Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease

6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammato ry bowel disease (IBD). Side effects include infection, leukopenia, hepatit is, and pancreatitis. The level of thiopurine methyltransferase (TPMT), whi ch metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects o f these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who receive d 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (R BC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester , MN. The occurrence of leukopenia, elevated aminotransferases, and pancrea titis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-M P or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/m L RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below t he accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed bo th elevation of aminotransferases and leukopenia. Of all, 20 children had n ormal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leuko penia (n = 1). We conclude that side effects of 6-MP or AZA occur despite n ormal TPMT levels.