Thyrotoxic Storm Following Thyroidectomy 

Updated: Jan 21, 2015
Author: Peter F Czako, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA 



Thyroid storm is a clinical manifestation of an extreme hyperthyroid state that results in significant morbidity or disability or even death. Previously, thyroid storm was a common complication of toxic goiter surgery during intraoperative and postoperative stages. Preoperative control of the thyrotoxic state and use of radioiodine ablation has greatly reduced this phenomenon. Today, thyroid storm more commonly is seen in a thyrotoxic patient with intercurrent illness or surgical emergency. Early recognition and prompt intervention are necessary to prevail in management of this phenomenon.




Presently, incidence is less than 10% among patients hospitalized for thyrotoxicosis.


Thyroid storm, considered a fulminating state, is fatal when untreated.

Although methods of diagnosis and management have improved considerably, reported mortality still is 20-30%.

Although it can develop in toxic adenoma or multinodular toxic goiter, thyroid storm is more commonly seen in toxicity secondary to Graves disease. See the image below.

Pathophysiologic mechanisms of Graves disease rela Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to hyperthyroidism and ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.


Age and sex predilection depends on the etiology of thyrotoxicity. Graves disease more frequently develops in females (ie, male-to-female ratio ranges from 1:7 to 1:10); multinodular goiter more often manifests in the elderly population.




Clinical features form the hallmark in diagnosing thyroid storm. Most patients have goiter, and many of those with Graves disease have concurrent ophthalmopathy. Frequently, a past history of thyroid disease that has been partially treated exists.


An accentuation of signs and symptoms is seen in uncomplicated thyrotoxicosis. The point of transition from uncomplicated thyrotoxicosis to thyroid storm is difficult to ascertain. Very few criteria define the change. However, certain clinical features (eg, high-grade fever, mental obtundation, decompensation of one or more organ systems secondary to the severe state of hypermetabolism) herald its onset.

The table below presents some changes in the symptoms and signs of thyroid storm when compared with uncomplicated thyrotoxicosis. Importantly, some findings of thyroid storm (eg, atrial dysrhythmia) may also prevail in uncomplicated thyrotoxicosis. Therefore, the table represents only guidelines, not specific criteria to define thyroid storm.

Table. Symptoms and Signs of Thyroid Storm When Compared with Uncomplicated Thyrotoxicosis (Open Table in a new window)

Uncomplicated Thyrotoxicosis

Thyroid Storm

1. Heat intolerance, diaphoresis

1. Hyperpyrexia, temperature in excess of 106o C, dehydration

2. Sinus tachycardia, heart rate 100-140

2. Heart rate faster than 140 beats/min, hypotension, atrial dysrhythmias, congestive heart failure

3. Diarrhea, increased appetite with loss of weight

3. Nausea, vomiting, severe diarrhea, abdominal pain, hepatocellular dysfunction-jaundice

4. Anxiety, restlessness

4. Confusion, agitation, delirium, frank psychosis, seizures, stupor or coma

Certain unusual presentations include chest pain, acute abdomen, status epilepticus, stroke, acute renal failure due to rhabdomyolysis, and apathetic thyroidism. Lahey first described apathetic thyroidism (ie, masked hyperthyroidism) 60 years ago.[1] Apathetic thyroidism more frequently was seen in elderly patients but since has been described in all ages. Patients in this variant group present without goiter, ophthalmopathy, or prominent symptoms of hyperthyroidism. These patients have a low pulse rate and a propensity to develop thyroid storm due to delay in diagnosis.


A precipitating factor usually is found with thyroid storm. Presently, the most common cause of thyroid storm is intercurrent illness or infection (ie, medical storm).[2, 3]

Some causes that rapidly increase the thyroid hormone levels include the following:

  • Surgery, thyroidal or nonthyroidal

  • Radioiodine therapy

  • Withdrawal of antithyroid drug therapy

  • Vigorous thyroid palpation

  • Iodinated contrast dye

  • Thyroid hormone ingestion

Other common precipitants include the following:

  • Infection

  • Emotional stress

  • Tooth extraction

  • Diabetic ketoacidosis

  • Hypoglycemia

  • Trauma

  • Bowel infarction

  • Parturition

  • Toxemia of pregnancy

  • Pulmonary embolism

  • Cerebrovascular accident

  • Gestational trophoblastic disease



Diagnostic Considerations

Postoperative complications (eg, sepsis, hemorrhage, septicemia, transfusion drug reactions) mimic the thyrotoxic state. Previous history of hyperthyroidism, precipitating factors, increased T3 and T4 levels, and decreased thyroid stimulating hormone (TSH) levels help to establish the diagnosis of thyroid storm.



