1/19/2019 Thyroid Storm: Background, Pathophysiology, Etiology

This site is intended for healthcare professionals

Thyroid Storm
Updated: Feb 18, 2018
Author: Madhusmita Misra, MD, MPH; Chief Editor: Robert P Hoffman, MD more...

OVERVIEW

Background
Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state
induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis. Thyroid
storm may be the initial presentation of thyrotoxicosis in undiagnosed children, particularly in
neonates. The clinical presentation includes fever, tachycardia, hypertension, and neurological and GI
abnormalities. Hypertension may be followed by congestive heart failure that is associated with
hypotension and shock. Because thyroid storm is almost invariably fatal if left untreated, rapid
diagnosis and aggressive treatment are critical. Fortunately, this condition is extremely rare in
children.

Diagnosis is primarily clinical, and no specific laboratory tests are available. Several factors may
precipitate the progression of thyrotoxicosis to thyroid storm. In the past, thyroid storm was commonly
observed during thyroid surgery, especially in older children and adults, but improved preoperative
management has markedly decreased the incidence of this complication. Today, thyroid storm occurs
more commonly as a medical crisis rather than a surgical crisis.

Pathophysiology
Thyroid storm is a decompensated state of thyroid hormone–induced, severe hypermetabolism
involving multiple systems and is the most extreme state of thyrotoxicosis. The clinical picture relates
to severely exaggerated effects of THs due to increased release (with or without increased synthesis)
or, rarely, increased intake of TH.

Heat intolerance and diaphoresis are common in simple thyrotoxicosis but manifest as hyperpyrexia in
thyroid storm. Extremely high metabolism also increases oxygen and energy consumption. Cardiac
findings of mild-to-moderate sinus tachycardia in thyrotoxicosis intensify to accelerated tachycardia,
hypertension, high-output cardiac failure, and a propensity to develop cardiac arrhythmias. Similarly,
irritability and restlessness in thyrotoxicosis progress to severe agitation, delirium, seizures, and
coma. [1] GI manifestations of thyroid storm include diarrhea, vomiting, jaundice, and abdominal pain,
in contrast to only mild elevations of transaminases and simple enhancement of intestinal transport in
thyrotoxicosis.

https://emedicine.medscape.com/article/925147-overview#showall 1/5
1/19/2019 Thyroid Storm: Background, Pathophysiology, Etiology

Etiology
Thyroid storm is precipitated by the following factors in individuals with thyrotoxicosis:

Sepsis
Surgery
Anesthesia induction [2]
Radioactive iodine (RAI) therapy [3]
Drugs (anticholinergic and adrenergic drugs, eg, pseudoephedrine; salicylates; nonsteroidal anti-
inflammatory drugs [NSAIDs]; chemotherapy [4]
Excessive thyroid hormone (TH) ingestion
Withdrawal of or noncompliance with antithyroid medications
Diabetic ketoacidosis [5]
Direct trauma to the thyroid gland
Vigorous palpation of an enlarged thyroid
Toxemia of pregnancy and labor in older adolescents; molar pregnancy

Thyroid storm can occur in children with thyrotoxicosis from any cause but is most commonly
associated with Graves disease. Other reported causes of thyrotoxicosis associated with thyroid storm
include the following:

Transplacental passage of maternal thyroid-stimulating immunoglobulins in neonates

McCune-Albright syndrome with autonomous thyroid function [6]
Hyperfunctioning thyroid nodule
Hyperfunctioning multinodular goiter
Thyroid-stimulating hormone (TSH)-secreting tumor

Graves disease may also occur in children with Down syndrome or Turner syndrome and in
association with other autoimmune conditions, including the following:

Juvenile rheumatoid arthritis

Addison disease
Type I diabetes
Myasthenia gravis
Chronic lymphocytic (Hashimoto) thyroiditis
Systemic lupus erythematosus
Chronic active hepatitis
Nephrotic syndrome

The pathophysiologic mechanisms of Graves disease are shown in the image below.

https://emedicine.medscape.com/article/925147-overview#showall 2/5
1/19/2019 Thyroid Storm: Background, Pathophysiology, Etiology

Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to hyperthyroidism and

ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.

