Showing papers on "Propylthiouracil published in 2014"

Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis

Abstract: Aims Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Methods and results Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. Conclusion These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease.

Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity

Abstract: Introduction: Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.Areas covered: This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.Expert opinion: PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm...

Lactating ptu exposure: i- alters thyroid-neural axis in neonatal cerebellum

Abstract: The purpose of this study was to determine the effects of lactating propylthiouracil (PTU) on the thyroid-neural development in newborns. PTU was administered to female rats in drinking water (0.1% w/v) from birth to lactation day (LD) 30. A hypothyroid state was recorded at LDs 20 and 30 in both dams and their offspring where a marked depression (P<0.01) was observed in serum thyroxine (T4) and triiodothyronine (T3) levels, while a reverse pattern was noticed in serum thyrotropin (TSH) level as compared to a control group. Also, the maternal administration caused a highly significant decrease in the level of neonatal growth hormone (GH) at postnatal days (PNDs) 20 and 30. This hypothyroid condition produced inhibitory effects on 5'-monodeiodinase (5'-DI), and on cholinergic enzymes (butyrylcholinesterase (BuchE) and acetylcholinesterase (AchE)) in the neonatal cerebellum at the studied PNDs. This may also delay partially the development of the cerebellar Purkinje cells (PCs) via altering the dendritic morphology at both examined PNDs. All tested parameters in the control group followed a synchronized course of development, and their progress may depend, largely on thyroid state. Thus, PTU may act as a developmental thyroid-neural disruptor, causing dyshormonogenesis and cerebellum dysgenesis.

Thyroid hormone function in the rat testis

Abstract: Thyroid hormones are emerging regulators of testicular function since Sertoli, germ, and Leydig cells are found to express thyroid hormone receptors (TRs). These testicular cells also express deiodinases, which are capable of converting the pro-hormone T4 to the active thyroid hormone T3, or inactivating T3 or T4 to a non-biologically active form. Furthermore, thyroid hormone transporters are also found in the testis. Thus, the testis is equipped with the transporters and the enzymes necessary to maintain the optimal level of thyroid hormone in the seminiferous epithelium, as well as the specific TRs to execute thyroid hormone action in response to different stages of the epithelial cycle of spermatogenesis. Studies using genetic models and/or goitrogens (e.g., propylthiouracil) have illustrated a tight physiological relationship between thyroid hormone and testicular function, in particular, Sertoli cell differentiation status, mitotic activity, gap junction function, and blood-testis barrier assembly. These findings are briefly summarized and discussed herein.

Fetal and Neonatal Iron Deficiency Exacerbates Mild Thyroid Hormone Insufficiency Effects on Male Thyroid Hormone Levels and Brain Thyroid Hormone-Responsive Gene Expression

Abstract: Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression.

Polybrominated Diphenyl Ether (DE-71) Interferes With Thyroid Hormone Action Independent of Effects on Circulating Levels of Thyroid Hormone in Male Rats

Abstract: Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues including cord blood and breast milk. PBDEs may interfere with thyroid hormone (TH) during development, which could produce neurobehavioral deficits. An assumption in experimental and epidemiological studies is that PBDE effects on serum TH levels will reflect PBDE effects on TH action in tissues. To test whether this assumption is correct, we performed the following experiments. First, five concentrations of diphenyl ether (0–30 mg/kg) were fed daily to pregnant rats to postnatal day 21. PBDEs were measured in dam liver and heart to estimate internal dose. The results were compared with a separate study in which four concentrations of propylthiouracil (PTU; 0, 1, 2, and 3 ppm) was provided to pregnant rats in drinking water for the same duration as for diphenyl ether. PBDE exposure reduced serum T4 similar in magnitude to PTU, but serum TSH was not elevated by PBDE. PBDE treatment did not affect the expression of TH response genes in the liver or heart as did PTU treatment. PTU treatment reduced T4 in liver and heart, but PBDE treatment reduced T4 only in the heart. Tissue PBDEs were in the micrograms per gram lipid range, only slightly higher than observed in human fetal tissues. Thus, PBDE exposure reduces serum T4 but does not produce effects on tissues typical of low TH produced by PTU, demonstrating that the effects of chemical exposure on serum T4 levels may not always be a faithful proxy measure of chemical effects on the ability of thyroid hormone to regulate development and adult physiology.

