Thyroid Storm

Aka: Thyroid Storm, Thyroid Crisis

1. See Also
   1. Hyperthyroidism
2. Definitions
   1. Thyroid Storm
      1. Severe Thyrotoxicosis
3. Causes
   1. 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. Trauma or surgery
      5. Gastrointestinal Illness
      6. Pregnancy (including Ectopic Pregnancy)
      7. Heat Illness
      8. Hypothermia
      9. Medications Affecting Thyroid Function (includes Drug-Induced Thyroiditis)
   2. Other, uncommon causes
      1. Graves Disease following Radioactive Iodine therapy
4. Pathophysiology
   1. 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
5. Precautions
   1. 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
   2. Young patients present more critically in Thyroid Storm
      1. Increased sensitivity to circulating Catecholamines results in severe, life-threatening presentations
6. Symptoms
   1. See Hyperthyroidism
   2. Compared with typical Hyperthyroidism, Thyroid Storm presents more severe secondary symptoms
      1. Fever
      2. Altered Mental Status (e.g. Delirium)
      3. Dyspnea (including Orthopnea)
      4. Chest Pain
7. Signs
   1. Fever >39 C (102 F)
   2. Hypertension
   3. Sinus Tachycardia or other tachydysrhythmia
   4. Profuse sweating
   5. High output cardiac failure (edema, pulmonary rales)
   6. Tachyarrhythmias (esp. Atrial Fibrillation)
   7. Altered Level of Consciousness (Delirium, Agitation or Psychosis)
8. Differential Diagnosis
   1. Sepsis
   2. Sympathomimetic Toxicity (Stimulant Overdose)
   3. Alcohol Withdrawal
   4. Malignant Hyperthermia
   5. Neuroleptic Malignant Syndrome
   6. Heat Related Illness
9. Associated Conditions
   1. New onset Atrial Fibrillation
   2. New onset, unexplained Congestive Heart Failure
10. Labs
    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. Broad based lab evaluation to cover differential diagnosis
       1. Comprehensive Metabolic Panel
          1. Liver Function Tests, Alkaline Phosphatase and Serum Calcium may be increased
       2. Complete Blood Count
       3. Pregnancy Test (bHCG) in women of child-bearing age
11. Imaging
    1. Consider Chest XRay
       1. May demonstrate high output Heart Failure, precipitating events (e.g. Pneumonia)
12. Diagnostics
    1. Electrocardiogram
       1. Evaluate for arrhythmia (e.g. Atrial Fibrillation, PSVT, Sinus Tachycardia)
13. Diagnosis
    1. See Thryoid Storm Diagnosis (Burch Wartofsky Score)
14. 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. 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
       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
    2. 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 10-20 mg IV every 4 hours (or 60 to 80 mg every 4 hours)
             1. Most common Beta Blocker used in Thyroid Storm
          3. Metoprolol 5-10 mg IV every 2-4 hours (or Metoprolol Tartrate 50 mg every 6 hours)
          4. Esmolol 50-100 mcg/kg/min IV
       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)
    3. Step 2: T4 and T3 Synthesis suppression with Thionamides
       1. Propylthiouracil (PTU) 200-400 mg every 8 hours PO, PR, or per NG
          1. Propylthiouracil is preferred in first trimester of pregnancy
          2. Most commonly used in Thyroid Storm, as it also decreases peripheral conversion of T4 to T3
       2. Methimazole 20-40 mg every 8 hours IV, PO, PR, per NG
          1. Methimazole is preferred in second and third trimesters of pregnancy
    4. 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 30-60 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
       2. Saturated Solution Potassium iodide (SSKI)
          1. Dose: 5 drops mixed in fluid or food every 6 hours for at least 2 days
          2. Initiate at least one hour after antithyroid medication
    5. Step 4: T4 to T3 conversion suppression with Glucocorticoids
       1. Preparations
          1. Hydrocortisone 100 mg IV every 8 hours 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
    6. Step 5: Apheresis
       1. Indicated in critically ill Thyroid Storm not responding to other measures
       2. In theory, removes from the serum, excess Thyroid hormone
15. 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)
16. References
    1. Swaminathan and Willis in Herbert (2019) EM:Rap 19(10): 13-5
    2. Swadron and Mason in Herbert (2019) EM:RAP C3 3(11): 1-10
    3. Carroll (2010) Ther Adv Endocrinol Metab 1(3): 139–145 [PubMed]
       1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475282/
    4. Idrose (2015) Acute Med Surg 2(3): 147-57 +PMID: 29123713 [PubMed]
    5. Kravets (2016) Am Fam Physician 93(5): 363-70 [PubMed]
    6. Nayak (2006) Endocrinol Metab Clin North Am 35(4): 663-6 [PubMed]