Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Abstract

Propylthiouracil (PTU) was introduced for clinical use in July 1947 for Graves' disease (GD) treatment. Over the 60 years that this medication has been used, reports of PTU-related liver failure and death have accumulated. On October 28, 2008, an expert panel evaluated PTU drug safety in children at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) It is estimated that about 4000 pediatric patients per year with GD are being treated with antithyroid drugs (ATDs) in the United States, and up to 30% of pediatric patients with GD are being treated with PTU. The risk of severe PTU-induced liver failure is estimated as 1 in 2000-4000 children. The number of children developing reversible PTU-induced liver injury is estimated to be at least 1 in 200. Routine biochemical surveillance of liver function and hepatocellular integrity is not useful in identifying children who will develop liver failure. Children appear to be at higher risk for PTU-induced liver injury than adults. PTU should not be used as first line therapy for the treatment of GD in children. Current PTU use in children taking this medication should be stopped in favor of alternate therapies.

Graves' Disease Presenting with Severe Cholestasis

“…Propylthiouracil was not used for treatment due to recent publications reporting higher rates of hepatotoxicity in children (16). The patient's improved thyroid status without further liver dysfunction suggests that methimazole can be used to treat hyperthyroidism in the setting of cholestasis.…”

Surgical management of pediatric Graves’ disease: an effective definitive treatment

“…GD is very uncommon among children, with an incidence of 0.1-3 per 100,000 children [17] and a prevalence of 1 in 10,000 children in the United States [18]. Despite its rarity, autoimmune hyperthyroidism remains of great interest to endocrinologists because there is still no consensus on the best therapeutic approach in children, leaving the final decision to physicians' personal experience.…”

Side Effects of Anti-Thyroid Drugs and Their Impact on the Choice of Treatment for Thyrotoxicosis in Pregnancy

“…Clear guidance therefore needs to be routinely given to all healthcare professionals but in particular general practitioners and midwifes about the risk of PTU and severe liver injury, as they may be the first point of contact. They should be informed that early symptoms of liver failure such as itching, should not be attributed to pregnancy, but instead result in an urgent medical review as worse outcomes occur if there is delay in stopping PTU [51]. …”