Showing papers on "Propylthiouracil published in 1997"
TL;DR: Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU and MMI were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses and in 6 of the 43 fetuses, respectively.
Abstract: Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence. We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T4 (FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M). Neither the mean fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant difference in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels. These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.
172 citations
TL;DR: It is concluded that PTU and MMI have similar placental transfer kinetics and there was no significant difference between drugs or drug doses and no effect of addition of albumin.
Abstract: Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 micrograms/mL and 40 micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170 +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174 +/- 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/- 0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/- 0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.
161 citations
TL;DR: Results suggest that UCP2 is a protein that may be involved in the nuclear‐mediated effect of T3 on resting metabolic rate in the rat.
108 citations
TL;DR: Pregnant women suffering from hyperthyroidism or any other thyroid disease should be metabolically compensated at time of conception-the need for contraception until the disease is controlled should be openly discussed.
Abstract: The prevalence of hyperthyroidism in pregnancy is about 0.2%. The most common cause is Graves' disease. Maternal, fetal, and neonatal morbidity and mortality may be reduced to a minimum with careful attention to the clinical symptoms and interpretation of thyroid tests. Ideally, hyperthyroid women should be rendered euthyroid before considering conception. The incidence of maternal and neonatal morbidity is significantly higher in those patients whose hyperthyroidism is not medically controlled. Even the incidence of thyroid storm is high in women who are under poor medical supervision in the presence of a medical or obstetric complication. Maternal morbidity includes a higher incidence of toxemia, premature delivery, placenta abruptio, congestive heart failure, and thyroid crisis. In some series, anemia and infections were also reported. Neonatal morbidity includes SGA neonates, intrauterine growth retardation, LBW infants, and prematurity. Fetal goiter and transient neonatal hypothyroidism is occasionally reported in infants of mothers who have been overtreated with ATD. Propylthiouracil and MMI are equally effective in controlling the disease. In most patients, symptoms improved and thyroid tests returned to normal in 3-8 weeks after initiation of therapy. Resistance to ATD is extremely rare, most cases are caused by patient poor compliance. Surgery for the treatment of hyperthyroidism is reserved for the unusual patient who is allergic to both ATD; to those who have large goiters; to those who require large doses of ATD; or to those patients who poorly comply. Fetal and neonatal hyperthyroidism can be predicted in the majority of cases by the previous maternal medical and obstetric history and by the proper interpretation of thyroid tests. Finally, hyperthyroidism may recur in the postpartum period.
74 citations
TL;DR: It is suggested that liver test abnormalities are frequently found at the time of diagnosis of hyperthyroidism, however, the presence or absence of these abnormalities does not predict elevations in liver test results, which are possibly induced by PTU during therapy.
Abstract: Changes in liver biochemical test results have been described in hyperthyroid patients before and after antithyroid therapy. In the present study, we analyzed liver tests at diagnosis and after 6 weeks of treatment with propylthiouracil (PTU) in 43 patients with hyperthyroidism. At diagnosis, 60.5% of the patients had at least one liver abnormality. Elevations of alkaline phosphatase, alanine and aspartate aminotransferase, and gamma-glutamyl transpeptidase levels were observed in 19 (44.2%), 10 (23.3%), six (14%), and six (14%) of the patients, respectively. At the end of the 6-week treatment with PTU, elevations in liver test values, possibly induced by PTU, were found in seven (16.3%) patients. Age, sex, type of goiter (either diffuse or multinodular), and presence or absence of abnormal liver biochemical tests at diagnosis were not significant in determining the possibility of PTU-induced elevations in liver tests. These data suggest that liver test abnormalities are frequently found at the time of diagnosis of hyperthyroidism. However, the presence or absence of these abnormalities does not predict elevations in liver test results, which are possibly induced by PTU during therapy.
63 citations
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TL;DR: Alveolar haemorrhage or pulmonary-renal syndrome associated with antineutrophil cytoplasmic antibody with myeloperoxidase specificity may be a new complication of propylthiouracil therapy.
Abstract: Propylthiouracil (PTU) is known to cause vasculitis as a rare complication. We report the case of a patient who developed alveolar haemorrhage and haematuria whilst treated with PTU. The serum was positive for antineutrophil cytoplasmic antibody (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). All symptoms resolved completely after discontinuation of PTU. Alveolar haemorrhage or pulmonary-renal syndrome associated with antineutrophil cytoplasmic antibody with myeloperoxidase specificity may be a new complication of propylthiouracil therapy.
