methimazole and Liver-Failure

To bring to the attention of healthcare professionals the additional information on propylthiouracil (PTU)-related hepatotoxicity, based on a reanalysis of medical files reported to the Food and Drug Administration (1982-2008) for acute liver failure in PTU-treated hyperthyroid patients, and propose recommendations for the clinical use of PTU. Thirteen files of PTU-related severe liver adverse effects were analyzed for the pediatric population, seventeen for nonpregnant adults and two for pregnant women.. The recent findings showed that the daily PTU dose administered was high in the children, with a mean of 300 mg/day for an average 10-year-old individual. With regard to treatment duration, PTU administration lasted for at least 4 months in 75% of pediatric cases. Similarly, in a majority of adult cases (64%), PTU-induced liver injury occurred after a relatively long treatment period (4 months to >1 year).. PTU should not be used in children, in whom methimazole (MMI) represents the logical alternative. In adults, PTU should be restricted to those rare patients with Graves' disease for whom no better alternative can be offered and in patients with thyroid storm. For the special circumstance of pregnancy, PTU is the preferred choice during early gestation; switching back to MMI during later gestational stages remains a matter of clinical judgment. It is unknown whether liver function tests monitoring is worthwhile to prevent life-threatening, PTU-related hepatotoxicity.

Topics: Adult; Age Factors; Antithyroid Agents; Child; Drug Administration Schedule; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Patient Selection; Pregnancy; Pregnancy Complications; Propylthiouracil; United States; United States Food and Drug Administration

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

Hyperthyroidism is a common endocrine disorder affecting 2% of females and 0.5% of males worldwide and antithyroid drugs constitute the first line of treatment in the majority of cases. These agents may cause severe adverse effects and among them liver failure, although rare, is a potential lethal one. This case illustrates the sudden and abrupt deterioration of hepatic function due to antithyroid drug administration. This case along with a concise literature review is presented aiming to increase the awareness of endocrinologists of possible fatal complications from the everyday use of common agents such as antithyroid drugs.

Topics: Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Failure; Methimazole; Propylthiouracil; Thyroidectomy

Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin.. Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Hepatomegaly; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Middle Aged; Neoplasms, Germ Cell and Embryonal; Pregnancy; Stomach Neoplasms; Testicular Neoplasms; Thyrotoxicosis; Tomography, X-Ray Computed

Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases.. We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation.. This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important.

Topics: Antithyroid Agents; Fatal Outcome; Humans; Hyperthyroidism; Liver Failure; Male; Methimazole; Trilogy of Fallot; Young Adult

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Societies, Medical; United States; United States Food and Drug Administration