Chief Complaint:

Defibrillator shock

HPI:

50-year-old biologic male who identifies as a female presented after reportedly being shocked by her defibrillator 5 times before calling EMS, EMS noted that they witnessed 1 shock. They also noted that blood pressure was in the low 100s and heart rate was between 200-260 before getting shocked. Patient has never been shocked in the past. Patient has history of rheumatic fever, had an aortic valve replacement in 2013 and at that time also had Boston Scientific dual-chamber biventricular and atrial pacing pacer defibrillator. She had sharp chest pain at the time of the shocks but just some mild achiness at time of arrival to ED. Reported she could feel her heart racing as well.

PMH
A. fib, hypertension hyperlipidemia, on hormone therapy for male to female
Rheumatic fever
Aortic valve replacement, defibrillator and pacemaker

Pertinent Exam Findings:

General Appearance: Pulse Ox 96%, B/P 163/98, Temp 35.7 °C, Pulse 143, Resp 17 Patient is alert awake and in no acute distress
Respiratory: Lungs are clear to auscultation patient is in no respiratory distress not using any accessory muscles and speaking full sentences
Cardiovascular: Tachycardic and irregularly irregular
Gastrointestinal: Abdomen is soft, nontender
Musculoskeletal: Extremities full range of motion. No calf tenderness or swelling

Data Interpretation:

CBC: demarginating>infectious leukocytosis
BMP: hyperglycemia without dka, + aki noted, no significant electrolytes
Trop: demand ischemia/traumatic from defib, not occlusive MI
TSH/FT4: Consistent with hyperthyroid

ED Course:

Discussed case with cardiologist, because patient is typically on amiodarone and missed two doses, he recommended starting an amiodarone drip as well as heparin drip with plan to see the patient in the morning. Patient remained in AF RVR while on amiodarone drip. Discussed with cardiology again, he agreed to discontinue amiodarone and start on esmolol. MTU was also given in the ED for hyperthyroid.

Hospital Course:

Additional medical history from outside records included unspecified CHF, CVA without residual deficit, hypertension, rheumatic heart disease and severe aortic regurgitation status post mechanical aortic valve replacement in 2009 complicated by prosthetic valve endocarditis in 2010, status post porcine aortic valve replacement 2013, history of VT status post ICD and previously undergone placement of watchman device. Patient seen and evaluated by electrophysiology. To differentiate between type I versus type II amiodarone-induced thyrotoxicosis, Color-flow Doppler sonography was ordered and was normal. The workup was most consistent with type II amiodarone-induced thyrotoxicosis. Patient was placed on esmolol initially but ultimately transitioned to sotalol for VT suppression. Acute kidney injury resolved. Patient in paced rhythm on day of discharge. Patient had scheduled follow-up with endocrinology. Further treatment for amiodarone thyrotoxicosis aside from discontinuation of amiodarone to be determined at the time of endocrinology follow up.

DISCUSSION:

Background:

Amiodarone is a class III antiarrhythmic drug indicated for the treatment of ventricular arrhythmias as well as for rate control and restoration of sinus rhythm in atrial fibrillation and other supraventricular tachyarrhythmias. The drug acts predominantly by blocking potassium channels in cardiac myocytes which results in increased action potential duration and a prolonged effective refractory period. Amiodarone is unique in that it also blocks sodium and calcium channels as well as beta-adrenergic pathways. This decreases SA node automaticity and AV node conduction velocity while also inhibiting ectopic pacemaker automaticity. Despite its utility in treating an array of cardiac arrhythmias, amiodarone usage is limited by the high prevalence of adverse effects. Up to 15% of patients using amiodarone will develop an adverse effect within the first year of use, and half of those on long-term amiodarone therapy will experience significant side effects while taking the drug.

One important adverse effect associated with amiodarone is thyroid dysfunction. Thyroid-related side effects can arise with amiodarone metabolism due to the drug containing a large amount of inorganic iodine which can alter the degree of thyroid hormone synthesis. Additionally, amiodarone itself can decrease T3 production and block T3 receptor binding due to its structural similarity to thyroxine. It has also been noted to have a direct toxic effect on thyroid cells. As a result of these effects, amiodarone can cause both hypo- and hyperthyroidism. Three percent of patients taking amiodarone in North America will develop amiodarone-induced thyrotoxicosis (AIT). AIT can be classified as one of two types. Type 1 AIT occurs in patients with a preexisting thyroid pathology and is due to the Jod-Basedow phenomenon triggering accelerated thyroid hormone synthesis. In Type 2 AIT, the direct toxic effects of amiodarone on thyroid tissue can lead to an acute thyroiditis releasing preformed thyroid hormones into circulation.