57 citations
TL;DR: It is concluded that methimazole intake during pregnancy may be associated with severe congenital malformations including oesophaeal atresia and tracheo-oesophaeals fistula and thyrotoxicosis during pregnancy.
45 citations
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TL;DR: It is strongly suggested that PTU-induced rapidly progressive glomerulonephritis associated with ANCA is associated with hyperthyroidism.
Abstract: We present a case study of a 52-year-old female patient with hyperthyroidism which had been diagnosed at the age of 35. However, the malfunction of thyroid had been poorly controlled. Thyroid function was returning to normal after the administration of propylthiouracil (PTU) 300 mg/day, however purpura appeared in both lower extremities. Renal function deteriorated rapidly, and the patient was admitted to our hospital. According to the biopsies, leukocytoclastic vasculitis in the skin was apparent, and crescent formation was observed in the glomerulus. Serological examination revealed positive antineutrophil cytoplasmic autoantibodies (ANCA) against proteinase 3 (Pr3) and myeloperoxidase (MPO). Antinuclear autoantibody was positive. After cessation of PTU and administration of prednisolone, the purpura disappeared and ANCA were becoming negative. Renal function recovered gradually. Thyroid function was kept within normal range using iodine solution. Thus, it is strongly suggested that PTU-induced rapidly progressive glomerulonephritis associated with ANCA.
42 citations
TL;DR: The existence of a sodium-iodide symporter in the mammary gland which has characteristics similar to the iodide transporter in the thyroid gland is suggested, which is sodium dependent and is inhibited by perchlorate and thiocyanate.
Abstract: We have recently reported that prolactin (PRL) stimulates iodide uptake into cultured mouse mammary tissues. This effect occurs in both TCA soluble and insoluble tissue fractions. The effect of PRL apparently involves an RNA-DNA-dependent mechanism, since actinomycin D and cyclohexamide abolish the PRL stimulation of iodide uptake and its incorporation into protein. Perchlorate and thiocyanate, inhibitors of the iodide transporter, also abolish the PRL effects on iodide uptake and incorporation. Similarly, propylthiouracil and aminotriazole, inhibitors of peroxidase, abolish both effects of PRL. Finally, the extent of iodide uptake in mammary cells is suppressed by about 50% in sodium-free medium. These studies thus suggest the existence of a sodium-iodide symporter in the mammary gland which has characteristics similar to the iodide transporter in the thyroid gland-that is, it is sodium dependent and is inhibited by perchlorate and thiocyanate. The fact that both iodide transporter inhibitors and peroxidase inhibitors abolish PRL-stimulated iodide uptake and incorporation suggests that there may be a coupled mechanism involving the iodide transporter and the peroxidase enzyme.
37 citations
TL;DR: The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia.
Abstract: Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. ...
34 citations
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TL;DR: Fetal cord blood sampling proved to be useful during these two pregnancies to ascertain the diagnosis of fetal hyperthyroidism and to monitor the dose of PTU administered to this euthyroid mother.
Abstract: We described here three individual pregnancies in a euthyroid mother with a past history of Graves disease and high levels of thyrotropin receptor stimulating antibodies. Ten years prior to her first pregnancy the mother underwent a partial thyroidectomy for Graves disease and remained euthyroid since, but still produced high levels of thyrotropin receptor stimulating antibodies. Fetal and postnatal hyperthyroidism was not recognized for the first child who was referred to us at one year of age for craniostenosis. During the two next pregnancies fetal hyperthyroidism was suspected on the basis of fetal tachycardia, growth retardation, fetal goiter and fetal cord blood sampling confirmed high levels of free T3, free T4, suppressed fetal TSH levels, and high levels of fetal TRAb. The mother received propylthiouracil to control fetal hyperthyroidism. Neither baby was premature and each had a more favorable outcome than the first. Fetal cord blood sampling proved to be useful during these two pregnancies to ascertain the diagnosis of fetal hyperthyroidism and to monitor the dose of PTU administered to this euthyroid mother.
TL;DR: A reduced set point seems to be an adaptive response that lowers the metabolic requirements for thermoregulation in the hypothyroid rat, suggesting that PTU-inducedhypothyroidism leads to a regulated reduction in body temperature.
