methimazole and Cholestasis

Rash and cholestatic liver injury caused by methimazole (MMI) in patients with Turner syndrome (TS) and Graves's disease (GD) are rarely reported, and there is a paucity of reports on the management of this condition. It is not clear whether propylthiouracil (PTU) can be used as a safe alternative in this case.. A 37-year-old woman was admitted to our hospital with rash, severe pruritus and a change in urine colour after 2 months of GD treatment with MMI. Physical examination showed rash scattered over the limbs and torso, mild jaundice of the sclera and skin, short stature, facial moles, immature external genitals and diffuse thyroid gland enlargement. Liver function tests indicated an increase in total bilirubin, direct bilirubin, total bile acid, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. The level of sex hormones suggested female hypergonadotropic hypogonadism. The karyotype of peripheral blood was 46, X, i(X)(q10)/45, X. After excluding biliary obstruction and other common causes of liver injury, combined with rash and abnormal liver function following oral administration of MMI, the patient was diagnosed as having TS with GD and rash and cholestatic liver injury caused by MMI. MMI was immediately discontinued, and eleven days after treatment with antihistamine and hepatoprotective agents was initiated, the rash subsided, and liver function returned to nearly normal. Because the patient did not consent to administration of. While patients with TS and GD are undergoing treatment with MMI, their clinical manifestations, liver functions, and other routine blood test results should be closely monitored. When patients with TS and GD manifest adverse reactions to MMI such as rash and cholestatic liver injury, it is necessary to discontinue MMI and treat with antihistamine and hepatoprotective agents. After the rash subsides and liver function returns to nearly normal, PTU can effectively control hyperthyroidism without adverse drug reactions.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Exanthema; Female; Graves Disease; Humans; Methimazole; Prognosis; Turner Syndrome

Early identification of the causes of cholestasis is important for appropriate management of patients with hyperthyroidism. We report a patient who had hyperthyroidism and severe cholestasis after methimazole (MMI) treatment. The patient was diagnosed as having MMI-induced cholestatic hepatitis. Treatment with MMI was stopped at admission to hospital. However, his serum total bilirubin (TBil) level rose from 410.5 µmol/L to 519.9 µmol/L and prothrombin time activity (PTA) dropped from 81.0% to 52.2% in 10 days. To prevent further deterioration of his liver function, plasma exchange was performed three times, and dexamethasone (10 mg, intravenously) was used each time. His PTA rose to 101% and his TBil continued to increase to 669.8 µmol/L after plasma exchange. He was subsequently diagnosed as having thyrotoxicosis-induced cholestasis and treated with radioactive iodine (380 MBq) 2 weeks after admission. His hyperthyroidism was significantly relieved, but the TBil level further increased to 776.8 µmol/L. Three weeks after admission, oral prednisone (30 mg/day) was used in this patient. Subsequently, his TBil levels gradually decreased and his liver function almost normalized within 3 months. We discuss the literature on cholestasis in the context of hyperthyroidism.

Topics: Cholestasis; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Thyroid Neoplasms

Topics: Alkaline Phosphatase; Aspirin; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Halothane; Humans; Hyperbilirubinemia; Jaundice; Liver; Liver Diseases; Male; Methimazole; Paraquat; Transaminases

We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment.. The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases.. The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out.. The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function.. The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

Topics: Adult; Antithyroid Agents; Cholestasis; Female; Humans; Hyperthyroidism; Jaundice, Obstructive; Methimazole

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Cholestasis; Humans; Hyperthyroidism; Male; Methimazole

