Case Report
Hyperammonemia encephalopathy due to gastrointestinal bleeding in a GIST formed portosystemic shunt


    Schuiveling1,6, M. Wijland2, W.G.N. Mares3, AS Fortuin4, I.M.E. Desar5, B. Festen2

    1 Departments of Internal Medicine, 2Intensive Care, 3Gastro-enterology, 4Radiology, Gelderse Vallei Hospital, Ede, the Netherlands, 5 Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands, 6 Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands


    M. Schuiveling –
    Case Report

    Hyperammonemia encephalopathy due to gastrointestinal bleeding in a GIST formed portosystemic shunt


    A 61-year-old male was admitted to the intensive care unit with melena and decreased consciousness due to hyperammonemic encephalopathy. The patient was intubated and diagnostic evaluation revealed a large fluid and air filled gastrointestinal stromal tumour (GIST) in the right abdomen with a fistula to the duodenum and draining veins to the right renal vein and the vena cava inferior. We hypothesized that the mechanism resulting in the hyperammonemia could be the gastrointestinal bleeding induced increased protein load which is converted into ammonia due to abdominal bacteria. In turn this ammonia was not hepatically metabolized due to a portosystemic shunt formed by the GIST. In case of hyperammonemia without hepatic failure one should consider portosystemic shunting.


    Hyperammonemia is toxic for the brain and leads to lethargy, coma and ultimately death. The primary source of ammonia is bacterial degradation of proteins in the gastrointestinal (GI) tract. Ammonia is transported to the liver where it is converted into urea through the urea cycle. Hyperammonemia can occur due to bypassing the liver via a portosystemic shunt and can be exacerbated due to an increased protein load in a GI bleed. In addition, it can be caused by decreased functioning of the urea cycle caused by a genetic defect, medication or liver disease.[1]


    We report the case of a 61-year-old, formerly healthy, male who presented to the emergency department with melena and decreased consciousness (E1M5V2, West Haven hepatic encephalopathy grade III). Diagnostic evaluation revealed a blood level ammonia of 271 µMol/L (reference <50 µMol/L) (figure 1), without signs of hepatic or renal impairment. Treatment with antibiotics, pantoprazole and lactulose was initiated. Unfortunately, the patient’s condition deteriorated and intubation was needed. Because of an increasing serum lactate level, a computed tomography scan was performed to rule out ischemia. This showed a solitary fluid and air-filled tumour in the right abdomen of 20 x 30 cm with a fistula to the duodenum and normal hepatic anatomy. The tumour was highly vascularized with arterial afferent vasculature. Efferent collaterals drained on the renal vein and vena cava inferior resulting in a portosystemic shunt (figure 2). Active bleeding or ischemia was not seen. A duodenoscopy was performed and showed duodenal ulceration. Entering of the fistula revealed a necrotic collection filled with dark fluid. Biopsy displayed a GIST with immunoreactivity for CD117 and DOG1, and a cKIT exon 11 mutation.

    Figure 1. Serum ammonia during admission
    CVVH = continuous venovenous hemofiltration GI = Gastrointestinal

    Figure 2. Computed tomography scan of abdominal mass A.Frontal plane image demonstrating abdominal mass size B.Transversal plane demonstrating with a blue arrow the fistula between the duodenum and abdominal mass C. Sagittal oblique image with blue arrows indicating collaterals superior and inferior to right renal vein and with yellow arrow indicating collateral vasculature D. Transversal oblique image with large collateral vein from tumour to inferior vena cava indicated with a blue arrow

    Due to increasing ammonia concentration (314 µMol/L) continuous venovenous hemofiltration was initiated lowering the ammonia concentration to 77 µMol/L resulting in return of consciousness. Upon cessation of hemofiltration but continuation of oral lactulose treatment ammonia lowered further to 38 µMol/L. Unfortunately, the GI bleeding re-occurred with again an increase in serum ammonia level (79 µMol/L) and decreased consciousness (West Haven grade II hepatic encephalopathy). Repeated endoscopy showed no active bleeding. Since resection of the tumour was judged difficult with major consequences, neoadjuvant treatment with KIT inhibitor imatinib 400 mg once daily was initiated, but failed to stop the bleeding. In addition, the patient developed thrombosis in the left jugular and brachial vein. Due to the GI blood loss anticoagulation was impossible. Therefore emergency resection of the abdominal mass was performed with removal of the right kidney, partial duodenum and right hemicolon. Histology showed a high risk necrotic and haemorrhagic GIST, group 6B. Adjuvant treatment with imatinib was continued. The patient recovered from surgery with no recurrent encephalopathy during a follow-up of five months.


    To our knowledge this is the first case report of a patient presenting with hyperammonemic encephalopathy due to GI-bleeding in a newly diagnosed GIST. We hypothesized that the mechanism resulting in the hyperammonemia could be the GI-bleed induced increased protein load which is converted into ammonia due to abdominal bacteria. In turn this ammonia was not hepatically metabolized due to portosystemic shunting formed by the GIST.

    Duodenal GISTs are known to have systemic draining veins.[2,3] Three previous cases have been described of patients with GIST induced hyperammonemia, all without GI-bleeding but with improvement with lactulose therapy. Chiu et al hypothesized that a GIST might induce altered amino acid metabolization thereby resulting in the formation of ammonia which is systemically absorbed due to a portosystemic shunt.[3] In addition Lee et al. presented two patients with confusion after initiation of sunitinib therapy which improved with lactulose therapy.[4] The effectiveness of lactulose therapy in all cases suggests a relationship with bowel ammonia production and GIST induced hyperammonemia. In our patient, lactulose treatment failed and hemofiltration was needed.

    In this case we found a hypothesised explanation of the hyperammonemia in the presence of a portosystemic shunt. However in the case of non-hepatic dysfunction hyperammonemia one should also think of a urea cycle defect. A urea cycle defect can be asymptomatic until a precipitating factor such as an increased protein load (such as gastrointestinal bleeding or parenteral nutrition), infection, pregnancy, surgery, chemotherapy or treatment with sodium valproate leads to hyperammonemia. In case of a suspected hyperammonemia induced by a urea cycle defect acute management is aimed at decreasing the protein load to decrease production of ammonia and clearing of ammonia through haemodialysis. Sodium valproate is a precipitating factor due to its inhibiting effect on the urea cycle. This effect is unpredictable but partly dose dependent and more common when combined with other anticonvulsant treatment. Another cause of hyperammonemia is a urinary tract infection combined with urinary stasis. Certain bacterial infections (Proteus species, Corynebacterium species or Staphylococcus species) lead to ammonia formation which in the case of urinary stasis is able to diffuse into the venous blood supply of the bladder which bypasses the liver. More rare causes of hyperammonemia are haematological malignancies such as multiple myeloma or leukaemia. It is hypothesized that the mechanism behind the hyperammonemia is due to increased catabolism.[1]


    We describe a patient with GIST associated hyperammonemic encephalopathy, induced by GI bleeding and the presence of a portosystemic shunt. In case of gastrointestinal bleeding and hyperammonemia without hepatic dysfunction, one must be aware of portosystemic shunting.


    All authors declare no conflicts of interest. No funding or financial support was received.

    Informed consent was obtained from the patient for the publication of this case report.



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