Definition: A life-threatening, pathologic state in which the body manifests a myriad of symptoms ranging from high-output cardiac failure to severe alterations of mental status in response to excess circulating thyroid hormone

  • Hyperthyroidism: Disorders resulting from overproduction of thyroid hormone
  • Thyrotoxicosis: Disorders resulting from any cause of excess thyroid hormone

Epidemiology (Nayak 2006)

  • Rare condition that is more common in women (80/100,000 per year) than in men (8/100,000 per year)
  • Extremely rare in children (0.9/100,000 per year)
  • Most cases are due to Graves’ disease

Hyperthyroidism Etiologies

  • Graves’ disease
  • Toxic adenoma (single responsible nodule)
  • Toxic multinodular goiter
  • Thyrotoxicosis with thyroiditis
    • Hashimoto’s thyroiditis
    • Subacute thyroiditis
    • Postpartum thyroiditis
  • Exogenous thyroid hormone abuse
  • Iatrogenic (i.e.) Amiodarone induced thyroiditis
  • Oncologic
    • TSH-producing pituitary tumor
    • Metastatic follicular thyroid carcinoma
  • hCG-mediated thyrotoxicosis
    • Hydatidiform mole
    • Metastatic choriocarcinoma

Precipitants of Thyroid Storm

  • Untreated/undertreated thyroid disease (i.e. medication non-compliance)
  • Trauma (direct trauma or as a result of stress to body)
  • Thyroid or non-thyroid surgery
  • Iodinated contrast (typically in susceptible patients with Graves’ disease or multi nodular goiter)
  • Myocardial infarction/ischemia
  • Infection
  • Diabetic Ketoacidosis/Hyperosmolar Nonketotic Coma
  • Ingestion of thyroid hormone

Pathophysiology

  • T4 produced by the thyroid is deiodinated to the more active T3 form
  • Most (> 99%) of thyroid hormone is protein bound and, thus inactive. Only free thyroid hormone is metabolically active
  • Thyroid hormone affects metabolism in all tissues in the body via a variety of mechanisms
  • Thyroid hormone increases the expression and sensitivity of beta-adrenergic receptors resulting in an increased response to endogenous catecholamines (this accounts for many of the symptoms seen in thyroid storm)
  • Wolff-Chaikoff Effect: Excess iodide transiently inhibits thyroglobulin iodination and release of thyroid hormone
  • Jod-Basedown Effect: Iodide load induces hyperthyroidism in susceptible subgroups (i.e. Graves’ disease, multi nodular goiter)

Clinical Manifestation

  • Classic presentation: fever, tachycardia and altered mental status
  • See below for common additional symptoms and signs
Organ System Symptoms Signs
CNS Anxiety

Confusion

Delirium

Psychosis

Lethargy

Seizures

Coma

Hyperreflexia

Cardiovascular Palpitations

Chest Pain

Dyspnea on exertion

Sinus Tachycardia

Atrial fibrillation

Widened pulse pressure

Heart failure

Gastrointestinal Abdominal pain

Nausea

Vomiting

Diarrhea

Jaundice
Thyroid Gland Neck fullness Tenderness over thyroid

Diffuse enlargement

Bruit

Diagnosis

  • Diagnosis is made based on clinical evaluation not serum testing
    • Serum testing results are often delayed or unavailable in many institutions
    • TSH, T3/T4 are unreliable in acute decompensated states
  • Burch-Wartofsky Scale (Burch 1993)
    • Most commonly used system for diagnosing thyroid storm
    • Does not rely on any laboratory values allowing for rapid recognition and diagnosis

Burch Wartofsky Scale (adapted from Burch 1993)

  • Common laboratory findings
    • Low (or non-detectable) TSH and elevated T3/T4
    • Hyperkalemia + hyponatremia (in concomitant adrenal insufficiency)
    • Anemia
    • Thrombocytopenia
    • Low serum creatinine
    • Hypercalcemia

Management Basics

  • Evaluate and address airway and breathing
  • Establish IV access
  • Place patient on cardiac monitor
  • Active cooling measures including ice packs and cooling blankets may be necessary if patient with severe hyperthermia
  • Consider empiric fluid administration
    • Insensible fluid losses from fever can be high in these patients
    • High output cardiac failure is common and preload should be maintained in these patients
    • Add dextrose to fluids (patients often have depleted glycogen stores)
  • Consider empiric broad spectrum antibiotics
    • Signs and symptoms in thyroid storm mimics sepsis and distinguishing the two can be difficult
    • Infection is a leading precipitant for thyroid storm