Abstract: A reduced body temperature is a common symptom of hypothyroidism and may result from a deficiency in metabolic heat production. However, a reduced metabolism does not necessarily imply a failure in thermoregulatory control if other thermoeffectors, in particular behavioral thermoregulation, are operative. To address this issue, selected ambient temperature (T a ) in a temperature gradient, core temperature (T c ), heart rate (HR), and motor activity (MA) were monitored via radiotelemetry in euthyroid rats and rats made hypothyroid by the administration of 0.05 mg/ml propylthiouracil (PTU) in drinking water for approximately 15 days. Core temperature of PTU-treated rats was reduced by 0.3°, whereas selected T a was increased by 2.3°. PTU treatment led to significant reductions in HR, whereas MA was unaffected. Thermoregulatory behavior did not reverse the PTU-induced hypothermia, suggesting that PTU-induced hypothyroidism leads to a regulated reduction in body temperature (i.e., decrease in the set point). A reduced set point seems to be an adaptive response that lowers the metabolic requirements for thermoregulation in the hypothyroid rat.
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TL;DR: The observation of cutaneous vasculitis during administration of propylthiouracil suggested that clinical awareness of this complication should be of considerable importance.
Abstract: Cutaneous reactions to propylthiouracil and methimazole occur in 3%-5% of adults. Generalized maculopapular and papular purpuric eruptions are perhaps the most common thionamide-induced reactions. We report 3 patients who developed cutaneous vasculitis which is a rare and serious side-effect during antithyroid drug therapy. The observation of cutaneous vasculitis during administration of propylthiouracil suggested that clinical awareness of this complication should be of considerable importance.
TL;DR: The outcome suggests long-lasting effects by developmental exposure to PCB 77 on the interaction between dopaminergic and serotonergic processes which may be mediated by effects on thyroid hormone levels.
TL;DR: The effects of methimazole and propylthiouracil on a rat model of experimental colitis is examined, finding that decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL‐2 receptors.
Abstract: Background: Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods: Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results: All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points (P<0.01).
Conclusions: Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.
TL;DR: The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied in this paper, where thyroidectomized (Tx) or sham Tx were injected with either propylthiouracil (PTU) 20 mg/kg intraperitoneally or saline for 2 weeks.
Abstract: The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx) or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20 mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats were injected intravenously with triiodothyronine ([T 3 ] 5 μg/kg) or saline 10 minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at 0, 10, 20, 30, 45, 60, and 90 minutes following glucose ingestion. Plasma levels of GIP and insulin were measured by specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased the basal level of plasma GIP, but decreased that of insulin. Insulin levels at 10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid rats. Furthermore, glucose-stimulated insulin secretion was unaltered by pretreatment with T 3 , whereas the glucose-induced increase in plasma GIP was completely abolished by preinjection of T 3 in thyroid-intact rats. These results suggest that thyroid functions are involved in the regulation of insulin and GIP secretion in rats.
TL;DR: Severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.
Abstract: We recently observed 2 lactase-deficient women with Graves' disease who consistently developed severe diarrhea after ingestion of thionamide (methimazole and propylthiouracil) tablets containing lactose as carrier. The strict temporal relationship between ingestion of lactose-containing tablets and appearance of intestinal symptoms, as well as the absence of side effects following ingestion of methimazole tablets without lactose as carrier, provided the clue for the diagnosis. To our knowledge, severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.
TL;DR: Evidence is provided that administration of PTU stimulates the synthesis and secretion of TG in the follicular epithelium in vivo, and, also, suppresses reabsorption and degradation of Tg.
Abstract: To clarify the effects of an antithyroid drug on the kinetics of thyroglobulin synthesis, secretion, and reabsorption in the thyroid follicles, propylthiouracil (PTU) was administered to rats and the thyroid glands were examined by a refined post-embedding immunogold technique during and after withdrawal of PTU. Seven-wk-old male Wistar rats were administered with S mg of PTU/d through a gastric tube, and sacrificed at 1 and 2 wk of administration and at 1, 2, and 3 d, and 1, 2, 3, and 4 wk, after discontinuation. The administration of PTU caused a remarkable dilatation of the rER and Golgi apparatus, but these areas gradually recovered after withdrawal of PTU. During the experiment, no significant change in the density of thyroglobulin (Tg) was observed except for a transient increase immediately after withdrawal of PTU. The expression of Tg on subapical vesicles (SV) and follicular colloid took a relatively parallel course; increasing during administration of PTU and decreasing with a transient peak immediately after treatment was discontinued. In contrast to the remarkable changes in the morphology of compartments involved in Tg synthesis, the development of colloid droplets and formation of secondary lysosomes were suppressed during and after discontinuing administration of PTU. However, the basic pattern of the gradient of Tg density among the cellular compartments was essentially retained in the experimental group. Thus the present immunoelectron-microscopic study provided evidence that administration of PTU stimulates the synthesis and secretion of Tg in the follicular epithelium in vivo, and, also, suppresses reabsorption and degradation of Tg. Further, it was speculated that the density gradient of Tg among the compartments involved in Tg synthesis, secretion and storage is regulated by an unknown constitutive mechanism and not by the thyroid-stimulating hormone (TSH)-TSH receptor-mediated system.