Inhibition of the activity of the human bile salt export pump (BSEP: ABCB11) has been proposed to play a role in drug-induced liver injury (DILI). To enhance understanding of the relationship between BSEP inhibition and DILI, inhibition of human BSEP (hBSEP) and its rat ortholog (rBsep) by 85 pharmaceuticals was investigated in vitro. This was explored using assays that quantified inhibition of ATP-dependent [(3)H]taurocholate uptake into inverted plasma membrane vesicles from Sf21 insect cells, which expressed the proteins. Of the pharmaceuticals, 40 exhibited evidence of in vitro transporter inhibition and overall a close correlation was observed between potency values for inhibition of hBSEP and rBsep activity (r(2) = 0.94), although 12 drugs exhibited >2-fold more potent inhibition of hBSEP than rBsep. The median potency of hBSEP inhibition was higher among drugs that caused cholestatic/mixed DILI than among drugs that caused hepatocellular or no DILI, as was the incidence of hBSEP inhibition with IC(50) <300 μM. All drugs with hBSEP IC(50) <300 μM had molecular weight >250, ClogP >1.5, and nonpolar surface area >180Å. A clear distinction was not evident between hBSEP IC(50) or unbound plasma concentration (C(max, u)) of the drugs in humans and whether the drugs caused DILI. However, all 17 of the drugs with hBSEP IC(50) <100 μM and C(max, u) >0.002 μM caused DILI. Overall, these data indicate that inhibition of hBSEP/rBsep correlates with the propensity of numerous pharmaceuticals to cause cholestatic DILI in humans and is associated with several of their physicochemical properties.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Bile Acids and Salts; Cell Line; Chemical and Drug Induced Liver Injury; Cholestasis; Drug-Related Side Effects and Adverse Reactions; Humans; Insecta; Rats; Risk Factors

Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported.. The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well.. Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.

Topics: Adolescent; Adrenergic beta-Antagonists; Antithyroid Agents; Bilirubin; Cholestasis; Female; Graves Disease; Hepatitis A; Hepatitis A Antibodies; Humans; Immunoglobulin M; Liver Function Tests; Methimazole; Propranolol; Thyroid Function Tests

Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Cholangiopancreatography, Magnetic Resonance; Cholestasis; Graves Disease; Humans; Liver; Liver Function Tests; Male; Methimazole; Middle Aged; Propranolol; Radionuclide Imaging; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine; Ultrasonography

Topics: Cholestasis; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged

Three female patients with cholestatic jaundice related to methimazole therapy are presented. The jaundice appeared after more or less 30 days of therapy. Markers for hepatitis A and B were negative in all. None of them had previous history of alcoholism or ingestion of potentially hepatotoxic drugs. Characteristically there was a marked elevation of alkaline phosphatase and gamma-glutamyltranspeptidase with only moderate increase of the aminotransferases. Liver biopsy performed in all showed intensive cholestasis with low degree of inflammatory reaction confined to the portal tracts. The three patients presented a prolonged duration of the liver injury in spite of the interruption of the drug lasting in one of them up to one year, but all ultimately resolved.

Topics: Adult; Alkaline Phosphatase; Bilirubin; Cholestasis; Female; gamma-Glutamyltransferase; Humans; Hyperthyroidism; Methimazole

Topics: Aged; Carbimazole; Cholestasis; Humans; Male; Methimazole

The typical propylthiouracil (PTU)-linked hepatotoxicity, is known to manifest itself by hepatocellular injury with greatly increased serum transaminase values and evidence of hepatic necrosis on liver biopsy. Herewith presented is a 33-year old, thyrotoxic woman who developed cholestatic jaundice two weeks after initiation of PTU therapy. The diagnosis was confirmed by liver biopsy. A causal link between PTU treatment and the cholestatic jaundice was suggested by: the time of onset, typical skin rash and a positive migration inhibition factor (MIF) test to PTU. Awareness of this rare complication of PTU treatment may prevent the performance of unnecessary, expensive and possibly harmful diagnostic procedures.

Topics: Adult; Cholestasis; Female; Humans; Liver; Macrophage Migration-Inhibitory Factors; Methimazole; Propylthiouracil

Topics: Adult; Carbimazole; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Male; Methimazole; Middle Aged

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Cholestasis; Dogs; Female; gamma-Glutamyltransferase; Iodine; Isoenzymes; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Liver; Methimazole; Protein Binding

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Cholestasis; Clinical Enzyme Tests; Enzyme Induction; Female; gamma-Glutamyltransferase; Humans; Hyperthyroidism; Isoenzymes; Leucyl Aminopeptidase; Methimazole; Middle Aged

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged