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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 2  |  Issue : 2  |  Page : 73-76

Severe cholestasis with marked weight loss mimicking malignancy: An overlooked etiology


1 Department of Medicine, Hamad General Hospital, Qatar University and Weill Cornell Medical College, Doha, Qatar
2 Department of Medicine, Weill Cornel Medical College, Doha, Qatar
3 Department of Medicine, Hamad General Hospital and Weill Cornell Medical College, Doha, Qatar

Date of Web Publication29-Jun-2018

Correspondence Address:
Prof. Wanis H Ibrahim
Department of Medicine, Hamad General Hospital, College of Medicine, Qatar University and Weill Cornell Medical College, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/LJMS.LJMS_10_18

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  Abstract 


Despite being classified as controlled substances in many countries, the use of anabolic androgenic steroids is becoming widespread and no longer limited to bodybuilders or elite athletes. A plausible reason that has fuelled increasing use of such drugs is the increase in modern perception of "ideal" body image and the desire to increase masculinity among younger people. Such drugs are illegally sold through the black market, websites, gyms, body building competitions, teammates, trainers, etc. the health consequences of these medications including their hepatotoxicity are often overlooked. Anabolic androgenic steroid-induced cholestasis may exhibit symptoms and signs indistinguishable from malignancy-induced cholestasis. Patients tend to deny or withhold information regarding the use of these medications. Specific and direct inquiry about the use of these drugs is imperative particularly in young men presenting with cholestatic jaundice. In this paper, we report a 40-year old man with severe cholestasis and marked weight loss (mimicking malignancy) secondary to anabolic androgenic steroid use for bodybuilding. We also performed extensive literature search regarding cholestasis as well other health consequences caused by these medications.

Keywords: Anabolic androgenic steroids, cholestasis, liver


How to cite this article:
Ibrahim WH, Choura M, Bshesh F, Paul T, Elzouki AN. Severe cholestasis with marked weight loss mimicking malignancy: An overlooked etiology. Libyan J Med Sci 2018;2:73-6

How to cite this URL:
Ibrahim WH, Choura M, Bshesh F, Paul T, Elzouki AN. Severe cholestasis with marked weight loss mimicking malignancy: An overlooked etiology. Libyan J Med Sci [serial online] 2018 [cited 2018 Jul 18];2:73-6. Available from: http://www.ljmsonline.com/text.asp?2018/2/2/73/235690




  Introduction Top


The evaluation of cholestatic jaundice is a frequent encounter in medical practice. Cholestasis, defined as a defect in bile acid transport from the liver to the intestine, may be classified as intrahepatic or extrahepatic. Intrahepatic cholestasis refers to all situations in which the impairment of bile secretion occurs primarily within the liver. It can result from hepatocellular functional defects or from obstructive lesions of the intrahepatic bile ducts. Involvement of large bile ducts that are visible at macroscopic imaging is excluded from the definition of intrahepatic cholestasis.[1] Extrahepatic causes of cholestasis include choledocholithiasis and obstruction of the biliary tract due to malignancy. Hepatic imaging (particularly ultrasound) to look for the evidence of intra- or extrahepatic bile duct dilation is usually the first step to be performed in the evaluation of a patient with cholestatic jaundice.[2] A nondilated biliary system suggests that the cause of cholestatic jaundice is intrahepatic. Cholangiography by magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography may be undertaken in certain causes of extrahepatic cholestasis that may not be apparent by ultrasound such as primary sclerosing cholangitis and acquired immune deficiency syndrome-related cholangiopathy.[3] Among the numerous drugs that can cause intrahepatic cholestasis, antibiotics (particularly penicillins) are the most common.[4] Mortality from drug-induced cholestasis can be as high as 10%.[5] Despite the worldwide increasing abuse of anabolic–androgenic steroids (AAS) (particularly among young men), the health consequences of these medications including their hepatotoxicity are often overlooked.[6] In this paper, we report a 40-year-old male with severe cholestasis and marked weight loss (mimicking malignancy) secondary to AAS use for bodybuilding. The use of AAS was initially overlooked. We also performed extensive literature search regarding cholestasis as well other health consequences caused by these medications.


