American Journal of Emergency Medicine 69 (2023) 127–135

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

High risk and low prevalence diseases: Thyroid storm

Samia Farooqi, MD a, Sonika Raj, MD a, Alex Koyfman, MD a, Brit Long, MD b,1,⁎
a
Department of Emergency Medicine, UT Southwestern, Dallas, TX, USA
b
SAUSHEC, Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, TX, USA

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Thyroid storm is a rare but serious condition that carries a high rate of morbidity and even mortality.
Received 23 January 2023 Objective: This review highlights the pearls and pitfalls of thyroid storm, including presentation, diagnosis, and
Received in revised form 12 March 2023 management in the emergency department (ED) based on current evidence.
Accepted 22 March 2023 Discussion: Thyroid storm is a challenging condition to diagnose and manage in the ED. It is characterized by ex-
aggerated signs and symptoms of thyrotoxicosis and evidence of multiorgan decompensation, usually occurring
Keywords:
in the presence of an inciting trigger. Clinical features of thyroid storm may include fever, tachycardia, signs of
Endocrinology
Thyroid
congestive heart failure, vomiting/diarrhea, hepatic dysfunction, and central nervous system disturbance.
Thyrotoxicosis There are several mimics including sympathomimetic overdose, substance use disorders, alcohol withdrawal,
Thyroid storm acute pulmonary edema, aortic dissection, heat stroke, serotonin syndrome, and sepsis/septic shock. Ultimately,
the key to diagnosis is considering the disease. While laboratory assessment can assist, there is no single labora-
tory value that will establish a diagnosis of thyroid storm. Clinical criteria include the Burch-Wartofsky point
scale and Japan Thyroid Association diagnostic criteria. ED treatment focuses on diagnosing and managing the
trigger; resuscitation; administration of steroids, thionamides, iodine, and cholestyramine; and treatment of hy-
perthermia and agitation. Beta blockers should be administered in the absence of severe heart failure. The emer-
gency clinician should be prepared for rapid clinical deterioration and employ a multidisciplinary approach to
treatment that involves critical care and endocrinology specialists.
Conclusions: An understanding of thyroid storm can assist emergency clinicians in diagnosing and managing this
potentially deadly disease.
Published by Elsevier Inc.

1. Introduction 1.1. Definition

This article series addresses high-risk, low-prevalence diseases that It is important to distinguish between the terms hyperthyroidism
are encountered in the emergency department (ED). Much of the pri- and thyrotoxicosis, which are often inappropriately conflated. Hyper-
mary literature evaluating these conditions is not specific to emergency thyroidism occurs as the result of excessive synthesis and secretion of
medicine. By their nature, many of these diseases and presentations thyroid hormone from the thyroid gland, whereas thyrotoxicosis refers
have little useful evidence available to guide the emergency physician to the clinical manifestation of symptoms due to excess T3 and T4 in pe-
in diagnosis and management. The format of each article defines the dis- ripheral tissues regardless of the source [1]. Thyrotoxicosis is a condition
ease or clinical presentation to be reviewed, provides an overview of the with a spectrum of severity that ranges from subclinical to overt thyro-
extent of what we currently understand, and finally discusses pearls and toxicosis; at its most extreme, with severe end organ dysfunction, is thy-
pitfalls using a question-and-answer format. This article will discuss roid storm [2].
thyroid storm. This condition's low prevalence but high morbidity and Thyroid storm was first defined in 1926 as a crisis of exophthalmic
mortality, as well as its variable atypical presentations and challenging goiter [3], seen as an exacerbation of Graves' disease with exaggerated
diagnosis, makes it a high-risk and low-prevalence disease. findings of hyperthyroidism. Although thyroid storm most commonly
occurs in patients with untreated or uncontrolled Graves' disease [4],
there are a variety of etiologies, and it can affect patients with previously
unrecognized hyperthyroidism [5]. The modern definition of thyroid
storm is a life-threatening condition characterized by (1) exaggerated
⁎ Corresponding author.
signs and symptoms of thyrotoxicosis and (2) evidence of multiorgan
E-mail address: brit.long@yahoo.com (B. Long).
1
Present Address: 3551 Roger Brooke Dr. Fort Sam Houston, TX 78234, USA.
decompensation [5]. Patients typically demonstrate some alteration in

https://doi.org/10.1016/j.ajem.2023.03.035
0735-6757/Published by Elsevier Inc.

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S. Farooqi, S. Raj, A. Koyfman et al. American Journal of Emergency Medicine 69 (2023) 127–135

