title: Pathogenesis of propylthiouracil-related hepatotoxicity in children: present concepts.
abstract: Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are the most common drugs used today in cases of adolescent thyrotoxicosis. Skepticism has been growing regarding the use of PTU in childhood and its association with severe liver failure. The aim of this review is to present all the recent data regarding pathogenesis of PTU hepatotoxicity in children and adolescents. Specifically, reactive drug metabolites and increased oxidative stress can directly activate inflammatory and immunological pathways. Drugs are not only immunogenic because of their chemical reactivity but also because they may bind through electrostatic forces to available T-cell receptors. Redox modulation is also a key regulatory strategy in the adaptive immune system. Subtle changes in the extracellular redox status may cause profound functional changes in redox-sensitive proteins. Genetic factors that affect drug biotransformation could also be implicated in this mechanistic model of PTU-related hepatotoxicity. Further studies are needed to fully understand the pathophysiology of PTU-induced liver damage.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Karras
authors.forename: Eleni
authors.initials: E
authors.lastname: Memi
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kintiraki
authors.forename: Gerasimos E
authors.initials: GE
authors.lastname: Krassas
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D013956:Antithyroid Agents / Q000493:pharmacokinetics / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D002648:Child; D003210:Concept Formation; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology; D008954:Models, Biological; D011441:Propylthiouracil / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D013956:Antithyroid Agents; D011441:Propylthiouracil