Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
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Propylthiouracil (PTU) is widely used to treat patients with hyperthyroidism. In rare cases this drug has been found to have toxic effects on the liver. We describe the second assymptomatic case, reported in the literature, of PTU induced hepatotoxicity. Sixteen cases have been published so far, all with clinical manifestations. A 20-year-old female patient developed an elevation of AST, ALT and GGT levels after 5 months of PTU (50 mg tid) therapy for Graves disease with hyperthyroidism. The patient showed normal levels of liver aminotransferases before starting PTU. She had no risk factors for or clinical evidence of pre-existing liver disease. She didn't take any regular medication. After stopping PTU, the plasma levels of hepatic enzymes normalised within 6 weeks. Thirteen days after the reinstitution of PTU (150 mg tid), because of the recurrence of hyperthyroidism, another episode of assymptomatic hepatotoxicity was documented. AST, ALT, GGT and AP levels rose again, but bilirrubin levels remained normal, which represents a very unusual laboratory constellation in this kind of patient. The serology for hepatitis A, B, C and for EBV and CMV was negative. After stopping PTU, methimazole (MMI) was started and the liver enzymes normalised within two weeks. After 12 months of MMI therapy, the patient is assymptomatic, with normal liver enzyme levels and normal thyroid function tests. This case is the second to be described where the diagnosis was confirmed by the rechallenge of PTU, being this a major diagnostic criteria. Despite its rarity the disease should be suspected in any patient receiving PTU in whom clinical or laboratorial evidence of hepatocellular injury develops. The drug should be discontinued immediately when the hepatic injury is detected. Recovery is usually complete after the withdrawal of the drug, but there were al least, three fatalities among the 17 cases described.
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PMID:[Asymptomatic hepatitis induced by propylthiouracil]. 1187 66

R1 The diagnosis of Graves' disease in children is based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies. 1/+++. R2 Thyroid ultrasound is unnecessary for diagnosis, but can be useful for assessing the size and homogeneity of the goiter. 2/+. R3. Thyroid scintigraphy is not required for the diagnosis of Graves' disease. 1/+++. R4. The measurement of T4L and T3L levels is not necessary for the diagnosis of Graves' disease in children but can be useful for the management and assessment of prognosis. 1/++. R5. In the absence of TSH receptor autoantibodies, the possibility of genetically inherited hyperthyroidism must be considered. 1/++. R6. Drug therapy is the primary line of treatment for children and consists of imidazole, carbimazole or thiamazole, with an initial dosage of 0.4 to 0.8mg/kg/day (0.3 to 0.6mg/kg/day for thiamazole) depending on the initial severity, up to maximum of 30mg. 1/++. R7. Propylthiouracil is contraindicated for children with Grave's disease. 1/+++. R8. Before starting treatment, it may be useful to perform a CBC in order to assess the degree of neutropenia caused by hyperthyroidism. It is not necessary to perform systematic CBCs during follow-up. 2/+. R9. An emergency CBC should be performed if symptoms include fever or angina. If neutrophil counts are <1000/mm3, synthetic antithyroid therapy should be discontinued or decreased and may be permanently contraindicated in severe (<500) and persistent neutropenia. Otherwise treatment may be resumed. 1/++. R10. Transaminases levels should be measured before initiating treatment. Systematic monitoring of liver function is not consensually validated. 2/+. R11. In cases of jaundice, digestive disorders or pruritus, measuring liver enzymes (AST, ALT), total and conjugated bilirubin and alkaline phosphatases is indicated. 1/++. R12. Patients and parents should be informed of the possible side effects of antithyroid agents. 1/+. R13. Therapeutic education of parents and children is important in ensuring the best possible treatment compliance. 2/++. R14. Given the specificities involved in the treatment of Graves' disease in children, medical care should be provided by a specialist accustomed to treating endocrinopathies in pediatric patients. 2/+. R15. Depending on patient age, the severity of the disease at diagnosis and the persistence of anti-TSH receptor antibodies, the initial course of treatment must take place over an extended period of 3 to 6 years. R16.The anticipated success rates of medical treatment (50% of patients in remission following several years of treatment) should be explained to the family and the child. The possibility that radical treatment may be required in case of failure or intolerance of medical treatment should also be discussed. 1/++. R17.In females with Graves' disease, it is important to explain that they must undergo an assessment by an endocrinologist before planning future pregnancies, from the start of pregnancy and during the course of pregnancy. This is true in all female patients, even those in remission after medical treatment, or those who have undergone radical treatment. R18.Indications for a radical treatment can arise in cases of: 1/+: contraindication to antithyroid agents; poorly controlled hyperthyroidism due to lack of compliance; relapse despite prolonged medical treatment; a request made by the family and child for personal reasons. R19.Surgery is the radical method of treatment used in children under 5 years of age, or in cases of very large, nodular, or compressive goiters. 2/++. R20. The surgeon's experience in dealing with thyroidectomies in children is likely to be the most significant determining factor in limiting the morbidity of the procedure (alongside any collaboration between a pediatric surgeon and an adult surgeon). 1/++. R21 When radical treatment is indicated, I-131 treatment may be discussed after 5 years (but more often after puberty), if the goiter is not too large. Experience from monitoring Graves' disease in North American children is reassuring. 1/++.
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PMID:Graves' disease in children. 3018 Sep 72