mental status, along with hyperpyrexia and cardiovascular dysfunction Thyrotoxicosis results from any cause of excessive thyroid hormone
[2-4]. This pathologic state often arises in the presence of a precipitating concentration, with thyroid storm representing an extreme manifesta-
event, which can include interruption in drug therapy for hyperthyroid- tion of thyrotoxicosis [10]. However, the process by which thyroid
ism or medication non-adherence, infection, thyroid/non-thyroid sur- storm arises is not as well understood. Thyroid storm may arise from a
gery, parturition, trauma, exposure to exogenous iodine, or use of a heightened tissue response to thyroid hormone, enhanced binding to
medication such as amiodarone [5-10]. To add to the complexity of thyroid receptors, decreased affinity of thyroid-binding proteins for thy-
this disease process, 24–43% of cases have no identifiable trigger [5,11]. roid hormone, and/or an abrupt increase in free thyroid hormone avail-
ability [5,7,10,15]. Absolute values of circulating thyroid hormone may
1.2. Pathophysiology be similar in patients with thyroid storm and in those with uncompli-
cated hyperthyroidism [11]. Therefore, the rate of thyroid hormone
The hypothalamus produces thyrotropin-releasing hormone (TRH) level increase is likely more important than the absolute values
which stimulates the anterior pituitary to release thyroid-stimulating themselves [5,11,16].
hormone (TSH) [11]. TSH then binds to specific receptors on the thyroid The loss of homeostatic interaction between thyroid hormone and
gland to prompt a cascade of intracellular processes to generate thyrox- the sympathoadrenal system is also implicated in thyroid storm [17].
ine (T4) and triiodothyronine (T3). This cascade begins with the In hyperthyroid states, increased beta-adrenergic receptor density and
transport of iodide into the thyroid follicular cell. Thyroid peroxidase upregulation of L-type dihydropyridine-sensitive calcium channels
(TPO) then iodinates tyrosine residues on thyroglobulin to form and plasma membrane calcium ATP-ase lead to enhanced responsive-
monoiodotyrosine (MIT) and diiodotyrosine (DIT) molecules. The cou- ness to endogenous catecholamines [18]. This results in tachycardia, in-
pling of one MIT and one DIT molecule forms triiodothyronine (T3), creased cardiac contractility, and rise in metabolic demand that are
and the coupling of two DIT molecules forms thyroxine (T4)10. T3 is central to the cardiovascular manifestations of thyroid storm [18].
the more potent, biologically active thyroid hormone [12]. Approxi-
mately 10–20% of circulating T3 is secreted by the thyroid gland, but 1.3. Epidemiology
the remainder is the result of peripheral conversion of T4 to T3 via 5′-
deiodinases (D1 and D2) [13]. In a normal state, 99% of T3 and T4 is The prevalence of hyperthyroidism in the U.S. is 1.2% [19]. The inci-
bound to thyroid binding globulin (TBG), transthyretin, and albumin; dence of thyroid storm ranges between 0.20 and 0.76 per 100,000 per-
free hormone is available for uptake by tissues [14]. T3 and T4 possess sons per year, with an incidence of 4.8–5.6 per 100,000 hospitalized
negative feedback control on both the hypothalamus and the pituitary patients [6,7,20]. Of those hospitalized with thyrotoxicosis in the U.S.,
[11] (Fig. 1). thyroid storm is diagnosed in 16% [20,21]. Prior studies suggested a

Fig. 1. Thyroid hormone activity and feedback loops. https://commons.wikimedia.org/wiki/File:1813_A_Classic_Negative_Feedback_Loop.jpg.

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S. Farooqi, S. Raj, A. Koyfman et al. American Journal of Emergency Medicine 69 (2023) 127–135