  Case Report Top


A 40-year-old male presented with a 2-month history of deep jaundice associated with severe itching and dark urine. During this period, he lost almost 30 kg of his weight. He suffered type 2 diabetes for 5 years which was controlled on metformin. He was happily married, had kids, and never smoked or drank alcohol. He was concerned about his illness fearing of being malignant. Blood tests at presentation showed a total bilirubin (TBL) of 32 mg/dl (0.2–1.2), a direct bilirubin of 31.7 mg/dl (0.1–0.4), aspartate transaminase (AST) of 42 U/L (5–45), alanine transaminase (ALT) of 62 U/L (13–45), gamma-glutamyl transferase of 70 U/L, alkaline phosphatase (ALP) of 1167 U/L (40–120), and International Normalized Ratio of 1.2 (0.8–1.2). Serologic testing for hepatotoxic viruses including hepatitis A, B, C, E, Epstein–Barr, cytomegalovirus, and human immunodeficiency virus was all negative. Workup for hemochromatosis, Wilson's disease, autoimmune hepatitis, and primary biliary cirrhosis was all unremarkable. Complete blood count, kidney function, serum electrolytes, and thyroid function were within normal range. Ultrasonographic examination of the abdomen was unremarkable with no evidence of intrahepatic bile duct dilatation. MRI and MRCP demonstrated normal calibers of pancreatic duct, common bile duct, common hepatic duct as well as intrahepatic biliary radicals with no filling defects. Intrahepatic form of cholestasis was the working diagnosis. Although the patient initially denied any drug intake other than metformin, subsequent specific questions on the use of AAS revealed that he started using methandrostenolone 30 mg/day for 2 months before his illness for bodybuilding. He did not volunteer taking methandrostenolone as he suspected it was irrelevant in relation to his illness. Methandrostenolone-induced intrahepatic cholestasis was suspected, and the drug was discontinued immediately. The patient was started on ursodeoxycholic acid. His liver function improved over a 3-month period following discontinuation of the AAS [Table 1]. Follow-up at 6 and 12 months after discontinuation of the drug revealed sustained normalization of his liver enzymes and bilirubin.
Table 1: Liver function test at presentation and after withholding methandrostenolone