TL;DR: Results demonstrate the specific localization of TR-β2 to the anterior pituitary, especially to the thyrotrope population, and its regulation by thyroid hormone, although contributions from the other TR isoforms may still remain important.
TL;DR: Extended elevation of serum enzymes is consistent with the diagnosis of PTU-induced hepatotoxicity, which may recover completely and be able to treat Graves' disease.
Abstract: We report a case of propylthiouracil (PTU)-induced cholestatic hepatotoxicity in Graves' disease that developed 1 day after beginning PTU. After clinical recover, liver abnormalities persisted for 5 years. Percutaneous liver biopsy and the eventual normalization of enzyme levels excluded permanent liver damage as a result of PTU therapy. Thus prolonged elevation of serum enzymes is consistent with the diagnosis of PTU-induced hepatotoxicity, which may recover completely.
TL;DR: The findings suggest that distinct hepatic acceleration of urea synthesis may contribute to the protein loss seen in both myxedema and in thyrotoxicosis in humans.
TL;DR: The hypothesis that chronic elevation of thyroid‐stimulating hormone (TSH) is related to the development of hyperparathyroidism in the rat model is tested.
Abstract: Reports of the coexistence of hyperparathyroidism and thyroid disease have raised the issue of a possible etiologic relationship. The present study tests the hypothesis that chronic elevation of thyroid-stimulating hormone (TSH) is related to the development of hyperparathyroidism. Four groups of 60 female rats were treated as follows: group 1, control; group 2, propylthiouracil (PTU) 0.0025%; group 3, PTU 0.0025% plus thyroxine, 5 μg two times per week; and group 4, only thyroxine. The animals' serum calcium, phosphorus, TSH, thyroxine, and parathyroid hormone (PTH) levels were evaluated at 0, 6, 12, and 18 months. Significant elevation of TSH was sustained throughout the 18 months in groups 2 and 3. The PTH levels were also significantly elevated in both group 2 and group 3 animals (P = 0.02). The histopathologic features of the parathyroids were evaluated at 18 months. In the group 2 (PTU only) animals, which had profound hypothyroid, 44% developed parathyroid adenomas. In the group 3 (PTU plus thyroxine) animals, who had mildly elevated TSH levels, 53% developed parathyroid adenomas. These findings are consistent with the hypothesis that prolonged TSH stimulation may lead to hyperparathyroidism in the rat model.
TL;DR: Thyroid hormone is likely to set the stage for the subsequent trophic control of renal development by neural input, and hypothyroidism during this critical window can be expected to result in abnormal renal functional development and increased perinatal risk.
Abstract: Adrenergic input influences renal cell replication/differentiation and the development of excretory function. Kidney cells make adrenoceptors before the arrival of the majority of nerve terminals, and the current study examines whether thyroid hormone plays a role in receptor development. Propylthiouracil (PTU) was given to pregnant and neonatal rats from gestational d 17 through postnatal d 5, a treatment that obtunds thyroid hormone levels throughout the first 2-3 wk postpartum. The PTU group showed significant deficits in the number of alpha1-receptors, and values resolved to normal in parallel with hormone level recovery. The effects were not secondary to alterations in cell differentiation or growth. as the period of receptor abnormalities did not correspond to that of growth inhibition. Similarly, the effects were selective for the alpha1-receptor, as no comparable effects were seen for total membrane protein or for alpha2-receptors. The role of thyroid hormone in alpha1-receptor ontogeny involved a critical developmental window; later in development neither treatment with PTU nor with large doses of thyroid hormone had any impact on alpha1-receptors. Studies of mRNAs encoding the alpha1-receptor subtypes indicated that hypothyroidism targets the alpha1a-subtype, which has been implicated in the transduction of neurotrophic signals; alpha1a-receptor mRNA also showed the largest proportional developmental increase compared with those encoding other alpha1-subtypes. Accordingly, thyroid hormone is likely to set the stage for the subsequent trophic control of renal development by neural input, and hypothyroidism during this critical window can be expected to result in abnormal renal functional development and increased perinatal risk.