Directed Management

  • Cardiovascular Effects of Thyrotoxicosis – Woeber 1992

    Block peripheral effects of thyroid hormone with beta blocker (Woeber 1992)

    • Propranolol most commonly used
      • Non-selectvie beta blockade effectively treated systemic effects
      • Additional benefit of blocking conversion of T4 to T3
      • Dose: 0.5 – 1 mg IV over 3-5 minutes
      • Can repeat dose q5-10 minutes
      • Titrate to HR < 100
      • Keep a close eye on blood pressure
    • Esmolol
      • Can be substituted if concern for hemodynamic collapse
      • Dose
        • Load: 250-500 mcg/kg
        • Infusion: 50-100 mcg/kg/min
    • Role of beta blocker with signs of heart failure
      • Heart failure typically high-output and beta blockade will still be beneficial
      • Start slow with test dose and follow response prior to additional doses
  • Inhibit thyroid hormone synthesis
    • Propylthiouracil (PTU)
      • Dose
        • Load: 600-1000 mg PO
        • 300 mg PO Q6
      • Impairs conversion of T4 to T3
      • Preferred in pregnancy
    • Methimazole: 20-30 mg Q6 hours
    • Both drugs can be given PO, NG or PR
  • Administer corticosteroids
    • Function
      • Block conversion of T4 to T3
      • Block release of hormone from the thyroid gland
      • Concomitant adrenal insufficiency is common
    • Hydrocortisone: 100 mg IV Q8 hours
    • Dexamethasone
      • Dose: 2-4 mg IV Q6 hours
      • Preferred if unsure if adrenal insufficiency present and will be doing cortisol stimulation testing later
  • Inhibit thyroid hormone release with inorganic iodine
    • Mechanism of action
      • Blocking synthesis does not stop release of preformed thyroid hormone
      • Blocks release of stored thyroid hormone
      • Can increase synthesis of thyroid hormone so should be held for at least 1 hour after initiation of PTU
    • Medication options
      • Potassium Iodide (SSKI): 5 gtt Q6 hours
      • Lugol’s solution: 4-8 gtt Q6 hours
      • Lithium 300 mg Q6-8 hours (alternative if SSKI/Lugol’s contraindicated)
  • Additional interventions
    • Cholestyramine
      • Blocks enterohepatic recirculation of thyroid hormone
      • Dose: 4 g PO Q6 hours
    • L-Carnitine
      • Blocks entry of thyroid hormone into cells
      • Dose: 1 g PO Q12 hours
  • Disposition: Admit to ICU or other highly monitored unit

Take Home Points

  • Thyroid storm is a clinical diagnosis and should be suspected in any patient with fever, altered mental status
  • Diagnosis can be rapidly made using the Burch-Wartofsky scale. This allows for rapid initiation of treatment and reduction of morbidity and mortality
  • Strongly consider covering all thyroid storm patients with broad spectrum antibiotics because of the frequency of concomitant infection
  • Directed management starts with beta blockade to reduce the peripheral effects of thyroid hormone. This should be followed by corticosteroids, thionamides and inorganic iodine

Read More

EM: RAP: Episode 105 – Hyperthyroidism

ALiEM: Diagnosing hyperthyroidism: Answers to 7 common questions

ALiEM: Thyroid Storm – Treatment Strategies

LITFL: Thyroid Storm

WikeEM: Burch and Wartofsky Diagnostic Criteria for Thyroid Storm

Sharma AN, Levy DL: Thyroid and Adrenal Disorders; in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 128: p 1676-94.

References

Nayak B, Burman K. Thyrotosicosis and thyroid storm. Endocrinol Metab Clin N Am 2006; 35: 663-686. PMID: 17127140

Burch HB, Wartofsky L: Life-threatening thyrotoxicosis: Thyroid storm. Endocrinol Metab Clin North Am 22:263-277, 1993. PMID: 8325286

Woeber KA. Thyrotoxicosis and the heart. NEJM 1992; 327(2): 94-8. PMID: 1603141

Franklyn JA. The management of hyperthyroidism. NEJM 1994; 330: 1731-8. PMID: 7910662