Showing papers on "Propylthiouracil published in 2011"

Thyroid function in pregnancy

Abstract: Advances in understanding the physiology of thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal function on obstetric outcome and foetal well-being. Pubmed search was done using the terms thyroid and pregnancy. Areas of agreement are the following: gestational normative reference ranges for thyroid function tests are required for proper interpretation of any abnormalities. Measurement of thyroid-stimulating antibodies and antithyroid peroxidase antibodies is useful for diagnosis of thyroid disease in pregnancy. Treatment of Graves' hyperthyroidism should be done with propylthiouracil for first trimester only, then carbimazole or methimazole. Patients on levothyroxine require an increase in dosage during gestation. Areas of controversy are the following: total thyroxine (TT4) versus Free T4 (FT4) assays in pregnancy. Screening for thyroid function in early gestation: should it be routinely performed on everyone? What tests are appropriate? Growing points are the following: physiology of thyroxine delivery to the foetus. Establishment of gestational thyroid hormone reference ranges. Evaluation of strategies to screen thyroid function in early pregnancy. Areas timely for developing research are the following: placental thyroid hormone physiology, thyroid hormone therapy and screening thyroid function.

Management of hyperthyroidism during pregnancy and lactation

Abstract: Introduction: Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods Aim: To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation Methods: A literature review was performed using MEDLINE with the terms ‘hyperthyroidism and pregnancy’, ‘antithyroid drugs and pregnancy’, ‘radioiodine and pregnancy’, ‘hyperthyroidism and lactation’, and ‘antithyroid drugs and lactation’, both separately and in conjunction with the terms ‘fetus’ and ‘maternal’ Results: Antithyroid drugs are the main therapy for maternal hyperthyroidism Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation Conclusion: Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate

Alterations along the Hypothalamic-Pituitary-Thyroid Axis of the Zebrafish (Danio rerio) after Exposure to Propylthiouracil

Abstract: In the past, various approaches have been developed to detect adverse effects of pollutants on the thyroid of vertebrates, most of these with special emphasis on the South African clawed frog, Xenopus laevis. Although fish are primarily affected by thyroid-disrupting chemicals, studies into alterations of the thyroid of fish are scarce. Therefore, effects of the reference compound propylthiouracil on histopathology of the thyroid axis were analyzed in a modified early life-stage test with zebrafish (Danio rerio) exposed to propylthiouracil. The test substance induced dose-dependent alterations of thyroidal tissue concomitant with increases in the number of surrounding blood vessels. Despite this massive proliferation of the thyroid, zebrafish were not able to maintain thyroxin concentrations. The pituitary was affected displaying significant alterations in thyroid-stimulating hormone cell counts. Quantitative evaluation of pituitary surface areas revealed a dose-dependent increase of adenohypophyseal tissue. Distinct histopathological effects may contribute to a more easy identification and interpretation of alterations induced by thyroid-disrupting chemicals.

Suspected Spontaneous Reports of Birth Defects in the UK Associated with the Use of Carbimazole and Propylthiouracil in Pregnancy

Abstract: The concept of a carbimazole embryopathy underlies current Endocrine Society advice to avoid this drug in early pregnancy, favouring propylthiouracil as an alternative for the treatment of maternal hyperthyroidism. We aimed to establish whether suspected spontaneous reporting of adverse drug reactions in the UK via the Yellow Card Scheme supports a carbimazole embryopathy and the lack of association between propylthiouracil and congenital anomalies. All birth defects related to maternal treatment with carbimazole or propylthiouracil reported over a 47-year period via the Yellow Card Scheme were analysed. 57 cases with 97 anomalies were reported following in utero exposure to carbimazole. These anomalies included aplasia cutis, choanal atresia, tracheo-oesophageal fistula, and patent vitellointestinal duct, which have previously been reported in association with carbimazole/methimazole exposure in utero. Only 6 cases with 11 anomalies were reported for propylthiouracil, all within the last 15 years. Therefore, these findings may support a carbimazole embryopathy. There are few birth defects associated with propylthiouracil, but this should be interpreted in the context of higher historical prescription rates for carbimazole.

Treatment of hyperthyroidism in pregnancy and birth defects

Abstract: Context: Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are propylthiouracil and methimazole/carbimazole. Objectives: In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research. Design: The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure. Results: Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphaloc...

Seizure and encephalopathy associated with thyroid storm in children.