Characteristics of agranulocytosis as an adverse effect of antithyroid drugs in the second or later course of treatment.

Abstract: Background: Agranulocytosis is a serious adverse effect of antithyroid drugs (ATDs) and mainly develops within three months after the start of uninterrupted ATD treatment. Agranulocytosis can also develop for the first time after interruption and subsequent resumption of the same ATD treatment. However, little is known with regard to agranulocytosis that develops after resumption of the same ATD treatment. Objectives: We investigated the characteristics of patients who developed agranulocytosis during their second or later course of ATD treatment. Methods: A total of 81 patients at our hospital were diagnosed with ATD-induced agranulocytosis. In 14 of the cases (methimazole (MMI), n=10; propylthiouracil (PTU), n=4), the agranulocytosis developed for the first time in the context of the second or later course of treatment with the same ATD; those patients were designated the “resumed group.” The 35 patients (MMI, n=28; PTU, n=7) who developed agranulocytosis during their first uninterrupted course of ATD t...

An update on the medical treatment of Graves’ hyperthyroidism

Abstract: Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.

Brain Tissues Oxidative Damage as a Possible Mechanism of Deleterious Effects of Propylthiouracil- Induced Hypothyroidism on Learning and Memory in Neonatal and Juvenile Growth in Rats

Abstract: Introduction: The role of brain tissues oxidative damage in learning and memory impairments has been well documented. It is also well known that thyroid hormones have a critical role for the brain functions. The purpose of this study was to investigate the role of brain tissues oxidative damage as a possible mechanism of deleterious effects of propylthiouracil (PTU) - induced hypothyroidism on learning and memory in neonatal and juvenile growth in rats.

Evaluation of developmental toxicity of propylthiouracil and methimazole.

Abstract: BACKGROUND Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs. METHODS We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20. RESULTS In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed. CONCLUSION We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy

Toxicities associated with 1-month treatment with propylthiouracil (PTU) and methimazole (MMI) in male rats

Abstract: Thionamides such as propylthiouracil (PTU) and methimazole (MMI) have been used for more than 50 years to treat the more common causes of thyrotoxicosis/hyperthyroidism such as Graves' disease. Serious adverse effects associated with thionamides in humans include idiosyncratic liver damage, agranulocytosis, aplastic anemia, and vasculitis. Both prospective and retrospective clinical studies with these drugs have failed to identify predictive biomarker for these adverse effects. To assess whether rat is a good model for predicting drug-related adverse events in the liver and in the bone marrow, we conducted a comprehensive study in male rats with multiple doses of PTU and MMI. As expected, euthyroid animals became hypothyroid along with several secondary changes associated with hypothyroidism. There were slight reductions in red blood cell parameters along with some marginal effects on the bone marrow elements. However, there was no evidence of significant neutropenia and liver injury in both PTU-treated and MMI-treated cohorts. MMI-related effects were noted in the seminiferous tubules of the testes. Overall, 1-month daily treatment of euthyroid rats with PTU or MMI resulted in hypothyroidism, minor bone marrow effects, and several secondary effects associated with hypothyroidism, but without any evidence of adverse effects reported in humans including liver injury and agranulocytosis.

