Showing papers on "Propylthiouracil published in 2009"

Ending propylthiouracil-induced liver failure in children.

Abstract: To the Editor: Graves' disease is treated with antithyroid drugs, radioactive iodine, or surgery.1,2 Propylthiouracil and methimazole are widely used in children as first-line therapy.1,2 Over the past 60 years of propylthiouracil and methimazole use, reports of propylthiouracil-related liver failure and death have accumulated.3–5 In contrast, this problem has not been reported with methimazole use in children.3,5 Several observations can be made on the basis of the medical literature, adverse event reports from the Food and Drug Administration (FDA), and extensive data presented at a workshop at the Eunice Kennedy Shriver National Institute of Child Health . . .

Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure to propylthiouracil: a controlled cohort study.

Abstract: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Human pregnancy experience with propylthiouracil has not shown an increased risk of major anomalies, but its use in pregnancy has been associated with fetal or neonatal thyroid dysfunction with or without goitre. • The rate of these complications has not been prospectively evaluated. WHAT THIS PAPER ADDS • Based on prospective data from the Israeli Teratology Information Service, propylthiouracil was not associated with an increased teratogenic risk. • Hypothyroidism was found in 9.5% (56.8% of whom with goitre) of fetuses or neonates, whereas hyperthyroidism was detected in 10.3%. • In most cases neonatal thyroid functions normalized without treatment. AIMS Propylthiouracil (PTU) is presently considered to be the treatment of choice for hyperthyroidism in pregnancy. It is known to cross the human placenta, and therefore may affect the fetus. The major aims of this study were to evaluate the rate of major anomalies and to report the rate of fetal goitre, accompanied by hypothyroidism, in fetuses/ newborns of mothers after in utero exposure to PTU. METHODS Prospective observational controlled cohort study of PTU-exposed pregnancies of women counselled by the Israeli Teratology Information Service between the years 1994 and 2004 compared with women exposed to nonteratogens. RESULTS We followed up 115 PTU-exposed pregnancies and 1141 controls. The rate of major anomalies was comparable between the groups [PTU 1/80 (1.3%), control 34/1066 (3.2%), P= 0.507]. Hypothyroidism was found in 9.5% of fetuses/neonates (56.8% of whom with goitre). Hyperthyroidism, possibly resulting from maternal disease, was found in 10.3%. Goitres prenatally diagnosed by ultrasound were successfully treated in utero by maternal dose adjustment. In most cases neonatal thyroid functions normalized during the first month of life without any treatment. Median neonatal birth weight was lower [PTU 3145 g (2655–3537) vs. control 3300 g (2968–3600), P= 0.018]. CONCLUSIONS PTU does not seem to be a major human teratogen. However, it could cause fetal/neonatal hypothyroidism with or without goitre. Fetal thyroid size monitoring and neonatal thyroid function tests are important for appropriate prevention and treatment.

Simple, rapid zebrafish larva bioassay for assessing the potential of chemical pollutants and drugs to disrupt thyroid gland function.

Abstract: Thyroid function may be altered by a very large number of chemicals routinely found in the environment Research evaluating potential thyroid disruption is ongoing, but there are thousands of synthetic and naturally occurring drugs and chemicals to be considered. European and United States policies call for the development of simple methodologies for screening endocrine-disrupting chemicals. Zebrafish are widely used as a model organism for assessing drug effects because of their small size, high fecundity, rapid organogenesis, morphological and physiological similarities to mammals, and easewithwhich large-scale phenotypic screening is performed. A zebrafish-based short-duration screening method was developed to detect the potential effect of chemicals and drugs on thyroid function. This method used a T4 immunofluorescence quantitative disruption test (TIQDT) to measure thyroid function. The 3 day exposure window protocol, from day 2 to day 5 postfertilization (dpf), avoided any potential side effects on thyroid gland morphogenesis. Methimazole, propylthiouracil, and potassium perchlorate, three well-known goitrogens, totally abolished T4 immunoreactivity in thyroid follicles in a dose-specific manner. Amiodarone, a human pharmaceutical with a reported cytotoxic effect on thyroid follicular cells, also decreased T4 levels. Moreover, exposure to 50 nM 3,3',5-triiodothyronine induced a significant decrease in T4 immunoreactivity as did DDT, 2,4-D, and 4-nonylphenol. In conclusion, these data indicated that TIQDT may be useful for obtaining initial information about the ability of environmental pollutants and drugs to impair thyroid gland function as well as assessing the combined effects of endocrine disruptors.

The Pharmacokinetics of Propylthiouracil

Abstract: The half-life of propylthiouracil was determined in 7 normal subjects after intravenous injection of 400 mg of the drug. An average value of 77 ± 17 minutes (mean ± S. D.) was found. As the concentration of the drug in the blood declined by a rapid phase followed by a more slow phase a two-compartment model was used for further calculations, and the rate constants between the 2 compartments and the overall elimination constant have been calculated. The same dose of propylthiouracil was later administered per os to the same 7 persons and the plasma concentration was followed to non-measurable values. An average maximum concentration of 9.1 ± 2.5 μg/ml was obtained after a period of 57 ± 22 minutes. The area under the “peroral” curve has been calculated in per cent of the area under the “intravenous” curve. An average value of 77 ± 13 % was found expressing the bioavailability of the drug after oral administration.

Antithyroid Drug-induced Agranulocytosis

Abstract: Antithyroid drugs are widely used to treat hyperthyroidism, especially Graves' disease, but they tend to cause agranulocytosis, which increases the mortality rate. Granulocyte colony-stimulating factor decreases the duration of recovery from agranulocytosis. We retrospectively studied cases of antithyroid drug-induced agranulocytosis over the past 10 years in a northern Taiwan medical center. A clinical evaluation was conducted, including a review of complete blood cell counts and differential counts. Four cases were included in this analysis. Agranulocytosis persisted in 2 cases despite a change in therapy from propylthiouracil to methimazole. Fever, sore throat, and diarrhea were common symptoms of agranulocytosis. Initial white blood cell counts ranged from 450 to 1,710/μL. Only 1 case had a positive result from a throat swab culture ( Staphylococcus aureus ). Three of 4 cases received granulocyte colony-stimulating factor therapy, and the recovery time ranged from 3 to 13 days. All of the patients recovered from agranulocytosis. We concluded that: (1) conducting a routine complete blood cell count is beneficial in alerting caregivers to the possibility of agranulocytosis; (2) educating patients about the common symptoms of agranulocytosis may contribute to an early diagnosis; (3) providing granulocyte colony-stimulating factor therapy to patients results in good prognosis; and (4) monitoring for cross-reactions between drugs should be performed to prevent further episodes of agranulocytosis.

C cells evolve at the same rhythm as follicular cells when thyroidal status changes in rats.

Abstract: C cells are primarily known for producing calcitonin, a hypocalcemic and hypophosphatemic hormone. Nevertheless, besides their role in calcium homeostasis, C cells may be involved in the intrathyroidal regulation of follicular cells, suggesting a possible interrelationship between the two endocrine populations. If this premise is true, massive changes induced by different agents in the activity of follicular cells may also affect calcitonin-producing cells. To investigate the behaviour of C cells in those circumstances, we have experimentally induced two opposite functional thyroid states. We hyperstimulated the follicular cells using a goitrogen (propylthiouracil), and we suppressed thyroid hormone synthesis by oral administration of thyroxine. In both scenarios, we measured T4, TSH, calcitonin, and calcium serum levels. We also completely sectioned the thyroid gland, specifically immunostained the C cells, and rigorously quantified this endocrine population. In hypothyroid rats, not only follicular cells but also C cells displayed hyperplastic and hypertrophic changes as well as increased calcitonin levels. When exogenous thyroxine was administered to the rats, the opposite effect was noted as a decrease in the number and size of C cells, as well as decreased calcitonin levels. Additionally, we noted that the two cell types maintain the same numerical relation (10 ± 2.5 follicular cells per C cell), independent of the functional activity of the thyroid gland. Considering that TSH serum levels are increased in hypothyroid rats and decreased in thyroxine-treated rats, we discuss the potential involvement of thyrotropin in the observed results.

Gene expression profiling in rat liver treated with various hepatotoxic-compounds inducing coagulopathy.

Abstract: A large-scale transcriptome database of rat liver (TG-GATEs) has been established by the Toxicogenomics Project in Japan. In the present study, we focused on 8 hepatotoxic compounds within TG-GATEs, i.e., clofibrate, omeprazole, ethionine, thioacetamide, benzbromarone, propylthiouracil, Wy-14,643 and amiodarone, which induced coagulation abnormalities. Aspirin was selected as a reference compound that directly causes coagulation abnormality, but not through liver toxicity. In blood chemical examinations, for all the coagulopathic compounds there was little elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), suggesting no severe cell death by treatment with the compounds. We extracted 344 probe sets from the data for these 8 typical drugs, which induced this phenotype at any time from 3 to 28 days of repeated administration. Principal component analysis using these probe sets clearly separated dose- and time-dependent clusters of the treated groups from their controls, except aspirin and propylthiouracil, both of which were considered to cause coagulopathy not due to their hepatotoxicity but due to their direct effects on the blood coagulation system. Reviewing the extracted genes, changes in lipid metabolism were found to be dominant. Genes related to blood coagulation were generally down-regulated by these drugs except that vitamin K epoxide reductase complex subunit 1 (Vkorc1) like 1, a paralogous gene of Vkorc1, was up-regulated. As expected, expression changes of these genes were least prominent in aspirin or propylthiouracil-treated liver. We concluded that these probe sets could be a good starting point in developing mechanism-based biomarkers for diagnosis or prognosis of hepatotoxicity-related coagulation abnormalities in the early stage of drug development.

Methimazole‐induced agranulocytosis: Growth inhibition of myeloid progenitor cells by the patient's serum

Abstract: The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Thyroid state and voluntary alcohol consumption of albino rats.

Abstract: Male Wistar rats were made hypo- and hyperthyroid in a period of three weeks by the daily administration of propylthiouracil or 3,3′,5-triiodo-L-thyronine, and the voluntary alcohol consumption of the animals was investigated. The triiodothyronine treatment increased, and propylthiouracil treatment decreased the total caloric intake of the animals. However, the portion of ethanol in the total caloric intake of the rats was significantly increased by propylthiouracil treatment and significantly decreased by triiodothyronine treatment while the total caloric intake did not correlate positively with the voluntary alcohol consumption of these animals. The absorption of ethanol from the intravascular space, the peritoneal cavity and the gastrointestinal tract as well as the rate of elimination of ethanol were increased by triiodothyronine treatment and decreased by propylthiouracil treatment. The acetaldehyde concentration during oxidation of ethanol was found to be higher (166 ± 22 nmol/ml of blood) in the hepatic venous blood of euthyroid animals, as compared with hypo- and hyperthyroid ones. Acetaldehyde accumulation was not found to be a factor regulating voluntary alcohol intake in these animals.

The kinetics of propylthiouracil in hyperthyroidism.

Abstract: The kinetics of propylthiouracil have been estimated in 10 hyperthyroid subjects according to a two-compartment model by giving the drug initially by the intravenous and subsequently by the oral route. The apparent half-life was 77 ± 34 min. (mean ± S.D.). This value and other pharmacokinetic parameters were compared with the corresponding values obtained in a previous study in normal subjects. No significant differences were found. A table showing studies in humans correlating drug metabolism and thyroid status is presented.

Thyroid peroxidase forms thionamide-sensitive homodimers: relevance for immunomodulation of thyroid autoimmunity

Abstract: Thyroid peroxidase (TPO) is the key enzyme in thyroid hormone production and a universal autoantigen in Graves' and other autoimmune thyroid diseases. We wished to explore the expression of TPO and whether it was affected by thionamide antithyroid drugs. We studied recombinant TPO, stably expressed by a Chinese hamster ovary cell line (CHO-TPO) and transiently expressed TPO-enhanced green fluorescent protein (eGFP) and -FLAG fusion proteins. Immunoblotting of CHO-TPO cell extracts showed high-molecular weight (HMW) TPO isoforms that were resistant to reduction, as well as 110 kDa monomeric TPO. Co-immunoprecipitation and enzyme-linked-immunosorbent assay (ELISA) binding studies of FLAG- and eGFP-tagged TPO demonstrated TPO dimerisation. CHO-TPO cells cultured in methimazole (MMI) for 10 days showed a significant reduction in HMW-TPO isoforms at MMI concentrations of 1 microM and above (p < 0.01), whereas monomeric TPO expression was unchanged. We observed a similar reduction in HMW-TPO in CHO-TPO cells cultured in propylthiouracil (10 microM and above). Binding of Graves' disease patient sera and TPO-Fabs to enzymatically active TPO that was captured onto solid phase was not abrogated by MMI. The cellular localisation of TPO in CHO-TPO cells was unchanged by MMI treatment. Our demonstration of homodimeric TPO and the reduction in HMW-TPO isoforms during thionamide treatment of CHO-TPO cells shows, for the first time, an effect of thionamides on TPO structure. This suggests a structural correlate to the effect of thionamides on TPO enzymatic activity and opens up a novel potential mechanism for thionamide immunomodulation of autoimmune thyroid disease.

Hyperthyroidism during pregnancy.

Abstract: QUESTION I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it? ANSWER In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight.

