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Jaundice Induced by Stanozolol Hypersensitivity S. D. SLATER J. F

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Jaundice Induced by Stanozolol Hypersensitivity S. D. SLATER J. F Postgrad Med J: first published as 10.1136/pgmj.52.606.229 on 1 April 1976. Downloaded from Postgraduate Medical Journal (April 1976) 52, 229-232. CASE REPORTS Jaundice induced by stanozolol hypersensitivity S. D. SLATER J. F. DAVIDSON M.D., M.R.C.P. M.B., F.R.C.P. R. S. PATRICK * M.D., D.P.H., F.R.C.Path. Department ofHaematology and * Department ofPathology, Royal Infirmary, Castle Street, Glasgow Summary During the eighth month of treatment he was A 66-year-old male patient developed jaundice after admitted to hospital with a 1-week history of 7 months of treatment with the anabolic steroid, jaundice, pruritus and dark urine. His appetite was stanozolol. When the drug was withdrawn he made a unimpaired and there was no nausea or abdominal full and uneventful recovery. A liver biopsy showed the pain, but he had lost 4-5 kg in weight during the histology of a hypersensitivity reaction. This is previous 3 weeks. There was no history oftransfusion believed to be the first time jaundice has been recorded or of a recent injection or known contact with with stanozolol therapy and the first time a hyper- jaundice, and he had been taking no other drugs. He sensitivity-type jaundice has been recorded with any was deeply icteric with an enlarged (3 f.b.), smooth anabolic steroid. and non-tender liver. There were no other physical abnormalities. copyright. Introduction CHOLESTATIC jaundice may occur as a complica- Investigations tion of treatment with certain anabolic steroids, and Serum bilirubin 8 mg/100 ml (direct acting fraction this is generally accepted to be due to a direct toxic 7 mg/100 ml), alkaline phosphatase 31 KA u/100 ml, effect upon the biliary canalicular cells (Sherlock, SGOT 51, and SGPT 74 RF u/ml, thymol turbidity 1968; Maxwell and Williams, 1973). This report con- 0 3 Maclagan units, albumin 4-1 g/100 ml and cerns a patient who developed globulin 3-2 g/100 ml. There was jaundice while taking bilirubinuria. http://pmj.bmj.com/ the anabolic steroid, stanozolol (Stromba, Winthrop) Prothrombin and kaolin cephalin clotting times were during a trial of its effect upon fibrinolysis in patients normal. Hb 14-1 g/100 ml, WBC 11,300/mm3, with ischaemic heart disease (Davidson et al., 1972). platelets 242,000/mm3, reticulocytes 2%Y, ESR 16 In this case thejaundice appeared to be the result of a rising to 57 mm/hr, and there were target cells in the hypersensitivity reaction. blood film. Urea and electrolytes were normal. Chest X-ray, barium meal and enema were all Case report normal. L.E. latex and L.E. cell test, and tests for The patient was 62 years old when he sustained a anti-nuclear factor, smooth muscle and mitochon- on September 24, 2021 by guest. Protected myocardial infarct. He was started on phenindione drial antibodies were negative. Six days after ad- and remained well after the incident with very stable mission he developed an itchy maculopapular rash control of his anticoagulant therapy. This was and was given chlorpheniramine 4 mg four times a discontinued 4 years later, and after 4 weeks off all day. therapy he was entered in a double-blind placebo- Cholestatic jaundice due to stanozolol was sus- controlled trial of the effect of stanozolol, and of pected but as there was no convincing improvement stanozolol plus phenformin, upon plasma fibrino- after 12 days (Fig. 1), percutaneous transhepatic lysis in patients with ischaemic heart disease. He was cholangiography was performed. Bile was not randomly allocated to treatment with stanozolol aspirated, suggesting that an extra-hepatic biliary 10 mg together with a phenformin placebo daily. obstruction was unlikely (George et al., 1965). A This was continued and he remained well for 7 percutaneous liver biopsy likewise revealed no months. The effect upon the fibrinolytic mechanism positive evidence of large bile duct obstruction. has been reported previously (Davidson et al., 1972). Cholestasis within bile duct canaliculi was prominent Correspondence: Dr S. D. Slater, Department of Medicine, in the centrilobular zones (Fig. 2), while an inflam- Law Hospital, Carluke, Lanarkshire. matory exudate was seen within and immediately Postgrad Med J: first published as 10.1136/pgmj.52.606.229 on 1 April 1976. Downloaded from 230 Case reports adjacent to all portal tracts (Fig. 3). Eosinophils were The patient developed no further symptoms and a conspicuous component of these lesions and they required no treatment. His subsequent progress was were present also in some sinusoids. Small foci of entirely satisfactory with an eventual return of liver inflammation were seen in relation to a few scattered function tests and ESR to normal (Fig. 1). hepatocytes showing acidophilic necrosis. These appearances were considered to be most consistent Discussion with a cholestatic jaundice of hypersensitivity type. Stanozolol is 17a-methyl-173-hydroxy-5a-andro- stane (3,2-c) pyrazole (androstanopyrazole). Many patients will develop a degree of sulphobromoph- IL thalein retention when given an oral anabolic H: 40 L steroid. However, in many cases this returns to q6 20F normal after 4 weeks despite continuing the treat- ment. Krulskemper (1968) carried out a quantitative comparison of the activity of oral anabolic steroids 0~ E 882 on sulphobromophthalein retention and found that stanozolol belonged to the group which had the least Er 60 _ effect. He also reported that stanozolol had very little influence on the serum transaminases. To date, no 0' E case of cholestatic jaundice has been reported with stanozolol although it is a well known complication oC of other oral 17a alkyl anabolic steroids (Sherlock, 1968; Kruskemper, 1968; Adlercreutz and Tenhunen, 1970). 