Laboratory Studies

Presently, no specific diagnostic criteria to establish the diagnosis of thyroid storm exist.

Burch and Wartofsky have constructed an excellent clinical diagnostic point scale to facilitate a semiquantitative distinction between uncomplicated thyrotoxicosis, impending storm, and established thyroid storm.[4] Laboratory findings in thyroid storm are consistent with those of thyrotoxicosis and include the following:

  • Elevated T3 and T4 levels

  • Elevated T3 uptake

  • Suppressed TSH levels

  • Elevated 24-hour radioiodine uptake

Elevated T4 and decreased TSH are the only abnormal findings needed for conformation of thyrotoxicosis. Treatment should not be withheld for any laboratory confirmation of hyperthyroidism when thyroid storm is suspected clinically. A 2-hour radioiodine uptake is advisable if thyroid storm is suspected and no past history of hyperthyroidism exists.

Other abnormal laboratory values that point toward decompensation of homeostasis include the following:

  • Increased BUN and creatinine kinase

  • Electrolyte imbalance from dehydration, anemia, thrombocytopenia, and leukocytosis

  • Hepatocellular dysfunction as shown by elevated levels of transaminases, lactate dehydrogenase, alkaline phosphatase, and bilirubin

  • Elevated calcium levels

  • Hyperglycemia



Medical Care

Management of thyroid storm is a multi-step process. Blocking the synthesis, secretion, and peripheral action of the thyroid hormone is the ideal therapy. Aggressive supportive therapy then is used to stabilize homeostasis and reverse multiorgan decompensation.[5] Additional measures are taken to identify and treat the precipitating factor, followed by definitive treatment to avoid recurrence. Thyroid storm is a fulminating crisis that demands an intensive level of care, continuous monitoring, and vigilance.

Blocking thyroid hormone synthesis

Antithyroid compounds propylthiouracil (PTU) and methimazole (MMI) are used to block the synthesis of the thyroid hormone. PTU also blocks peripheral conversion of T4 to T3 and hence is preferred in thyroid storm over MMI. MMI is the common agent used in hyperthyroidism. PTU and MMI block the incorporation of iodine into thyroglobulin within 1 hour of ingestion. A history of hepatotoxicity or agranulocytosis from previous thioamide therapy precludes use of PTU and MMI.

The US Food and Drug Administration (FDA) had added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for propylthiouracil. The boxed warning emphasizes the risk for severe liver injury and acute liver failure, some of which have been fatal. The boxed warning also states that propylthiouracil should be reserved for use in those who cannot tolerate other treatments such as methimazole, radioactive iodine, or surgery.

The decision to include a boxed warning was based on the FDA's review of postmarketing safety reports and meetings held with the American Thyroid Association, the National Institute of Child Health and Human Development, and the pediatric endocrine clinical community.

The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil (PTU). Of the adults, 12 deaths and 5 liver transplants occurred, and among the pediatric patients, 1 death and 6 liver transplants occurred. PTU is indicated for hyperthyroidism due to Graves disease. These reports suggest an increased risk for liver toxicity with PTU compared with methimazole. Serious liver injury has been identified with methimazole in 5 cases (3 resulting in death).

PTU is considered as a second-line drug therapy, except in patients who are allergic or intolerant to methimazole, or for women who are in the first trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis, have been reported with methimazole during pregnancy. The FDA recommends the following criteria be considered for prescribing PTU. For more information, see the FDA Safety Alert.

  • Reserve PTU use during first trimester of pregnancy, or in patients who are allergic to or intolerant of methimazole.

  • Closely monitor PTU therapy for signs and symptoms of liver injury, especially during the first 6 months after initiation of therapy.

  • For suspected liver injury, promptly discontinue PTU therapy and evaluate for evidence of liver injury and provide supportive care.

  • PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of methimazole, and no other treatment options are available.

  • Counsel patients to promptly contact their health care provider for the following signs or symptoms: fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin.

Blocking thyroid hormone secretion

After initiation of antithyroid therapy, hormone release can be inhibited by large doses of iodine, which reduce thyroidal iodine uptake. Lugol solution or saturated solution of potassium iodide can be used.

Iodine therapy should be administered after approximately 1 hour following administration of PTU or MMI; iodine used alone helps to increase thyroid hormone stores and may increase the thyrotoxic state.