mortality rate ranging between 8 and 30% for those with thyroid storm while blood cultures and chest radiograph should be obtained in those
[6], but more recent literature suggests the rate is 1.2%–3.6% in the U.S., with concern for infection. If toxic ingestion is suspected, acetamino-
which may be due to high-quality, aggressive intensive care [20]. Thyroid phen and salicylate levels should be obtained.
storm occurs most commonly in patients with underlying Graves' disease Diagnosis of thyroid storm is based on the presence of severe signs
and those who are non-adherent with treatment for hyperthyroidism and symptoms with evidence of thyrotoxicosis. There is no single set
[11,22,23]. The majority of cases occur in women, with an average age of clinical criteria, laboratory testing, or thyroid hormone threshold
of 50 years [20]. The most common cause of death in thyroid storm is that will establish a diagnosis of thyroid storm, though there are two
multisystem organ failure, followed by congestive heart failure, respira- scoring systems that may assist, including the Burch-Wartofsky scale
tory failure, dysrhythmia, disseminated intravascular coagulation (DIC), and the Japan Thyroid Association criteria. In 1993, Burch and
gastrointestinal (GI) perforation, hypoxic brain injury, and sepsis [4,6]. Wartofsky formulated a novel scoring system in an effort to standardize
the diagnosis (Table 2) [4,6,15]. The other most often-used set of diag-
2. Discussion nostic criteria was proposed by the Japan Thyroid Association in 2012
(Table 3) [6]. Unlike Burch and Wartofsky's scale, thyrotoxicosis is a pre-
2.1. Presentation requisite condition when applying the Japan Thyroid Association diag-
nostic criteria.
Thyroid hormone receptors are ubiquitous in the human body, and
deiodinases that are responsible for converting T4 to T3 are expressed 2.3. ED management
in every organ system. This, in addition to the adrenergic hyperactivity
of a profound thyrotoxic state, accounts for the vast array of clinical With the high morbidity and mortality associated with thyroid
manifestations of thyroid storm. The most common of these are sum- storm, emergent resuscitation while determining and treating the un-
marized in Table 1, with hyperpyrexia, cardiovascular dysfunction, derlying trigger is necessary. Infection is the second most common trig-
and altered mental status present in almost all cases [5,7]. ger for thyroid storm, and thus early administration of broad-spectrum
In addition to the presentations above, there exist case reports of antibiotics is recommended [4]. Management of thyroid storm includes
thyroid storm presenting as a multitude of other disease entities, includ- cardiovascular stabilization; administration of steroids, thionamides, io-
ing severe abdominal pain with peritonitis, status epilepticus, rhabdo- dine, and cholestyramine; and treatment of hyperthermia and agitation
myolysis, hypoglycemia, lactic acidosis, and DIC [24–27]. [5,7,30]. Beta blockers are recommended as well in the majority of pa-
tients with thyroid storm. Beyond the insensible fluid losses from
2.2. ED evaluation fever, patients with thyroid storm often have vomiting and diarrhea re-
sulting in severe dehydration. However, IV fluids should be
Thyroid storm poses a diagnostic challenge due to its varied and
nonspecific presentation. Evaluation including complete blood count Table 2
(CBC), electrolytes, renal and liver function, creatine kinase, coagulation Burch-Wartofsky point scale for diagnosis of thyroid storm.15
panel, TSH, free T4 and T3, electrocardiogram (ECG), and urinalysis are Criteria Points
recommended. Although laboratory testing will not diagnose thyroid
Thermoregulatory dysfunction
storm in isolation, it serves as an important adjunct. TSH is most com- Temperature (°C) 5
monly suppressed with elevated T4 and T3 levels, although critical ill- 37.2–37.7 10
ness itself may lower T3 levels [28]. Furthermore, there is often no 37.8–38.3 15
difference in thyroid hormone levels between patients with thyroid 38.4–38.8 20
38.9–39.3 25
storm and those with uncomplicated hyperthyroidism [5,7,11,15]. Leu- 39.4–39.9 30
kocytosis is common and can be present with or without underlying in- ≥40.0
fection [5]. Patients with thyroid storm may also have decreased renal Cardiovascular
function, liver function test (LFT) derangements, hypercalcemia due to Tachycardia (bpm) 5
90–109 10
increased bone resorption, or abnormal serum glucose (usually hyper-
110–119 15
glycemia and rarely hypoglycemia) [5,10,27,29]. Further testing is 120–129 20
based on clinical presentation. Patients presenting with altered mental 130–139 25
status should receive head computed tomography (CT) noncontrast, ≥140
Atrial fibrillation
Absent 0
Table 1 Present 10
Common presentations of thyroid storm.5 Congestive heart failure
Absent 0
System Signs and symptoms
Mild 5
Systemic • Fever is nearly universal (may reach 104-106F) Moderate 10
• Diaphoresis Severe 15
• Weight loss Gastrointestinal dysfunction
Cardiovascular • Tachycardia (sinus tachycardia, atrial fibrillation, ventricular Absent 0
fibrillation) Moderate (diarrhea, abdominal pain, nausea/vomiting) 10
• Systolic heart failure with pulmonary and peripheral edema Severe (jaundice) 20
• High-output heart failure (vasodilated, warm peripheral Central nervous system disturbance
extremities) Absent 0
• Wide pulse pressure with systolic hypertension Mild (agitation) 10
Gastrointestinal • Nausea, vomiting, diarrhea Moderate (delirium, psychosis, extreme lethargy) 20
• Abdominal pain Severe (seizure, coma) 30
• Jaundice, hepatic injury/failure Precipitating event
Neurologic • Tremor, restlessness Absent 0
• Agitation, anxiety, delirium, emotional lability, hallucinations Present 10
• Confusion, stupor, coma Total Score
Other • Goiter ≥45 Thyroid storm
• Scar from partial thyroidectomy 25–44 Impending storm
• Exophthalmos <25 Storm unlikely

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Table 3
Japanese Thyroid Association diagnostic criteria for thyroid storm.4,6

Prerequisite for diagnosis

Presence of thyrotoxicosis with elevated levels of free triiodothyronine (FT3) or free thyroxine (FT4)
Symptoms
1. Central nervous system (CNS) manifestations: restlessness, delirium, mental aberration/psychosis, somnolence/lethargy, psychosis (≥1 on the Japan Coma Scale or ≤14 on
the Glasgow Coma Scale)
2. Fever (≥38 °C)
3. Tachycardia: ≥130 beats per minute or heart rate ≥ 130 in atrial fibrillation
4. Congestive heart failure (CHF): pulmonary edema, moist rales over more than half of the lung field, cardiogenic shock, or class IV by the New York Heart Association or
≥Class III in the Killip classification
5. Gastrointestinal (GI)/hepatic manifestations: nausea, vomiting, diarrhea, or a total bilirubin ≥3.0 mg/dL

Grade of thyroid storm (TS) Combinations of features Requirements for diagnosis

TS1 (definite thyroid storm) First combination Thyrotoxicosis + at least 1 CNS manifestation + fever, tachycardia, CHF, or GI/hepatic manifestation
Alternate combination Thyrotoxicosis + at least 3 combinations of fever, tachycardia, CHF, or GI/hepatic manifestations
First combination Thyrotoxicosis + a combination of 2 of the following: fever, tachycardia, CHF, or GI/hepatic manifestations
TS2 (suspected thyroid storm) Alternate combination Patients who met the diagnosis of TS1 except that serum FT3 or FT4 level are not available

Exclusion and provisions:

Cases are excluded if other underlying diseases clearly causing any of the following symptoms: fever (i.e., pneumonia and malignant hyperthermia), impaired consciousness
(i.e., psychiatric disorders and cerebrovascular disease), heart failure (i.e., acute myocardial infarction), and liver disorders (i.e., viral hepatitis and acute liver failure).
Therefore, it is difficult to determine whether the symptom is caused by thyroid storm or simply a manifestation of an underlying disease; the symptom should be regarded as
being due to a thyroid storm that is caused by these precipitating factors. Clinical judgment in this matter is required.

administered with caution, with frequent assessments of fluid- 3. Pearls and pitfalls
responsiveness due to concern for decompensated heart failure and
fluid overload. If the patient appears dehydrated on history and exami- 3.1. What are common and uncommon triggers of thyroid storm?
nation, IV fluids are recommended [5,7,30]. Vasopressors may be needed
to improve peripheral perfusion. Beta blockers may be administered in There are many potential triggers of thyroid storm, and diagnosing
thyroid storm to manage adrenergic hyperactivity, often manifested as and managing the trigger are essential to improving patient outcomes.
profound tachycardia. Propranolol has traditionally been used due to its Abrupt discontinuation of antithyroid medications and infection are
ability to decrease peripheral conversion of T4 to T3. Of note, there is a the most common underlying triggers [5,6,10,15]. However, when
risk of beta blockers precipitating cardiogenic shock in those with severe,
overt heart failure. However, if there is no evidence of severe heart failure, Table 4
beta blockers are recommended. If beta blockers are administered, short- Precipitants of thyroid storm.6,40
acting intravenous agents like esmolol are preferred [4].
Most common • Underlying Graves' disease
Steroids play an integral role in blocking T4 release from the thyroid causes • Infection
and conversion of T4 to T3, and they also treat any concomitant adrenal • Treatment non-adherence, or interrupted treatment, with
insufficiency [30,31]. Hydrocortisone 300 mg IV loading dose followed antithyroid medications
by 100 mg every 8 h is recommended, though dexamethasone (8 mg/ Other common • Amiodarone
causes • Emotional stress
day) may also be used [4,30].
• Non-thyroid surgery
Thionamides such as propylthiouracil (PTU) and methimazole re- • Preeclampsia
duce new thyroid hormone synthesis. While both inhibit TPO, PTU • Pregnancy/labor
also has the added benefit of inhibiting peripheral conversion of T4 to • Psychosis
• Trauma
T3 [4,30]. PTU is the preferred agent in the first trimester of pregnancy
Rarer causes • Thyroid surgery (previously a common trigger but is now rare
due to its lower risk of teratogenicity [32]. However, methimazole given advances in adequate preoperative preparation)
may be safer overall with fewer adverse effects compared to PTU and • Postpartum thyroiditis
is recommended in the second and third trimesters of pregnancy • Struma ovarii
[4,33]. Inorganic iodine inhibits new thyroid hormone production and • Molar pregnancy
• Toxic multinodular goiter (most common in low- and
blocks release of preformed T3 and T4 from thyroglobulin [4,34,35]. Io-
middle-income countries due to associated dietary iodine
dine should be given 1 h after the thionamide to avoid it being used as a deficiency)
substrate for new thyroid hormone production [30]. Cholestyramine • Metastatic thyroid cancer
may be used, as it binds thyroid hormone in the intestinal system and • Radioiodine exposure or treatment
reduces enterohepatic absorption [36-38]. • Thyroid hormone overdose (either intentional or accidental)
• Treatment with checkpoint inhibitors
Patients may demonstrate severe hyperthermia and agitation. • Vigorous palpation of the thyroid gland
Hyperthermia is primarily due to increased tissue heat generation and • Post-viral thyroiditis
results in increased cardiac demand and end organ damage. Manage- • Suppurative thyroiditis (more common in the immunocom-
ment includes acetaminophen, along with peripheral cooling tech- promised)
• Salicylate toxicity
niques (i.e., ice packs in groin/axillae, cooling blankets) [4,5,19].
• Organophosphate toxicity
However, non-steroidal anti-inflammatory drugs or salicylates should • Neurotoxins
be avoided [5,39]. Agitation may also worsen hyperthermia. Options • Cytotoxic chemotherapy (i.e., interferon)
for treatment include benzodiazepines or olanzapine [4]. • Burns
Early consultation with critical care, endocrinology, and potentially • Myocardial infarction
• Pulmonary embolism
the cardiology specialists is an integral component of management. • Stroke
Patients with thyroid storm should be admitted to an intensive care • Diabetic ketoacidosis
unit. Depending on severity of illness and end organ dysfunction, this • Hypoglycemia
may require transfer to a facility that is capable of managing advanced • H1N1 infection
• Intense exercise
heart, renal, and/or liver failure.

