The accurate diagnosis of jaundice is established by the association of other symptoms and the performance of liver function and special diagnostic procedures. For example, jaundice with fever, a prodromal phase of anorexia, malaise, and a tender liver suggests hepatitis. Jaundice with itching suggests xanthomatous or primary biliary cirrhosis. Jaundice and anemia suggest hemolytic anemia. Jaundice, back pain, and an abdominal mass suggest a carcinoma of the pancreas.

When liver functions show only an elevated indirect bilirubin level, Gilbert disease or hemolytic anemia is suggested. A normal urine urobilinogen will make Gilbert disease even more likely. Liver function analyses showing only elevated bilirubin, GGT, and alkaline phosphatase levels suggest bile duct obstruction by a stone or tumor. Liver function results showing an impressive elevation of the bilirubin, serum aspartate aminotransferase, and serum alanine aminotransferase levels suggest hepatitis.

In cases in which obstruction versus parenchymal disease remains a dilemma after routine tests, several newer procedures have been developed that may help avoid an exploratory laparotomy. Endoscopic retrograde cholangiopancreatography (ERCP), cutaneous transhepatic cholangiography, and peritoneoscopy are very useful in these cases. Computed tomography (CT) scans and ultrasonography are also valuable. The old steroid whitewash is still useful. This is done by administering 20 mg of prednisone daily for 5 days and monitoring the bilirubin level. A positive test, indicating drug-induced cholangitis, is considered a drop of the bilirubin to one-half its original value or more. Exploratory laparotomy may be necessary despite an extensive workup.