10 2346 345 78 0 Since the observations of Werner, Hanger and Kritzler (1950) on jaundice induced in man by 9~~~~Tm methyltestosterone, it has been accepted that thecopyright. cholestasis of anabolic steroid therapy is not a drug sensitization phenomenon. Schaffner, Popper and Chesrow (1959) studied liver biopsies in twenty-seven Weeks Months patients before and after the administration of norethandrolone. In none of their patients, including FIG. 1. Liver function tests from time of presentation to four who developed cholestatic jaundice, was there recovery (Interrupted lines = upper limits of normal). any hepatitis greater than the very minor degrees http://pmj.bmj.com/ on September 24, 2021 by guest. Protected ..^.......e..~ ~ ~~~~~~ A:^ .. FIG. 2. Liver biopsy. In the centrilobular area (right) there are many small dark bile thrombi within bile capillaries (arrows). There is a mild inflam- matory reaction in the portal tract (left). Neutral red x 250. Postgrad Med J: first published as 10.1136/pgmj.52.606.229 on 1 April 1976. Downloaded from Case reports 231 :5N ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~-U =_....................................................'.: FIG. 3. Liver biopsy. A typical portal tract infiltrated with inflammatory cells including numbers ofeosinophils. There is no cholangiolar proliferation. A pyknotic hepatocyte is present (arrow). Haematoxylin and eosin x 565. seen in control biopsies. These drugs may interfere Anabolic steroids are now widely used and with the excretion of conjugated bilirubin from the recently have been considered worthy of further hepatocyte, and electron miscroscopy of both study in thrombosis prophylaxis (Prentice and human and experimental livers has shown some Davidson, 1973). It is suggested that all patients on copyright. damage to bile canaliculi (Schaffner, Popper and long-term anabolic steroid therapy should have Perez, 1960; Arias et al., 1961). There is no hyper- regular assessment of liver function. sensitivity reaction such as characterizes the chole- stasis due to the phenothiazine group of drugs References (Sherlock, 1968; Maxwell and Williams, 1973). ADLERCREUTZ, H. & TENHUNEN, R. (1970) Some aspects of Kruskemper (1968) reported that allergic side effects the interaction between natural and synthetic female sex to anabolic steroids had not been observed but hormones and the liver. American Journal of Medicine, 49, postulated that a heterocyclic substitution in ring A, 630. http://pmj.bmj.com/ as is found in stanozolol, might cause allergic ARIAS, I.M., GOLDFISHER, S., NovIKOFF, A.B. & ESSNER, E. (1961) The effect of 17-ethyl-19-nortestosterone and symptoms similar to those elicited by other pyrazole Icterogenin on the hepatic metabolism of bilirubin in derivatives. normal and Gunn rats. Journal of Clinical Investigation, 40, In this case the histological appearance of the liver 1023 (Abstract). was most consistent with cholestasis of the hyper- DAVIDSON, J.F., LOCHHEAD, M., MCDONALD, G.A. & sensitivity type. The clinical presentation with a rash McNIcoL, G.P. (1972) Fibrinolytic enhancement by Stanozolol: a double blind trial. British Journal of Haema- and a high ESR also favours this mechanism. It is tology, 22, 543. on September 24, 2021 by guest. Protected possible, of course, that the jaundice was the out- DAVIDSON, J.F., CONKIE, J.A. & McDONALD, G.A. (1974) come of a combination of direct toxicity and hyper- Stanozolol as a fibrinolytic agent in men with ischaemic sensitivity. As far as can be determined, features heart disease-a thirty-month study. In: Synthetic Fibrino- suggesting hypersensitivity have not previously been lytic Thrombolytic Agents: Chemical, Biochemical, Pharma- implicated in the cholestasis associated with anabolic cological and Clinical Aspects (Ed. by K. N. von Kaulla steroids. The risk of stanozolol causing cholestasis of and J. F. Davidson), p. 328. Thomas: Springfield, Illinois. GEORGE, P., YOUNG, W.B., WALKER, J.G. & SHERLOCK, S. a non-hypersensitivity type remains theoretical. None (1965) The value of percutaneous cholangiography. of the other eighteen patients in the trial who received British Journal of Surgery, 52, 779. it daily for up to 30 months developed any clinical or HOWARD, R.P. & FURMAN, R.H. (1962) Metabolic and serum biochemical evidence of this (Davidson, Conkie and lipid effects of methylandrostane and methylandrostene McDonald, 1974).
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