Reminder of important clinical lesson CASE REPORT Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient Reham Mohammed Shamloul,1 Ahmed Fathy Aborayah,1 Assem Hashad,2 Foad Abd-Allah1 1 Department of Neurology, Cairo University, Cairo, Egypt 2 Department of Cardiology, Cairo University, Cairo, Egypt Correspondence to Dr Reham Mohammed Shamloul, reham_neuro@yahoo.com Accepted 6 February 2014 SUMMARY We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects. BACKGROUND The abuse of anabolic-androgenic steroids (AAS) has increased in recent years, being not confined only to bodybuilders or high-level sportsmen but also spread to casual fitness enthusiasts and subelite sportsmen and even women.1 Supraphysiological doses and high-frequency usage of AAS may cause a wide spectrum of clinical manifestations which are usually ignored or at best unfollowed, though some may be life-threatening.2 A literature search revealed few case reports that suggested an association of intracoronary thrombosis, sudden death, myocardial necrosis, cardiomyopathy and stroke as possible consequence of ASS overuse. We report a particular case with a clinical scenario which indicates a strong association between ASS abuse and fatal cerebrocardio manifestations. A hypothesis for the underlying causation of these fatal manifestations is further addressed. On examination, the patient was lethargic and confused. General examination revealed normal blood pressure and temperature. The patient had sinus tachycardia ( pulse rate was 120/min), mild bilateral lower limb pitting oedema, but with no evidence of jugular venous congestion or bilateral basal crepitation. Also the patient had an enlarged tender liver with no stigmata of chronic liver disease. Neurological examination revealed rightsided hemiparesis (grade 3) with right-sided facial weakness. INVESTIGATIONS Laboratory testing showed increased haemoglobin concentration (18 gm/dL), increased serum transaminases (aspartate aminotransferase, 280 IU/L; alanine aminotransferase, 310 IU/L), coagulopathy (International Normalised Ratio 1.6), hyperbilirubinemia (total bilirubin 2 mg/dL), renal impairment (creatinine 3.03 mg/dL, urea 110 mg/dL), hyponatraemia (122 mmol/L) and hyperkalaemia (5.8 mmol/L). Virology, drug screen and immune profile were negative and thyroid functions were within normal range. Initial brain CT scan revealed two lesions, one less hypodense than the other. A diagnosis of chronic infarction in the left frontal lobe and a subacute left temporoparietal infarction was proposed (figure 1). Further brain imaging with MRI confirmed such results. EEG did not elicit epileptiform activities and chest X-ray showed augmented cardiothoracic index. An abdominal ultrasound revealed hepatomegaly, mild ascitis and bilateral pleural effusion in addition to grade I nephropathy. During the performance of the abdominal ultrasound, the operator noticed intraventricular thrombus in the heart. Urgent echocardiography showed a dilated cardiomyopathy with an estimated ejection fraction of 13% and multiple thrombi in the left ventricle. Toxic cardiomyopathy secondary to AAS over use was suspected. CASE PRESENTATION To cite: Shamloul RM, Aborayah AF, Hashad A, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2013203033 A patient presented to the neurocritical care unit at Kasr Al-Aini Hospital with an acute right-sided weakness associated with a confusional state which followed a first-ever experienced generalised tonic clonic seizure. The patient had a history of anabolic steroid abuse over the past 2 years. The most frequently used anabolic steroids were: methandienone (active ingredient) and methenolone acetate as reported by the caregiver. There was no history of alcohol or other substance abuse. The medical and family histories were unremarkable. Shamloul RM, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-203033 DIFFERENTIAL DIAGNOSIS A diagnosis of severe toxic cardiomyopathy associated with anabolic steroids was made after ruling out other causes of non-ischaemic dilated cardiomyopathy, including infectious, autoimmune and metabolic causes. TREATMENT After initial correction of hyponatraemia with slow isotonic saline infusion, symptoms and signs of congestive heart failure became evident. The patient was transferred to the intensive care unit 1 Reminder of important clinical lesson Figure 1 The chronic left frontal infarction (black arrow) and subacute left temporoparietal infarction (white arrow). (ICU), where aggressive therapy with cardiac inotropes and intensive diuresis was rapidly initiated, on which the liver and kidney functions improved dramatically. Low-molecular-weight heparin therapy was started followed by oral anticoagulation. A follow-up echocardiogram (2 weeks from admission), by the same operator, showed the disappearance of one of the intraventricular thrombi and improvement in left ventricular function (EF 20%). Thus, the patient was discharged from the ICU to the normal ward. OUTCOME AND FOLLOW-UP Unfortunately few days later, the patient developed disturbed consciousness, gaze deviation to the right side and dense left hemiplegia and became hypotensive, tachycardiac, tachypnic and sweaty. An urgent CT of the brain was performed, which revealed no new insult. ECG showed acute massive inferior myocardial infraction (MI) (troponin I=8 ng/mL). The patient was immediately transferred to the ICU and died on the same day. DISCUSSION The present history of this case was significant for chronic selfadministration of massive doses of anabolic steroids, of various natures. AAS are a family of hormones that include the natural male hormone testosterone, together with its many synthetic relatives, all of which exhibit anabolic (‘muscle building’) and androgenic (‘masculinising’) properties. Potential mechanisms of cardiovascular toxicity of AAS include direct myocardial injury, atherogenic, thrombotic, haemostasis and vasospastic effects.2 The direct myocardial injury has been proposed to result from increased fibrosis of the myocardium