Thyroid Storm

by Shabana Walia

Introduction

Thyrotoxicosis occurs when there is an excess of circulating thyroid hormone in the body, whereas hyperthyroidism refers to thyrotoxicosis that arises from a hyperfunctioning thyroid gland. Thyroid storm, a true endocrine emergency, is the most extreme form of thyrotoxicosis. It consists of a triad of severe hyperthermia, cardiovascular dysfunction and altered mental state. Although it occurs in less than 2% of patients with thyrotoxicosis, Emergency Physicians must maintain a high index of suspicion for thyroid storm because mortality approaches 80-100% if untreated. Prompt identification and appropriate treatment can reduce the mortality to 15-50%.

Case Presentation

A 68-year-old female with hypertension presented to the emergency department (ED) with worsening of lower extremity swelling for the last few months. She appeared to be confused over the last three days according to her husband. He also noted that she had a fever. She had intermittent chest discomfort and was feeling “anxious.” She was compliant with the prescribed antihypertensive (lisinopril and hydrochlorothiazide). She used no tobacco or illicit drug. She had a family history of hypertension and hyperthyroidism.

Her vitals at triage were as follows: BP 170/86mmHg, HR 136/min, RR 18/min, Temp 40.2°C and SpO2 100% on room air. She appeared agitated and flushed, with bilateral exophthalmos and lid lag. Her thyroid was diffusely enlarged with bruit noted. Her pulse was irregularly irregular. She had pitting edema up to the mid-shin. Bilateral plantar reflexes were 3+. The rest of the physical examination was unremarkable.

Bedside ECG is below

38 - atrial fibrillation

Her blood test results were as follow:
Normal CBC and renal function.
Calcium: 11.5 mg/dL (8.6-10.2)
Thyroid stimulating hormone (TSH) < 0.01 mlU/L (0.34-5.6)
Free T3: > 30 pg/ml (2.5- 3.9)
Free T4: > 6 ng/dL (0.58-1.64)
Troponin: 0.10 (<0.04)
Pro-BNP: 3,000 pg/mL (0-100)

A diagnosis of hyperthyroidism was made, and she was evaluated for possible thyroid storm.

Critical Bedside Actions

A patient with suspected thyroid storm should be placed in the resuscitation area. Evaluate the patient’s ABCs and establish intravenous access. Vitals signs, including temperature, must be closely monitored.

Initiate aggressive supportive care, including temperature control. Treatment of the thyrotoxic state is aimed at inhibition of thyroid hormone release, inhibition of new hormone synthesis, inhibition of peripheral conversion of T4 to T3, and lastly blockage of peripheral beta-adrenergic receptors.

Evaluate the patient for precipitants (e.g., sepsis, noncompliance of anti-thyroid medications, trauma to the thyroid, radioactive iodine therapy, chemotherapy, recent surgery, and molar pregnancy) and complications of the thyroid storm (e.g., high output cardiac failure, atrial fibrillation). The underlying precipitant has to be addressed early and concurrently with treatment for complications of the thyroid storm.

Differential Diagnosis

Differentials of thyroid storm include:

  • Acute psychosis
  • Alcohol or benzodiazepine withdrawal
  • Anticholinergic overdose
  • Encephalitis/meningitis
  • Heat stroke
  • Hypertensive encephalopathy
  • Malignant hyperthermia
  • Neuroleptic malignant syndrome (NMS)
  • Sepsis
  • Serotonin syndrome
  • Sympathomimetic overdose

History and Physical Exam Hints

As thyroid hormones act on almost every cell in the human body, thyroid storm will result in multi-organ dysfunction.

A thorough history and physical exam are keys to diagnosing thyroid storm. Patients often have a personal or family history of thyrotoxicosis. Initial symptoms may be vague and nonspecific. Symptoms of weight loss, ravenous appetite, emotional labiality or irritation, and heat intolerance suggest thyrotoxicosis. In a patient with prequel symptoms, hypermetabolic state, and deranged vital signs, the diagnosis of thyroid storm should be considered.

While the differentiation between thyrotoxicosis and thyroid storm is a clinical one, the diagnostic criteria by Burch and Wartofsky can help to identify a thyroid storm (modified in Table 1). A key diagnostic criterion is severe hyperthermia, as heat production becomes excessive and unregulated. Temperature above 38.5°C is common, and can even exceed 41°C. Patients also present with altered mental state and severe cardiovascular dysfunction.

