Thyroid Storm

  • Author: Robert W. Wolford, M.D., M.M.M, Visiting Clinical Associate Professor, Department of Emergency Medicine, University of Illinois College of Medicine at Peoria, Director of Quality and Process Improvement, Department of Emergency Medicine, OSF Saint Francis Medical Center, Peoria, Illinois
  • Last Update: 2015

Introduction

Thyroid storm is an uncommon but potentially fatal endocrine emergency at the severe end of the spectrum of thyrotoxicosis. Thyrotoxicosis is thought to affect approximately 1.2% of the United States population and, of those, only 1 to 2% develop thyroid storm. (1) Thyroid storm is more common in women and in the 3rd and 4th decades of life. Thyroid storm typically presents with the signs and symptoms of a hypermetabolic state; however co-existing illnesses, patient age, and the severity of the patient may muddy the waters and delay the diagnosis. To reduce the morbidity and mortality of thyroid storm, the clinician must consider the diagnosis, particularly in any patient with a history of thyroid disease, and implement treatment in a timely fashion. Even with recognition and treatment, mortality is high, ranging from 10% to 75% (2).

Objectives

Upon finishing this module, the student will be able to:

  1. Describe the potential presenting symptoms and signs of thyroid storm.
  2. List common causes of thyroid storm.
  3. Discuss the diagnostic approach to thyroid storm.
  4. Describe the treatment of thyroid storm.

Initial Actions and Primary Survey

Thyroid storm is exceedingly uncommon in the ED but it should be considered in any patient presenting with a hypermetabolic state, and especially those with a history of thyroid disease. Determining where the symptoms of subacute or chronic thyrotoxicosis end and thyroid storm begins is difficult. The focus of the primary survey and the subsequent detailed history and physical examination is to identify those patients at risk for thyroid storm.

  • Before I enter the room: If available, quickly review the chief complaint, nurse’s note, and vital signs. Fever and tachycardia are common findings in thyroid storm. Tachypnea may be seen, particularly in the setting of complicating heart failure. Hypertension and a widened pulse pressure may also be present.
  • As I enter the room, what do I see?
    a. Anxiety and agitation may be seen. The patient may appear cachectic.
  • ABCs:
    • Airway: The airway is typically not compromised by thyroid storm. However, these patients are often critically ill and the complications or inciting etiology of the patient’s thyroid storm may require active airway intervention.
    • Breathing: Tachypnea may occur for numerous reasons: increased basal metabolic rate; underlying heart failure as a complication of longstanding thyrotoxicosis (high output heart failure, dilated cardiomyopathy, or cor pulmonale); or other diseases that precipitated thyroid storm (pneumonia).
    • Circulation: Tachycardia is common, either sinus tachycardia (most common rhythm) or atrial fibrillation (most common dysrhythmia). Supraventricular and ventricular dysrhythmias, including ventricular fibrillation, may occur. A widened pulse pressure and hypertension are frequently seen. However, hypotension and shock may be seen as a complication of the thyroid storm or as a result of the inciting event (ex. septic shock).
    • While the physician is performing a primary survey, as with any seriously ill patient, the following should be obtained:
      • Reliable vascular access, cardiac, spO2, and BP monitoring. Supplemental oxygen if needed.
      • Bedside point of care glucose.
      • Electrocardiogram.
      • Chest radiograph.
      • Complete blood count.
      • Electrolytes, renal function, and serum glucose (metabolic profile).
      • Urinalysis.
      • Appropriate cultures.
      • Serum lactate.
      • If history of thyroid disease or if thyrotoxicosis\thyroid storm are suspected:
        • Thyroid stimulating hormone (TSH) level.
        • Free thyroxine (T4) level.
        • Free triiodothyroxine (T3) level.
      • Dependent on patient presentation, consider:
        • Venous or arterial blood gas.
        • Hepatic function tests.
        • Cardiac markers.

After the initial primary survey is completed, an appropriate history and physical examination should be obtained. Key components of the history and physical examination on secondary survey that suggest the presence of thyrotoxicosis and thyroid storm are:

