Amiodarone Deposition in Liver

History of arrhythmias • Xray of the Week

What is the diagnosis?

Figure 1. What is the important finding seen on these CT images?

Figure 1A: Axial CT image of abdomen with hyperdense liver Figure 1B: Zoomed-in axial CT image of liver- note the ROI is 154 HU Figure 1C: Zoomed-in axial CT image of spleen- note the ROI is 63 HU Figure 1D: Coronal CT image of abdomen with hyperdense liver

Discussion:

Amiodarone is an antiarrhythmic agent used to treat ventricular arrhythmias and atrial fibrillation. It is a class III drug, based on the Vaughan Williams classification, and works by prolonging the QT interval (1). The drug can also cause bradycardia, atrioventricular nodal conduction, increased refractoriness, and decreased intracardiac conduction (1). Moreover, since amiodarone is highly lipid soluble, it is stored in high concentrations in the liver, lungs, eyes, thyroid, and skin (1). One study found that all patients undergoing ophthalmologic examinations were found to have asymptomatic corneal microdeposits (2). It was further noted that a rise in hepatic enzyme levels was correlated to dosage and plasma drug and metabolite concentrations (2). Older patients pose a higher risk of developing hypothyroidism and those with abnormal lung functions prior to therapy may be predisposed to pulmonary alveolitis (2). Most of the observed unwanted effects resolve when amiodarone is decreased in dose or discontinued (2). Though it is uncommon, liver toxicity can occur and is manifested by elevated liver transaminase levels (1). Since amiodarone accumulates in lipid reservoirs and is released slowly, the concentration in the liver can be as high as 500-fold of the serum level (3,4). Characteristics of amiodarone-induced hepatotoxicity include histologic steatosis, inflammation, fibrosis, and phospholipidosis (5).

On imaging, we can appreciate increased density in the liver on non-contrast CT which is thought to be secondary to increased iodine content from the amiodarone (3,4). Increased liver attenuation on CT is a nonspecific finding and can also be seen with iron deposition in primary hemochromatosis, thalassemia, and hemosiderosis(6). Increased attenuation can also be seen with gold deposition, copper deposition in Wilson disease, and type IV glycogen storage disease (6). In Figure 1A, 1B, and 1D we can visualize the increased density of the liver on CT due to the chronic use of amiodarone. Normally, the liver has a similar density to the spleen on non-contrast CT scans (7), whereas in this case the liver is markedly hyperdense (154 HU) compared to spleen (63 HU). In the initial paper on hepatic Amiodarone deposition, liver hyperdensity measured 95 to 145 HU (Normal is 30-70) (4). Treatment of amiodarone toxicity involves reducing the dosage or discontinuing the usage (2); however, hepatic deposition without toxicity is usually an incidental finding that does not require any treatment.

References:

1. Siddoway, L. A. (2003). Amiodarone: guidelines for use and monitoring. American family physician, 68(11), 2189-2196. https://www.aafp.org/afp/2003/1201/p2189.html

2. Harris, L., McKenna, W. J., Rowland, E., & Krikler, D. M. (1983). Side effects and possible contraindications of amiodarone use. American heart journal, 106(4), 916-923. doi:10.1016/0002-8703(83)90016-9

3. Hussain, N., Bhattacharyya, A., & Prueksaritanond, S. (2013). Amiodarone-induced cirrhosis of liver: what predicts mortality?. Isrn Cardiology, 2013. doi:10.1155/2013/617943

4. Goldman IS, Winkler ML, Raper SE, et al. Increased hepatic density and phospholipidosis due to amiodarone. AJR Am J Roentgenol. 1985;144(3):541-546. doi:10.2214/ajr.144.3.541

5. Buggey J, Kappus M, Lagoo AS, Brady CW. Amiodarone-Induced Liver Injury and Cirrhosis. ACG Case Rep J. 2015;2(2):116-118. Published 2015 Jan 16. doi:10.14309/crj.2015.23

6. Ros P.R. (2018) Imaging of Diffuse and Inflammatory Liver Disease. In: Hodler J., Kubik-Huch R., von Schulthess G. (eds) Diseases of the Abdomen and Pelvis 2018-2021. IDKD Springer Series. Springer, Cham. doi:10.1007/978-3-319-75019-4_22

7. Herring W. Learning Radiology: Recognizing the Basics. Elsevier; 2015.​

Amer Ahmed is a fourth-year medical student at Midwestern University Chicago College of Osteopathic Medicine. There, he has served as the President for the Medical Business Association and Secretary for the Radiology Interest Group. Before medical school, Amer earned a degree in Economics at Loyola University Chicago and spent some time as an Investment Specialist at Merrill Edge before deciding to pursue his interest in medicine. Radiology intrigued Amer following a back injury requiring him to get an MRI. That is when he was able to appreciate the eye for detail Radiologists possess. Amer is passionate about finance, medicine, and technology.

Follow Amer Ahmed on Twitter @amer_ahmed401

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Kevin M. Rice, MD is the president of Global Radiology CME

Dr. Rice is a radiologist with Renaissance Imaging Medical Associates and is currently the Vice Chief of Staff at Valley Presbyterian Hospital in Los Angeles, California. Dr. Rice has made several media appearances as part of his ongoing commitment to public education. Dr. Rice's passion for state of the art radiology and teaching includes acting as a guest lecturer at UCLA. In 2015, Dr. Rice and Natalie Rice founded Global Radiology CME to provide innovative radiology education at exciting international destinations, with the world's foremost authorities in their field. In 2016, Dr. Rice was nominated and became a semifinalist for a "Minnie" Award for the Most Effective Radiology Educator.

Follow Dr. Rice on Twitter @KevinRiceMD

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