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TL;DR: The treatment with propylthiouracil induces the normalization of thyroid hormone status and consequently of OCTT with the disappearance of gastrointestinal symptoms, such as diarrhea and steatorrhea, with a better efficacy if compared to other drugs utilized in the treatment of hyperthyroidism.
Abstract: BACKGROUND/AIMS Gastrointestinal disturbances such as diarrhea and malabsorption with steatorrhea may show up in hyperthyroid patients. The aim of our study was to evaluate oro-caecal transit time (OCTT) and gastrointestinal symptoms in hyperthyroid patients before and after propylthiouracil administration. MATERIALS AND METHODS Twenty hyperthyroid patients (15 Females and 5 Males, mean age 47 years) were studied. Eight of them had diarrhea and 10 steatorrhea. The control group was composed of 20 healthy volunteers (13 F and 7 M, mean age 49 yrs). OCTT and fecal fat excretion were measured before and after propylthiouracil administration (300 mg/day for 10 day and then 200 mg/day for 30 days). RESULTS Before the treatment in hyperthyroid patients had began the mean OCTT was significantly lower than in the control group (64 min. versus 107 min; p < 0.0001). After treatment mean OCTT became similar to the controls (p = ns); diarrhea disappeared in all affected patients and mean fecal fat excretion was reduced from 7.9 gr/24h to 3.4 gr/24h, with a statistically significantly difference (p < 0.0001). CONCLUSIONS The treatment with propylthiouracil induces the normalization of thyroid hormone status and consequently of OCTT with the disappearance of gastrointestinal symptoms, such as diarrhea and steatorrhea, with a better efficacy if compared to other drugs utilized in the treatment of hyperthyroidism.
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TL;DR: The results indicate that not only p-ANP but also serum ACE activity was markedly increased in experimental hyperthyroid rabbits, and the relationships between ANP, ACE and thyroid hormones were investigated.
Abstract: BACKGROUND It is known that serum angiotensin-converting enzyme (ACE), and plasma atrial natriuretic peptide (p-ANP) levels increase in hyperthyroidism. However, the precise mechanism of the effects of thyroid hormone on ANP release remains to be clarified. No study investigating serum ACE together with p-ANP levels has been performed in experimental hyperthyroid and hypothyroid rabbits. The present study was designed in order to provide additional evidence of increased ANP production and secretion in hyperthyroidism and to investigate the relationships between ANP, ACE and thyroid hormones. METHODS Male New Zealand white rabbits (2.3-3.4 kg) were used throughout the study. Hyperthyroidism was induced by daily intraperitoneal administration of L-thyroxin (50 micrograms/100 g). Hypothyroidism was induced by daily intraperitoneal injection of propylthiouracil (2 mg/100 g body weight). Twelve days after the end of treatment, animals were sacrificed under anesthesia and blood samples were obtained from the aorta for serum ACE and thyroid hormone and p-ANP determinations. RESULTS Serum ACE, plasma renin activity (PRA) and p-ANP were higher in hyperthyroid rabbits and lower in hypothyroid rabbits than in euthyroid rabbits. ANP concentration in atria was lower in hyperthyroid rabbits and higher in hypothyroid rabbits than in euthyroid rabbits. p-ANP, PRA and serum ACE levels were positively correlated with serum thyroxin levels. Inverse correlation was found between serum thyroxin and ANP concentration in atria (a-ANP), and between p-ANP and a-ANP. CONCLUSIONS Our results indicate that not only p-ANP but also serum ACE activity was markedly increased in experimental hyperthyroid rabbits. It was thought that there were both direct and indirect effects of thyroxin on the release of ANP.
TL;DR: In patients with alcoholic cirrhosis, acute administration of propylthiouracyl has no effect on systemic and splanchnic hemodynamics or on oxygen contents.
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TL;DR: It is recognised that agranulocytosis from carbimazole is a rare, life-threatening complication, and instead of awaiting spontaneous recovery, the use of haemopoietic growth factors certainly seems a justifiable option, with a promise of a reduction in morbidity and mortality.