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considering precipitants of thyroid storm, 25%–43% of patients will not presenting symptoms [41]. A condition called apathetic thyrotoxi-
have an identifiable trigger [5,11]. Table 4 lists both the most common cosis, or masked hyperthyroidism, has been described in older
triggers and rarer precipitants of thyroid storm. patients, characterized by apathy, depression, profound weight
loss, muscle weakness and wasting, ptosis, dry skin, mild tachycar-
3.2. When should thyroid storm be considered? dia, and often congestive heart failure [42]. Although it may present
atypically, apathetic thyrotoxicosis remains just as potentially
Due to the variety of presenting signs and symptoms, rarity of thy- fatal [3]. In these cases, thyroid studies may provide helpful infor-
roid storm, and severe morbidity and mortality, diagnosis is vital but mation to establish a diagnosis. Of the signs and symptoms that
can be challenging. One of the main components of diagnosis is first are commonly associated with thyrotoxicosis, elderly patients
considering the disease. Thyroid storm should be considered in any pa- often present with atrial fibrillation, shortness of breath, and weight
tient with known hyperthyroidism plus any acute illness/deterioration, loss [41].
new-onset atrial fibrillation and/or dilated cardiomyopathy, new-onset
delirium/psychosis plus abnormal vital signs, hyperthermia (tempera- 3.3. What conditions may mimic thyroid storm?
ture above ∼40 °C), sepsis without a focus of infection (i.e., distributive
shock of unknown etiology), and advanced age, as elderly patients Thyroid storm is a difficult diagnosis, in part because there are mul-
may present with apathetic thyroid storm. tiple conditions which mimic it. Table 5 describes several of these con-
Elderly patients warrant special consideration. The majority of ditions and considerations that can assist in differentiating them from
thyrotoxic patients over 61 years have fewer than three classic thyroid storm.

Table 5
Thyroid storm mimics [43-52].

Diagnosis Considerations

Acute pulmonary • Typically occurs in the context of established structural cardiac disease; history of coronary artery disease and/or myocardial infarction
edema • History may include paroxysmal nocturnal dyspnea, orthopnea, exertional dyspnea, peripheral edema, decreased exercise tolerance
• Examination may reveal rales, wheezing, peripheral edema, dyspnea, hypoxia, S3 gallop, jugular venous dissension may be present on examination
• Chest x-ray with pulmonary venous congestion, interstitial edema, and/or cardiomegaly; point-of-care ultrasound with sonographic B lines
• Treatment includes airway management with supplemental oxygen and noninvasive positive pressure ventilation as needed, preload and afterload
reduction with nitroglycerin, diuresis
Aortic dissection • History may include sudden onset tearing/ripping chest pain radiating to between the scapulae, sense of impending doom, abdominal pain, back
pain, syncope, stroke symptoms, history of hypertension or collagen vascular disorders, history of cocaine or amphetamine use, history of cardiac
surgery
• Examination may reveal neurological or pulse deficits, aortic insufficiency murmur, hypertension, hypotension, shock
• Imaging with CT with IV contrast is diagnostic evaluating for dissection and false lumen; chest x-ray may demonstrate pleural effusion, tracheal
deviation, abnormal aortic contour, and/or widened mediastinum; point-of-care ultrasound may be used to demonstrate false lumen and evaluate
for tamponade
• Treatment includes resuscitation, consult surgical specialist, provide heart rate control and blood pressure control
Alcohol withdrawal • History of chronic alcohol use with recent discontinuation or reduction, nausea, vomiting, headache, appetite loss
• Examination may reveal tremor, agitation, tachycardia, hypertension, diaphoresis, insomnia, fever, anxiety, seizures, psychosis
• Evaluate for metabolic derangement, toxic alcohol ingestion, drug ingestion, primary seizure disorder, intracranial hemorrhage, and/or infection
• Treatment includes benzodiazepines, phenobarbital, seizure management
Neuromuscular • History may reveal a hereditary component (i.e., hypokalemic periodic paralysis), malaise, weakness, cramps, paresthesias
disease • Examination may reveal fasciculations, paralysis, tetany
• Evaluation should include electrolytes and ECG
• Treatment includes correction of metabolic derangements, intubation and mechanical ventilation as needed, neurology consultation
Pheochromocytoma • History includes episodes of headache, flushing, diaphoresis
• Examination may reveal severe hypertension, tachycardia
• Testing includes 24-h urine assay, plasma fractionated metanephrines
• Treatment includes IV phentolamine, resection
Serotonin syndrome • History of serotonergic medication use
• Examination may reveal altered mental status, agitation, dysautonomia, muscle rigidity, tremor, hyperreflexia, myoclonus, ataxia
• Diagnosis is based on history and examination; electrolytes, creatine kinase, ECG, and evaluation for metabolic acidemia can assist
• Treatment includes discontinuation of offending medication, benzodiazepines, supportive care, mechanical ventilation as needed
Salicylate toxicity • History includes ingestion, either accidental or intentional
• Examination may reveal altered mental status, tachypnea, fever, nausea, vomiting, tinnitus, hearing loss, diaphoresis, agitation, lethargy, confusion,
seizure, coma
• Evaluation includes serial salicylate levels, electrolytes, renal function, acetaminophen level, determination of acid-base status, ECG
• Treatment includes volume repletion, metabolic derangement correction, GI contamination as indicated, reduction in total salicylate burden via
urinary alkalinization with sodium bicarbonate infusion, and hemodialysis in refractory/severe cases
Septic shock • History includes focal symptoms concerning for an infectious source with severe inflammatory response
• Examination may reveal fever or hypothermia, tachycardia, hypotension, delirium, disorientation, confusion, pallor, diaphoresis, hypoperfusion,
tachypnea, respiratory failure
• Evaluation should be based on the underlying site of infection, CBC, lactic acid, evaluation for end organ injury, urinalysis, chest x-ray, ECG, blood and
urine cultures; further testing (e.g., lumbar puncture and CT, determined by suspected site of infection)
• Treatment includes antibiotics, volume repletion, vasopressors as needed
Sympathomimetic • History includes cocaine, amphetamine, PCP, or LSD use
toxicity • Examination includes tachycardia, diaphoresis, chest pain, mental status changes, mydriasis, hyperthermia
• Evaluation includes ECG to evaluate for dysrhythmias, electrolytes, creatine kinase, coagulation studies, renal and liver function, troponin
• Treatment includes benzodiazepines, aggressive cooling for hyperthermia, fluids
Psychiatric illness • History includes a psychiatric disorder as primary presenting issue, typically occurs in the context of established related medical/psychiatric history
• Examination may reveal response to internal stimuli, hallucinations, delusions, flight of ideas, grandiose thinking, magical thinking, disordered
thoughts, pressured speech, no focal neurological deficits, anger, sadness, agitation, paranoia, no findings suggestive of organic disease
• Evaluation should include electrolytes, TSH, pregnancy test, ECG, acetaminophen and aspirin levels, neuroimaging if indicated, lumbar puncture if
indicated
• Treatment includes de-escalation, behavior control if necessary, maintenance of a safe environment, psychiatry consultation