Abstract: Thyroid storm with seizures is very rare in children. The authors report 3 children with thyroid storm who had a seizure in the absence of a history of neurologic disease. Acute medical management with propylthiouracil, Lugol's iodine solution, hydrocortisone, and propranolol led to a complete resolution of the symptoms. Patients with thyroid storm may be predisposed to the development of neuropsychiatric change. Early recognition and treatment of thyroid storm are essential to reduce morbidity and mortality from this disorder.

Aplasia cutis congenita in surviving co-twin after propylthiouracil exposure in utero

Abstract: Aplasia cutis congenita (ACC) has been observed after fetal exposure to the antithyroid drug methimazole (MMI), but not reported after propylthiouracil (PTU), the current antithyroid drug of choice during pregnancy. This occurrence has implications for patient information and causal research.

A Report of Three Girls with Antithyroid Drug-Induced Agranulocytosis; Retrospective Analysis of 18 Cases Aged 15 Years or Younger Reported between 1995 and 2009

Abstract: Agranulocytosis is an extremely serious, although rare, adverse effect of antithyroid drugs (ATDs), including methimazole (MMI) and propylthiouracil (PTU), in children and adolescents. There are few reports about the characteristics of ATD-induced agranulocytosis in Japanese children and adolescents. This report presents the cases of three girls with ATD-induced agranulocytosis and a retrospective analysis of 18 patients with ATD-induced agranulocytosis, whose cases had been referred to the drug manufacturer, Chugai Pharmaceutical Co., Ltd. Our 3 patients, ranging in age from 12 to 14 yr, developed ATD-induced agranulocytosis between the 15th and 57th day of ATD treatment for hyperthyroidism. Fever and sore throat were the earliest symptoms of agranulocytosis. The patients were rescued by ceasing ATD therapy and administering antibiotics, potassium iodide, glucocorticoid, immunoglobulin and granulocyte colony-stimulating factor (G-CSF). We retrospectively analyzed 18 cases of ATD-induced agranulocytosis treated with MMI in 16 cases and PTU in 2 cases. Twelve patients were treated with 20–45 mg/d MMI. Agranulocytosis developed between the 15th and 1,344th day of therapy. In conclusion, considering the risk of ATD-induced agranulocytosis, we recommend low-dose MMI therapy for treatment of Graves’ disease.

Successful remission of Evans syndrome associated with Graves' disease by using propylthiouracil monotherapy.

Abstract: A 46-year-old woman with Graves' disease was admitted for anemia and thrombocytopenia. She had previously been treated with methimazole but she self-discontinued the treatment 6 months prior to admission. She was diagnosed with Evans syndrome associated with Graves' disease and treated with propylthiouracil without corticosteroids, which normalized her thyroglobulin level. Surprisingly, while Evans syndrome is characterized by frequent relapses, this patient has been in remission of Evans syndrome for approximately 4 years. The remission of Evans syndrome associated with Graves' disease in the absence of immunosuppressive therapy suggests that these 2 diseases have a common pathogenetic mechanism.

Pituitary resistance to thyroid hormones: pathophysiology and therapeutic options

Abstract: Thyroid hormone secretion suppresses the expression of thyroid stimulating hormone (TSH), both of which are strictly controlled by a negative feedback loop between the hypothalamus-pituitary and thyroid. Pituitary resistance to thyroid hormone (PRTH) is defined as resistance to the action of thyroid hormone that is more severe in the pituitary than at the peripheral tissue level. Although the molecular basis of PRTH is not well understood, the clinical issue mainly involves imbalance between the hypothalamus-pituitary and peripheral thyroid hormone responsivity, which may induce peripheral thyrotoxic phenomena. Here, we review the pathogenesis and molecular aspects of PRTH, present a single case with inappropriate TSH secretion suffering from thyrotoxicosis treated with PTU, and discuss the possible choice of therapeutic options to correct the imbalance of thyroid hormone responsivity in both the hypothalamus–pituitary and peripheral tissues.

