Metastatic carcinoid tumour presenting as hepatic encephalopathy

Abstract

Background

Hepatic encephalopathy is rarely encountered with carcinoid syndrome, but massive hepatic replacement by carcinoid tumour can cause neuropsychiatric alterations.

Case outline

A man of 42 years presented with carcinoid syndrome accompanied by features of hepatic encephalopathy. Following extended right hepatectomy his mental status returned to normal in line with markers of hepatic failure.

Conclusion

Extensive replacement of liver parenchyma by carcinoid tumours can lead to hepatic dysfunction as circulating levels of unmetabolised ammonia rise secondary to porto systemic shunting.

Introduction

Neurological complications of carcinoid tumours are generally due to metastatic disease. We present a rare case of hepatic encephalopathy secondary to a massive deposit of carcinoid tumour in the liver, with neurological recovery following resection.

Case Report

A 42-year-old man presented with a two year history of upper abdominal pain, cutaneous flushing, intermittent watery diarrhoea and headaches. Over the preceding three months he had suffered declining mental status, initially characterised by forgetfulness, mild confusion, incoordination and irritability but ultimately progressing to somnolence, disorientation, marked deterioration in thought processes and inappropriate behaviour that was at times aggressive. Past medical history included hyperlipidaemia, tobacco use and migraine headaches. There was no history of diabetes, peripheral or coronary artery disease, intravenous drug or alcohol abuse, seizure disorder, head injury, past liver disease, psychiatric disorder, psychoactive drug or salicylate use, recent febrile illness, constipation or gastrointestinal haemorrhage.

On physical examination the patient appeared ill and dishevelled but was well developed and adequately nourished; he was somnolent but arousable, confused, disoriented and dysarthric. Vital signs were normal. The sclerae were anicteric, the jugular veins flat, and the neck free of bruits, masses or adenopathy. The lung sounds were normal as were the cardiac and peripheral vascular examinations. There was no gynaecomastia, palmar erythaema, spider naevi, caput medusae or testicular atrophy. The abdomen appeared moderately distended and was without signs of ascites. A large, solid tumour was palpable in an enlarged liver. Rectal examination was normal and the stool negative for occult blood. Neurological examination showed asterixis, hypoactive deep tendon reflexes and ataxia but no muscular rigidity.

Laboratory data revealed normal complete blood count, serum electrolytes, arterial blood gas and thyroid function studies. Serum toxicology screen was negative. The blood urea was 3.9 mmol/L and creatinine 106.1 µmol/L. Liver function tests were: aspartate aminotransferase 38 U/L (normal 7–40), alanine aminotransferase 69 U/L (normal 6–53), alkaline phosphatase 107 U/L (normal 40–130), lactate dehydrogenase 761 U/L (normal 300–620), total bilirubin 15.4 µmol/L (normal 1.7–23.9 µmol), gamma-glutamyl transferase, 223 U/L (normal 10–88), albumin 42 g/L (normal, 35–50), prothrombin time 13.0 seconds (11.9–14.5). Serum ammonia level was elevated at 235 µmol/L (normal 9–33 µmol/L), but alphafetoprotein and carcinoembryonic antigen levels were normal. Twenty-four-hour 5′-hydroxy-indolacetic acid (5′-HIAA) levels were abnormally elevated at 77 mg/24 hours (normal 0.8–2.0).

Computed tomography (CT) scan of the head at the referring hospital was normal. Hepatic ultrasound revealed a large, solid hepatic mass that was further characterised by CT scan as a 15×17 cm mass with compensatory left hepatic lobe hypertrophy; there was no ascites, splenomegaly or other intra-thoracic or abdominal pathology (Figure 1). Search for a primary gastrointestinal carcinoid tumour with contrast radiography and endoscopy was unrevealing. Treatment was instituted for hepatic encephalopathy including dietary protein restriction, oral lactulose and oral neomycin. The serum ammonia level fell to 70 µmol/L and was associated with improvement in mental status. The intermittent flushing, headache and right upper abdominal pain persisted, however. In the light of a symptomatic hepatic mass that was probably secondary to metastatic carcinoid tumour, the patient was prepared for operation, with octreotide as prophylaxis against carcinoid crisis.

Figure 1. .

CT scan demonstrates massive tumour replacement of the right liver.

The abdomen was explored through a bilateral subcostal incision. Massive hepatomegaly was identified with a right hepatic lobe tumour extending into segment IV. The left hepatic lobe was hypertrophied. Intraoperative ultra-sound revealed tumour thrombus in the right and middle hepatic veins (Figure 2). Ultrasound examination of the pancreas was normal. Careful examination of the stomach, small bowel, adrenal glands, spleen, colon, appendix and intraperitoneal rectum revealed no gross pathology. An extended right hepatic lobectomy was performed, and histopathological examination was consistent with metastatic neuroendocrine tumour. The patients recovery was uncomplicated, and his mental status returned to normal together with serum ammonia levels and 24-hr urinary 5′–HIAA. He remains well and disease-free, three and a half years later.

Figure 2. .

Intraoperative ultrasound scan shows tumour thrombus in the middle hepatic vein.

Discussion

Carcinoid tumours are derivatives of the amine precursor uptake decarboxylation (APUD) neuroectodermal cell line that oversecrete biologically active substances such as serotonin. The carcinoid syndrome is characterised by intermittent secretory diarrhoea, flushing, paroxysmal dyspnoea and vasomotor instability. Neurological complications of carcinoid tumours occur in 16% of patients and are most frequently associated with widespread metastatic disease (not unlike other systemic malignancies), which can cause epidural spinal cord compression or deposits in the brain and lepto-meninges ¹.

Non-metastatic neurological complications of carcinoid tumours such as metabolic encephalopathy are rare (<3% in one large reported series) and typically occur with extensive liver replacement and fulminant hepatic failure ¹. Hepatocellular dysfunction, particularly with marked portosystemic shunting, results in excess accumulation of unmetabolised ammonia. Other pathophysiological mechanisms involved in hepatic encephalopathy include the production of false neurotransmitters, altered cerebral metabolism and endogenous activation of central nervous system receptors for gamma-aminobutyric acid and benzodiazepines ². Alterations in mental status in patients with carcinoid syndrome have been attributed to a relative deficiency of serotonin or its precursors in the central nervous system ³. The clinical improvement following current medical management of hepatic encephalopathy argues against relative tryptophan, niacin or serotonin deficiency as a cause of the neuropsychiatric syndrome seen in this patient. The cause of his hepatic encephalopathy remains elusive in the absence of hepatic failure.