsiveness to
catecholamines, which also appears to play a key role in the systemic
symptoms associated with thyroid storm.

Most organs express adrenergic receptors and respond to catecholamine

stimulation. Therefore, a significant number of organs are impacted by the
hyper-adrenergic state, leading to a variety of possible signs and
symptoms.

Thyroid storm causes death most commonly via multi-organ failure. This
results from tissue hypoxia due to hypoperfusion in a shock state, along
with systemic overdrive and subsequent decompensation due to an
exaggerated inflammatory response. Heart failure, DIC, and bleeding
complications are also known causes of mortality in thyroid storm.

The effects on the cardiovascular system are significant.

The hypermetabolic state causes increased cardiac myocyte production of

adenosine triphosphate, which increases the contractility and heart rate,
leading to a high cardiac output. This state also causes increased oxygen
consumption, which leads to arterial relaxation and decreased systemic
vascular resistance. This activates the renin-angiotensin system, resulting
in an expanded blood volume and leading to an increased preload and a
decreased afterload, ultimately leading to high-output heart failure.
Eventually, the myocardium becomes overwhelmed from the increased
work, leading to low-output heart failure.

Diagnostic Considerations
Clinical Presentation
Precipitating events can include infection, major trauma, non-compliance
with hyperthyroid treatment, amiodarone, neck manipulation, IV contrast,
and numerous other triggers.

Patients may have a personal history of Graves’ disease or a family history

of thyroid dysfunction. Practitioners should ask about recent rapid weight
loss.

Vital sign abnormalities and altered mental status are present in almost all
 patients with thyroid storm. Hyperpyrexia is the most common vital sign
abnormality and can be markedly elevated.

Hypertension is present in most cases, with a widened pulse pressure.

Tachycardia is almost always present as well. It is usually elevated

disproportionately from what is usually seen with fever. Sinus tachycardia is
commonly observed. Atrial fibrillation is the most common dysrhythmia.

Altered mental status can vary by patient, ranging from agitation to coma
with potentially rapid progression. In the elderly, mental status alterations
can present with apathetic thyroid storm. These patients will be more
depressed and apathetic with an accompanying fever.

Exophthalmos is a common finding in thyroid storm; 20% of patients with

thyroid disease have exophthalmos.

The presence of a goiter is another common finding in thyroid storm.

Hepatic congestion also occurs and is thought to be multifactorial. This is

most commonly thought to result from decreased blood flow to the liver
despite increased metabolic activity. Another proposed mechanism is heart
failure causing hepatic congestion. Patients can present with jaundice and
right upper quadrant pain. Jaundice is associated with a poor prognosis, as
it can lead to hepatic failure and coagulation abnormalities.

Clinical Manifestations of Thyroid Storm table shows a list of organ

systems and signs and/or symptoms associated with the hyperthyroid
state.

Thyroid storm can have a variable presentation with a combination of signs

and symptoms. The clinical manifestations are very non-specific.

Diagnosis is very difficult unless the suspicion is high, given its variable
presentation and similar appearance compared to more common
alternative diagnoses.

Scoring tools are available to aid the diagnosis, such as the Burch-
Wartofsky scoring system, but they are limited by low specificity and a lack
of external validation.

Radiographic Evaluation
 The diagnosis of thyroid storm is made clinically. Radiologic imaging of the
neck may show thyroid nodules or increased vascularity of an enlarged
thyroid, which may suggest a cause, but this is not sufficient for the
diagnosis.

Computed tomography (CT) with iodinated contrast should be used

cautiously in patients with suspected thyroid storm, as the introduced
iodine can increase the production of circulating thyroid hormone.

A low threshold should be used to search for inciting etiologies.

Chest X-ray should be obtained to evaluate for pneumonia, pleural

effusions, enlarged cardiac silhouette (possibly indicative of congestive
heart failure or pericardial effusion), or pulmonary edema.

Head CT may be indicated to rule out other causes of altered mental

status.

Bedside ECHO should be performed to evaluate for pericardial effusion

and tamponade.

Laboratory Evaluation
In most settings, laboratory testing is available to aid the
diagnosis. However, the diagnosis is still primarily clinical. For settings in
which the diagnosis is suspected and laboratory testing is not readily
available, it is recommended to start therapy while awaiting confirmatory
testing.

Thyroid function tests

Serum TSH is sensitive for thyroid storm and is the best screening test
available. Serum TSH is most likely very low in the thyrotoxic state.
However, TSH-secreting tumors can produce elevated values in
thyrotoxic states, although this is much less common.

Serum free T4 level is confirmatory. The level will be high in the large
majority of cases. In less than 5% of cases, there is isolated T3
thyrotoxicosis, and a free T3 level should be sent for in those
circumstances.
 Total T4 and total T3 are not helpful because most of the hormone is
bound to protein, making levels difficult to interpret.

ECG

ECG will most commonly show sinus tachycardia and atrial fibrillation.

Most other testing is used to help identify an etiology or to monitor for

multi-organ dysfunction.

A complete blood count may show leukocytosis with a left shift.

An electrolyte panel will likely show hypercalcemia and elevated alkaline

phosphatase levels.

A comprehensive metabolic panel can help evaluate for acute kidney

injury, acute liver injury, pancreatitis, etc.

Obtain a urinalysis and chest X-ray to assess for signs of infection.

Consider obtaining blood cultures.

Determine the human chorionic gonadotropin level in women of child-

bearing age, as ectopic pregnancy and trophoblastic disease can
precipitate thyroid storm.