Resistant Thyrotoxicosis in a Patient with Graves Disease: A Case Report

Abstract: Background. Conventional management of thyrotoxicosis includes antithyroid drugs, radioactive iodine, and surgery while adjunctive treatment includes beta-blockers, corticosteroids, inorganic iodide and iopanoic acid. Very rarely, patients may be resistant to these modalities and require additional management. Case Presentation. A 50-year-old lady presented with weight loss and palpitations diagnosed as atrial fibrillation. Her past history was significant for right thyroid lobectomy for thyrotoxicosis. Thyroid functions tests at this presentation showed free T4 of 6.63 ng/dl (normal range: 0.93–1.7) and TSH of <0.005 μIU/mL (normal range: 0.4–4.0). She was given aspirin, propranolol, heparin and carbimazole; however free T4 failed to normalize. Switching to propylthiouracil (PTU) did not prove successful. She was then given high doses of prednisolone (1 mg/kg/day) and lithium (400 mg twice daily) which prepared the patient for radioactive iodine treatment by reducing free T4 levels (2.82 ng/dl). Two doses of radioactive iodine were then administered 6 months apart. Subsequently she became hypothyroid and was started on thyroid replacement therapy. Conclusion. This case highlights management options in patients with resistant thyrotoxicosis. Radioactive iodine and surgery are definitive modes of treatment in such complex cases while steroids and lithium play an important role in preparing patients for more definitive treatment.

A case of autoimmune hepatitis with graves’ disease treated by propylthiouracil

Abstract: A 58-year-old woman was referred to our hospital because of liver dysfunction. Her serum levels of AST (619 IU/l) and ALT (603 IU/l) had increased. Histological findings in the liver biopsy were compatible to autoimmune hepatitis (AIH), and the diagnosis of AIH was confirmed by the diagnostic criteria. She was admitted to a nearby hospital 3 years ago, and diagnosed with Graves' disease. She received methimazole (MMI) at first, which was discontinued due to liver injury in one month, then propylthiouracil (PTU) was administered. One year later, transaminase increased and was decreased by stopping PTU administration. PTU was restarted after her transaminase decreased, but a recurrence of hepatotoxicity was observed, and she was referred to our hospital. Oral prednisolone decreased liver function immediately. In this case, PTU-induced liver injury was suspected as a possible trigger of AIH. While PTU remains a commonly used drug in the treatment of hyperthyroidism, severe liver injury is reported in some cases. If liver injury is observed in patients treated with PTU, rechallenge is not recommended in order to avoid severe hepatotoxicity.

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

Abstract: The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.

Propylthiouracil-Induced Lupus, Antiphospholipid Syndrome, and Stroke in a Patient With Graves Hyperthyroidism

Abstract: Objective To describe a case of propylthiouracil-induced lupus, complicated with antiphospholipid syndrome and acute ischemic stroke. Design Case report. Setting Academic medical center. Patient A 27-year-old man with a diagnosis of Graves disease developed multiple ischemic strokes 2 weeks after starting treatment with propylthiouracil. Thyrotoxicosis and abnormal hypercoagulable and rheumatological profiles were remarkable, with prolonged partial thromboplastin time, elevated anticardiolipin antibody level, and positive antinuclear antibody, lupus anticoagulant, Sjogren antibody, and anti–double-stranded DNA antibody test results, which were more than 8-fold greater than normal values. No clinical manifestations of systemic lupus erythematosus were present. Intervention Discontinuation of propylthiouracil and treatment with radioactive iodine. Results Hyperthyroidism resolved and anti–double-stranded DNA antibodies returned to normal levels. Eventually, antiphospholipid syndrome was diagnosed. He was treated with oral anticoagulation and remained asymptomatic for 1 year of follow-up. Conclusion In this young man with Graves hyperthyroidism, treatment with propylthiouracil was associated with transient autoimmune reactions suggestive of drug-induced lupus, antiphospholipid syndrome, and acute ischemic stroke.

Propylthiouracil-induced interstitial pneumonia in a Caucasian woman with amiodarone-induced thyrotoxicosis.

Abstract: Background: Propylthiouracil (PTU) therapy is associated with a variety of adverse reactions, among the most rare being interstitial pneumonia. To date, this has been reported in four Asian patients with autoimmune hyperthyroidism. Here we describe a Caucasian woman who developed a bronchiolitis obliterans organizing pneumonia (BOOP)-like interstitial pneumonia after PTU administration for amiodarone-induced thyrotoxicosis. Patient Findings: The patient was a 68-year-old woman who had been treated with amiodarone for chronic atrial fibrillation starting in May 2004. She had been a heavy smoker with a history of hypertension but no dust exposures. In October 2006, amiodarone was stopped after she developed thyrotoxicosis. In January 2007 serum thyroid-stimulating hormone (TSH) was 0.01 mIU/L (0.35–4.94) and free T4 was 17.5 pg/mL (7 to 15). She was initially started on methimazole and then changed to PTU after she developed pruritus. She developed severe dyspnea 9 months after starting PTU. At the time she...