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3.4. What are essential components of the evaluation, and where can implementation of timely treatment. One retrospective study found
emergency clinicians go wrong? that 15% of patients with diagnosed thyroid storm suffered cardiac ar-
rest prior to ICU admission [40]. This may delay consultation of critical
The first pitfall in the diagnosis of thyroid storm is failing to consider care specialists or transfer to a facility equipped with advanced thera-
the diagnosis. The condition has a variety of nonspecific signs and symp- pies for refractory cases.
toms and is rare, making diagnosis challenging. Laboratory thyroid as- Cardiac stabilization and resuscitation are integral components of
sessment can assist. However, the results may be misinterpreted, and therapy. Beyond the insensible fluid losses from high fever, patients
they may be similar to patients with uncomplicated hyperthyroidism. with thyroid storm often have copious vomiting and diarrhea resulting
TSH specifically can be misleading, as some patients will have thyroid in severe dehydration [5,10]. The decision for resuscitation with IV
storm due to TRH release stimulating TSH production. TSH release can fluids should be based on the clinical evaluation [5]. If the patient ap-
also be stimulated by pituitary tumors [4]. In both of these scenarios, pears dehydrated, fluids should be administered [5]. However, IV fluids
TSH would be elevated. TSH can also be low in patients on should be administered carefully, with frequent assessments of fluid re-
levothyroxine, amiodarone, steroids, metformin, carbamazepine, or do- sponsiveness and with caution if concomitant signs of decompensated
pamine agonists [10]. heart failure are present [5].
As discussed, several clinical score systems (the Burch-Wartofsky Cardiac dysfunction can be profound in thyroid storm. Beta blockers
scoring system and the Japan Thyroid Association diagnostic criteria) are typically considered a key component of therapy. Sinus tachycardia
have been created to assist in the diagnosis of thyroid storm [4,13]. and atrial fibrillation are the most common tachyarrhythmias, with
However, clinicians should not solely rely on these systems for diagno- heart rates >150 and the presence of atrial fibrillation associated with
sis. The Burch-Wartofsky scoring system assigns points based on the de- higher mortality [4]. Propranolol is often considered the beta blocker
gree of impairment in several systems, but this score is not a definitive of choice in thyroid storm due to its ability to decrease peripheral con-
means of diagnosis [12]. For example, a patient with a score > 45 points version of T4 to T3 and is recommended by the American Thyroid Asso-
may have sepsis, rather than thyroid storm. A second scoring system ciation [14]. However, beta blockers may worsen shock in those with
published by the Japan Thyroid Association requires thyrotoxicosis as overt or severe heart failure, and the tachycardia is not the primary
a prerequisite diagnosis prior to assessing for thyroid storm [6]. A retro- issue in thyroid storm but may serve as a compensatory response. Ulti-
spective cohort study found that the Burch-Wartofsky scoring system is mately, just as fluid resuscitation should be performed with caution in
more sensitive and less specific for the diagnosis of thyroid storm when patients with evidence of congestive heart failure, so should administra-
compared with the Japan Thyroid Association criteria [21]. Neither diag- tion of beta blockers. With the risk of developing cardiogenic shock with
nostic tool is thought to be superior, but the scores can provide a frame- beta blocker administration, especially in patients with low EF, the clini-
work by which clinicians can consider the diagnosis of thyroid storm. cian should evaluate for evidence of severe heart failure and consider
Current recommendations are to apply both when considering a diag- use of point of care ultrasound (POCUS) with echocardiogram to assess
nosis of thyroid storm [4,19]. the patient's cardiac function prior to beta block administration. If the
In conclusion, diagnosing thyroid storm is based on considering the patient demonstrates evidence of severe heart failure on evaluation or
disease using a combination of history and examination findings, with depressed EF on POCUS, beta blockers may cause further hemodynamic
laboratory assessment providing supporting evidence for the diagnosis. decompensation. However, if the patient does not demonstrate evi-
The diagnosis should not be based on laboratory assessment alone, al- dence of severe or overt heart failure or a severely depressed EF, a
though a low TSH and elevated T3/T4 suggest the disease in the appro- beta blocker should be administered. Current literature advocates for
priate clinical setting [5]. Other laboratory findings that support the the use of short acting intravenous beta blockers like esmolol [4,53].
diagnosis include hyperglycemia, hypercalcemia, leukopenia, leukocy- The Japan Thyroid Association and Japan Endocrine Society Task Force
tosis, or abnormal hepatic studies [5,10,27,29]. Lastly, the ECG is an inte- cite increased mortality rates with propranolol versus esmolol or
gral component of the evaluation, as tachydysrhythmias such as atrial landiolol (super short-acting beta blocker used in Japan) in those with
fibrillation are common findings in thyroid storm. Indeed, current liter- thyroid storm [4]. Esmolol has a significantly shorter half-life compared
ature suggests that atrial fibrillation occurs in 10–35% of patients with to propranolol, which may be beneficial in thyroid storm, as the infusion
thyroid storm [10,53]. may be rapidly discontinued if decompensation occurs [4,30]. The elim-
ination half-life (rate of decline in drug concentration related to metab-
3.5. What are essential components of the management, and where can olism) of propranolol is 2.3 h, compared to 9 min for esmolol. Once the
emergency clinicians go wrong? infusion is stopped, the effect of esmolol will have completely disap-
peared by 18 minutes [4]. The goal heart rate once beta blockers are ad-
By definition, thyroid storm is characterized by rapid deterioration ministered is less than or equal to 130 beats per minute [4]. Patients
of multiple organ systems. As such, treatment must be timely, aggres- presenting with unstable dysrhythmias may require cardioversion,
sive, and involve a multidisciplinary and collaborative approach with while those in cardiogenic shock may require vasopressors and
critical care and endocrinology specialists, as well as clinical pharma- inotropes. Severe hemodynamic instability and cardiogenic shock may
cists when available. Resuscitation of patients in thyroid storm can be require even more advanced therapies including therapeutic plasma
complex, with simultaneous attention paid to systemic symptoms and exchange, intra-aortic balloon pump, or extracorporeal membrane
signs (high fever, dehydration, shock), organ-specific manifestations oxygenation (ECMO) [4,7,40,53].
(cardiac, neurologic, psychiatric, GI/hepatic), identification and treat- Steroids serve the dual purpose of preventing adrenal insufficiency in
ment of potential triggers, and reduction of thyroid hormone secretion thyroid storm as well as reducing peripheral conversion of T4 to T3. Even
and production [5,7,30]. The majority of these steps can occur concur- though thyroid storm is often described as a state of hyperadrenergic
rently, with several exceptions discussed in the following content. stimulation, prolonged stimulation of the hypothalamus-pituitary-
Given these complexities, there are a number of potential pitfalls for adrenal axis may ultimately lead to compromised adrenal functional
emergency clinicians. Firstly, any delay in considering an already reserve [31]. Hydrocortisone is the first line recommended steroid. If
difficult-to-make diagnosis with a multitude of potential mimics will this is not available, dexamethasone may be administered [4].
delay treatment initiation. Secondly, emergency clinicians may fail to Treatment aimed at reduction of thyroid hormone secretion and
appreciate how rapidly these patients may decompensate, even with production may need to begin even before thyroid tests have resulted.