Therapeutic exploration of betulinic acid in chemically induced hypothyroidism

Abstract: Hypothyroidism is a chronic condition characterized by abnormally low thyroid hormone production. The decreased serum level (>5.1 mIU/l) of thyroid-stimulating hormone (TSH) in blood indicates hypothyroidism. The study was an attempt to access the effect of betulinic acid on chemically induced hypothyroidism in female albino rats. Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as anticancer potential, by inhibiting topoisomerase. Hypothyroidism was induced in female albino rats using propylthiouracil (PTU) at a dose of 60 μg/kg body weight orally for 1 month. Induction of hypothyroidism was confirmed by increased TSH level. At the end of second month, blood was collected, centrifuged and serum was analyzed for TSH, T3, and T4 level and protocol was terminated by killing of animals. The animals exposed to PTU were treated with pure standard drug thyroxine at a dose of 10 μg/kg of body weight by oral route and the test drug betulinic acid 20 mg/kg by oral route through force feeding in their respective groups. Treatment was carried out for a period of 2 months. Group with PTU-induced hypothyroidism showed an elevation in serum TSH and reduction level, which was restored by the betulinic acid in treated female albino rats. Betulinic acid also reduced the damage caused in the thyroid tissues by PTU, thus minimizing the symptoms of hypothyroidism. Histopathological examinations of the thyroid tissue showed changes in the thyrocytes of PTU-treated group while thyroxine group showed normal thyroid follicles cell architecture and the group treated with betulinic acid also showed marked improvement in the follicles integrity which shows that betulinic acid has some protective activity. This study shows that the betulinic acid has thyroid-enhancing potential by lowering down the TSH levels and reducing the damage caused in the thyroid tissues, thus minimizing the symptoms of hypothyroidism when used anaphylactically in rats.

Hypoglycemic coma due to insulin autoimmune syndrome induced by methimazole: A rare case report

Abstract: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of human leukocyte antigen (HLA) genotype with this disease in adolescents in China is limited. This is the case report of a 17-year-old female patient with Graves’ disease who was treated with methimazole (MTZ). After 4 weeks of continuous MTZ treatment, the patient suffered an episode of unconsciousness during the late postprandial phase and was admitted to the hospital, where the blood glucose level was found to be 2.88 mmol/l. The symptoms were relieved following intravenous glucose administration. Imaging studies of the pancreas were unremarkable, but the laboratory investigations on admission revealed high serum levels of total insulin, associated with relatively low levels of free insulin and markedly elevated insulin autoantibody (IAB) levels. HLA testing revealed DRB1*0406/0901 and the patient discontinued MTZ and was prescribed propylthiouracil. During the long-term follow-up, the total insulin and IAB levels gradually declined. There was no other episode of hypoglycemia. Therefore, in adolescents with Graves’ disease receiving antithyroid treatment with MTZ who experience hypoglycemia, the IAB levels should be assessed to exclude or confirm IAS as the underlying cause.

Management of hyperthyroidism during pregnancy in Asia.

Abstract: Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.

Luteal activity of pregnant rats with hypo-and hyperthyroidism

Abstract: Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats. Seventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2α receptor using real time RT-PCR. The data were analyzed by SNK test. Hypothyroidism reduced COX-2 expression on day 10 and 19 (P < 0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p < 0.05), apoptotic cell numbers on day 19 (p < 0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p < 0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P < 0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P < 0.05). Hypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period.

Luteal expression of thyroid hormone receptors during gestation and postpartum in the rat.

Abstract: Background: Progesterone (P4) is the main steroid secreted by the corpora lutea (CL) and is required for successful implantation and maintenance of pregnancy. Although adequate circulating levels of thyroid hormone (TH) are needed to support formation and maintenance of CL during pregnancy, TH signaling had not been described in this gland. We determined luteal thyroid hormone receptor isoforms (TR) expression and regulation throughout pregnancy and under the influence of thyroid status, and in vitro effects of triiodothyronine (T3) exposure on luteal P4 synthesis. Methods: Euthyroid female Wistar rats were sacrificed by decapitation on gestational day (G) 5, G10, G15, G19, or G21 of pregnancy or on day 2 postpartum (L2). Hyperthyroidism and hypothyroidism were induced in female Wistar rats by daily administration of thyroxine (T4; 0.25 mg/kg subcutaneously) or 6-propyl-2-thiouracil (PTU; 0.1 g/L in drinking water), respectively. Luteal TR expression of mRNA was determined using real-time reverse-transcri...

