Endocrinology Metabolism

Thyroid storm

Are you sure the patient has thyroid storm?

Thyroid storm (also known as hyperthyroid crisis, thyroid crisis, or thyrotoxic crisis) is a rare, life-threatening complication of thyrotoxicosis, which is usually precipitated by an intercurrent medical problem.

The incidence of thyroid storm was once relatively high because of a liberal definition of the condition. For example, some reports included all post-operative thyroidectomy cases that manifested a febrile reaction higher than 38.3 C, but many, if not most, of these early cases do not fit the current criteria for thyroid storm. Thyroid storm in the post-operative period is rarely observed currently, as patients are better prepared for surgery than was once the case. Certain clinical and socioeconomic factors, including the lack of insurance, age younger than 30 or older than 50, and serum T4 concentrations greater than twice the upper limit of normal, have also been suggested as being associated with complicated hyperthyroidism.

Hyperthyroidism is the most common cause of thyrotoxicosis leading to thyroid storm. While the cause of the rapid clinical decompensation is unknown, a sudden inhibition by the precipitating factor(s) of thyroid hormone's ability to bind to plasma proteins, which causes an acute rise in the free hormone pool, may play a role in the pathogenesis of thyroid storm. Thyroid storm is a medical emergency that should be managed in the intensive care unit (ICU).

Thyroid storm is primarily a clinical diagnosis with features similar to those of thyrotoxicosis, but more exaggerated. The physician must have a high clinical index of suspicion for thyroid storm, as therapy in most cases must be instituted before the return of thyroid function tests. Clues to the diagnosis of thyroid storm are a history of thyroid disease, a history of iodine ingestion, and the presence of a goiter or stigmata of Graves’ disease.

Cardinal features of thyroid storm include fever, tachycardia/tachyarrhythmias, and changes in mental status. Thyroid storm should be considered in any patient who presents with this triad, especially if there is accompanying evidence of a goiter, thyroid ophthalmopathy, and tremors. Any patient with fever, tachyarrhythmias, and changes in mental status in the setting of increased FT4/FTI and T3 levels and suppressed thyroid-stimulating hormone (TSH) levels should be considered to have thyroid storm until proven otherwise. See Table I.

Table I.

Clinical features of Thyroid Storm

While the cause of the rapid clinical decompensation in thyroid storm is unknown, a sudden inhibition by the precipitating factor(s) of thyroid hormone's binding to plasma proteins, causing an acute rise in the free hormone pool, may play a role in the pathogenesis of thyroid storm. See Table II.

Table II.

Precipitating Factors of Thyroid Storm

Thyroid storm appears most commonly following infection, which causes the thyrotoxic state to decompensate. Pneumonia, upper respiratory tract infections and enteric infections are common precipitating infections. Other precipitating factors include stress, trauma, non-thyroidal surgery, diabetic ketoacidosis, labor, heart disease, and iodinated contrast studies in the unrecognized or partially treated hyperthyroid patient. Latrogenic thyroid storm has been reported as a result of thyroid hormone overdose. Thyroid storm that occurs after 131I therapy is extremely rare, especially considering the frequency of the use of radioiodine in the definitive treatment of hyperthyroidism. When reported, radioiodine-induced thyroid storm usually occurs if there was no pretreatment with antithyroid drugs.

Coma and death may occur in up to 20 percent of patients, frequently as a result of cardiac arrhythmias, congestive heart failure, hyperthermia, or the precipitating illness. There are no distinct laboratory abnormalities. Thyroid hormone levels are similar to those found in uncomplicated thyrotoxicosis; there is little correlation between the degree of elevation of thyroid hormone and the presentation of thyroid storm.

What else could the patient have?

The differential diagnosis of thyroid storm includes sepsis, neuroleptic malignant syndrome, malignant hyperthermia, and acute mania with lethal catatonia, all of which can precipitate thyroid storm in the appropriate setting.

Key laboratory and imaging tests

There are no distinct laboratory abnormalities, and thyroid hormone levels are similar to those found in uncomplicated thyrotoxicosis; there is little correlation between the degree of elevation of thyroid hormones and the presentation of thyroid storm.

Thyroid function tests, including an estimate of the free thyroxine concentration (FT4 or FTI), the total T3 concentration and the TSH concentration, should be obtained. A total T4 value on its own is of limited or no use. A free T3 by analog is a less accurate test than a total T3 in this clinical situation. While there is little correlation between thyroid function tests and thyroid storm, a slightly low TSH that remains in the detectable range or a suppressed TSH with FT4/FTI and Total T3 in the normal range renders the diagnosis untenable.

Thyroid antibodies may provide an etiology to the underlying thyroid disorder, but they play no role in the acute management. Similarly, imaging studies, such as nuclear thyroid scanning, have no role in the initial management of thyroid storm.