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Thionamides such as PTU and methimazole reduce new thyroid hor- be administered orally or rectally. If anaphylactic to iodine, patients
mone synthesis. While they both inhibit TPO, PTU also has the added can be given lithium instead, which will impede T3 and T4 synthesis
benefit of inhibiting peripheral conversion of T4 to T3 and has been and potentially block release of preformed hormone from binding pro-
found to decrease thyroid hormone levels more rapidly than teins as well [4,5,10,57]. However, use of lithium is limited by the poten-
methimazole [19]. Use of methimazole has been associated with tial for renal and neurologic toxicity.
fewer adverse effects in Japanese populations, including reduced hepa- Bile acid sequestrants reduce thyroid hormone levels and interfere
totoxicity, and is recommended over PTU in non-pregnant patients by with enterohepatic reabsorption and recycling of thyroid hormone.
the Japan Thyroid Association [4]. Methimazole is recommended in These may act as adjunctive therapies, particularly in those who do
pregnant patients with thyroid storm in the second and third trimester, not tolerate thionamides. The most commonly utilized agent is chole-
though PTU is recommended in the first trimester [19,54]. Of note, liter- styramine [36-38].
ature has not found a mortality difference between PTU and For hyperthermia, acetaminophen can be administered, along with
methimazole in thyroid storm [4]. Both can be administered either implementation of peripheral cooling techniques (ice packs in groin/ax-
orally or rectally, although the latter may require special formulation illae, cooling blankets) [4]. Salicylates and NSAIDs should be avoided, as
by a hospital pharmacist [5,10,55]. Options are limited when the patient they can increase circulating free T4 levels [5,39].
is unable to tolerate oral intake. The rectal route may be utilized in this Neuropsychiatric manifestations of thyroid storm are potentially
setting, or a nasogastric tube may be placed for administration. IV broad [10]. Restlessness, delirium, and psychosis can be treated with an-
methimazole is not commercially available in the U.S., although it tipsychotics like risperidone or olanzapine, or benzodiazepines [4,58].
could theoretically be formulated through combination of methimazole Haloperidol may precipitate thyroid storm, albeit by an unclear mecha-
powder and normal saline [5,56]. This may require close communica- nism, so it should be avoided if possible [4]. For seizures and status ep-
tion with ED or inpatient pharmacists when available to determine ilepticus, benzodiazepines remain the first line treatment, followed by
best available options. fosphenytoin and phenobarbital [4]. Although not mentioned specifi-
Inorganic iodine inhibits new thyroid hormone production and cally within thyroid storm literature, there do not appear to be any con-
blocks release of preformed T3 and T4 from thyroglobulin. It is typically traindications to the administration of levetiracetam, which may be an
recommended that iodine be given 1 h after the thionamide to avoid it optimal second-line agent given its widespread availability in most EDs.
being used as a substrate for new thyroid hormone production [14,30]. Recommended routes and doses of commonly used medications for
Of note, the Japan Thyroid Association states that iodine may be admin- management of thyroid storm in the ED are outlined in Table 6, and
istered with the thionamide in the setting of Graves' disease compli- Table 7 lists pearls and considerations in the evaluation and manage-
cated by thyroid storm, though this is controversial [4]. Iodine can also ment of thyroid storm.