Other common physical exam findings of thyroid storm include sweating, tachycardia, hypertension with a widened pulse pressure, anxiety, atrial fibrillation, tremors, exophthalmos, goiter, and hyperreflexia. Note that the tachycardia seen in a thyroid storm is often out of proportion to the fever.

Criterion for Diagnosing Thyroid Storm

CategorySituationScore
Thermoregulatory Dysfunction99-99.9
100-100.9
101-101.9
102-102.9
103-103.9
104
5
10
15
20
25
30
CNS EffectsAbsent
Mild-Agitation
Moderate-Psychosis, Delirium, Fatigue
Severe-Seizures/Comatose
0
10
20

30
Gastrointestinal or Liver DysfunctionAbsent
Moderate- Diarrhea/N/V/Abdominal pain
Severe-Jaundice
0
10

20
Cardiovascular DysfunctionTachycardia
99-109
110-119
120-129
130-139
140
5
10

15
20
25
Congestive Heart Failure
Absent
Mild-Pedal edema
Moderate-Bibasilar rales
Severe-Pulmonary edema
0
5
10
15
Atrial Fibrillation
Absent
Present
0
10
Precipitant History
Negative
Positive
0
10
Table 1: Criterion for diagnosing thyroid storm, Modified from the original Burch HB, Wartofsky L. Criteria: Life-threatening thyrotoxicosis: Thyroid storm. Endocrinol Metab Clin North Am 22:263-277, 1993. Please read the article for more information.

SCORING SYSTEM Add total points based on patient’s history and physical exam:

>45: Highly suggestive of thyroid storm
25-44: Suggestive of an impending thyroid storm or thyrotoxicosis
<25: Unlikely thyroid storm based on presentation

 

The patient in our case presentation above
Temp: 30
CNS effects: 10
GI-Liver: 0
Tachycardia: 20
CHF: 5
Atrial Fibrillation: 10
Precipitant History: 0
TOTAL POINTS: 75

Emergency Diagnostic Tests and Interpretation

The following investigations are indicated in patients with suspected thyroid storm: CBC, renal function test, liver function test, thyroid function tests, metabolic panel (including calcium), ECG, CXR.

While confirming the presence of thyrotoxicosis, thyroid function tests alone cannot be used to rule in or rule out thyroid storm reliably. Thyroid stimulating hormone (TSH) will be low or undetectable, with elevated free triiodothyronine (T3) and its prohormone, thyroxine (T4). Hypercalcemia, elevated alkaline phosphatase, and hyperglycemia are other common lab abnormalities seen due to bone resorption, bone remodeling, and glycogenolysis, respectively. Abnormalities on ECG include premature atrial, premature ventricular contractions, atrial fibrillation, or atrial flutter The CXR may show cardiomegaly and pulmonary vascular congestion – indicating heart failure. If global or focal neurological deficits are found, it is reasonable to consider a head CT scan to rule out a precipitating or concurrent intracranial process.

Use the Burch and Wartofsky criteria to evaluate for the likelihood of thyroid storm. If the diagnosis is suspected, treatment with the medications listed in Table 2 should be initiated. The primary goals are blocking the peripheral effects of thyroid hormone, preventing the synthesis of T3 and T4, and inhibiting the release of preformed thyroid hormone.

Emergency Treatment Options

Initiate supportive care expeditiously. Administer intravenous fluid to correct volume depletion, supplemental oxygen for hypoxia and external cooling measures for severe hyperthermia. Acetaminophen alone is not helpful as the hyperthermia in thyroid storm is not a central, hypothalamic regulatory problem. Cooling blankets, ice packs or even cold intravenous fluids can be used. In patients with airway compromise, rapid sequence intubation and paralysis should be considered with a secondary aim of temperature control. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided as they can increase peripheral free T3 and T4 due to their protein binding properties.