Burch and Wartofsky published a modified "Apache" score for the diagnosis of thyroid storm, which says that the diagnosis of thyroid storm is possible with a score of 25-45, likely with a score higher than 45, and unlikely with a score lower than 25. See Table III.

Table III.

Treatment of Thyroid Storm

Other tests that may prove helpful diagnostically

Abnormal liver function tests are common. Hypocalcemia may be observed because of increased osteoclast-mediated bone resorption in the hyperthyroid patient. Hematocrit concentrations may be elevated because of volume contraction, and leukocytosis is common even in the absence of infection.

Management and treatment of the disease

Thyroid storm is a major medical emergency that must be treated in an intensive care unit. Treatment should target four areas: 1) supportive measures, 2) control of tachyarrhythmias, 3) inhibition of thyroid function, and 4) treatment of the underlying precipitating illness. See Table IV.

Table IV.

Clinical Scoring System for the Diagnosis of Thyroid Storm

Within 2-3 hours after large doses of methimazole or propylthiouracil have been administered, 2-3 drops of Lugol's solution (saturated solution of potassium iodide, SSKI) should be given orally every 6-8 hours. Methimazole (but not propylthiouracil, PTU) may also be given rectally if it cannot be administered generally. Beta-blocking drugs and 1-2 mg dexamethasone orally or parentally every 12 hours (to inhibit conversion of T4 to T3) should be administered.

Management of the patient with thyroid storm in the ICU setting should be continued until the clinical score for thyroid storm drops under 25. FT4/FTI and Total T3 levels should be repeated daily in patients who are not clinically improving. If the patient is stabilized, repeat FT4/FTI and Total T3 levels can be performed on an outpatient basis. After the initial TSH determination, there is no need to repeat a serum TSH for at least six weeks, as it will remain suppressed for at least that length of time.

Antithyroid drugs should be started before administration of any iodine-containing compound, whether that compound is SSKI or Lugol's solution or, in Europe, iopanoic acid (which is not available in the U.S.) In fact, if thyroid storm is considered as a diagnosis and the patient needs an imaging procedure that requires IV contrast, it is better to give a one-time dose of Methimazole (20-40 mg) or PTU (200-300 mg) prior to the procedure before the diagnosis is confirmed. Any iodine load in the absence of antithyroid blockade will exacerbate the hyperthyroid state and prolong the time to recovery.

In patients who have not responded to medical therapy with antithyroid drugs, steroids, and iodine, peritoneal dialysis or removal of the thyroid hormones from circulation by plasmapheresis can be performed.

What’s the Evidence?

Burch, HB, Wartofsky, L. "Life threatening thyrotoxicosis: Thyroid storm". Endocrinol Metab Clin North Am. vol. 22. 1993. pp. 263-77.

(Classic article describing a modified "Apache" score to diagnose thyroid storm.)

Nayak, B, Burman, K. "Thyrotoxicosis and thyroid storm". Endocrinol Metab Clin North Am. vol. 35. 2006. pp. 663-86.

(In-depth reviews on the pathophysiology, presentation, and management thyroid storm.)

Yeung, SC, Go, R, Balasubramanyam, A. "Rectal administration of iodide and propylthiouracil in the treatment of thyroid storm". Thyroid. vol. 5. 1995. pp. 403-5.

(This study documents alternatives to oral administration of antithyroid drugs.)

Duggal, J, Singh, S, Kuchinic, P, Butler, P, Arora, R. "Utility of esmolol in thyroid crisis". Can J Clin Pharmacol. vol. 13. 2006. pp. e292-5.

(Adjunctive therapy for the management of thyroid storm.)

Vijayakumar, V, Nusynowwitz, ML, Ali, S. "Is it safe to treat hyperthyroid patients with I-131 without fear of thyroid storm". Ann Nucl Med. vol. 20. 2006. pp. 383-5.

(Adjunctive therapy for the management of thyroid storm.)

Lazarus, JH, Addison, AJ, Richards, AR. "Treatment of thyrotoxicosis with lithium carbonate". Lancet. vol. 2. 1974. pp. 1160-3.

(Adjunctive therapy for the management of thyroid storm.)

Shakir, KM, Michaels, RD, Hays, JH, Potter, BB. "The use of bile acid sequestrants to lower serum thyroid hormone concentrations in iatrogenic hyperthyroidism". Ann Int Med. vol. 118. 1993. pp. 112-3.

(Adjunctive therapy for the management of thyroid storm.)

Candrina, R, DiStefano, O, Spandrio, S. "Treatment of thyrotoxic storm by charcoal plasma perfusion". J Endocrinol Invest. vol. 12. 1989. pp. 133-4.

(Adjunctive therapy for the management of thyroid storm.)

Wartofsky, L, Braverman, LE, Cooper, C. "Thyroid storm". Werner and Ingbar, The Thyroid. Lippincotte William & wilkins.

(Excellent source on and summary of thyroid storm.)
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