April 14, 2009

The Letter to the Editor in this week’s New England Journal of Medicine¹ by Drs. Rivkees and Mattison highlights concern about potential severe liver disease in children of the commonly used antithyroid drug, propylthiouracil (PTU), an adverse effect not seen with the other thionamide derivative, methimazole. On the basis of several lines of evidence and frequency estimates some of which were presented at the NICHD workshop “Hepatic Toxicity Following Treatment for Pediatric Graves’ Disease” on October 28, 2008² , these authors suggest that PTU no longer be used as first-line treatment for Graves’ disease in the pediatric age range.

The Endocrine Society endorses this recommendation. Despite the relative rarity of Graves’ disease in the young, children and adolescents account for as many as 13 of 42 cases of serious PTU-related liver failure reported to date in the medical literature and a similar disproportionate number (4 of 13) of those requiring liver transplant for this indication between 1990-2002³. Although precise numbers are not known with certainty, it can be estimated that there are 4000 children treated each year for Graves’ disease in the United States.  If 40% are treated with PTU, then as many as 1-2 children a year could develop severe liver disease, with some requiring a liver transplant or potentially suffering a fatal outcome.

Even one excess death is too many if it can be prevented. Until data from more thorough prospective studies or peer-reviewed retrospective studies become available, it would seem reasonable to use methimazole preferentially in the pediatric population.

For further information, please contact Stephanie Kutler, Director, Government Affairs, at skutler@endo-society.org.  

References:
1. Rivkees SA, Mattison DR Ending propylthiouracil-induced liver failure in children. N Engl J Med 2009;360:1574-5
2. Eunice Kennedy Shriver National Institute of Child Health and Human Development./ Hepatic Toxicity Following Treatment for Pediatric Graves’ Disease Meeting: October 28,2008. Conference Proceeding.  http://bpca.nichd.nih.gov/outreach/index.cfm
3. Russo MW, Galanko JA, Shrestha R et al. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transplantation 2004;10:1018-23