Thyroid Storm

Aka: Thyroid Storm, Thyroid Crisis, Apathetic Thyroid Storm

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II. Definitions

  1. Thyroid Storm
    1. Severe Thyrotoxicosis

III. Epidemiolgy

  1. Incidence: 0.57 to 0.76 per 100,000 persons per year in U.S.
    1. Rare in developed countries due to earlier recognition and treatment of Hyperthyroidism
    2. Hyperthyroidism by contrast is relatively common (0.5% of U.S. adults have symptomatic Hyperthyroidism)

IV. Causes: Underlying Hyperthyroidism

  1. See Hyperthyroidism
  2. Common
    1. Graves Disease (most commonly associated with Thyroid Storm)
    2. Multinodular Goiter
    3. Toxic adenoma
  3. Other
    1. Thyroiditis
    2. Struma ovarii tumor
    3. TSH-Secreting Pituitary Tumor

V. Causes: Thyroid Storm Triggers

  1. Thyroid Storm results from Hyperthyroidism that is exacerbated by a triggering event
  2. Uncontrolled Hyperthyroidism (esp. Graves Disease) with concurrent acute stress
    1. Pulmonary Infection (most common cause)
    2. Myocardial Ischemia or Myocardial Infarction
    3. Cerebrovascular Accident
    4. Diabetic Ketoacidosis
    5. Trauma
    6. Surgery
    7. Gastrointestinal Illness
    8. Pregnancy (including Ectopic Pregnancy, Molar Pregnancy)
    9. Heat Illness
    10. Hypothermia
    11. Medications Affecting Thyroid Function (includes Drug-Induced Thyroiditis, e.g. Amiodarone, iodinated contrast)
    12. Non-compliance with antithyroid medications
  3. Other, uncommon causes
    1. Graves Disease following Radioactive Iodine therapy
    2. Thyroid surgery for Hyperthyroidism (rare with modern protocols)

VI. Pathophysiology

  1. See Thyroid Physiology
  2. Excess T3 Hormone and increased T3 sensitivity result in increased circulating Catecholamines
  3. Up-regulation of Beta Adrenergic Receptors are more responsive to circulating Catecholamines (except in elderly)
    1. Even a seemingly minor trigger, may precipitate the appearance of a hyperadrenergic state
    2. Results in hypermetabolic state

VII. Precautions

  1. Thyroid Storm may mimic other conditions (e.g. Sepsis) or be overshadowed by a triggering condition (e.g. DKA)
  2. Elderly may present with minimal signs of Thyrotoxicosis (Apathetic Thyroid Storm) with CHF, stupor to coma
    1. Cell surface Beta Adrenergic Receptors are present less in elderly and therefore decreased adrenergic response
    2. Have a low threshold for Thyroid testing in the elderly
  3. Young patients present more critically in Thyroid Storm
    1. Increased sensitivity to circulating Catecholamines results in severe, life-threatening presentations

VIII. Symptoms

  1. See Hyperthyroidism
  2. Compared with typical Hyperthyroidism, Thyroid Storm presents with more severe secondary symptoms
    1. Fever
    2. Altered Mental Status (e.g. Delirium)
    3. Dyspnea (including Orthopnea)
    4. Chest Pain
    5. Diplopia
  3. Gastrointestinal symptoms may also be present
    1. Nausea or Vomiting
    2. Abdominal Pain
    3. Hepatic dysfunction

IX. Signs

  1. See Thryoid Storm Diagnosis (Burch Wartofsky Score)
  2. Constitutional
    1. Fever >39 C (102 F)
    2. Profuse sweating
  3. Cardiovascular
    1. Hypertension
    2. Sinus Tachycardia (often >130 bpm)
    3. Tachydysrhythmias (e.g. Atrial Fibrillation)
    4. High output cardiac failure (edema, pulmonary rales, wide Pulse Pressure)
  4. Neuropsychiatric
    1. Altered Level of Consciousness
    2. Delirium
    3. Agitation or Psychosis
    4. Hyperreflexia
    5. Tremor

X. Differential Diagnosis

  1. Sepsis
  2. Sympathomimetic Toxicity (Stimulant Overdose)
  3. Alcohol Withdrawal
  4. Malignant Hyperthermia
  5. Neuroleptic Malignant Syndrome
  6. Heat Related Illness

XI. Associated Conditions: Presentations

  1. New onset Atrial Fibrillation
    1. Atrial Fibrillation is seen in up to 10 to 22% of Hyperthyroidism patients
  2. New onset, unexplained Congestive Heart Failure
  3. Advanced Hyperthyroidism Findings (e.g. Exophthalmos, Thyroid Goiter)
  4. Gastrointestinal Findings in Multiorgan Failure (e.g. Vomiting, Abdominal Pain, Diarrhea, hepatic dysfunction)
  5. Apathetic Thyroid Storm (elderly)
    1. Generalized weakness and Fatigue
    2. Apathy and Depressed Mood
    3. Altered Mental Status (stupor to coma)