Abnormal gamma globulin binding of thyroid hormones.

Abstract: Thyroid hormone levels were studied in a thyrotoxic patient, who was treated with propylthiouracil. He had heavily increased triiodothyronine concentrations, measured by radioimmunoassay, in spite of only mild clinical symptoms of thyrotoxicosis. A moderately increased serum triiodothyronine concentration was observed in another patient, who was euthyroid and who had recently recovered from subacute thyroiditis. By gel electrophoresis and precipitation tests with human anti-IgG and anti-IgA, a binding to the gamma globulins of both triiodothyronine and thyroxine was detected in patient 1, and of triiodothyronine in patient 2. Such abnormal binding may result in serious errors in the determination of thyroid hormone concentration by radioimmunoassay.

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

Abstract: Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42. The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42. Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.

Polychlorinated biphenyls affect thyroid function and induce autoimmunity in Sprague-Dawley rats.

Abstract: Polychlorinated biphenyls (PCBs) have been reported to cause a variety of toxic effects. In order to assess the thyroid function after exposure to PCBs and investigate whether PCBs induce autoimmune process in the thyroid gland, we determined the levels of serum thyroid hormones (FT3, FT4, and T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) in Sprague-Dawley rats treated with a commercial mixture of PCBs, Aroclor 1,254 (PCBs group), or the antithyroid drug, propylthiouracil (PTU group). The histopathology of the thyroid was also examined. Serum FT3, FT4, and T4 concentrations were significantly reduced, while TSH values were dramatically increased in PCBs group and PTU group compared with control rats (p 0.05). In contrast to the controls, treatment with PCBs lead to distinct histopathological changes in the thyroid gland, such as hyperplasia of the epithelia in follicles, colloid content reduction, vascularization, and lymphocytic infiltration in the perifollicular areas, whereas the major changes in the thyroid in PTU-treated rats were follicles shrinkage or collapse and colloid content reduction compatible with induced hypothyroidism. The results indicate that PCBs affect thyroid function via the induction of autoimmunity, which is a mechanism different from the effect of antithyroid drug on the thyroid gland.

A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

Abstract: The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

Hydroxyproline excretion in the urine and calcium metabolism during long-term treatment of thyrotoxicosis with propylthiouracil.

Abstract: . Thirty hyperthyroid patients have been studied before and during long-term treatment with propylthiouracil for the purpose of evaluating changes in the excretion of urinary hydroxyproline and relating these to some parameters of calcium metabolism and thyroid function. Urinary hydroxyproline and urinary calcium were found to be significantly raised before treatment. A very rapid fall in urinary calcium was noted within the first two weeks of treatment. BMR and PBI showed a parallel fall to euthyroid values following six weeks of treatment, while there was a slow fall in the mean value of urinary hydroxyproline. After three months the mean value was still elevated and normal values of urinary hydroxy-proline were not obtained until six months after the beginning of treatment. A possible causal relation between collagen metabolism and calcium metabolism during antithyroid treatment is discussed. Our results may indicate that many hyperthyroid patients do not reach a metabolic steady state until about three months after the beginning of antithyroid treatment.

Effect of orally administered propylthiouracil in pregnant and lactating rats on isolated aorta contractility of their adult male offspring.

Abstract: Summary Background: The effect of propylthiouracil (PTU) administration to pregnant and lactating rats on isolated aorta contractility of their adult offspring was investigated. Material/Methods: Three groups of female rats were selected; in the fetal group (FG), PTU was added to their drinking water during gestation; in the neonatal group (NG), PTU was added to the mothers’ drinking water for 25 days after delivery; untreated rats were controls (CG). Thyroid hormone concentrations were measured in the sera of the mothers and their adult offspring. Aortic contractility of the offspring was measured with an isometric transducer in the presence of different concentrations of potassium chloride (KCl) and phenylephrine. Results: The mothers were hypothyroid at the time of PTU cessation. Thyroid hormone levels in offspring were not signifi cantly different from those of controls except for TSH, which was signifi cantly (p<0.05) higher in the FG offspring. Recorded tension in FG offspring with 5, 10, 20, 40, and 60 mmol/l KCl were 0.21±0.02, 0.75±0.07, 1.07±0.07, 1.38±0.08, and 1.5±0.09 g/mm2 , respectively, signifi cantly (p<0.05) lower than the control values (0.43±0.05, 1.19±0.17, 1.76±0.23, 2.06±0.22, 2.5±0.09). Aortic contractility with 10 –8

Pharmacologic treatment of hyperthyroidism during lactation.