Inhibitory effects of (+-)-tetrahydropalmatine on thyrotropin-stimulating hormone concentration in hyperthyroid rats

Abstract: The effects of (+/-)-tetrahydropalmatine ((+/-)-THP) on the hypothalamus-pituitary-thyroid system in rats were investigated. Thyroid function experiments indicated that (+/-)-THP produces significant decreases in thyroid function in hyperthyroid rats after 14 days of treatment. These effects were the same as those of propylthiouracil. However, propylthiouracil also decreased thyroid function in normal rats. Measurements of thyrotropin-stimulating hormone (TSH) demonstrated that (+/-)-THP decreased TSH in hyperthyroid rats after 14 days of treatment; however, propylthiouracil increased TSH in hyperthyroid rats. (+/-)-THP had no influence on TSH, or thyroid and pituitary weight in normal and hyperthyroid rats. We conclude that (+/-)-THP has an antithyroid function and the mechanism of action may be related to the inhibition of TSH in the pituitary.

[Risk factors and subjective symptoms of drug-induced leucopenia].

Abstract: The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

[Supra-His complete atrioventricular block in a patient with subclinical hyperthyroidism].

Abstract: Subclinical hyperthyroidism is a difficult entity to diagnose because of silent clinical features and it may be easily underdiagnosed unless it is suspected and thyroid hormone levels are examined. Although atrioventricular (AV) conduction abnormalities such as complete heart block may occasionally be seen in hyperthyroidism, its association with subclinical hyperthyroidism has not been reported previously. We report on a 50-year-old female patient who did not have any systemic or cardiovascular disease or history of drug use that could affect AV conduction and presented with presyncope and complete heart block with narrow QRS complexes. Thyroid function tests showed subclinical hyperthyroidism and an electrophysiological study showed the supra-His level as the site of complete AV block. After initiation of antithyroid treatment (propylthiouracil), the patient's rhythm improved to second-degree AV block on the third day and returned to normal sinus rhythm on the fourth day.

Choice of antithythroid drugs in pregnancy.

Abstract: I read with interest the Guest Editorial by Boelaert (1) recently published in Thyroid. I believe that some of the comments made about the choice of antithyroid drug in pregnancy require comment. First, the article by Chattaway and Klepser (2) quoted as supporting the notion that propylthiouracil (PTU) crosses the placenta less than methimazole (MMI) in fact does the opposite. Chattaway and Klepser reviewed a study from our group (3), using the perfused placental lobule, that indicates similar transfer kinetics for the two drugs. They also reviewed a series of clinical studies that show, essentially, no differences in maternal or fetal outcome between PTU and MMI treatment. The authors state in their summary that ‘‘The selection of PTU over MMI as the drug of choice to treat Graves’ disease in pregnancy should not be based solely on misleading statements in the literature that PTU has less placental transfer than methimazole..’’ Second, the article by Cooper and Rivkees (4) is referenced by Boellaert as supporting use of PTU as a ‘‘first line drug’’ in pregnancy. Cooper and Rivkees discuss risks of aplasia cutis and more major teratogenesis from MMI versus risks of severe hepatotoxicity from PTU. The authors estimate that in the United States four pregnant women per year will have severe PTUrelated liver damage. They go on to say that ‘‘because of our limited understanding of the risk of birth defects associated with Graves’ disease and the use of antithyroid drugs, until we have additional information on MMI drug safety for the fetus, it is reasonable to recommend that pregnant hyperthyroid women be treated with PTU during the first trimester rather than with MMI. This is in accord with The Endocrine Society Guideline (5). The risk of PTU for expectant mothers can be reduced by limiting PTU use to the first trimester and then changing to MMI.’’ PTU has not, however, been totally absolved from suspicions of teratogenicity. A recent large international caseaffected study (6) of antithyroid drug treatment-related birth defects confirmed an association between maternal use of MMI and omphalocele and choanal atresia in offspring. The study also identified three malformations (situs inversus, unilateral renal agenesis/dysgenesis, and cardiac outflow tract lesions) associated with prenatal PTU exposure. The results were, however, of marginal statistical significance and the authors point out that a firm conclusion that PTU is teratogenic will require further studies. Congenital malformations in infants of women with Graves’ disease who take antithyroid drugs are fortunately rare. This and uncertainties about the relative roles of antithyroid drugs, maternal and fetal thyroid status, and interactions between drugs and thyroid status, in inducing fetal malformations, mean that a definitive conclusion about PTUinduced teratogenicity is unlikely to be reached quickly. While recommendations that PTU be used in the first trimester but then changed to MMI may, in the light of present knowledge, seem reasonable they do not recognize the reality that many women taking MMI for Graves’ disease may be well into the first trimester before pregnancy is diagnosed.