mediated by aldosterone-like effects.3 Several studies show that high doses of AAS, such as nandrolone, may lead to growth-promoting effects on cardiac tissue, as seen in hypertrophic cardiomyopathy, followed by apoptotic cell death that is mediated by membrane 2 receptor second messenger cascades that increase intracellular Ca2+ influx and mobilisation, leading to apoptosis and injury of the cardiac muscle.3 4 The atherogenic effects of AAS abuse arise from their ability to decrease high-density lipoprotein cholesterol by 20% and increase low-density lipoprotein (LDL) cholesterol by 20% through modification of apolipoprotein A-I and B synthesis.5 In addition to its atherogenic effects, the excess LDL-C (caused by exogenous androgens) may oxidise at the arterial endothelium and consequently impair endothelium-dependent arterial relaxation by inhibiting nitric oxide production, predisposed the patient to coronary vasospasm.6 These lipoprotein abnormalities increase the risk for coronary artery disease by threefold to sixfold and may occur within 9 weeks of AAS self-administration.7 8 Finally, the effect of AAS abuse on the haemostatic system may fluctuate from an antithrombotic to a prothrombotic profile, and this variation may be dose dependent. Using low doses decreases platelet threshold activation to collagen, whereas higher doses are associated with increased platelet aggregation and may influence the activity of vascular cyclooxygenase enzyme which may yield to a procoagulant state.9 The reversibility of such myocardial and vascular effects after discontinuation of the drugs is still controversial.10 The presenting symptoms were explained as a result of end-organ hypoperfusion due to the severe cardiomyopathy. The early rise in the liver enzymes and the renal impairment which rapidly improved with treatment suggests an ischaemic injury rather than toxic or viral cause. The CT and MRI which revealed brain infarctions and the Q wave in the first ECG indicate vascular insults. Possible mechanisms can be attributed to adverse effects of AAS on the cardiovascular system. The subsequent fatal event that presented with sudden disturbed consciousness level, right-sided weakness and ST segment elevation may have resulted from dislodgement of an intracardiac Shamloul RM, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-203033 Reminder of important clinical lesson thrombus leading to an embolic stroke with the development of an acute MI. The literature contains very few reports of cardiovascular events associated with anabolic steroid abuse.11–13 This case is unique as the patient developed an embolic stroke in the absence of any risk factors for the disease, and not as a complication of dilated cardiomyopathy with left ventricle thrombus formation which were deduced to be the result of AAS abuse. article critically for important intellectual content and approved the final version to be published. Competing interests None. Patient consent None. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1 2 Learning points 3 ▸ Disparity and lack of precise consistency of medical knowledge on the effects of these widely abused drugs requires detailed controlled studies to verify these effects. ▸ The quick and uncontrolled spread of anabolic-androgenic steroids (AAS) abuse among athletes and body builders mandate a worldwide collective endeavour to educate the public and physicians about these potentially fatal hazards and propose a battery of follow-up for the consumers. ▸ Prompt and proper management of hazards of AAS carries a high chance of reversal of their complications. 4 5 6 7 8 9 10 Acknowledgements The authors are grateful to Professor Maha Hasaballah, Endemic Medicine, Cairo University, who provided us with much technical and scientific support. Contributors RMS was involved in acquisition and interpretation of the data, writing and preparing the case report and the metadata. AFA, followed up the case during the hospital stay, made considerable efforts in acquisition and collecting the data. AH contributed in management of the critical cardiological condition of the patient and had a significant role in data analysis and revision. FA-A revised the 11 12 13 Hoffman JR, Ratamess NA. Medical issues associated with anabolic steroid use: are they exaggerated? J Sports Sci Med 2006;5:182–93. Kathleen S, Joseph JB, Robin M, et al. Anabolic steroids, acute myocardial infarction and polycythemia: a case report and review of the literature. Vasc Health Risk Manag 2008;4:1475–80. Achar S, Rostamian A, Narayan SM. Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. Am J Cardiol 2010;106:893–901. D’Ascenzo S, Millimaggi D, Di Massimo C, et al. Detrimental effects of anabolic steroids on human endothelial cells. Toxicol Lett 2007;169:129–36. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34:513–54. Sullivan ML, Martinez CM, Gennis P, et al. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41:1–15. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev 2003;24:313–40. Maravelias C, Dona A, Stefanidou M, et al. Adverse effects of anabolic steroids in athletes. A constant threat. Toxicol Lett 2005;158:167–75. Winkler UH. Effects of androgens on haemostasis. Maturitas 1996;24:147–55. D’Andrea A, Caso P, Salerno G, et al. Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis. Br J Sports Med 2007;41:149–55. Ferrera PC, Putnam DL, Verdile VP. Anabolic steroid use as the possible precipitant of dilated cardiomyopathy. Cardiology 1997;88:218–20. Bispo M, Valente A, Maldonado R, et al. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder. World J Gastroenterol 2009;15:2920–2. Youssef MY, Alqallaf A, Abdella N. Anabolic androgenic steroid-induced cardiomyopathy, stroke and peripheral vascular disease. BMJ Case Rep 2011;2011: pii: bcr1220103650. Copyright 2014 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact consortiasales@bmjgroup.com Visit casereports.bmj.com for more articles like this and to become a Fellow Shamloul RM, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-203033 3