A 24-year-old woman comes to the office due to yellowing of the eyes that was first noted by her college roommate yesterday. The patient otherwise feels well and has no symptoms. She has no chronic medical conditions. The patient recently completed a prolonged fast in observance of a religious holiday. Her only medication is an oral contraceptive. Temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, and pulse is 76/min. Scleral icterus is present. Cardiopulmonary examination is normal. The abdomen is soft, nondistended, and nontender without hepatosplenomegaly or masses. Laboratory results are as follows: Which of the following is the most appropriate diagnostic step in management?

Question

A 24-year-old woman comes to the office due to yellowing of the eyes that was first noted by her college roommate yesterday.  The patient otherwise feels well and has no symptoms.  She has no chronic medical conditions.  The patient recently completed a prolonged fast in observance of a religious holiday.  Her only medication is an oral contraceptive.  Temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, and pulse is 76/min.  Scleral icterus is present.  Cardiopulmonary examination is normal.  The abdomen is soft, nondistended, and nontender without hepatosplenomegaly or masses.  Laboratory results are as follows:  Which of the following is the most appropriate diagnostic step in management?

Quizplus · Accepted Answer

11ec25c8_d3f2_4686_bc81_098c9b7036ee_MD0003_00 Hepatic metabolism of bilirubin is a multistep process involving uptake from the bloodstream, storage and conjugation, and excretion into the biliary system. Increased direct bilirubin levels can be seen in hepatobiliary disease (eg, cirrhosis, hepatitis) because bilirubin conjugates are shunted into the plasma when excretion into bile is slowed. In contrast, elevated unconjugated (indirect) bilirubin levels, as in this patient, typically indicate increased bilirubin production (eg, hemolysis) or reduced bilirubin conjugation. Hepatic metabolism of bilirubin This patient likely has Gilbert syndrome, a familial disorder caused by reduced bilirubin glucuronidation. Clinical manifestations include intermittent jaundice due to a mild, unconjugated hyperbilirubinemia (<3 mg/dL) without evidence of hemolysis (ie, normal hemoglobin and reticulocyte count). Jaundice may be triggered by periods of stress, which include fasting, dehydration, febrile illness, vigorous exercise, menstruation, and surgery. A presumptive diagnosis of Gilbert syndrome is made by the presence of persistent unconjugated hyperbilirubinemia in the absence of other laboratory abnormalities (eg, hepatic aminotransferases, complete blood count, reticulocyte count). This condition is benign and requires no treatment other than reassurance. (Choice A) The estrogen component of oral contraceptives can inhibit bilirubin excretion into the biliary system, leading to cholestatic liver injury in rare cases. Laboratory findings would include conjugated hyperbilirubinemia and elevated alkaline phosphatase, not an isolated unconjugated hyperbilirubinemia. (Choice C) Liver biopsy may be indicated when liver function test abnormalities cannot be explained despite extensive noninvasive diagnostic workup. This patient with mild jaundice and unconjugated hyperbilirubinemia almost certainly has Gilbert syndrome, making a liver biopsy unnecessary. (Choice D) Right upper quadrant ultrasonography is typically indicated for evaluation of conjugated hyperbilirubinemia to identify biliary obstruction (eg, choledocholithiasis, stricture). This test is not helpful in the workup of unconjugated hyperbilirubinemia. (Choice E) Acute and chronic viral hepatitis usually cause nonspecific symptoms (eg, fatigue, anorexia) with elevations in aminotransferases, which are not present in this patient. In addition, jaundice due to hepatitis is typically caused by conjugated, not unconjugated, hyperbilirubinemia. Educational objective: Gilbert syndrome is caused by reduced bilirubin glucuronidation and results in intermittent jaundice due to mild, unconjugated (indirect) hyperbilirubinemia. Jaundice may be triggered by periods of stress, including fasting. This condition is benign and requires no treatment. References: Hereditary hyperbilirubinemias. (http://www.ncbi.nlm.nih.gov/pubmed/24839786) New insights in bilirubin metabolism and their clinical implications. (http://www.ncbi.nlm.nih.gov/pubmed/24151358)

A 24-Year-Old Woman Comes to the Office Due to Yellowing