Comparison of high-sensitivity C-reactive protein and fetuin-A levels before and after treatment for subjects with subclinical hyperthyroidism

Abstract: This study was designed to show the effect of propylthiouracil treatment on sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels on subjects with subclinical hyperthyroidism. After checking sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels of 35 patients with subclinical hyperthyroidism, each was given 50 mg tablets of propylthiouracil three times daily. After 3 months, sCD40L, high-sensitivity C-reactive protein, and fetuin-A levels were then compared to the levels before treatment. Although high-sensitivity C-reactive protein and sCD40L levels were normal in the subclinical hyperthyroidism patients compared to the healthy controls, fetuin-A levels were statistically significantly higher (*p = 0.022). After treatment, fetuin-A levels of subclinical hyperthyroidism patients decreased statistically significantly compared to the levels before treatment (**p = 0.026). sCD40L and high-sensitivity C-reactive protein levels did not have a statistically significant difference compared to the control group and post-propylthiouracil treatment. In subclinical hyperthyroidism patients, high fetuin-A levels before propylthiouracil treatment and decreases in these levels after treatment in cases with subclinical hyperthyroidism indicated the possibility of preventing long-term cardiac complications with propylthiouracil treatment.

Study the Effects of Ginger (Zingiber officinale) Extract on Serum Lipid in Hypothyroidism Male Rats Induce by Propylthiouracil

Abstract: This study was undertaken to investigate the protective role of Ginger against the hypothyroidism induce by Propylthiouracil in male rats on serum lipids. Eighteen adult male rats were randomly divided into three equal groups (each of six) and treated as follows for four weeks, First group (C) was daily orally gavages with saline solution served as control.. Second group (G1) was daily orally gavages with Propylthiouracil (6 mg/kg B.W.). Third group (G2) was daily orally gavages with Propylthiouracil (6 mg/kg B.W.) in addition to ginger (200 mg/kg B.W.) Overnight fasting blood samples were collected from the all animals of the experiment at end week of experiment for the determination of serum triiodothyonine (T3), thyroid stimulation hormone (TSH), total cholesterol (TC), triacylglycerol (TAG), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C). The results showed that the A significant (P 0.05) depression in the elevated TAG and VLDL-C concentration in G2 group compared to G1 and control groups . From these results indicating that the effect of orally administration of propylthiouracil to induced hypothyroidism and induction of Dyslipidemia. On conclusions, the present study confirmed the beneficial effects of ginger extract as a hypolipidemic effects gains the dyslipidemia due to hypothyroidism.

Hyperthyroidism and antithyroid medications: a friend and an enemy of psychosis.

Abstract: Since the middle of the past century three classes of antithyroid medications, namely thionamides (carbimazole, methimazole and propylthiouracil), anion inhibitors (potassium perchlorate) and iodides (potassium iodide), are used for the pharmacological treatment of hyperthyroidism [1,2]. Their use has had a fundamental therapeutic impact in the management of patients with overactive thyroid function and these medications are largely used worldwide, though with some geographical differences in the use of one rather than another drug of the thionamide class and with some selective indications or restrictions with regard to the use of potassium perchlorate and potassium iodide. The possible impact of thyroid hormone abnormalities on the development of a new onset or the worsening of a pre-existing neurological or psychiatric disorder, including psychosis, is historically well defined. On the contrary, the safety profile of antithyroid medications in connection with the risk of occurrence of a neurological or psychiatric illness has never been precisely documented, with the exception of only few sporadic reports raising a doubtful and uncertain warning. In the current issue of Expert Opinion on Drug Safety, Vita et al. have reviewed the relationship between the administration of antithyroid drugs and the development of psychosis [3]. Interestingly, the review of the literature led the authors to explore such issue deep back in the past as most of the reports of a suspicious manifestation of psychosis following the use of antithyroid medications are just historical. Though the universal clinical experience and the routine practice induce the physicians to safely prescribe antithyroid drugs for the treatment of hyperthyroidism without any specific concern regarding the risk of occurrence of iatrogenic psychosis, an evidencebased conclusion supported by the analysis of the reported cases has never been done so far. Following a careful review of the literature, the authors have now put a stone in favor of the safe use of antithyroid medications against the hypothetical and never confirmed risk of development of psychosis when managing patients with hyperthyroidism.