Abstract: QUESTION I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close to delivery and might require antithyroid therapy in the postpartum period. Can methimazole cross into human milk, and is breastfeeding safe for her infant? ANSWER The exposure of infants to methimazole or propylthiouracil through breast milk is minimal and not clinically significant. Women with hyperthyroidism using methimazole or propylthiouracil should not be discouraged from breastfeeding, as the benefits of breastfeeding largely outweigh the theoretical minimal risks.

Antithyroid drugs used in the treatment of hyperthyroidism during breast feeding. An update and new perspectives

Abstract: Traditionally, these agents produce minor side effects (rash, fever, urticaria) in 5-10% of the treated patients and ma-jor side effects (agranulocytosis, vasculitis, hepatic toxicity) much less frequently. These side effects ap-pear more likely to be dose-related for methimazole (MMI) rather than propylthiouracil (PTU).

Influence of propylthiouracil and methimazole pre-treatment on the outcome of iodine-131 therapy in hyperthyroid patients with Graves' disease.

Abstract: There is ongoing controversy about potential differences in the influence of the anti-thyroid drugs propylthiouracil (PTU) and methimazole (MMI) on radioiodine treatment of Graves' hyperthyroidism. This retrospective study investigated the influence of PTU and MMI pre-treatment, individually or sequentially, on the outcome of iodine-131 ((131)I) therapy in 199 patients with Graves' disease who had been treated with (131)I for the first time and followed up at 3 and 6 months after treatment. Pre-treatment with PTU, or sequential PTU and MMI pre-treatment, increased the failure rate of (131)I therapy and reduced the rate of hypothyroidism. MMI pre-treatment alone had no significant influence on the results of (131)I therapy. Logistic regression analyses indicated that PTU pre-treatment and having a thyroid gland of > 60 g were both significantly related to (131)I therapy failure.

Propylthiouracil: clinical overview of its efficacy and its side effects more than 50 years after the introduction of its use in thyrostatic treatment.

Abstract: This minireview gives a clinical overview of the efficacy and of the side effects of the thyrostatic drug propylthiouracil, which is in use for the treatment of Graves' disease for more than 5 decades. It is the aim of this minireview to give convincing evidence of the value of propythiouracil in the treatment of thyrotoxic patients with Graves' disease: The modalities of treatment are given. The advantages in comparison to methimazole are mentioned: Especially for thyrotoxic nursing mothers it represents the only thyrostatic drug approved by the American Academy of Pediatrics. Patients who experience side effects with methimazole usually can be switched successfully to propylthiouracil and vice versa. Its use for the treatment of thyrotoxicosis in pregnant women is recommended by many centres because of the comparatively little placental transfer of the drug, although the effect for the newborn does not seem to differ from that of methimazole. The minireview should remind the medical community of the value of propylthiouracil as a very valuable thyrostatic drug representing a good alternative to methimazole. It should attract interest in the drug, in spite of the fact that after 5 decades in the market there is probably only little financial profit left in selling it.

Predictors of time to remission and treatment failure in patients with Graves' disease treated with propylthiouracil.

Abstract: Purpose: Propylthiouracil is one of the thionamides used in the treatment of Graves’ disease. The drug has serious side effects and long-term treatment might be needed to achieve remission. We designed this study to evaluate the clinical and thyroid Doppler characteristics that might predict time to remission and treatment failure in propylthiouracil treated Graves’ patients. Methods: 26 patients, among 134 presenting to our university hospital outpatient clinic between Feb -July 2007 and with first time diagnosis of clinical thyroid dysfunction, were clinically and ultasonographically diagnosed with Graves’ disease. Doppler parameters, serum thyrotropin, free thyroxine and free triiodothyronine were measured at the beginning of the study and thyroid studies were repeated every 4 weeks until remission. Propylthiouracil 300 mg/day was started for each patient at the time of diagnosis and doses were titrated according to repeat thyroid studies. Patients were treated and followed up for 18 months. Results: Treatment failure was associated with smoking (P = 0.001) and male gender (P= 0.037). Stepwise multiple regression analysis revealed that age, free thyroxine and superior thyroid artery flow rate were predictors of time to remission (P= 0.001, 0.002 and 0.003, respectively). Conclusion: The time to remission in Graves patients treated with propylthiouracil can be predicted using age, serum free thyroxine and superior thyroid artery flow rate. This may help early consideration of alternative treatment for the patients requiring prolonged treatment for remission or for those who fail medical treatment. This would decrease unnecessary, long-term propylthiouracil exposure with its serious side effects.