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  Discussion Top


Drug-induced liver injury can present in several forms including hepatocellular, cholestatic, or mixed. The pattern of liver injury is classified based on R-values (ALT value/ALT upper limit of normal divided by the ALP value/ALP upper limit of normal). A case is considered hepatocellular when R is 5 or greater, cholestatic when R is 2 or less, and mixed when the R-value is between 2 and 5.[7] For patients with hepatocellular injury due to drugs, the risk of death or liver transplantation is >10% according to Hy's law. The criteria that define the Hy's law include: (1) ALT or AST elevation of >3 times the upper limit of normal; (2) TBL elevation of >2 times the upper limit of normal; (3) absence of initial findings of cholestasis (absence of elevation of ALP to >2 times the upper limit of normal); and (4) no other reason can be found to explain the combination of increased ALT and TBL, such as viral hepatitis A, B, C, D, or E; other preexisting or acute liver disease or another drug capable of causing the observed injury.[8],[9] The two main actions of testosterone (the male sex hormone) in the body are enhancing male sexual characteristics (androgenic action) and stimulating muscle mass growth (anabolic action). In the attempt to minimize the androgenic effects and improve the anabolic ones, several synthetic analogs of testosterone (named as AAS or designer steroids) have been produced.[10],[11] Despite being classified as controlled substances in many countries, the use of AAS is becoming widespread and no longer limited to bodybuilders or elite athletes.[12] Such drugs are illegally sold through the black market, websites, gyms, bodybuilding competitions, teammates, and trainers.[13] Sagoe et al., in a recent meta-analysis, estimated the global lifetime prevalence rate of AAS use to be 3.3%. The prevalence rate for males was as high as 6.4%.[14] A plausible reason that has fueled the development and use of such body image drugs is the increase in modern perception of "ideal" body image and the desire to increase masculinity among younger people.[12] A recent retrospective database analysis of over 6000 patients who sought treatment for hypogonadism between 2005 and 2010 revealed that AAS-induced hypogonadism was the most common etiology of profound hypogonadism in younger patients.[15] AAS have been linked to many adverse health effects. Besides their effects on the reproductive system, AAS can cause increase in hematocrit and coagulation causing thromboembolism, intracardiac thrombosis, and stroke and other cardiac disturbances including arrhythmias, hypertension, cardiomyopathies, and possibly sudden death. AAS abuse may induce psychological disturbances such as exaggerated self-confidence, reckless behavior, aggressiveness, and other psychotic symptoms. Furthermore, AAS withdrawal may be accompanied by depression and suicidal intentions.[6],[16],[17] Among the striking side effects of AAS is hepatotoxicity. The mechanisms underlying AAS-related hepatotoxicity remain speculative. It is the 17 α-alkylated AAS (e.g., methandrostenolone and methyltestosterone) that have the greatest potential for liver injury, attributed to delayed metabolism that results in prolonged hepatocellular and cholangiocellular drug exposure.[10],[11] The use of AAS may cause cholestasis, hepatic peliosis, adenomas, and carcinomas. Hepatic peliosis is a rare syndrome characterized by vascular changes in the liver leading to the formation of blood-filled enlarged sinusoids. The condition can lead to internal hemorrhage and death from hepatic failure. It may or may not revert by stopping AAS.[13] Hepatic tumors including adenomas and carcinomas are the most serious hepatic complications of prolonged anabolic steroid use (over 2 years). Despite being benign neoplasms, hepatic adenomas carry the risk of sudden rupture and bleeding leading to hemoperitoneum. Spontaneous regression of adenomas may occur following discontinuation of the drugs.[13],[17] The diagnosis of intrahepatic cholestasis induced by the use of AAS is often overlooked and challenging, particularly if direct and specific inquiry about the use of these agents is not made. The reasons behind this diagnostic difficulty are the presence of large differential diagnosis of intrahepatic cholestasis, the variability in clinical presentation, the lack of serologic biomarkers associated with this condition, and the tendency of patients to hide or deny the use of these medications.[5],[6],[18] The diagnosis is usually based on temporal association between the use of AAS and the development of cholestatic jaundice. A liver biopsy is usually not essential but may prove useful for uncertain cases. Drug-induced cholestasis, in general, can have several histological forms such as cholestatic hepatitis, bland cholestasis, and idiosyncratic liver injury including vanishing bile duct syndrome. Cholestatic hepatitis is the most common form of drug-induced cholestasis. Bland cholestasis is typically seen with oral contraceptives and anabolic steroids and is characterized by canalicular dilatation and bile plugs but without significant inflammation (canalicular cholestasis).[5],[19],[20],[21],[22],[23],[24] The main therapy for AAS-induced cholestasis is discontinuation of the culprit drug and reversal of complications produced by its hepatic toxicity such as coagulopathy. This usually results in complete recovery and improvement in liver biochemistry. The use of ursodeoxycholic acid can speed up the recovery of drug-induced cholestasis. It should be noted that complete recovery may take as long as 5 months.[25] Our patient presented with severe cholestasis that was associated with marked weight loss leading to initial suspicion of malignancy as a cause. He did not report taking AAS initially despite was asked about medication use in general.


  Conclusion Top


This case emphasizes the importance of keeping AAS as a diagnostic consideration in young men with cholestatic jaundice to withhold the drugs, prevent further liver injury, and minimize unnecessary investigations. AAS-induced cholestasis may exhibit symptoms and signs indistinguishable from malignancy-induced cholestasis. Patients may not volunteer the information of using AAS, and hence, direct inquiry about these drugs is imperative particularly in young men presenting with cholestatic jaundice.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Coward RM, Rajanahally S, Kovac JR, Smith RP, Pastuszak AW, Lipshultz LI, et al. Anabolic steroid induced hypogonadism in young men. J Urol 2013;190:2200-5.  Back to cited text no. 15
    
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Silva Ruiz MD, Giráldez Gallego Á, Serrano Jiménez M. Canalicular cholestasis induced by anabolic steroids. Rev Esp Enferm Dig 2017;109:735-6.  Back to cited text no. 24
    
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