Surgical management of an atypical presentation of a thyroid storm.

Abstract: Introduction: Thyroid storm is a rare complication of Graves' disease that can carry a poor prognosis. In order to prevent major complications, thyroid storm must be quickly identified in patients and treatment must be promptly implemented. Medical treatment is usually initiated with antithyroid medications, such as propylthiouracil (PTU), methimazole, and beta-blockers. However, some patients may experience adverse reactions to these medications and alternate treatment options must be explored. Case Presentation: We report a case of a 30-year-old female initiated on PTU after diagnosis with Graves' disease that later presented an acute thyroid storm. Discussion: Therapy was changed to methimazole, yet the patient subsequently developed angioedema and dyspnea. Medical management was discontinued and emergent thyroidectomy was performed without complication.

The occurrence of agranulocytosis due to antithyroid drugs in a cohort of patients with Graves disease treated with radioactive iodine 131I during 14 years

Abstract: INTRODUCTION Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit. PATIENTS AND METHODS We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU). RESULTS Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8). CONCLUSION Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

Research Article Evaluation of Developmental Toxicity of Propylthiouracil and Methimazole

Abstract: BACKGROUND: Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs. METHODS: We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20. RESULTS: In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed. CONCLUSION: We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or

Neutropenic enterocolitis secondary to propylthiouracil-induced agranulocytosis.

Abstract: First described by Cooke in 1930 (1), neutropenic enterocolitis (NE), also termed necrotizing enterocolitis or neutropenic typhlitis, is a necrotizing inflammatory disease of the ileocecal region. Its pathogenesis is not entirely known. It is a complication of severe neutropenia and often occurs after high-dose chemotherapy. An association between NE and the use of certain antineoplastic drugs has been described (2,3). Propylthiouracil (PTU) is used widely in the treatment of hyperthyroid disorders. Its most notable side effect is decrease in the neutrophilic granulocyte count. Development of agranulocytosis is related to the dose of the anti-thyroid drug administered (4).

Fetal Tachycardia Treated Successfully with Maternally Administered Propylthiouracil

Abstract: Background. Fetal tachycardia may result from the transplacental passage of thyroid stimulating immunoglobulins in a patient with hypothyroidism secondary to ablation of Graves' disease. Case. A 32-year-old woman, gravida 4, para 2, and abortus 1, with hypothyroidism and a history of Graves' disease, presented at 23 6/7 weeks of gestation with a persistent fetal tachycardia. The treatment of the fetal tachycardia with maternally administered digoxin and Sotalol was unsuccessful. Maternal thyroid stimulating immunoglobulins were elevated, and treatment with maternally administered propylthiouracil (PTU) resulted in a normal sinus rhythm for the remainder of the pregnancy. An induction of labor was performed at 37 weeks. Four to five days after delivery, the neonate exhibited clinical signs of hyperthyroidism necessitating treatment. Conclusion. Fetal tachycardia resulting from the transplacental passage of thyroid stimulating immunoglobulins can be successfully treated with maternally administered PTU. The neonate needs to be followed up closely as clinical signs of hyperthyroidism may occur as thyroid stimulating immunoglobulins continue to circulate in the neonate, while the serum levels of PTU decline.

