Factors affecting drug-induced liver injury: antithyroid drugs as instances

Abstract

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease

“…For these reasons, the levels of free T4 in our case were not always consistent with the ALT levels. However, thyrotoxicosis and MMI can induce liver injury (17)(18)(19). In general, thyrotoxicosis-induced liver injury improves after thyrotoxicosis is removed by proper treatment for hyperthyroidism.…”

The Postulated Hepatotoxic Metabolite of Methimazole Causes Mitochondrial Dysfunction and Energy Metabolism Disturbances in Liver

“…However, methimazole reactive metabolites seem to be involved in the liver injury induced by this drug. [14][15][16]35 The ring cleavage metabolite of methimazole, NMT is a postulated hepatotoxic intermediate of this drug. 16 The exact mechanism of cell injury induced by NMT has not been revealed so far.…”

“…4,[11][12][13] Although the precise mechanism(s) of methimazole-induced liver injury is not known, but oxidative stress and its associated events might play a role in methimazole hepatotoxicity. [14][15][16] The importance of drug bioactivation and its relevance to DILI has been widely investigated.…”

The Opportunities of Metabolomics in Drug Safety Evaluation

“…Therefore, novel concepts and techniques are needed to illustrate the mechanisms of idiosyncratic ADRs. For idiosyncratic ADRs, multiple risk factors have been found in clinical studies [50, 73, 74]. It is possible that a drug disturbs certain metabolic pathways of endobiotics in the body, and that the cofactors that double hit on these metabolic pathways will potentiate drug toxicity.…”