Diagnosis:

Patients taking amiodarone may begin to develop thyroid related adverse effects as early as a few weeks after starting treatment, and due to the drug’s long half-life, the patient is still at risk of AIT after discontinuing amiodarone therapy. In an emergency medicine setting, AIT should be considered in any patient currently taking or who recently stopped taking amiodarone and is now presenting with hyperthyroid symptoms. Cardiac symptoms are frequently seen in AIT patients and include tachyarrhythmias such as atrial fibrillation and ventricular tachycardia, as well as angina, and heart failure. Noncardiac signs associated with AIT include unexplained weight loss, tremor, restlessness, weakness, fever, and an enlarging goiter. Patients may also present after developing abnormal results on routine thyroid function tests.

Upon arrival in the ED, vital signs may reveal hyperthermia and tachycardia which should increase the index of suspicion for AIT. To diagnose AIT, total and free T4, total and free T3, and TSH should be obtained. These thyroid function tests are expected to show elevated T3 and T4 levels with an accompanying dramatic decrease in TSH level. CMP, CBC and LFTs should also be obtained to evaluate for additional metabolic or hematologic abnormalities. Additional testing in the ED includes getting an ECG to check for dysrhythmias as well as laboratory troponin and BNP testing to evaluate for and potentially rule out cardiac issues including ACS and CHF. A CXR, blood culture, and urinalysis should also be performed to rule out infection as a possible alternative cause of the patient’s symptoms.

Distinguishing between Type 1 and type 2 AIT is outside the scope of the emergency department. However, patients with an underlying autonomous nodule or goiter and who develop symptoms of AIT soon after the initiation of amiodarone treatment are much more likely to have Type 1 AIT. If symptom onset is later during therapy or occurs after cessation of amiodarone, then Type 2 AIT is significantly more likely to be the cause. Differentiating between the two forms of AIT is further complicated by the fact that patients can have a mixed form of the disease. There are several additional tests that can be performed to help differentiate the two forms of the disease. Color flow Doppler ultrasonography usually shows increased intra-thyroidal vascular flow in Type 1 and reduced or absent flow in Type 2. Another test that can be used is 24-hour radioactive iodine uptake. Uptake is more likely to be detected in Type 1 whereas it is expected to be <1 in Type 2.

Management in ED:

Treatment of AIT is challenging and depends both on the type of AIT and the necessity of the patient remaining on amiodarone to control potentially life threatening arrhythmias. If the patient was prescribed the drug for a life-threatening arrhythmia, then amiodarone will usually be continued despite the presence of AIT. If the arrhythmia for which amiodarone was prescribed is not considered a direct life threat, then it may be possible to discontinue the medication. Ultimately, the decision on amiodarone cessation should be made in consultation with the patient’s cardiologist.

While differentiating between Type 1 and Type 2 AIT is typically beyond the scope of what will be done in the emergency department, treatment in the acute setting of the emergency department will follow that of typical hyperthyroidism. In addition to stopping the administration of amiodarone after coordinating this decision with the patient’s cardiologist, treatment should be focused on supportive care of symptoms while taking steps to blunt thyroid hormone’s effect and prevent further hormone synthesis. If the patient is febrile, take efforts to cool them via ice packs and acetaminophen. It is important to avoid NSAIDs due to their ability to increase thyroid hormone through displacement from thyroid binding globulin. Any dehydration and hypoglycemia should be addressed utilizing D5NS. Any agitation the patient may be experiencing can be treated with benzodiazepines.

