Thyroid Storm

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. ^[4] 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.

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

• Sepsis
• Surgery
• Anesthesia induction ^[5]
• Radioactive iodine (RAI) therapy ^[6]
• Drugs (anticholinergic and adrenergic drugs, eg, pseudoephedrine; salicylates; nonsteroidal anti-inflammatory drugs [NSAIDs]; chemotherapy ^[7]
• Excessive thyroid hormone (TH) ingestion
• Withdrawal of or noncompliance with antithyroid medications
• Diabetic ketoacidosis ^[8]
• Direct trauma to the thyroid gland
• Vigorous palpation of an enlarged thyroid
• Preeclampsia, hydatidiform mole, labor

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 ^[9]
• 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.

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.

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.

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%. ^[10]

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.

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, ^[11] 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%. ^[12]  In the same study, the following factors were associated with increased mortality risk in thyroid storm ^[12] :

• 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. ^[13]

Using the National (Nationwide) Inpatient Sample database, a study by Waqar et al indicated that in hospitalized patients with thyroid storm, the inhospital mortality rate is higher in those with cardiovascular events than in persons without (3.5% vs 0.2%, respectively). The cardiovascular events that were most frequently associated with thyroid storm in hospitalized patients were arrhythmia (96.8%), acute heart failure (14.2%), and ischemic events (3.9%). Of patients with an ischemic event, 16.7% suffered inhospital mortality, compared with 3.6% and 3.2% of those with acute heart failure or arrhythmia, respectively. ^[14]

A retrospective study by Bourcier et al of 31 French intensive care units (ICUs) found that in ICU patients with thyroid storm, multiple organ failure (as evaluated using the Sequential Organ Failure Assessement [SOFA] score, absent the cardiovascular component), and the occurrence, within 48 hours following ICU admission, of cardiogenic shock are independent risk factors for mortality in the ICU. ^[15]

A study by Burmeister reported a mortality rate of 38% in patients with thyroid storm–related coma, including 70% between 1935 and 1977, and 11% between 1978 and 2019. The investigator found that there was a greater tendency for patients to awaken from their coma when total and free T4 values, and possibly the total T3 value as well, was reduced. Moreover, the employment of antithyroid drugs, corticosteroids, beta blockers, and intubation correlated positively with lower death rates. Although plasmapheresis-related awakenings occurred in 67% of patients in which plasmapheresis was used, the procedure was not linked to a reduction in the death rate. ^[16]

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