It is a diagnosis of exclusion - typically made after ruling out other causes of raised unconjugated bilirubin (1).
Diagnosis of Gilbert's syndrome can be based on when the person has:
- unconjugated hyperbilirubinaemia with normal plasma bile acids - an increase in unconjugated plasma bilirubin can be seen following:
- low energy diet for 24-48 hours, especially a reduction in lipids - but a similar magnitude of increase may be seen in hepatitis
- intravenous injection of nicotinic acid - normally rises to a maximum within 90 minutes; in Gilbert's disease, levels reach more than twice the basal level with a peak after 2 to 3 hours. The nicotinic acid causes a red cell haemolysis and thus a bilirubin load
- this is non specific and cannot be used to differentiate Gilbert’s syndrome form other causes of unconjugtaed hyperbilirubinemia (2)
- no overt or clinically recognised haemolysis
- normal liver function tests
- no systemic symptoms (3)
- a fall in bilirubin with phenobarbitone - a non-specific liver enzyme induction effect
There is no bilirubinuria; unlike haemolytic anaemia, urinary urobilinogen is not increased.
Liver biopsy is not indicated.
A heuristic for whether there should be further investigation has been stated as (1):
In an asymptomatic adult who presents with an increased bilirubin level that is:
- < 3 times the upper limit of normal with > 70% of bilirubin unconjugated and liver function tests are otherwise normal - the diagnosis is probably Gilbert's syndrome
- interval retest in 1-3 months with proportion of indirect (unconjugated) bilirubin should be done
- if the level of unconjugated bilirubin is non progressive, no further testing is needed
- if unconjugated bilirubin levels are rising consider haemolysis and request serum haptoglobin, lactase dehydrogenase, full blood count with reticulocyte count (1)
- > 3 times the upper limit of normal with > 70% of bilirubin unconjugated and liver function tests are otherwise normal - consider haemolysis (1)
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