Table 6
Medications used in thyroid storm.

Class Medication Mechanism of action Oral route Rectal route Intravenous route Considerations

Thionamides Propylthiouracil Decrease new thyroid hormone Loading dose of 400–600 mg Preferred agent in early pregnancy
synthesis, inhibit peripheral 500–1000 mg every 6 ha
conversion of T4 to T3 followed by
250 mg every 4 h
Methimazole Decrease new thyroid hormone Loading dose of 20–40 mg 10–30 mg every 6 ha Fewer overall adverse effects, reduced
synthesis 40 mg followed by every 6 ha hepatotoxicity
20 mg every 4 h
Iodine Potassium Decrease new thyroid hormone 5 drops every 6 h 250–500 mg To be given 30 min to 1 h after
iodide (SSKI) synthesis, block release of every 6 h administration of thionamides to prevent
preformed thyroid hormone from its use as a substrate for new thyroid
thyroglobulin hormone production
Lugol's Solution Decrease new thyroid hormone 8 drops every 6 h 80 drops per To be given 1 h after administration of
synthesis, block release of day/5–10 thionamides to prevent its use as a
preformed thyroid hormone from drops every substrate for new thyroid hormone
thyroglobulin 6h production
Lithium Block release of preformed 300 mg every Alternative to SSKI or Lugol's solution in
thyroid hormone from 6–8 h patients with anaphylaxis to iodine
thyroglobulin
Steroids Hydrocortisone Prevent adrenal insufficiency, 300 mg loading dose,
inhibit peripheral conversion of followed by 100 mg
T4 to T3 every 8 h
Dexamethasone Prevent adrenal insufficiency, 2 mg every 6 h up to
inhibit peripheral conversion of 8 mg/day
T4 to T3
Beta blockers Propranolol Adrenergic blockade, inhibit 60–80 mg PO 0.5–1 mg slow IV May lead to cardiogenic shock and should
peripheral conversion of T4 to T3 every 4 h or push, then 1–2 mg at be avoided in patients with CHF
80–120 mg every 15-min intervals
6h
Esmolol Adrenergic blockade Bolus 250–500 μg/kg
followed by infusion
rate of 50–100
μg/kg/min
Bile acid Cholestyramine Decrease reabsorption of thyroid 4 mg every 6 h Adjunctive therapy
sequestrants hormone from enterohepatic
circulation
a
Rectal (retention enema or suppository) and IV formulations that are not readily available in the U.S. and would need to be specially prepared by a pharmacist.

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Table 7
Thyroid storm pearls.

-Thyroid storm is a life-threatening condition characterized by exaggerated signs and symptoms of thyrotoxicosis along with evidence of multiorgan decompensation.
-A variety of underlying triggers may result in thyroid storm, including infection, medication noncompliance, thyroid/non-thyroid surgery, parturition, trauma, exposure to
exogenous iodine, or use of amiodarone. However, up to 43% of cases have no identifiable trigger.
-Several conditions may mimic thyroid storm, including acute pulmonary edema, aortic dissection, alcohol withdrawal, neuromuscular disease, pheochromocytoma, serotonin
syndrome, salicylate toxicity, septic shock, sympathomimetic toxicity, and psychiatric illness.
-Patients most commonly present with fever, diaphoresis, tachycardia, gastrointestinal signs and symptoms, and neurologic issues including alteration in mental status; heart
failure may be present.
-Consider thyroid storm in any patient with new-onset atrial fibrillation or CHF, new-onset psychosis or delirium, sepsis without a focus of infection, or in any undifferentiated
critically ill patient.
-Utilize the Burch-Wartofsky point scale and Japan Thyroid Association diagnostic criteria in conjunction with history and examination to assist in diagnosis.
-Laboratory analysis may demonstrate end organ injury, but do not rely on thyroid studies alone to establish a diagnosis.
-ED treatment includes diagnosing and managing the trigger; hemodynamic and end organ stabilization; administration of steroids, thionamides followed by iodine 1 h later,
and cholestyramine; and treatment of hyperthermia and agitation. Beta blockers should also be administered if there is no evidence of severe heart failure.

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