Medical Treatment for Thyroid Storm

GOALMEDICATIONMECHANISM OF ACTIONEXTRA CONSIDERATIONS
STEP 1: Block peripheral adrenergic effects of thyroid hormonePropranolol: 60-80mg PO q4hrs or 0.5-1 mg IV q1h (slow infusion)

Esmolol:250-500micrograms/kg IV bolus, then 50-100micrograms/kg infusion
Beta blockade, shorter half life with esmolol

Propranolol has the additive mechanism of blocking conversion of T4 to T3 in peripheral tissues
Use propranolol with caution in those with signs and symptoms of congestive heart failure, as this can cause cardiogenic shock and collapse

Esmolol is a selective B-1 blocker, thus can be used in patients with bronchospasm or asthma
STEP 2: Prevent synthesis of thyroid hormonePropylthiouracil (PTU): 600-1000mg PO initial dose, then 200-250 q4h

Methimazole: 20-30mg PO initial dose, then 20-30 q6h

Dexamethasone: 2mg IV q6h

Hydrocortisone: 300mg IV initial dose, then 200 mg q8h
Central mechanism of PTU and MMI: Inhibits thyroid peroxidase. Thyroid peroxidase oxidizes iodide to create iodine, which is then added to tyrosine residues on thyroglobulin, creating T3 and T4

Steroids decrease the conversion of T4 to T3 in the periphery
PTU also inhibits peripheral conversion of T4 to T3 by inhibiting the enzyme 5’deiodinase
STEP 3: Inhibit release of thyroid hormoneLugol’s Solution (Iodine): 8 drops PO q6h

SSKI: 5 drops PO q6h
Decreases the release of thyroid hormone from the thyroid glandMust be given at least one hour after PTU or it can increase thyroid stores by iodinating tyrosine
Table produced by author.

 

Pediatric, Geriatric, Pregnant Patients And Other Considerations

Pediatric patients may not present with the classic symptoms of hyperthyroidism. They may only demonstrate jitteriness, agitation, restlessness without typical ophthalmologic or other systemic findings.

The presentation in geriatric patients may be even more subtle. These vague complaints may be easily dismissed by the patients themselves or care provider, or even mistaken as normal aging. Alternatively, they may also present with primarily cardiovascular complaints, such as palpitations, chest discomfort or signs of heart failure. Therefore, a high index of suspicion should always be maintained in the elderly.

Pregnancy can trigger thyrotoxicosis in up to 10% of patients, even up to 6 months postpartum. High estrogen and human chorionic gonadotropin level have weak TSH-like effects and contribute to an overall hyperthyroid state. Propylthiouracil (PTU) is preferred over methimazole (MMI) in this population, as it does not cross the placenta as readily. Methimazole is also associated with choanal atresia and aplasia cutis. Both drugs are FDA category D in pregnancy.

Disposition

Admit all patients with thyroid storm to the ICU or high dependency unit for ongoing monitoring and treatment.

Admit the patients with partially-controlled thyrotoxicosis symptoms for further management. Patients with mild controlled symptoms and stable vital signs may be discharged with close follow up with the primary care physician or endocrinologist.

References and Further Reading

  • Sherman SC. Thyroid Emergencies. In: Wolfson AB, Hendey GW, et al. eds. Harwood-Nuss’ Clinical Practice of Emergency Medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010: 1021-1026.
  • Misra Madhusmita (2015). “Thyroid Storm” Medscape. http://emedicine.medscape.com/article/925147-overview.
  • Douglas S Ross, MD. Thyroid Storm In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on November 20, 2015.)
  • Shah AA, Lettieri CJ (2007). “Endocrine Emergencies”. Medscape. http://www.medscape.org/viewarticle/567307.
  • Burch HB, Wartofsky L: Life-threatening thyrotoxicosis: Thyroid storm. Endocrinol Metab Clin North Am 22:263-277, 1993.
  • Sharma AN, Levy DL. Chapter 128: Thyroid and Adrenal Disorders. In: Marx JA, Hockberger RS, Walls RM, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia, PA. Saunders/Elsevier: 2014. 1676-1692.
  • Idrose, Alzamani Mohammad. (2011). Chapter 224: Thyroid disorders: Hyperthyroidism and Thyroid Storm. In J. Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T. eds Tintinalli’s emergency medicine: A comprehensive study guide, 7e.
  • Marini JJ, Wheeler AP. Critical Care Medicine: The Essentials. 4th ed. Philadelphia, PA. Lippincott Williams & Wilkins; 2010.