  • History:
    • Onset\Duration?
      • Did the patient have subacute or chronic symptoms of thyrotoxicosis and the patiently has acutely worsened? If so, this mandates a search for an inciting event (ex. Infection, myocardial infarction, etc.).
    • History of “thyroid problems” and what were they?
      • Was the patient being treated for hyperthyroidism and stopped their medications?
      • Does the patient have a history of treatment of hypothyroidism and did they intentionally\unintentionally take too much thyroxine or thyroid supplement?
      • Were they taking thyroxine for weight loss?
    • Are symptoms of thyrotoxicosis found on review of systems? (Table 1)
    • Has the patient recently started any new medications, had radioiodine, or been given iodinated contrast? (Table 2)
    • Has there been a change in the patient’s mental status?
      • New symptoms of anxiety, nervousness, emotional liability?
      • Apathy, or symptoms of depression? Often seen in elderly – apathetic hyperthyroidism.
    • Are there associated cardiovascular complaints?
      • Dyspnea?
      • Chest pain? Acute myocardial infarction can trigger or be triggered by thyroid storm.
    • Any other recent physiologic stressors?
      • Infection? Most common trigger of thyroid storm.
      • Recent surgery, thyroid or otherwise?
      • Trauma or any other stressors?
  • Physical Examination (Table 1)
    • Constitutional signs.
      • Elevated temperature.
      • Tachycardia.
      • Tachypnea.
      • Altered mental status (Spectrum from anxiety and agitation to coma).
    • Eyes
      • i. Stare and lid lag common
      • ii. Suggestive of Graves disease:
        • Proptosis
        • Periorbital edema
        • Chemosis
        • Diplopia
    • Neck.
      • Abnormal thyroid
        • Diffusely enlarged, possible bruit
          • Graves disease
        • Palpable nodules (or nodules on ultrasound)
          • Toxic multinodular goiter
        • Enlarged, tender thyroid
          • Subacute thyroiditis
          • Suppurative thyroiditis
    • Lungs.
      • Findings suggestive of heart failure
    • Cardiovascular.
      • Sinus Tachycardia or A-fib
      • Hyperdynamic precordium
      • Widened pulse pressure
      • Rub
    • Neuro\psychiatric
      • Anxiety to agitation to psychosis to coma
      • Fine tremor, especially on extension of arms
      • Paralysis
        • Stroke
        • Thyrotoxic periodic paralysis (Especially Asian men)
      • Apathy\depression
      • Seizures
      • Proximal muscle weakness
      • Hyper-reflexia
Table 1. Symptoms & Signs of Thyrotoxicosis
Symptoms Signs
Weight loss despite increased appetite
Anxiety\Nervousness\Emotional liability
Fatigue
Heat intolerance
Diaphoresis\Increased perspiration
Palpitations
Dyspnea
Difficulty getting out of chair\ Combing hair (Weakness)
Frequent bowel movements\Diarrhea
Amenorrhea
Decreased libido
Cachexia
Hyperthermia
Anxious\Agitated
Tremor
Hypertension
Widened pulse pressure
Thyroid mass\Goiter
Tachycardia (Sinus tachycardia, atrial fibrillation)
Proximal muscle weakness
Diaphoresis\Damp skin
Gynecomastia
Additional Signs Associated with Graves Disease
Proptosis
Chemosis
Periorbital edema
Diplopia\Extra ocular muscle dysfunction
Non-pitting pretibial edema
Diffusely enlarged thyroid gland
Table 2. Medication associated thyrotoxicosis. (3)
Medication Mechanism
Amiodarone Iodine induced, contains 37% iodine by weight, Thyroiditis
Lithium, Painless thyroiditis.
Interferon α Painless thyroiditis, Graves disease
Interleukin-2 Painless thyroiditis, Graves disease
Iodinated contrast Induction of thyroid autonomy
Radioactive iodine Thyroid destruction (Early in therapy), Graves disease (Late in therapy)
Increased iodine intake Iodine induced. (Jod-Basedow phenomenon)

Presentation

Thyroid storm is a rare disease characterized by hypermetabolic activity and for whom there is a high mortality, even with treatment. Although the most common presentation is a patient with a history of thyroid disease (thyrotoxicosis), thyroid storm may be the initial manifestation of the patient’s thyroid disease. Patients classically present with evidence of multisystem decompensation, fever, tachycardia out of proportion to the temperature, and central nervous system dysfunction. As mentioned earlier, thyroid storm is part of the spectrum of thyrotoxicosis and it can be difficult to distinguish from severe thyrotoxicosis. A scoring system has been proposed (Table 3) to identify the likelihood of thyroid storm. Thyroid storm should be near the top of the differential diagnoses for any patient with a history of thyrotoxicosis presenting with CNS dysfunction.

