1. Amiodarone Toxicity: Preventable With Proper Monitoring Jeffrey Spence MD 1, Melver L. Anderson III MD 1,2 1 University of Colorado Denver, 2 Denver VA Medical Center Clinical Presentation History: 64 year old male with a history of paroxysmal atrial fibrillation treated with amiodarone presented with one year of: Worsening tremor Heat intolerance Palpitations Generalized weakness Physical Exam: Heart rate 91 Full body tremor, generalized symmetrical muscle weakness No findings of proptosis, thyroid enlargement, tenderness or nodules Laboratory and Imaging Data TSH of less than 0.01µU/ml, T4 of 17.7µg/dl and normal electrolytes Thyroid ultrasound showed diffusely hypoechogenic and heterogeneous thyroid with a thickened isthmus and a 4mm x 3mm x 5 mm nodule in the left lobe Thyroid uptake study showed diminished uptake at six hours Thyroglobulin and microsomal antibodies were negative Chest radiograph showed no acute cardiopulmonary process References Side EffectIncidence, Percent Lung Cough, CXR infiltrates, decreased DLCO5-15 (>400mg/day), 1-2 (<400mg/day) Thyroid Hypothyroidism or Hyperthyroidism2-24 (>400mg/day), 3-4 (<400mg/day) Heart Bradycardia and AV block3-5 Proarrhythmia<1 Liver AST or ALT greater than 2x normal15-50 (>400mg/day), 1-2 (<400mg/day) Hepatitis and cirrhosis<3 Eye Corneal microdeposits>90 Halo vision, especially at night<5 Optic neuritis1 Skin Photosensitivity25-75 Blue discoloration<10 Gastrointestinal tract Nausea, anorexia, constipation30 (>400mg/day), 4-5 (<400mg/day) CNS Ataxia, paresthesias, peripheral neuropathy, sleep disturbance, impaired memory, and tremor 3-30 (>400mg/day), 4-5(<400mg/day) Genitourinary tract Epididymitis and erectile dysfunction<1 Monitoring SystemBaselineFollow-up Cardiac EKG at baseline and during loading phase Yearly DermatologicPhysical exam As needed for signs, symptoms EndocrineThyroid function testsEvery 6 months HepaticAST or ALTEvery 6 months NeurologicPhysical exam As needed for signs, symptoms OpthalmologicEye exam As needed for signs, symptoms Pulmonary Pulmonary function tests As needed of signs, symptoms Chest radiographYearly Hospital Course and Diagnosis Amiodarone was stopped and prednisone was initiated Patient was readmitted 2 months later with increasing T4 levels, so methimazole was started Reviewing the chart found only one TSH performed when amiodarone was initiated four years earlier Presentation was consistent with type II thyrotoxicosis secondary to direct toxicity from amiodarone Thyrotoxicosis can also occur from the high levels of iodine found in amiodarone (Type I thyrotoxicosis) Learning Points Amiodarone has many toxicities and requires close monitoring both at initiation and throughout the course of therapy Initiating amiodarone treatment in the hospital setting necessitates good communication with outpatient providers to ensure proper long term monitoring Failure in this case to follow commonly accepted monitoring guidelines likely delayed the diagnosis and increased the severity of the resultant thyroid toxicity Conclusion Providers should be familiar with both the indications for and toxicities of amiodarone therapy and follow commonly accepted monitoring guidelines to quickly identify and possibly prevent complications from occurring Common Amiodarone Toxicities by Organ System Recommended Monitoring by Organ System Reproduction of UpToDate table, Type and incidence of major side effects associated with amiodarone therapy, using data from: Goldschlager, N, Epstein, AE, Naccarelli, G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med 2000; 160:1741; Vorperian, VR, Havighurst, TC, Miller, S, et al. Adverse effects of low dose amiodarone: A meta-analysis. J Am Coll Cardiol 1997; 30:791; and Harjai, KJ, Licata, AA. Effects of amiodarone on thyroid function. Ann Intern Med 1997; 126:63 Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. J Can Cardiol. 2009 Jul;25(7):421-4. Vassallo P, Trohman RG. Prescribing amiodarone: an evidence-based review of clinical indications. JAMA. 2007 Sep 19;298(11):1312-22. Adapted from UpToDate table, see references. Adapted from Vassallo et al.