A 62-year-old woman comes to the physician complaining of 6-8 weeks of fatigue and yellowish skin discoloration. She feels tired, has lost 4.5 kg (10 lb), and has occasional mild nausea. She has no change in bowel habits or abdominal pain. The patient had a colposcopy for an abnormal Pap smear 15 years ago. Her last mammogram 6 months ago was normal. She is a nonsmoker and drinks 2 or 3 beers each night. The patient's father has hypertension and hyperlipidemia and had a stroke. Her temperature is 36.7 C (98 F), blood pressure is 110/70 mm Hg, pulse is 88/min, and respirations are 14/min. There is marked scleral icterus. Abdominal examination shows normal bowel sounds and no organomegaly. No occult blood is detected in her stool. Laboratory results are as follows: Which of the following is the most likely cause of this patient's condition?

Question

A 62-year-old woman comes to the physician complaining of 6-8 weeks of fatigue and yellowish skin discoloration.  She feels tired, has lost 4.5 kg (10 lb), and has occasional mild nausea.  She has no change in bowel habits or abdominal pain.  The patient had a colposcopy for an abnormal Pap smear 15 years ago.  Her last mammogram 6 months ago was normal.  She is a nonsmoker and drinks 2 or 3 beers each night.  The patient's father has hypertension and hyperlipidemia and had a stroke.  Her temperature is 36.7 C (98 F), blood pressure is 110/70 mm Hg, pulse is 88/min, and respirations are 14/min.  There is marked scleral icterus.  Abdominal examination shows normal bowel sounds and no organomegaly.  No occult blood is detected in her stool.  Laboratory results are as follows:  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d3ff_3ee8_bc81_21024dacfd58_MD0003_00 This patient has predominantly conjugated (direct) hyperbilirubinemia. Predominantly unconjugated hyperbilirubinemia is due to increased bilirubin production (eg, hemolysis), decreased bilirubin uptake by the liver (eg, portosystemic shunt), or abnormal bilirubin conjugation (eg, Gilbert's syndrome). Predominant conjugated hyperbilirubinemia is due to hepatocellular injury, decreased bilirubin excretion in bile canaliculi (eg, Dubin-Johnson syndrome), intrahepatic cholestasis (eg, primary biliary cirrhosis), or extrahepatic cholestasis from biliary obstruction (eg, malignancy). The liver enzyme pattern can help differentiate the etiology of conjugated hyperbilirubinemia. Normal transaminases (aspartate aminotransferase, alanine aminotransferase) and alkaline phosphatase suggest inherited bilirubin metabolism disorders (eg, Dubin-Johnson syndrome). Predominantly elevated transaminases with normal alkaline phosphatase favor intrinsic liver disease (eg, viral hepatitis, hemochromatosis). Elevated alkaline phosphatase out of proportion to the transaminases suggests intrahepatic cholestasis or biliary obstruction. 11ec25c8_d3ff_3ee9_bc81_897ecd9f447a_MD0003_00 This patient's conjugated hyperbilirubinemia, elevated alkaline phosphatase, painless jaundice, and systemic symptoms (fatigue, weight loss) suggest malignant obstruction of the biliary system. Likely etiologies include pancreatic adenocarcinoma or cholangiocarcinoma. The next step in this patient's evaluation should be abdominal imaging (ultrasound or computed tomography), with consideration for endoscopic retrograde cholangiopancreatography if initial imaging is nondiagnostic. (Choice A) Acute choledocholithiasis can present similarly, with conjugated hyperbilirubinemia and markedly elevated alkaline phosphatase. However, patients typically have acute-onset right upper quadrant or epigastric pain rather than the painless jaundice seen in this patient. Pancreatic cancer causes epigastric pain in the majority of patients, but compared to acute choledocholithiasis, the pain is more chronic and typically worsens in the supine position and at night. (Choice B) Chronic autoimmune hepatitis usually causes elevated aminotransferases and conjugated hyperbilirubinemia. However, it is usually not associated with significantly elevated alkaline phosphatase. (Choice C) Chronic pancreatitis typically presents with recurrent bouts of abdominal pain and/or symptoms of fat malabsorption with steatorrhea. Liver function tests are usually normal in chronic pancreatitis. Recurrent episodes of pancreatitis can lead to fibrosis, stricture of the intrapancreatic portion of the bile duct, and elevated bilirubin and alkaline phosphatase. However, this usually develops later in patients with known chronic pancreatitis. (Choice D) Intrinsic liver disorders (eg, sarcoidosis, hemochromatosis, hepatic malignancy) usually cause hepatocellular injury with predominantly elevated transaminases. Hemochromatosis is also associated with diabetes mellitus, erectile dysfunction, skin pigmentation, arthropathy, and increased risk of cirrhosis and hepatocellular carcinoma. However, bilirubin and alkaline phosphatase levels are usually normal or mildly elevated without clinically obvious jaundice. (Choice F) Primary biliary cholangitis may present with fatigue, itching, jaundice, weight loss, and elevated alkaline phosphatase levels. However, antimitochondrial antibodies would be positive. Educational objective: Painless jaundice in a patient with conjugated hyperbilirubinemia and markedly elevated alkaline phosphatase should raise concern for biliary obstruction due to pancreatic or biliary cancer. Other common causes of biliary obstruction include choledocholithiasis and benign biliary strictures. References: Malignant biliary tract obstruction: evaluation and therapy. (http://www.ncbi.nlm.nih.gov/pubmed/20876543)

A 62-Year-Old Woman Comes to the Physician Complaining of 6-8