Although the exact pathogenesis of thyroid storm is not fully understood, the following theories have
been proposed:

Patients with thyroid storm reportedly have relatively higher levels of free THs than patients with
uncomplicated thyrotoxicosis, although total TH levels may not be increased.
Adrenergic receptor activation is another hypothesis. Sympathetic nerves innervate the thyroid
gland, and catecholamines stimulate TH synthesis. In turn, increased THs increase the density
of beta-adrenergic receptors, thereby enhancing the effect of catecholamines. The dramatic
response of thyroid storm to beta-blockers and the precipitation of thyroid storm after accidental
ingestion of adrenergic drugs such as pseudoephedrine support this theory. This theory also
explains normal or low plasma levels and urinary excretion rates of catecholamines. However, it
does not explain why beta-blockers fail to decrease TH levels in thyrotoxicosis.
Another theory suggests a rapid rise of hormone levels as the pathogenic source. A drop in
binding protein levels, which may occur postoperatively, might cause a sudden rise in free
hormone levels. In addition, hormone levels may rise rapidly when the gland is manipulated
during surgery, during vigorous palpation during examination, or from damaged follicles following
RAI therapy.
Other proposed theories include alterations in tissue tolerance to THs, the presence of a unique
catecholaminelike substance in thyrotoxicosis, and a direct sympathomimetic effect of TH as a
result of its structural similarity to catecholamines.

Epidemiology
Frequency
In the US, the true frequency of thyrotoxicosis and thyroid storm in children is unknown. The incidence
of thyrotoxicosis increases with age. Thyrotoxicosis may affect as many as 2% of older women.
Children constitute less than 5% of all thyrotoxicosis cases. Graves disease is the most common
cause of childhood thyrotoxicosis and, in a possibly high estimate, reportedly affects 0.2-0.4% of the
pediatric and adolescent population. About 1-2% of neonates born to mothers with Graves disease
manifest thyrotoxicosis.

https://emedicine.medscape.com/article/925147-overview#showall 3/5
1/19/2019 Thyroid Storm: Background, Pathophysiology, Etiology

Based on nationwide surveys conducted between 2004 and 2008, the incidence of thyroid storm in
Japan has been estimated to be 0.2 persons per 100,000 population, with the rate of thyroid storm in
all thyrotoxic patients being 0.22%, and in hospitalized thyrotoxic patients, 5.4%. [7]

Sex
Thyrotoxicosis is 3-5 times more common in females than in males, especially among pubertal
children. Thyroid storm affects a small percentage of patients with thyrotoxicosis. The incidence is
presumed to be higher in females; however, no specific data regarding sex-specific incidence are
available.

Age

Neonatal thyrotoxicosis occurs in 1-2% of neonates born to mothers with Graves disease. Infants
younger than 1 year constitute only 1% of cases of childhood thyrotoxicosis. More than two thirds of
all cases of thyrotoxicosis occur in children aged 10-15 years. Overall, thyrotoxicosis occurs most
commonly during the third and fourth decades of life. Because childhood thyrotoxicosis is more likely
to occur in adolescents, thyroid storm is more common in this age group, although it can occur in
patients of all ages.

Prognosis
Thyroid storm is an acute, life-threatening emergency. If untreated, thyroid storm is almost invariably
fatal in adults (90% mortality rate) and is likely to cause a similarly severe outcome in children,
although the condition is so rare in children that these data are not available. Death from thyroid storm
may be a consequence of cardiac arrhythmia, congestive heart failure, hyperthermia, multiple organ
failure or other factors [8] , though the precipitating factor is often the cause of death.

With adequate thyroid-suppressive therapy and sympathetic blockade, clinical improvement should
occur within 24 hours. Adequate therapy should resolve the crisis within a week. Treatment for adults
has reduced mortality to less than 20%. In one retrospective study from Japan of 1324 patients who
were diagnosed with thyroid storm, the overall mortality was 10% [9] . In the same study, the following
factors were associated with increased mortality risk in thyroid storm [9] :

Age 60 years or older

Central nervous system (CNS) dysfunction at admission
Lack of antithyroid drug and beta-blockade use
Need for mechanical ventilation and plasma exchange along with hemodialysis

In addition, a study by Swee et al of 28 patients with thyroid storm reported that CNS dysfunction of
greater than mild severity appeared to be a risk factor for mortality. [10]

Patient Education

https://emedicine.medscape.com/article/925147-overview#showall 4/5
1/19/2019 Thyroid Storm: Background, Pathophysiology, Etiology

For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center.
Also, see eMedicineHealth's patient education articles Thyroid Problems and Thyroid Storm.

Clinical Presentation

https://emedicine.medscape.com/article/925147-overview#showall 5/5