propylthiouracil and Liver-Diseases

The aim of this study was to determine the optimal management of patients with propylthiouracil (PTU) hepatotoxicity. A MEDLINE search for English language cases of PTU hepatotoxicity between 1966 and April 1996 was performed, and additional cases were cross-referenced. Twenty-seven cases were selected based on the availability of information on patient management after the onset of hepatotoxicity. Eighty-five percent of the selected cases met this criterion. A detailed summary of the management of two cases of PTU hepatotoxicity at our institutions is also provided. Although most patients recovered once PTU was stopped, seven patients died. Patients with PTU hepatotoxicity who survived were more likely to have received 131I during the course of their illness than those who died (P < 0.03, by Fisher's exact test). In our two patients, hyperbilirubinemia was linearly associated with progressively decreasing T4 levels (r = 0.91; P < 0.001) despite the presence of clinical thyrotoxicosis in one of the patients. These findings demonstrate the need for appropriate clinical evaluation and treatment of thyroid disease during the course of hepatotoxicity. Additionally, we report the first pediatric patient with PTU hepatotoxicity to undergo liver transplantation. The emerging role of liver transplantation in these patients is discussed.

Topics: Adolescent; Chemical and Drug Induced Liver Injury; Endocrinology; Female; Humans; Liver Diseases; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis

The etiology and the pathogenesis of different forms of hepatotoxicity are discussed; case reports are included to illustrate the importance of history-taking and examination of liver tissue in establishing a specific diagnosis. The role of alcohol as a hepatotoxin as well as an enzyme-inducing agent is stressed. Genetic factors have been identified that may determine susceptibility to alcoholism and the hepatotoxic effects of alcohol and other compounds. Some cases of drug-induced cholestasis may be explained by disturbances in the known pathways of bile acid uptake, transport, and excretion. The importance of small duct destruction in patients with progressive drug-induced cholestasis is discussed. Finally, the potential hepatic complications of some nonprescription remedies used by adherents of "alternative medicine" are described, emphasizing the relevance of thorough etiological inquiry in all patients presenting with hepatic dysfunction.

Topics: Acetaminophen; Acetylcysteine; Adenoma, Liver Cell; Adult; Amoxicillin; Anabolic Agents; Beverages; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Contraceptives, Oral; Female; Humans; Isoniazid; Liver Diseases; Liver Diseases, Alcoholic; Liver Neoplasms; Male; Nonprescription Drugs; Propylthiouracil; Rifampin

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Liver Diseases; Middle Aged; Propylthiouracil

Aggressive management to prevent alcoholic cirrhosis should include the use of biopsy results to diagnose and to monitor alcoholic liver disease. Guidelines for the interpretation of the liver biopsy are highlighted. The diagnosis, course, and treatment of alcoholic hepatitis and cirrhosis are presented in detail.

Topics: Adrenal Cortex Hormones; Biopsy; Colchicine; Diagnosis, Differential; Fatty Liver, Alcoholic; Glucagon; Hemosiderosis; Humans; Insulin; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Diseases, Alcoholic; Porphyrias; Propylthiouracil

The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.. Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy.. After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.. (131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; China; Female; Humans; Hyperbilirubinemia; Hyperthyroidism; Iodine Radioisotopes; Jaundice; Liver Diseases; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Severity of Illness Index

Topics: Adult; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Incidence; Liver Diseases; Liver Transplantation; Male; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; United States

To describe the association of the rare and serious complication of jaundice with severe thyrotoxicosis, a potentially lethal endocrine disorder.. We report the clinical, laboratory, and pathologic findings of 2 cases of severe jaundice (total bilirubin levels: 35.2 mg/dL in case 1 and 42 mg/dL in case 2) associated with thyroid storm in the absence of a history of liver disease, thionamide exposure, or congestive heart failure. We also present other relevant reports available in the literature.. Case 1 was a 38-year-old woman who presented with nausea, vomiting, fatigue, pruritus, and frequent nonbloody diarrhea. She was transferred to our institution because of worsening hyperbilirubinemia. Case 2 was a 35-year-old woman admitted to a community hospital with thyroid storm and jaundice. Upon transfer to our institution, the patient was unconscious, mechanically ventilated, and in atrial fibrillation. In case 2, liver biopsy results revealed diffuse hepatocellular ballooning with intrahepatic cholestasis with mild portal lymphocytic infiltration. Both patients presented with severe cholestatic jaundice in the absence of congestive heart failure; underlying liver disease (infectious or autoimmune); or previous exposure to thionamides, other hepatotoxic agents, or complementary and alternative medications. In both cases, jaundice responded to therapy with antithyroid medications. Both patients eventually underwent thyroidectomy with complete resolution of the jaundice.. The data strongly suggest that in these patients, the hepatic dysfunction was primarily due to hyperthyroidism. These cases indicate that the mere presence of hyperbilirubinemia during severe thyrotoxicosis should not per se delay the use of potentially life-saving thionamides once a thorough evaluation for other causes of liver disease has been completed.