Clinical effectiveness of Carbimazole and Propylthiouracil for Hyperthyroidism in Patients of Punjab, Pakistan

Abstract: Background: The primary objective of any drug for hyperthyroidism is to control clinical manifestations and maintenance of normal levels of hormonal concentrations. It also targets to prevent the recurrence of disease along with minimizing associated risk factors. In this study, effectiveness of oral anti thyroid agents was checked to normalize altered levels of thyroid hormones due to hyperthyroidism. Methods: The study was comprised of 40 subjects of whom 30 were experiencing hyperthyroidism and were administered anti-hyperthyroid drugs. 10 patients of hyperthyroidism were not taking any medication. Standard dose regimens of carbimazole and propylthiouracil were employed for all 30 hyperthyroid patients under closed monitoring. Physical as well as biochemical analyses of all subjects were done and thyroid profiling was performed for measuring levels of free thyroxine (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH) and antibodies against thyroglobulin (Tg). Results: Thyroid profiles of medicated hyperthyroid patients were compared with the profiles of non-medicated group. Statistical analysis appeared with non-significant values for all four parameters. Conclusion: No significant difference was found between medicated and non-medicated groups. We recommend that combinatorial drugs and new derivatives with better efficacy and fewer side effects should be employed to treat hyperthyroidism.

[The time course of experimentally altered thyroid status manifestations in female C3H-A mice].

Abstract: The female C3H-A mice with agouty fur color were used to model hyper- and hypothyroidism in the long lasting experiment. The study was carried out for 44 weeks. Hyperthyroidism was induced by the administration of the L-thyroxine injections on alternate days during the whole period of the investigation. Hypothyroidism was achieved by adding propylthiouracil to the drinking water. The change of thyroid state was characterized by biphasic change in body weight. At the beginning of the experiment the hypothyroid animals were retarding by their weight. Otherwise the hyperthyroid animals were advancing by their weight. But since the 18th-21st week the initial trends changed, i. e. the hypothyroid mice body weight started ahead the hyperthyroid one. In the open field test both hypo- and hyperthyroid animals demonstrated the higher level of the investigating activity in comparison with the euthyroid mice. In the hyperthyroid mice the frequency of side-activity acts (grooming) increased significantly. Thus, the hyperthyroid animals appeared to be more anxious. To the 18th week of the experiment the animals of study groups started to demonstrate the apparent visual difference in their fur color. The hyperthyroid mice fur color became darker than one of the hypothyroid and the euthyroid mice. It is worthy of note that the hyperthyroid mice fur color was getting lighter than one of the euthyroid animals. The results are discussed in the context of hypothalamic-pituitary-thyroid axis functioning. The possible mechanisms of hormonal regulation of the fur color in mice are considered to include the hypothalamic-pituitary-thyroid axis hormones activities.

Modulation of nitric oxide synthase and superoxide dismutase gene expression by altered thyroid levels in adult rat brain

Abstract: The effects of altered thyroid hormones level (through induction of Hypothyroidism or Hyperthyroidism) on oxidative stress and antioxidant biomarkers as well as on gene expression of neuronal nitric oxide..

Managing paediatric Graves’ disease -

Abstract: Graves’ disease is the most common cause of hyperthyroidism in children. Anti-thyroid drug treatment with carbimazole or its active metabolite methimazole is offered as first line initial treatment but it induces remission in only 30%of children. Propylthiouracil is not recommended in children because of its association with severe hepatic toxicity. For those who relapse after ATD, radioactive iodine can be offered as definitive therapy except in cases with severe Graves’ ophthalmopathy or patients with large goitre who are the candidates for surgery. Total (or near total) thyroidectomy is the surgical procedure of choice for treating paediatric patients with Graves’ disease as it reduces the risk of recurrent hyperthyroidism which was seen in patients undergoing subtotal or partial thyroidectomy.