Thyroid storm is also known to trigger coagulopathies, and the patient

can progress to DIC; therefore, a coagulation panel may be useful.

Therapeutic Considerations
The treatment of thyroid storm effectively relies on 3 basic tenets:

1. Blocking the effects of thyroid hormone

2. Decreasing the levels of circulating thyroid hormone

3. Treating the inciting event and providing supportive care

Treatment should begin before the diagnosis of thyroid storm is confirmed,

as the risk of mortality is high and delayed treatment increases the risk of
death.

Blocking the effects of thyroid hormone

 Controlling tachycardia is an important aspect of treatment. Given the
increased adrenergic receptor expression, beta blockers are the
preferred initial medication. Propranolol is the preferred agent, as it
treats the tachycardia and decreases the body’s conversion of T4 to T3.
While all beta blockers decrease the conversion to the active form,
propranolol has the highest activity. Additionally, propranolol has no
sympathomimetic properties, making it the preferred agent for thyroid
storm.

For patients with severe chronic obstructive pulmonary disease or

asthma or who may have contraindications to beta blocker usage,
verapamil and diltiazem are alternative choices for lowering heart rate,
with the understanding that these agents do nothing to help with the
conversion of thyroid hormone.

Use beta blockers with caution in patients with signs or symptoms of

heart failure.

Patients with thyroid storm can present with low-output or high-output

heart failure. Beta blockers will make low-output heart failure worse.
Use bedside echocardiography to help distinguish between the two
clinical entities.

Alternatively, instead of the less selective propranolol, use the more

cardioselective esmolol, which will focus more on heart rate and less
on inotropy.

Lowering the patient’s heart rate to <100 bpm will improve high-output
heart failure.

After the beta blocker has been administered, an anti-thyroid medication

should be given.

Propylthiouracil (PTU) and methimazole are equally effective, and either

can be used for treatment.

Propylthiouracil has the added benefit of decreasing peripheral

conversion of thyroid hormone.

Propylthiouracil is preferred in the first trimester of pregnancy, while

methimazole is preferred in the second and third trimesters.
 Both medications are given orally. There are no parenteral formulations.
Patients who cannot take oral medications may receive extemporaneous
compounded formulations as enemas. These formulations can be made
by a compounding pharmacist.

Iodine can be administered at least 1 h after the chosen anti-thyroid

medication to inhibit thyroid hormone synthesis through a negative
feedback loop.

PITFALLS

Mistakenly giving iodine prior to the anti-thyroid medication will intensify

the thyroid storm by increasing hormone synthesis and release worsening
symptoms.

A comparison of anti-thyroid medication plus iodine vs. anti-thyroid

medication alone showed faster normalization of thyroid hormone levels
and a lower mortality for the combined treatment.

Glucocorticoids decrease the conversion of T4 to T3 and should be used in

patients with severe symptoms. This carries the additional benefit of
treating any concomitant adrenal insufficiency.

Hyperpyrexia due to thyroid storm should also be addressed.

Acetaminophen is the drug of choice for treating fever.

PITFALLS

NSAIDs are known to remove the thyroid hormone from the protein
binding site, freeing the thyroid hormone to be readily converted into
active hormone. Therefore, NSAIDs should not be used for the
management of fever.

For extreme hyperthermia, cooling may be necessary.

There is some consensus that active cooling (the use of cooling

blankets, cooled IV fluids, and ice packs) is contraindicated.

PITFALLS

Active cooling will increase peripheral vasoconstriction, potentiating a

 hypertensive crisis. Passive cooling using techniques such as removing
the patient’s clothes and lowering the temperature of the room is
preferred.

PEARLS

Agitation and seizures should be managed with benzodiazepines, which

have been shown to be safe in thyroid storm.

Antiepileptic drugs should also be used in the setting of refractory seizure.

Phenytoin can falsely lower the levels of free T4, and levels should
therefore be drawn before the medication is administered.

Patients refractory to medical therapy may require plasmapheresis.

Patients will require admission to the hospital for treatment of thyroid storm
and for further evaluation of the etiology of their hyperthyroidism. After
discharge, they will require close endocrinology follow-up and strict
medication compliance.

Prevention
Poor medication compliance with anti-thyroid drugs is the most common
trigger for thyroid storm in patients with known thyroid disease.

Any patient diagnosed with Graves’ disease should be counseled about

the risks of thyroid storm. If patients are unable to reliably take their
medication, then thyroidectomy or radioiodine treatments should be
considered.

In patients with known thyrotoxicosis, any elective surgeries should wait

until the patient achieves euthyroidism.

Many medications, such as iodinated contrast dye and amiodarone, have

been shown to increase the risk of thyroid storm and should be avoided in
patients with uncontrolled thyrotoxicosis.

The American Thyroid Association recommends screening for thyroid

disease at age 35 years old and every 5 years thereafter. Physicians
should also recommend screening to high-risk patients such as pregnant
women, elderly women, type 1 diabetics, and those with a history of
 radiation to the neck.

Additional Information
Suggested EM:RAP Links
Thyroid Storm audio

Hyperthyroidism audio

Hyperthyroidism and Thyroid Storm: 2019 audio

Guidelines
Japan Thyroid Association: thyroid storm

American Thyroid Association: Hyperthyroidism and Other Causes of

Thyrotoxicosis.

American Thyroid Association Guideline: Hypothyroidism and Use of

Thyroid Hormone Analogs

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