A 26-year-old woman comes to the office due to yellowish discoloration of the eyes and dark urine for the past several days. She has no abdominal pain, anorexia, or nausea. The patient has been told a few times that her eyes look yellow in the past. She has no significant medical history other than mild acne vulgaris. The patient started taking oral contraceptives 2 weeks ago. Her father has diabetes mellitus, and her grandfather has heart failure. The patient is a doctoral student and moved to the United States from abroad a year ago. Vitals signs are normal. Examination shows mild scleral icterus. Laboratory results are as follows: During further evaluation, the sample from a liver biopsy shows dark, granular pigments in the hepatocytes. Which of the following is the most likely cause of this patient's current condition?

Question

A 26-year-old woman comes to the office due to yellowish discoloration of the eyes and dark urine for the past several days.  She has no abdominal pain, anorexia, or nausea.  The patient has been told a few times that her eyes look yellow in the past.  She has no significant medical history other than mild acne vulgaris.  The patient started taking oral contraceptives 2 weeks ago.  Her father has diabetes mellitus, and her grandfather has heart failure.  The patient is a doctoral student and moved to the United States from abroad a year ago.  Vitals signs are normal.  Examination shows mild scleral icterus.  Laboratory results are as follows:  During further evaluation, the sample from a liver biopsy shows dark, granular pigments in the hepatocytes.  Which of the following is the most likely cause of this patient's current condition?

Quizplus · Accepted Answer

11ec25c8_d3f9_7282_bc81_157faeb4a84c_MD0003_00 This patient with scleral icterus and hyperbilirubinemia has a positive urine bilirubin assay. In contrast to unconjugated bilirubin (water insoluble), conjugated bilirubin (water soluble) can be excreted through the urine, making this patient's findings consistent with conjugated (direct) hyperbilirubinemia. Her intermittent symptoms and otherwise normal liver function tests suggest benign hereditary hyperbilirubinemia. This patient has Dubin-Johnson syndrome, a rare condition caused by a defect in a hepatocyte transporter protein responsible for bilirubin excretion into the biliary system. Impaired hepatic excretion of conjugated bilirubin results in chronic or fluctuating direct hyperbilirubinemia and bilirubinuria (ie, dark urine). Episodes of scleral icterus typically begin in puberty or early adulthood and are provoked by illness, pregnancy, or oral contraceptive use, the likely trigger in this patient. Dubin-Johnson syndrome biliary system Although not required for the diagnosis, liver biopsy would show a grossly black liver and dark, granular pigment accumulation within hepatocytes, which differentiates this syndrome from other benign hereditary causes of conjugated hyperbilirubinemia in which biopsies are normal (eg, Rotor syndrome). Dubin-Johnson syndrome has no long-term sequelae, and treatment is not required. (Choice A) Choledocholithiasis causing bile duct obstruction presents with abdominal pain, nausea, and vomiting, findings not seen in this patient. In addition, direct bilirubin as well as alkaline phosphatase would be elevated; liver biopsy may show portal tract inflammation but not granular hepatocyte deposits. (Choices B and C) Gilbert syndrome (ie, decreased bilirubin glucuronidation) and intravascular hemolysis (eg, autoimmune hemolytic anemia) can present with episodic jaundice due to elevated unconjugated (indirect) bilirubin, which is metabolized to urobilinogen for urinary excretion (ie, positive urobilinogen on urinalysis). Bilirubin would not be present in the urine, and liver biopsy would be normal. (Choice D) Although conjugated hyperbilirubinemia may occur in hereditary hemochromatosis (eg, hepatic iron overload), this condition more commonly causes elevated transaminases, and other disease manifestations, including fatigue, hyperpigmentation, arthralgias, and diabetes, are usually present. Moreover, presentation in most women occurs after menopause because menstrual blood loss typically prevents excessive iron accumulation. (Choice F) Jaundice due to viral hepatitis is usually accompanied by fatigue, nausea, and right upper quadrant pain. In addition, transaminases would be significantly elevated, and liver biopsy would show hepatocyte injury and/or fibrosis rather than granular hepatocyte deposits. Educational objective: Intermittent scleral icterus and conjugated hyperbilirubinemia with otherwise normal liver function tests suggest benign hereditary hyperbilirubinemia (eg, Dubin-Johnson syndrome). This condition impairs hepatic excretion of conjugated bilirubin and is characterized by dark granular pigments within hepatocytes on histopathology. References: Inherited disorders of bilirubin clearance. (http://www.ncbi.nlm.nih.gov/pubmed/26595536)

A 26-Year-Old Woman Comes to the Office Due to Yellowish