XII. Labs

  1. Precautions
    1. Thyroid Storm is a clinical diagnosis
    2. Labs reflect Hyperthyroidism, but not severity
  2. Thyroid specific testing
    1. Thyroid Stimulating Hormone (TSH)
      1. Suppressed in most cases
      2. Increased in TRH-Secreting Tumors (10-15% of Thyroid Storm cases)
    2. Free T4
      1. Increased
    3. Total Triiodothyronine (T3)
      1. Increased (preferred over Free T3)
  3. Broad based lab evaluation to cover differential diagnosis
    1. Bedside Glucose
    2. Comprehensive Metabolic Panel
      1. Liver Function Tests, Alkaline Phosphatase and Serum Calcium may be increased
    3. Complete Blood Count
      1. Reactive Leukocytosis or Leukopenia
    4. Pregnancy Test (bHCG) in women of child-bearing age
    5. Serum Troponin
    6. Urinalysis
    7. Venous Blood Gas
    8. Lactic Acid
    9. Blood Cultures
    10. Coagulation Studies
      1. Coagulopathy including DIC may be present

XIII. Imaging

  1. Avoid iodinated contrast studies (e.g. CT with contrast)
  2. Chest XRay
    1. May demonstrate high output Heart Failure, precipitating events (e.g. Pneumonia)
  3. Head CT (non-contrast)
    1. Indicated in Altered Mental Status

XIV. Diagnostics

  1. Electrocardiogram
    1. Evaluate for Arrhythmia (e.g. Atrial Fibrillation, PSVT, Sinus Tachycardia)
  2. Echocardiogram (bedside POCUS)
    1. Identify Heart Failure
    2. Differentiate low output from high output Heart Failure

XV. Diagnosis

  1. See Thryoid Storm Diagnosis (Burch Wartofsky Score)

XVI. Management

  1. General Measures
    1. Manage Airway
    2. Supplemental Oxygen
    3. Intravenous Fluids
      1. Dehydration may occur due to gastrointestinal loss, increased basal metabolic rate
    4. Cooling blanket and other external cooling
      1. Avoid active cooling due to worsening the Vasoconstriction already present with Thyroid Storm
    5. Use Acetaminophen for fever
    6. Neuropsychiatric Management
      1. Treat Agitation with Benzodiazepines and Antipsychotics
      2. Treat Seizures with Benzodiazepine and antiepileptics
    7. Treat concurrent infection (often inciting event)
      1. Thyroid Storm alone (without infection) can also result in fever, and distinguishing the two may be difficult
    8. Precautions
      1. Follow the stepped protocol below in sequential steps
      2. Consult Endocrinology
      3. Intensive Care Unit admission
  2. Avoid provocative medications
    1. Avoid iodinated contrast and other Iodine sources (except as specifically described below)
    2. Avoid Nitroglycerin
      1. Abruptly reduces Preload and worsens high output Heart Failure
    3. Avoid Salicylates and NSAIDS due to their increase of T4 and T3
      1. NSAIDS and Salicylates dislodge T4 from Protein binding and allow for conversion to the more active T3
  3. Step 1: Heart Rate control (Beta Blockers are preferred)
    1. Beta Blockers (preferred)
      1. Beta Blockers slow rate AND decrease peripheral conversion from T4 to the more active T3
      2. Propranolol
        1. Most common Beta Blocker used in Thyroid Storm
        2. Most effective at blocking T4 to T3 conversion
        3. Dosing
          1. Oral 60 to 80 mg every 4 to 6 hours as needed
          2. Intravenous 0.5 to 1 mg over 10 minutes every few hours as needed while transitioning to oral dosing
      3. Metoprolol 5-10 mg IV every 2-4 hours (or Metoprolol Tartrate 50 mg orally every 6 hours)
        1. Consider in COPD or Asthma, where its cardioselective activity is less likely to affect respiratory function
      4. Esmolol
        1. Allows for titration with rapid response and quick discontinuation
        2. Consider in Systolic Heart Failure or Hypotension risk in which Beta Blocker may need rapid discontinuation
        3. Dosing
          1. Load: 250 to 500 mcg/kg
          2. Maintenance: 50-100 mcg/kg/min IV, titrated to Blood Pressure and Heart Rate targets
    2. Diltiazem (if Beta Blockers are contraindicated)
      1. Calcium Channel Blockers do NOT decrease peripheral conversion from T4 to the more active T3
      2. Diltiazem 0.25 mg/kg IV bolus over 2 min, then 10 mg/h IV (or 60-90 mg orally every 6-8 hours)
  4. Step 2: T4 and T3 Synthesis suppression with Thionamides
    1. Propylthiouracil (PTU)
      1. Dosing
        1. Load 500 to 1000 mg PO, PR, or per NG
        2. Maintenance 200 to 250 mg (up to 400 mg) every 4 hours PO, PR, or per NG
      2. Propylthiouracil is preferred in first trimester of pregnancy
      3. Most commonly used in Thyroid Storm
        1. More effectively decreases peripheral conversion of T4 to T3
        2. More potent and rapid onset than methimiazole
        3. PTU in first day, decreases T3 by 45%, compared with 10-15% with Methimazole
    2. Methimazole 20-40 mg every 6 to 8 hours IV, PO, PR, per NG
      1. Methimazole is highly Teratogenic in first trimester pregnancy and should be avoided
      2. Methimazole is preferred in second and third trimesters of pregnancy
  5. Step 3: T4 and T3 Release suppression with Iodine
    1. Do NOT give before synthesis suppression (see step 2)
      1. May otherwise promote new Thyroid Hormone synthesis
      2. With all the focus on medication order in Thyroid Storm, this is the one critical step not to give too early
        1. Must only be given at least 60 minutes AFTER Thionamide (PTU or Methimazole)
        2. Iodine has two mechisms of action
          1. Increases Thyroid Hormone synthesis (worsening Thyroid Storm in absence of Thionamide)
          2. Blocks release of stored Thyroid Hormone and decreases Iodine transport (Wolff-Chaikoff Effect)
            1. Effects limited to 2 weeks (after which T4 secretion resumes)
    2. Saturated Solution Potassium iodide (SSKI)
      1. Dose: 5 drops (50 mg Iodide/drop) mixed in fluid or food every 6 hours for at least 2 days
      2. Initiate at least one hour after antithyroid medication
    3. Lugols Solution
      1. Dose: 10 drops (6.25 mg Iodide/drop) orally, rectally or in IV fluids three times daily
  6. Step 4: T4 to T3 conversion suppression with Glucocorticoids
    1. Preparations
      1. Hydrocortisone load 300 mg, then 100 mg IV every 8 hours (preferred) OR
      2. Dexamethasone 2 mg orally or IV every 6 hours OR
      3. Betamethasone 0.5 mg orally, IV or IM every 6 hours
    2. Additional benefits of Corticosteroids (beyond T4 to T3 suppression)
      1. Also counters autoimmune process in Graves Disease
      2. Manages concurrent Adrenal Insufficiency
  7. Step 5: Bile Acid Sequestration
    1. Mechanism
      1. Precaution: May reduce other oral medication absorption
      2. Reduces Thyroid Hormone intestinal reabsorption and enterohepatic circulation, and increases fecal excretion
        1. Thyroid Hormone is normally hepatically metabolized and then reabsorbed from intestinal tract
    2. Cholestyramine 4 grams orally four times daily
  8. Step 6: Plasmapheresis
    1. Indicated in critically ill Thyroid Storm not responding to other measures
    2. In theory, removes from the serum, excess Thyroid Hormone

