A 24-year-old man presents after his colleagues noticed yellowing of his sclera. He reports a history of taking over-the-counter (OTC) pain medications for a recent gym injury but denies any recent illness. Blood tests reveal elevated bilirubin levels, but ALT and AST are within normal limits. A provocation test with intravenous nicotinic acid causes a further rise in bilirubin levels. He denies any alcohol use or family history of liver disease.
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The most likely diagnosis in this case is Gilbert’s syndrome. Gilbert’s syndrome is a common, benign hereditary condition that causes mild, intermittent elevations of unconjugated bilirubin, often triggered by stress, fasting, illness, or physical exertion. The normal liver enzyme levels (ALT and AST) and lack of other signs of liver dysfunction, along with a rise in bilirubin levels following a nicotinic acid provocation test, strongly point to Gilbert’s syndrome.
Key features of Gilbert’s syndrome include:
- Mild, intermittent jaundice, particularly during periods of physical stress or fasting
- Normal liver function tests (other than elevated unconjugated bilirubin)
- Absence of haemolysis or significant liver disease
- A benign course with no requirement for specific treatment
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Gilbert’s syndrome is typically a clinical diagnosis based on the following:
- Elevated unconjugated bilirubin levels with normal liver enzymes (ALT, AST, ALP) and no evidence of haemolysis.
- Nicotinic acid provocation test: As seen in this case, a further rise in bilirubin after administering intravenous nicotinic acid supports the diagnosis, though this test is rarely used in clinical practice today.
- Genetic testing: Genetic testing can confirm mutations in the UGT1A1 gene, although it is not routinely required.
In most cases, a detailed history, the presence of intermittent jaundice, and normal liver function tests are sufficient to diagnose Gilbert’s syndrome.
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Gilbert’s syndrome is caused by a mutation in the UGT1A1 gene, which encodes the enzyme uridine diphosphate-glucuronosyltransferase (UGT1A1). This enzyme is responsible for conjugating bilirubin in the liver, allowing it to be excreted in bile. In Gilbert’s syndrome, reduced activity of UGT1A1 results in a decreased ability to conjugate bilirubin, leading to periodic elevations in unconjugated bilirubin.
The rise in bilirubin is usually mild and often occurs in response to physical stress, fasting, dehydration, or illness. Since the liver is otherwise normal, liver function tests such as ALT, AST, and alkaline phosphatase remain within normal limits.
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No specific treatment is required for Gilbert’s syndrome as it is a benign condition. The jaundice typically resolves on its own, and patients are usually asymptomatic apart from the mild yellowing of the skin and eyes during episodes.
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