The iodinated x-ray contrast agent, sodium ipodate, can be administered instead of iodine and also inhibits peripheral conversion of T4 to T3. Potassium iodide (KI) decreases thyroidal blood flow and hence is used preoperatively in thyrotoxicosis.

Patients intolerant to iodine can be treated with lithium, which also impairs thyroid hormone release. Patients unable to take PTU or MMI also can be treated with lithium, as use of iodine alone is debatable. Unlike iodine, lithium is not subject to the escape phenomenon; lithium blocks the release of thyroid hormone throughout its administration.

Plasmapheresis, plasma exchange, peritoneal dialysis exchange transfusion, and charcoal plasma perfusion are other techniques used to remove excess circulating hormone. Presently, these techniques are reserved for patients who do not respond to the initial line of management.[6]

The intravenous preparation of sodium iodide (given as 1 g slow infusion q8-12h) has been taken off of the market.

Blocking peripheral action of thyroid hormone

Propranolol is the drug of choice to counter peripheral action of thyroid hormone. Propranolol blocks beta-adrenergic receptors and prevents conversion of T4 to T3. It produces dramatic improvement in clinical status and greatly ameliorates symptoms. Propranolol produces the desired clinical response in thyroid storm only after large doses. Intravenous administration of propranolol requires continuous monitoring of cardiac rhythm.

Presently, esmolol is the ultra-short-acting beta-blocking agent used successfully in thyrotoxicosis and thyroid storm.

Noncardioselective beta-blockers (eg, propranolol, esmolol) cannot be used in patients with congestive cardiac failure, bronchospasm, or history of asthma. Guanethidine or reserpine can be used instead in these cases.[7]

Successful treatment with reserpine in cases of thyroid storm resistant to large doses of propranolol has been documented. However, guanethidine and reserpine cannot be used in the presence of cardiovascular collapse or shock.

Supportive measures

Aggressive fluid and electrolyte therapy is needed for dehydration and hypotension. This excessive hypermetabolic state, with increased intestinal transit and tachypnea, leads to immense fluid loss. Fluid requirements may increase to 3-5 L/day. Therefore, invasive monitoring is advisable in elderly patients and in those with congestive cardiac failure.

  • Pressor agents can be used when hypotension persists following adequate fluid replacement.

  • Add glucose to IV fluids for nutritional support.

Multivitamins, especially vitamin B-1, are added to prevent Wernicke encephalopathy.

Hyperthermia is treated through central cooling and peripheral heat dissipation.

Acetaminophen is the drug of choice, as aspirin may displace thyroid hormone from binding sites and increase severity of thyroid storm.

Cooling blankets, ice packs, and alcohol sponges encourage dissipation of heat. Use of a cooled humidified oxygen tent is advised.

Use of glucocorticoids in thyroid storm is associated with improved survival rates. Initially, glucocorticoids were used to treat potential relative insufficiency due to accelerated production and degradation owing to the hypermetabolic state. However, the patient may have type 2 autoimmune deficiency, in which Graves disease coexists with absolute adrenal insufficiency.

Glucocorticoids reduce iodine uptake and antibody titers of thyroid-stimulating antibodies with stabilization of the vascular bed. In addition, dexamethasone and hydrocortisone have an inhibitory effect on conversion of T4 to T3. Therefore, a stress dose of glucocorticoid (eg, hydrocortisone, dexamethasone) now is routine.

Cardiac decompensation, although seen more frequently in elderly patients, may appear in younger patients and in patients without underlying cardiac disease.

Digitalization is required to control the ventricular rate in patients with atrial fibrillation.

Anticoagulation drugs may be needed for atrial fibrillation and can be administered in the absence of contraindications.[8] Digoxin may be used in larger doses than those normally used in other conditions. Closely monitor digoxin levels to prevent toxicity. As the patient improves, reduce digoxin dose.

Congestive cardiac failure is seen as a result of impaired myocardial contractility and may require Swan-Ganz catheter monitoring.



Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antithyroid agents

Class Summary

These agents block thyroid hormone synthesis.

Propylthiouracil (PTU)

Thiourea agent that blocks production of thyroid hormones. In addition, inhibits peripheral deiodination of T4 to T3. Preferred over MMI in thyroid storm.

Methimazole (Tapazole)

Active moiety of parent compound carbimazole. Blocks incorporation of iodine into thyroglobulin within 1 h of ingestion.

Methimazole was initially thought to be associated with neonatal aplasia cutis (ie, defect in the neonatal scalp) and was thought to be more likely to cross the placenta than PTU. However, recent studies by Wing et al concluded that PTU and MMI are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Lithium (Eskalith, Lithotabs)

Used in patients intolerant to iodine; impairs thyroid hormone release.