Topics: Adult; Alanine Transaminase; Antithyroid Agents; Bilirubin; Dexamethasone; Female; Glucocorticoids; Humans; Jaundice, Obstructive; Liver Diseases; Propylthiouracil; Thyroid Crisis; Thyroxine; Triiodothyronine

Topics: Antithyroid Agents; Blood Cell Count; Female; Graves Disease; Humans; Liver Diseases; Middle Aged; Pancytopenia; Propylthiouracil; Recovery of Function; Thyroid Function Tests; Transaminases; Treatment Outcome

To study the incidence, clinical features and related factors of propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.. A prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin) and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun.. Sixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt hepatic injury in 5 patients (7.8%) after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury.. PTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Follow-Up Studies; Humans; Hyperthyroidism; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Prospective Studies

To study the clinical characteristics and factors of symptomatic propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.. A retrospective study of the patients diagnosed with symptomatic PTU-induced hepatic injury, admitted to Peking Union Medical College (PUMC) Hospital from January 1993 to December 2002, were carried out with regard to clinical characteristics, laboratory findings and management. In addition, a comparative study was carried out in hyperthyroidism with symptomatic, asymptomatic and without PTU-induced hepatic injury at the same time. Symptomatic PTU induced hepatic injury was defined as the development of hepatitis symptoms or jaundice with at least 3-times elevation of liver function test without other causes.. Nine hundred fourteen patients were admitted to PUMC Hospital from January 1993 to December 2002. Clinically overt symptomatic hepatic injury developed in twelve patients [1.3%, age (30 +/- 9) yr, male:female ratio, 1:11] between 7 and 77days after PTU administration. Abdominal distention and fatigue developed in all patients. Serum level of ALT and total bilirubin (TBil) increased to (531.7 +/- 352.0) 113 - 1425 U/L and 67.6 (17.1 - 567.7) micro mol/L, respectively. Prothrombin time prolonged in three cases and plasma ammonia elevated in one case. The types of hepatic injury were hepatocellular in eight, cholestatic in one and mixed in two. None resulted from viral hepatitis and autoimmune hepatitis. There was significant difference in history of side effects of antithyroid agents, PTU dose and abnormal ratio of serum ALT among patients with symptomatic, asymptomatic and without hepatic injury (P < 0.05). However, there were no statistic differences in age, sex, serum levels of T(4), T(3), and increased thyroglobulin antibody, thyroid peroxidase antibody and thyrotrophin receptor antibody at initial diagnosis. The liver function test normalized in all patients from 14 to 140 days after the PTU withdrawal.. Symptomatic hepatic injury usually develops with PTU administration in the first few months, though it is unusual. It may be difficult to predict its development and the patient should be monitored for the liver function in the early stage of PTU administration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Hyperthyroidism; Liver Diseases; Liver Function Tests; Male; Middle Aged; Propylthiouracil; Retrospective Studies

Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course.. Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes.. Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal.. Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Topics: Adult; Age Distribution; Aged; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hyperthyroidism; Incidence; Korea; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged; Probability; Propylthiouracil; Retrospective Studies; Risk Factors; Sex Distribution

To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism.. Cohort study.. Outpatient clinic of a university-based hospital.. Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism.. Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d.. Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate.. Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048).. Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.

Topics: Adult; Alanine Transaminase; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Cohort Studies; Female; Hepatitis, Viral, Human; Humans; Hyperthyroidism; Incidence; Liver; Liver Diseases; Male; Propylthiouracil; Severity of Illness Index

Topics: Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Child; Diagnosis, Differential; Female; Hepatitis, Chronic; Humans; Liver Diseases; Propylthiouracil

The effect of pair feeding of euthyroid rats compared with propylthiouracil (PTU) treated rats on acetaminophen (APAP)-induced hepatotoxicity was studied. Also, the effect of food deprivation of both the euthyroid and PTU-induced hypothyroid rats for 24 h, as well as forced feeding of the euthyroid rats after a toxic dose of APAP, was determined. Pair feeding decreased both protein and energy intake compared with ad libitum-fed controls and resulted in decreased growth rate similar to that for the PTU treated rats. In contrast to the protective effect of PTU pretreatment, decreased protein energy intake by the euthyroid rats either tended to make them more susceptible to acetaminophen-induced hepatotoxicity or had no effect as assessed by elevation of serum transaminases (SGOT,SGPT) and by hepatic necrotic score. Pair feeding also significantly altered drug disposition with an increase in the molar ratio of urinary APAP-mercapturic acid conjugate, but not the absolute amount, suggesting possible increased cytochrome P-450 dependent drug metabolizing enzyme activity. Compared with PTU-fed, in the pair-fed the molar ratio of glucuronide conjugate decreased and sulfate conjugate increased. Hepatic reduced glutathione (GSH) concentrations before and 4 h after a toxic dose of acetaminophen administration were higher in the PTU pretreated compared with euthyroid rats. Fasting of the PTU pretreated rats for 24 h after acetaminophen administration abolished the PTU-induced protective effect. Forced feeding of the euthyroid rats after a toxic dose of acetaminophen increased rather than decreased the toxicity when compared with euthyroid ad libitum-fed rats. Data suggest that higher concentrations of hepatic glutathione in the PTU pretreated compared with euthyroid rats before and 4 h after acetaminophen administration contribute to PTU-induced protection. Forced feeding of rats when the liver is severely damaged and its function compromised is harmful rather than protective. We conclude that the nutritional state of the animal significantly influences drug toxicity and should be taken into consideration in designing drug therapy and evaluation of drug toxicity.

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Food; Food Deprivation; Liver Diseases; Male; Propylthiouracil; Rats; Rats, Inbred Strains

Topics: Administration, Oral; Animals; Cat Diseases; Cats; Chemical and Drug Induced Liver Injury; Hyperthyroidism; Liver Diseases; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Amino Acids; Ammonia; Animals; Caseins; Dietary Proteins; Hypoxia; Liver; Liver Diseases; Male; Necrosis; Oxygen Consumption; Propylthiouracil; Rats; Time Factors; Urea

Topics: Agranulocytosis; Humans; Jaundice; Liver Diseases; Porphyrias; Propylthiouracil