Table 3. Diagnostic criteria for thyroid storm. (4)
Criteria Score
Thermoregulatory dysfunction (Temperature)
99 – 99.9 (37.2-37.7) 5
100 -100.9 (37.8-38.2) 10
101-101.9 (38.3-38.8) 15
102-102.9 (38.9-39.3) 20
103-103.9 (39.4-39.9) 25
>104 (40) 30
Central Nervous System dysfunction
Absent 0
Mild (Agitation) 10
Delirium\psychosis\lethargy 20
Seizure or coma 30
Gastrointestinal dysfunction
Absent 0
Diarrhea\nausea\vomiting\abdominal pain 10
Unexplained jaundice 20
Cardiovascular dysfunction (Heart rate bpm\min)
90-109 5
110-119 10
120-129 15
130-139 20
>140 25
Congestive heart failure
Absent 0
Mild (edema) 5
Moderate (bibasilar edema) 10
Severe (pulmonary edema) 15
Atrial fibrillation
Absent 0
Present `0
Precipitating event
Absent 0
Present 10
Interpretation: Likelihood of Thyroid Storm
Score: < 25 – Unlikely
25-44 – Impending
>45 – Highly likely

The patient’s presentation may reflect complications of thyroid storm (stroke, myocardial infarction, congestive heart failure, etc.) or the triggering event (sepsis, stroke, myocardial infarction, etc.). Common triggers of thyroid storm are listed in Table 4.

Table 4. Thyroid storm triggers.
Triggers
Infection
Discontinuing medications for hyperthyroidism
Myocardial infarction
Stroke
Thyroid surgery
Self-administration of thyroxine or thyroid supplements
Treatment with radioactive iodine
Pregnancy
Diabetic ketoacidosis
Non-thyroid surgery
Trauma
Iodinated contrast exposure

Diagnostic Testing

Although the diagnosis of thyroid storm is primarily a clinical diagnosis, if thyroid storm is suspected thyroid specific laboratory studies should be obtained and usually include:

  • Thyroid stimulating hormone (TSH) level.
  • Free thyroxine (T4) level.
  • Free triiodothyroxine (T3) level.

Most patients will demonstrate elevated free T4 and T3 levels and a low or undetectable TSH level. The TSH level may be normal in pituitary dependent thyrotoxicosis (pituitary not subject to negative feedback – very rare!). The free T4 may be normal with an elevated free T3 in cases of T3 thyrotoxicosis. The turnaround time for these labs can be hours to days; if thyroid storm is suspected treatment should be started without waiting for confirmatory tests.

Other tests should be obtained as described in the Initial Actions section.

Treatment

Before discussing the management of thyroid storm, a brief review of normal thyroid function is necessary. Thyroid production of hormones is dependent on dietary iodine intake. Plasma iodide enters the thyroid cells through the sodium iodide symporter and specific thyroglobulin (produced by the thyroid cells) tyrosines are iodinated by thyroid peroxidase, creating mono and di-iodotyrosines. The iodotyrosines combine to form T3 and T4 within the thyroglobulin. In response to TSH, T4 and T3 are cleaved from the thyroglobulin and released into the circulation. T4 is the pro-hormone and T3 the active form of the hormone. Eighty percent of the circulating T3 is formed by the conversion of T4 to T3 in the peripheral tissues and the remaining 20% directly released from the thyroid gland. Approximately 99.97 % of T4 and 99.7% of T3 are non-covalently bound to serum proteins (primarily thyroxine binding globulin) and it is only the free hormones that are metabolically active. Any factor which changes the amount of protein bound hormone (ex. salicylates, diphenylhydantoin, and heparin) may have an impact. Thyroid hormones increase the metabolic rate, increase the use of glucose and oxygen, increase body temperature, and stimulate lipolysis. Thyroid function is tightly controlled by a negative feedback loop. (Figure 1)

483px-thyroid_vector-svg
Hypothalamic-Pituitary-Thyroid Axis
Wikimedia Commons

Patients with thyroid storm are usually critically ill and stabilization should be initiated immediately. These patients are frequently severely volume depleted and require aggressive fluid resuscitation, unless cardiac failure is suspected. Severe hyperthermia should be addressed with cooling and acetaminophen. Salicylates should be avoided as they will displace T4 and T3 from thyroxine binding globulin and result in increased free hormone levels and potentially worsen symptoms. Electrolyte abnormalities should be corrected and dysrhythmias recognized and treated. The inciting etiologies and complications of thyroid storm must be identified and appropriately managed.
Specific treatment for thyroid storm utilizes 3 sequential steps: 1. Block the peripheral effect of the thyroid hormones, 2. Stop the production of hormone in the thyroid, and 3. Stop the release of T3 and T4 from the thyroid. Commonly used medications are listed in Table 5.

Table 5. Medications used in the treatment of thyroid storm. (Adult doses)
Medication Mechanism Dosage
1. Stop new hormone production
Propylthiouracil (PTU) Inhibits T4 & T3 production by inhibiting iodination of thyroglobulin.
Blocks T4 to T3 conversion by peripheral tissues.
500 – 1000 mg loading dose and then 250 mg every 4 hours. PO, NG, PR
Methimazole Blocks new hormone synthesis. 60 – 80 mg\day. PO, NG
2. Inhibit hormone release
(Do Not Start Until at Least 1 hour After PTU or Methimazole)
Potassium Iodide (SSKI) Blocks release of hormone from thyroid. 5 drops (0.25 ml or 250 mg) every 6 hours. PO, NG.
Lugol’s Solution Blocks release of hormone from thyroid. 4 – 10 drops every 6 to 8 hours. PO, NG
Sodium ipodate Blocks release of hormone from thyroid.
Inhibits T4 to T3 conversion.
1 – 3g every day. PO
Iopanoic acid Blocks release of hormone from thyroid.
Inhibits T4 to T3 conversion.
1g every 8 hours for 24 hours, then 500mg every 12 hours. PO
3. Inhibit peripheral effects of thyroid hormone
Propranolol Reduces symptoms due to increased adrenergic tone.
Inhibits T4 to T3 conversion.
40 – 80 mg every 4 hours. PO, NG

1 – 2 mg IV every 4 hours. IV

Esmolol Reduces symptoms due to increased adrenergic tone. May be preferred in setting of possible heart failure due to short half-life. 500 μg\kg\min over 1 minute and then 50 – 100 μg\kg\min. IV
4. Glucocorticoids.
Dexamethasone (Preferred) Inhibit the peripheral conversion of T4 to T3. Promote vascular stability. Treat relative possible relative adrenal insufficiency. 2 mg every 6 hours. IV, PO, NG
Hydrocortisone Inhibit the peripheral conversion of T4 to T3. Promote vascular stability. Treat relative possible relative adrenal insufficiency. 300 mg load and then 100 every 8 hours. IV
  1. Peripheral symptom control (ex. tachycardia, chest pain, dyspnea, etc.) is done primarily through β blockade. Traditionally this has been done with either oral or intravenous propranolol. However, the serum half-life of propranolol is relatively long (3 to 6 hours) and may worsen symptoms of cardiac failure. Esmolol, with a markedly shorter half-life, may be a better choice in the setting where the patient’s cardiac status is unclear or if the patient has underlying reactive airway disease.
  2. Inhibition of thyroid hormone synthesis is undertaken before inhibition of hormone release. Thioureas, either PTU or methimazole, are used to block additional hormone synthesis. PTU is preferred as it has the additional benefit of blocking peripheral conversion of T4 to T3. PTU is approved for use in pregnancy. However, it does have significant risks, including liver injury and failure and has received a black box warning from the US Food and Drug Administration.
  3. Inhibition of hormone release by iodine therapy. Iodine therapy should not be started any sooner than one hour after the initiation of a thiourea. In the absence of a thiourea, iodine may actually stimulate release of preformed thyroid hormone. Iodine, in the presence of a thiourea, blocks the release of preformed hormone and decreases iodide transport into thyroid follicular cells and subsequent oxidation. The inhibition is short lived and is ineffective after 48 hours of therapy.

Glucocorticoids are also frequently given in thyroid storm as they may decrease the conversion of T4 to T3, although the significance of this effect is unknown. An unknown percentage of patients in thyroid storm have adrenal insufficiency. Dexamethasone is typically preferred due to its lack of interference on an ACTH stimulation test. A random cortisol level should be obtained prior to administration of a steroid.

All patients in thyroid storm should be admitted to an intensive care unit after stabilization and initiation of thyroid specific interventions. Even with aggressive care, a significant percentage of patients will die.

Pearls and Pitfalls

  • Suspect thyroid storm in any patient with a history of thyroid disease (esp. thyrotoxicosis) and a hypermetabolic state.
  • The diagnosis of thyroid storm is a clinical diagnosis.
  • Always look for the trigger (ex. Infection, myocardial infarction, etc.)
  • Do not initiate iodine therapy before thiourea treatment.
  • These patients are critically ill and have a high mortality rate, even with appropriate therapy.

References

  1. Devereaux D, Tewelde SZ: Hyperthyroidism and Thyrotoxicosis. Emerg Med Clin N Am 2014;32:277-92.
  2. Kubo-Gwiezdzinska J, Wartofsky L: Thyroid emergencies. Med Clin N Am 2012;96:385-403.
  3. Bahn RS (Chair), Burch HB, Cooper DS, et al. The American Thyroid Association and American Association of Clinical Endocrinologists Taskforce on Hyperthyroidism and Other Causes of Thyrotoxicosis: Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. American Thyroid Association. http://www.thyroid.org/thyroid-guidelines/hyperthyroidism/ Last accessed Sept. 5, 2014.
  4. Burch HB, Wartofsky L: Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin N Am 1993;22(2):263-77.
  5. Nayak B, Burman K: Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin N Am 2006;35:663-86.
  6. Mills L, Lim S: Identifying and treating thyroid storm and myxedema coma in the Emergency Department. Emerg Med Pract 2009;11(8).

2 thoughts on “Thyroid Storm

  1. Figure 1 is missing. The table of medications has an error with the IV dosing of propranolol in the esmolol section.

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