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

Heidari R, Niknahad H, Jamshidzadeh A, Abdoli N - Clin Mol Hepatol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

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.

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Antithyroid drugs prescription in US, from year 1991 to 2008. This figure is reprinted from reference "78" with permission from corresponding author ( Dr. David Cooper, Professor of Medicine, Division of Endocrinology, Diabetes, & Metabolism, The Johns Hopkins University, School of Medicine). MMI, Methimazole; PTU, propylthiouracil.
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Figure 3: Antithyroid drugs prescription in US, from year 1991 to 2008. This figure is reprinted from reference "78" with permission from corresponding author ( Dr. David Cooper, Professor of Medicine, Division of Endocrinology, Diabetes, & Metabolism, The Johns Hopkins University, School of Medicine). MMI, Methimazole; PTU, propylthiouracil.

Mentions: Some comparative evaluation of adverse events including hepatotoxicity, related to antithyroid drugs has been done previously.29,77,78 In these investigations, the authors tried to find a relationship between the age of patients and the development of hepatotoxicity induced by methimazole and/or PTU. One of these investigations resulted that methimazole administration caused lower severe hepatotoxic events and vasculitis in children than the other drug, PTU.29 Interestingly, it has been reported that there are no reports of liver failure or liver transplantation in association with methimazole use in children in united states.11 Furthermore, there are fewer and less serious adverse events reported in FDA database for methimazole than for PTU.11 A substantial amount of data obtained from evidence based and prospective studies are indicated that methimazole is a safer pharmaceutical in management of hyperthyroidism in children.11,79 Some severe and even fatal PTU-induced liver injury cases are reported in children treated with this medication.80,81 Hence, some investigators suggested that PTU should no longer be used as a first line treatment for Graves' disease in children.11 Some studies showed that a shift in propylthiouracil prescription has occurred during years (Fig. 3) and methimazole is more prescribed in lower ages,78 probably due to its lower risk of liver damage in children.29,78


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

Heidari R, Niknahad H, Jamshidzadeh A, Abdoli N - Clin Mol Hepatol (2014)

Antithyroid drugs prescription in US, from year 1991 to 2008. This figure is reprinted from reference "78" with permission from corresponding author ( Dr. David Cooper, Professor of Medicine, Division of Endocrinology, Diabetes, & Metabolism, The Johns Hopkins University, School of Medicine). MMI, Methimazole; PTU, propylthiouracil.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197171&req=5

Figure 3: Antithyroid drugs prescription in US, from year 1991 to 2008. This figure is reprinted from reference "78" with permission from corresponding author ( Dr. David Cooper, Professor of Medicine, Division of Endocrinology, Diabetes, & Metabolism, The Johns Hopkins University, School of Medicine). MMI, Methimazole; PTU, propylthiouracil.
Mentions: Some comparative evaluation of adverse events including hepatotoxicity, related to antithyroid drugs has been done previously.29,77,78 In these investigations, the authors tried to find a relationship between the age of patients and the development of hepatotoxicity induced by methimazole and/or PTU. One of these investigations resulted that methimazole administration caused lower severe hepatotoxic events and vasculitis in children than the other drug, PTU.29 Interestingly, it has been reported that there are no reports of liver failure or liver transplantation in association with methimazole use in children in united states.11 Furthermore, there are fewer and less serious adverse events reported in FDA database for methimazole than for PTU.11 A substantial amount of data obtained from evidence based and prospective studies are indicated that methimazole is a safer pharmaceutical in management of hyperthyroidism in children.11,79 Some severe and even fatal PTU-induced liver injury cases are reported in children treated with this medication.80,81 Hence, some investigators suggested that PTU should no longer be used as a first line treatment for Graves' disease in children.11 Some studies showed that a shift in propylthiouracil prescription has occurred during years (Fig. 3) and methimazole is more prescribed in lower ages,78 probably due to its lower risk of liver damage in children.29,78

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

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.

Show MeSH
Related in: MedlinePlus