A 16-year-old boy is evaluated due to new-onset jaundice. The patient was admitted to the hospital 24 hours ago after an emergency appendectomy, as well as drainage and irrigation of the peritoneal cavity, due to a perforated appendicitis. He has no chronic medical conditions. Current medications are intravenous morphine and piperacillin-tazobactam. The patient has not received blood products. Temperature is 38.1 C (100.6 F), blood pressure is 118/80 mm Hg, and pulse is 98/min. On examination, there is mild scleral icterus. Cardiopulmonary examination is normal. The laparotomy site is mildly tender; there is no rigidity or rebound tenderness. No drain was placed. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 14.4 g/dL |
| Platelets | 260,000/mm3 |
| Leukocytes | 11,500/mm3 |
| Liver function studies | |
| Total bilirubin | 3.3 mg/dL |
| Direct bilirubin | 0.3 mg/dL |
| Alkaline phosphatase | 70 U/L |
| Aspartate aminotransferase (SGOT) | 27 U/L |
| Alanine aminotransferase (SGPT) | 24 U/L |
Which of the following is the most likely diagnosis?
Gilbertsyndrome | |
Epidemiology |
|
Pathogenesis |
|
Clinical findings |
|
Diagnosis |
|
Treatment |
|
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count. | |
This patient with mild scleral icterus following surgery has elevated indirect (unconjugated) bilirubin levels with otherwise normal liver function tests and no evidence of hemolysis (ie, normal hemoglobin). This presentation is consistent with Gilbert syndrome, a benign inherited disorder of bilirubin glucuronidation.
Gilbert syndrome is characterized by decreased activity of UDP glucuronosyltransferase, the enzyme responsible for bilirubin conjugation within the liver. This results in indirect hyperbilirubinemia, which is exacerbated by stressors such as febrile illness, fasting, vigorous exercise, and surgery. Physical examination is normal other than mild jaundice during an episode. Although Gilbert syndrome does not cause additional laboratory or examination findings, the underlying trigger may explain other presenting signs; for example, this patient's low-grade fever and mild leukocytosis are likely related to resolving appendicitis and peritonitis.
The diagnosis of Gilbert syndrome is confirmed by elevated levels of unconjugated bilirubin on repeat testing with normal liver function tests and complete blood count results. Patients should be reassured that the condition is benign and that no treatment is required.
(Choice A) Ischemic injury to the gallbladder can cause acalculous cholecystitis in critically ill patients. Although fever and leukocytosis are common, most patients also have conjugated hyperbilirubinemia and mild elevations in alkaline phosphatase and aminotransaminases; an isolated unconjugated hyperbilirubinemia is atypical.
(Choice B) Glucose-6-phosphate dehydrogenase deficiency can cause hemolytic anemia following red blood cell exposure to oxidative stress (eg, infection). Although unconjugated hyperbilirubinemia is typical, a low hemoglobin level should be present.
(Choice D) Ischemic hepatopathy due to profound hypotension (eg, septic shock, blood loss) causes significantly elevated aminotransaminases (>1,000 U/L) and, frequently, elevated conjugated bilirubin and alkaline phosphatase levels, none of which are seen in this patient. He is also hemodynamically stable, making this diagnosis unlikely.
(Choice E) Iatrogenic biliary injury can manifest as a bile leak, causing fever, abdominal pain, and jaundice. Laboratory findings would include elevated aminotransaminases, alkaline phosphatase, and conjugated bilirubin. Moreover, this injury is typically associated with cholecystectomy, not appendectomy.
(Choice F) Intraoperative use of inhaled halogenated anesthetics (eg, halothane) can cause hepatoxicity with significantly elevated aminotransaminase levels, which are not present in this patient.
Educational objective:
Gilbert syndrome, caused by decreased hepatic glucuronosyltransferase activity, is a benign disorder characterized by recurrent episodes of mild jaundice precipitated by stressors (eg, illness, surgery). Laboratory findings show an isolated unconjugated hyperbilirubinemia (ie, normal transaminases and complete blood count).