XVII. Complications

  1. Atrial Fibrillation
  2. Congestive Heart Failure
    1. Critical to distinguish between high output Heart Failure and low output Heart Failure
    2. Often related to secondary Atrial Fibrillation with Rapid Ventricular Rate (which improves with Beta Blockers)
    3. Bedside Ultrasound
      1. Hyperdynamic heart activity is more consistent with high output Heart Failure
    4. Consider Non-Invasive Positive Pressure Ventilation (e.g. BIPAP)
    5. Avoid Diuretics (patients in Thyroid Storm are often hypovolemic)
  3. Multisystem organ failure
    1. Congestive Heart Failure (as above)
    2. Acute Kidney Injury
    3. Acute Hepatic Insufficiency
    4. Pancreatic insufficiency
    5. Disseminated Intravascular Coagulation
    6. Adrenocortical Insufficiency
  4. Neurologic dysfunction
    1. Altered Mental Status (Stupor or coma)
    2. Seizures
    3. Thyrotoxic periodic paralysis
      1. Gradual extremity paralysis associated with rapid intracellular Potassium shifts

XVIII. Prognosis

  1. Mortality of Thyroid Storm approaches 8 to 25%
    1. Multisystem organ failure is the most common cause of death

XIX. References

  1. De Groot (2022) Thyroid Storm inFeingold, Endotext
    1. https://www.ncbi.nlm.nih.gov/books/NBK278927/
  2. Elidritz (2023) Crit Dec Emerg Med 37(5): 4-11
  3. Swaminathan and Willis in Herbert (2019) EM:Rap 19(10): 13-5
  4. Swadron and Mason in Herbert (2019) EM:RAP C3 3(11): 1-10
  5. Carroll (2010) Ther Adv Endocrinol Metab 1(3): 139–145 [PubMed]
    1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475282/
  6. Idrose (2015) Acute Med Surg 2(3): 147-57 +PMID: 29123713 [PubMed]
  7. Kravets (2016) Am Fam Physician 93(5): 363-70 [PubMed]
  8. Nayak (2006) Endocrinol Metab Clin North Am 35(4): 663-6 [PubMed]

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