Not All Jaundice Is Concerning

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A 15-year-old high school student stayed up all night to finish a term paper and in the morning, he looked in the mirror and noticed that his eyes were yellow. A 40-year-old woman develops a viral upper respiratory infection with a low-grade temperature. On a routine visit to the doctor, her eyes are noted to be yellow. A 56-year-old man is seen by his doctor for a routine physical examination. His laboratory tests reveal an elevated bilirubin. Further testing shows no other abnormality other than a mildly elevated indirect bilirubin. A 22-year-old man returns from the gym after a heavy workout, looks in the mirror and notices that his eyes are yellow. What commonality do these four people share? They all have jaundice (yellowing of the eyes) and they all are affected by a genetic disorder called Gilbert’s syndrome.

Gilbert’s syndrome is a common disorder characterized by an elevated indirect bilirubin fraction. Bilirubin is a yellow breakdown product of normal heme catabolism. Bilirubin may occur in the body in an insoluble form called indirect bilirubin or in a soluble form called direct bilirubin. The insoluble, indirect form is transformed into a soluble or direct form in the liver. Total and direct bilirubin levels are measured from the blood, but indirect bilirubin is calculated from the total amount of bilirubin minus the amount of direct bilirubin.

Gilbert’s syndrome is a benign condition. It does not cause any harm. It is extremely common occurring in about five percent of our population. The syndrome is caused by a decreased level in the enzyme, glucuronyl transferase, which conjugates bilirubin. It is a hereditary condition, which is autosomal recessive. Gilbert’s syndrome is not associated with any increased disease or mortality. This syndrome is usually diagnosed after puberty and is more common in men than in women. Affected individuals often come to medical attention after a fast, during an infection, after vigorous exercise or in any period of extreme stress as these circumstances can lead to decreased bilirubin conjugation and therefore an increase in indirect bilirubin levels. The physical examination of these patients is usually normal except for some mild yellowness of the eyes. Laboratory tests other than an elevated bilirubin should all be normal.

There is a potential consequence of having a low level of the bilirubin-processing enzyme and that is people with Gilbert’s have increased side effects with certain medications. In particular, certain medications used to treat HIV, elevated triglycerides, colon cancer and chronic myeloid leukemia, should be used with extreme caution. Because of this potential effect with certain medications, talk to your doctor before taking any new medications.

There are no therapies needed for Gilbert’s syndrome as it is a benign condition. Interestingly, some studies have suggested a decreased colon and rectal cancer risk in people with Gilbert’s. This, however, has not been proven.

David Bernstein, MD, FAASLD,FACG, AGAF, FACP, is the chief of hepatology at Sandra Atlas Bass Center for Liver Diseases and a professor of medicine at Hofstra-Northwell School of Medicine.

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