Thyroid Storm Management

Background

Thyroid storm is a rare clinical picture seen in severe thyrotoxicosis. The condition is a critical emergency presentation occurring in 1-2% of hyperthyroid patients, with treated mortality rates reported between 10-30%.1 While it can occur as the result of uncontrolled or poorly controlled hyperthyroidism, more often it is the result of an acute precipitating event acting on the increased catecholamine receptor expression of hyperthyroid patients.

Precipitating Factors

  • Trauma
  • Infection
  • Drug Related (Exogenous Iodine, Non-Compliance, Amiodarone, Anesthesia, Contrast)
  • DKA
  • Psychiatric
  • CVA
  • Pulmonary Embolism
  • Myocardial Infarction
  • CHF Exacerbation

Presentation and Diagnosis

Thyroid storm is a clinical diagnosis of a severe and exaggerated form of thyrotoxicosis.  The hallmarks of the condition are the following triad:

  • Extreme Fever (often >104F)
  • Tachycardia (can be accompanied with AFib, widened pulse pressure)
  • Altered Mental Status

Other findings associated with thyrotoxicosis include the following:

  • Tremor
  • Lid Lag
  • Proptosis/Periorbital Edema
  • Pretibial plaques/nodules/non-pitting edema
  • Goiter/Thyroid Nodules

Few scoring systems or guidelines have been suggested or validated, and the scoring system proposed by Burch and Wartofsky has become the most widely used and accepted.

  • >45 = Highly suggestive of thyroid storm
  • 25-44  = Suggestive of impending storm
  • <25 = Unlikely to Represent thyroid storm

I. Thermoregulatory Dysfunction

Temperature (oC) Pts
37.2-37.7 5
37.8-38.2 10
38.3-38.8 15
38.9-39.4 20
39.4-39.9 25
>40.0 30

II. Central Nervous System Effects

Mild (agitation) 10
Moderate (Delerium, Psychosis, Extreme Lethargy) 20
Severe (Seizure, Coma) 30

III. GI-Hepatic Dysfunction

Moderate (Diarrhea, Nausea/Vomiting, Abd pain) 10
Severe (unexplained jaundice) 20

IV. Cardiovascular Dysfunction

Tachycardia
99-109 5
110-119 10
120-129 15
130-139 20
>139 25
Atrial fibrillation 10

V. Heart Failure

Mild (Pedal Edema) 5
Moderate (Bibasilar Rales) 10
Severe (Pulmonary Edema) 15

VI. Precipitant History

Positive 10

*It is always critical to rule out other causes of the clinical picture of thyroid storm, or previously mentioned acute conditions that provoked the condition.  The differential for the condition is broad.

Management

Supportive Care

  • Fever: Cooling measures and antipyretics. The antipyretic of choice for persistent fever in thyroid storm is acetaminophen, as salicylates can interfere with thyroid hormone binding increasing serum T3/T4.
  • Agitation: Benzodiazepines are the preferred method of management.
  • Vascular instability: Should be aggressively treated with IV fluids. IV Fluids should be started immediately for the patient, but care should be given especially in the patient with high-output heart failure. If hemodynamic instability persists, using vasoactive drugs can be used but should only be continued for a short duration.

Block Peripheral Effects (β-Blockers)
β blockade is critical in the management of the peripheral actions of increased thyroid hormone.

  • Propranolol 0.5-1mg IV over 10 mins followed by redosing 1-3mg every few hours OR 60-80mg PO q4h
    • Most widely used β-blocker for thyroid storm due to culturally taught peripheral action of decreased conversion of T4 to T3. However, other beta-blockers, such as metoprolol, have also been shown to do this and require less frequent dosing.
    • Non-selective effects of blockade improve tremor, hyperpyrexia, agitation.
    • Relative contraindications include previous heart failure not due to thyrotoxicosis and reactive airway disease.
  • Esmolol 250-500 mcg/kg IV bolus followed by 50-100 μg/kg/min IV
    • Shorter half-life than propranolol, so consider in a patient with unknown cause of heart failure.
  • Reserpine 1mg IM loading dose followed by 2.5-5mg IM q4-6h
    • In patients with strict contraindications to β-blockade.
  • Atenolol 50-200mg PO qday
    • Consider in patients with reactive airway disease, as it is more cardioselective agents.