Potassium Iodide (Thyro-Block, Pima)

Inhibits thyroid hormone secretion. Contains 8 mg of iodide per drop. May be mixed with juice or water for intake.

Iodide treatment is reserved for the treatment of thyroid storm. It is also used for 10-14 d prior to surgical procedure, including thyroidectomy. Can be used with Graves thyrotoxicosis but exacerbates thyrotoxicosis from toxic multinodular goiter and toxic adenoma.

Sodium ipodate (Oragrafin)

One of the most effective inhibitors of deiodinase, which converts T4 to the more biologically active T3. Reduction in conversion of T4 to T3 can greatly reduce T3 levels and thyrotoxic symptoms.


Class Summary

These agents reduce iodine uptake and antibody titers of thyroid-stimulating antibodies with stabilization of the vascular bed.

Dexamethasone (Decadron, Dexone)

Has many pharmacologic benefits but significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates and improves pulmonary microcirculation. Has inhibitory effect on conversion of T4 to T3.

Adverse effects include hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.

Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.

Patients can be switched from an IV to PO regimen in a 1:1 ratio.

Hydrocortisone (Cortef, Solu-Cortef)

Elicits anti-inflammatory properties and causes profound and varied metabolic effects. Modifies the body's immune response to diverse stimuli.


Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties.

Acetaminophen (Feverall, Panadol)

Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increases the dissipation of body heat via sweating and vasodilation.

Beta-adrenergic blockers

Class Summary

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

Propranolol (Inderal, Betachron E-R)

DOC to counter peripheral action of thyroid hormone; blocks beta-adrenergic receptors; prevents conversion of T4 to T3.

Esmolol (Brevibloc)

Ultra–short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. Used successfully in thyrotoxicosis and thyroid storm. Can be discontinued abruptly if necessary.

Useful in patients at risk for experiencing complications from beta-blockade; particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Antihypertensive agents

Class Summary

These agents reduce blood pressure.

Guanethidine (Ismelin)

For use in patients with congestive cardiac failure, bronchospasm, or history of asthma.


For use in patients with congestive cardiac failure, bronchospasm, or history of asthma; successful treatment has been documented in cases of thyroid storm resistant to large doses of propranolol.



Further Inpatient Care

Combined use of propylthiouracil, iodine, and dexamethasone has an effect within 24-48 hours, and the serum levels of T3 and T4 return to normal. Clinical signs of decreasing pulse, normal temperature, and improved mental status mark effective management. Complete recovery takes 10-12 days. Dexamethasone can be tapered thereafter.

The three modalities of definitive management are radioiodine, antithyroid drugs, and surgery.[9]

Prior to radioiodine therapy or surgery, a patient should be made euthyroid with antithyroid drugs and propranolol. Antithyroid drugs are administered for 12-24 months, during which, a remission may occur. Antithyroid drugs are continued until a normal metabolic state is reached. If in remission, the patient should be closely monitored for 6 months, as relapse is more common during this period after discontinuation of therapy. Iodine is progressively withdrawn. Serially monitor patients until the thyroid gland is sufficiently depleted of its hormone to allow radioiodine therapy. Delaying radioiodine ablation for several months may be necessary because of the large doses of iodine used in management of thyroid storm. Some surgeons may reintroduce iodine for 10 days prior to surgery if subtotal thyroidectomy is planned. Follow patients for up to 5 years.

Criteria established by Burch and Wartofsky help in early recognition of impending storm. In thyroid storm, management as described improves the chance of survival.[4]


Identification of precipitating factors

  • Surgery and anesthesia induction, labor, thioamide withdrawal, and use of radioiodine are known precipitants of thyroid storm. However, these precipitants may not be discovered frequently.

  • Precipitating factors are not found in all patients, but a meticulous search improves chances for a successful outcome.

  • Chest radiographs and blood, urine, and sputum cultures may be needed to identify intercurrent illness (eg, infection).

  • Judicious use of empiric antibiotics is needed if no obvious source is found.

Prevention of recurrence

  • Prevention of a recurrent crisis should be the main objective until completion of definitive therapy.

  • Vigilant monitoring of signs and symptoms of hyperthyroidism during preoperative or pre-anesthetic evaluation is paramount.

  • Consider precipitating factors when deciding on treatment modalities.

  • Adequate control of the thyrotoxic state prior to initiation of definitive therapy is important. Carry out procedures only after the patient is euthyroid.

Patient Education

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