Abstract: Carbimazole is a useful antithyroid drug with a rare potentially fatal complication of agranulocytosis. We report 2 cases presenting with this problem. One was treated supportively with barrier nursing and broad spectrum antibiotics, and the other needed use of a haemopoietic growth factor, granulocyte colony stimulating factor (G-CSF). As it is indeed possible for thyrotoxic patients who developed agranulocytosis with carbimazole to have the same complication with propylthiouracil, once agranulocytosis had resolved, both patients were treated with radioiodine to maintain euthyroidism. Carbimazole-induced agranulocytosis usually spontaneously resolves within 1 to 2 weeks of stopping the drug. The use of haemopoietic growth factors to stimulate the proliferation and differentiation of progenitor cells, accelerates neutrophil recovery, as in our first case discussed. We recognise that agranulocytosis from carbimazole is a rare, life-threatening complication. Instead of awaiting spontaneous recovery, the use of haemopoietic growth factors certainly seems a justifiable option, with a promise of a reduction in morbidity and mortality.
TL;DR: A case of ANCA-positive rapidly progressive glomerulonephritis caused by propylthiouracil administration is reported, and renal function was improved by discontinuation of the drug and initiation of steroid therapy.
Abstract: Propylthiouracil, which is used as an antithyroid drug, is associated with many side effects. Vasculitis is a rare complication of this drug. Recently, antineutrophil cytoplasmic antibodies (ANCA) have been described in association with vasculitic disorders, including rapidly progressive glomerulo-nephritis. We report a case of ANCA-positive rapidly progressive glomerulonephritis caused by propylthiouracil administration. Although renal function was improved by discontinuation of the drug and initiation of steroid therapy, assay results for ANCA to myeloperoxidase remained positive throughout the clinical period.
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TL;DR: Pregnant women with overt and subclinical hypothyroidism should be treated using L-Thyroxine with the bTSH between 1 and 2 mU/l, most studies show, that both methimazole (MI) and propylthiouracil (PTU) can be used in pregnancy.
Abstract: Therapy of thyroid dysfunction needs a close cooperation between endocrinologist and gynecologist. In addition to a number of metabolic changes during pregnancy, the diaplacentar transfer of different substances (thionamides, antibodies) has to be considered. Pregnant women with overt and subclinical hypothyroidism should be treated using L-Thyroxine with the bTSH between 1 and 2 mU/l. Many of the women need an increase of the L-Thyroxine dose during pregnancy. Overt hyperthyroidism (mostly due to Graves' disease) has to be treated immediately after diagnosis using thionamides. Because thionamides cross the placenta, the dose should be as low as possible with the fT4 in upper level and bTSH in the lower level of normal range. Most studies show, that both methimazole (MI) and propylthiouracil (PTU) can be used in pregnancy. Although PTU is preferred especially in the USA, an advantage of PTU over MI is not proven. Surgery is necessary in only few cases of hyperthyroidism during pregnancy with the optimal time for surgery during the second trimester. In case of subclinical hyperthyroidism and HCG induced hyperthyroidism several controls of thyroid function should be performed to decide whether treatment is necessary.
TL;DR: It is concluded that thyroid hormone status alone does not regulate LRAT, nor does thyroid status affect the ability of RA to induce hepatic LRAT in retinoid-deficient animals, however, in retInoid-sufficiency, repeated treatment with T3 may reduce the hepatic esterification of retinol by LRAT.
Abstract: The activity of the enzyme lecithin; retinol acyltransferase (LRAT) is extremely low in the liver of vitamin A-deficient rats, but is rapidly induced after administration of retinoic acid (RA). The nuclear receptors for RA are closely related to the receptors for thyroid hormone, and molecular cross-talk between these receptors has been observed in vitro and in cultured cells. Therefore we have examined whether retinoid status and thyroid hormone status interact in the regulation of hepatic LRAT activity in vivo. Vitamin A-deficient male Lewis rats, either euthyroid or made hypothyroid by treatment with propylthiouracil, were treated once or three times with 20 μg of all-trans-RA, 10 μg/100 gm body weight of triiodothyronine (T3), or both hormones. Hepatic LRAT activity, which was negligible in all retinoid-deficient rats, was induced by RA (P < 0.0001) regardless of the animal's thyroid hormone status. T3 by itself had no ability to induce hepatic LRAT activity (P = 0.42), nor did co-administration of T3 with RA increase or decrease the response to RA (P = 0.13). In retinoid-sufficient rats, hypothyroidism did not alter hepatic LRAT activity; however, LRAT activity was reduced by half (P < 0.05) after three treatments with T3. Therefore we conclude that thyroid hormone status alone does not regulate LRAT, nor does thyroid status affect the ability of RA to induce hepatic LRAT in retinoid-deficient animals. However, in retinoid-sufficiency, repeated treatment with T3 may reduce the hepatic esterification of retinol by LRAT.