In regards to treating the increased adrenergic tone seen in these patients, propranolol IV 1-2mg over 10 minutes followed by 1-2mg q15 minute boluses until the heart rate is no longer tachycardic is recommended. Propranolol PO 60-80 mg every four hours may also be used if patient can tolerate PO. For those patients that may have active CHF or asthma esmolol IV 250-500 mcg/kg loading dose followed by 50-100 mcg/kg/min is recommended due to being beta-1 selective. Keep in mind, propranolol has the advantage of blocking T4s conversion to T3. If beta-blockers are contraindicated reserprine 2.5-5mg IM every four hours is a possible alternative.

To prevent the further synthesis of thyroid hormone, thionamides such as propylthiouracil (PTU) and methimazole are recommended. PTU is preferred over methimazole as it will block the conversion of T4 to T3 in addition to the inhibition of thyroid peroxidase enzymes. Typical doses of PTU range from 500-1000mg PO initially followed by 250mg every four hours after. While you typically give potassium iodide as well in cases of hyperthyroidism to block further hormone release, this is contraindicated in patients who are prescribed amiodarone. Instead, it is recommended for amiodarone induced hyperthyroidism to receive lithium carbonate as the treatment alternative to potassium iodide. These patients typically require admission for further work-up and differentiation of Type 1 vs Type 2 AIT.

Prognosis:

Patients with Type 1 AIT usually respond, albeit slowly, to prolonged thionamide therapy. Patients with Type 2 AIT generally respond well to corticosteroid therapy. In both Type 1 and Type 2 AIT, all therapies run the risk of inducing transient, or potentially permanent, hypothyroidism. When this occurs, patients tend to respond well to T4 replacement therapy. Studies in patients with AIT have shown variable recurrence rates after resolution regardless of if amiodarone was discontinued. One patient population that is at particularly high risk is older individuals with compromised left ventricular function. In this subset of patients, it is thought that AIT may result in increased morbidity and mortality. In the emergency medicine setting, AIT should be suspected in all patients taking amiodarone who present with potential hyperthyroidism. With prompt recognition of AIT and the initiation of therapy to restore a euthyroid state, patient outcomes can be improved.

Differential Diagnoses:

• • Graves disease
    
  • Toxic nodular goiter
    
  • Toxic multinodular goiter
    
  • Hashimoto thyroiditis
    
  • Subacute painful thyroiditis (formerly de Quervain thyroiditis)
    
  • Postpartum thyroiditis
    
  • Radiation thyroiditis
    
  • Amiodarone-induced thyroiditis
    

Clinical Pearls:

• • Amiodarone-induced thyrotoxicosis, while a rare cause of hyperthyroidism, is a dangerous side effect of chronic amiodarone administration.
    
  • In instances where a patient relies on chronic amiodarone treatment due to life threatening arrhythmias, care should be coordinated with the patient’s cardiologist.
    
  • When possible, amiodarone-induced thyrotoxicity should be treated by discontinuing amiodarone administration and continuing to treat for hyperthyroidism, taking care to provide supportive treatment in addition to blocking existing thyroid hormone and slowing the production of additional hormones.
    

References:

1. Bogazzi F, Martino E, Dell’Unto E, et al. Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis. J Endocrinol Invest. 2003;26(7):635-640.
   
2. Florek JB, Girzadas D. Amiodarone. In: StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2022, StatPearls Publishing LLC.; 2022.
   
3. Macchia PE, Feingold KR. Amiodarone Induced Thyrotoxicosis. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc. Copyright © 2000-2022, MDText.com, Inc.; 2000.
   
   
4. Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. The Canadian journal of cardiology. 2009;25(7):421-424.
   
5. Bartalena L et al (1996): Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J Clin Endocrinol Metab 81(8):2930-3. DOI: http://dx.doi.org/10.1210/jcem.81.8.8768854
   
6. Hume JR, Grant AO (2014): Agents used in cardiac arrhythmias (Chapter 14). In: Basic and Clinical Pharmacology. 13e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange.
   
7. Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen’s Emergency Medicine (9th ed). Philadelphia, PA. Elsevier/Saunders
   
8. Trohman RG, Sharma PS, McAninch EA, Bianco AC. Amiodarone and the thyroid physiology, pathophysiology, diagnosis and management. Trends Cardiovasc Med. 2018 Sep 20. pii: S1050-1738(18)30195-6.
   

Authors

Mark O’Brien, MS4

Justin Evans, MS2

Peter Haskins, MD