Inhibit New Synthesis (Thionamides)

Methimazole and PTU interfere with thyroperoxidase-catalyzed coupling process, decreasing new synthesis of T3 and T4. Also shown to have inhibitory effects on follicular cell growth and function.

  • Propylthiouracil (PTU) 600-1000mg PO loading dose with 200-400mg PO q6-8h
    • PTU works peripherally as well to decrease the conversion of T4 to T3.
    • Black Box Warning: Hepatotoxicity.
  • Methimazole 20-25mg PO q4-6h
    • Once stable, the dosing interval of methimazole can become qDaily due to longer half-life compared to PTU.
    • Both can cause agranulocytosis at any time during treatment, so be mindful.

*Both thionamides can be given rectally. In very rare situations, IV administration should be made by the hospital pharmacy (IV formulation not available in US).

Inhibit New Release (Iodines)

Iodine therapy blocks the release of pre-stored hormone, and decreases follicular transport and oxidation.

  • SSKI 5 drops PO q6h or Lugol’s Solution 4-8 drops PO q6-8h
    • Works through “Wolff-Chaikoff effect,” in which high levels of iodide will inhibit T3/T4 synthesis and release. Escape has been reported, but not sooner than 10 days following iodine administration.
    • Must be given AFTER antithyroid drugs have been given due to the observed “Jod-Basedow effect,” in which high levels of iodide will increase T3/T4 synthesis and release.
    • Exact time frame after has been debated, but no sooner than 30-60 mins following PTU/Methimazole.
    • Evidence of irritation of gastric/oral mucosa and should be diluted in fluid (juice or milk).
    • Can substitute radiocontrast dyes (Iopanoic acid, ipodate and iopanoate).

*Can be given rectally

  • Lithium 300mg PO q6-8h
    • Consider for iodine allergy or contraindication to iodine usage (ie amiodarone-induced thyrotoxicosis).

Inhibit Peripheral Conversion

  • Hydrocortisone 300mg IVx1 and then 100mg IV q8h or Dexamethasone 2-4mg IV q6h
    • Improved survival seen with early administration, especially in the hypotensive patients.4
    • Glucocorticoids have a known inhibitory effect on peripheral conversion of T4 to T3.
    • Especially in hypotensive patients given potential adrenal insufficiency.

Alternative Therapies

  • Cholestyramine: 4g PO QID – Adjunct therapy to thionamides, acting as an anion exchange resin used to decreases reabsorption of thyroid hormone in enterohepatic circulation.
  • Plasmapheresis: Offers temporary stabilization for a patient that has been unresponsive to antithyroid medications, but is not a definitive therapy.
  • Antithrombotic Therapy: Proceed with antithrombotic therapy as you would other patients with atrial fibrillation. Retrospective study (n=610) showed no difference in CVAs between patients with atrial fibrillation due to thyrotoxicosis, and age matched patient with AFib due to other causes.5

Special Cases

Pregnancy

PTU has been the antithyroid drug of choice over methimazole, due to the belief that PTU does not cross the placenta as freely as methimazole.  Furthermore, methimazole has shown to have congenital anomalies (aplasia cutis/choanal atresia).  Recent studies have called these differences between the two drugs into question, but PTU is still the most widely used and accepted drug in pregnancy.6

References

  1. Marx JA, Hockberger RS, Walls RM. Rosen’s Emergency Medicine, Eighth Edition. 2014; 128:1676-1692.
  2. Cline DM, Ma OJ, Cydulka RK, Meckler GD, Handel DA, Thomas SH. Tintinalli’s Emergency Medicine, Seventh Edition. 2012; 131:637-640.
  3. Nayak B, Burman K 2006 Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 35:663–686.
  4. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am 1993;22:263–77.
  5. Peterson P, Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988;19(1):15-8.
  6. Cooper D. Antithyroid Drugs. New England Journal of Medicine 2005; 352:905-917.
Edited by Manpreet Singh, MD

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