Showing papers on "Propylthiouracil published in 1987"
TL;DR: The administration of propylthiouracil can reduce mortality due to alcoholic liver disease and no clinically important side effects were observed at the dose used.
Abstract: Propylthiouracil has been shown experimentally to protect against alcohol-induced hepatocellular necrosis in hypoxic conditions. An earlier, short-term study of patients with alcoholism and liver disease indicated clinical improvement with propylthiouracil, but the effect on mortality could not be assessed. In the present study, we investigated the effect of propylthiouracil on mortality in patients with alcoholic liver disease in a long-term, double-blind, randomized clinical trial involving 310 compliant patients who received propylthiouracil (n = 157) or placebo (n = 153) for a maximum of two years. There were no differences between the two groups in demographic and clinical characteristics and biopsy-confirmed diagnoses at randomization, or in daily urinary alcohol levels during the study. The cumulative dropout rate over two years was not significantly different (propylthiouracil group, 0.68; placebo group, 0.60). The group receiving propylthiouracil (300 mg per day) had a cumulative mortality rate half that in the group receiving placebo (0.13 vs. 0.25 [P less than 0.05] in the total sample, and 0.25 vs. 0.55 [P less than 0.03] in a subgroup of severely ill patients [propylthiouracil group, n = 56; placebo group, n = 41]). Proportional-hazards stepwise regression analyses indicated that only propylthiouracil treatment, prothrombin time, hemoglobin levels, and mean daily urinary alcohol levels significantly affected mortality. The hazards ratio for the complete group indicated that mortality in the propylthiouracil group was 0.38 (95 percent confidence interval, 0.20 to 0.83) that of the placebo group. Protection by propylthiouracil was not observed in patients with high morning urinary alcohol levels. No clinically important side effects of propylthiouracil were observed at the dose used. We conclude that the administration of propylthiouracil can reduce mortality due to alcoholic liver disease.
168 citations
TL;DR: Results indicate that in the patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.
Abstract: The effects of methylmercaptoimidazole (MMI) and propylthiouracil (PTU) were compared in patients with Graves' hyperthyroidism. Firstly, the duration of action of the drugs was studied by the perchlorate discharge test, which was performed 2, 12, or 24 h after administering a single dose of 15 mg MMI or 300 mg PTU. After 2 h, the 9 MMI-treated patients who were tested had marked discharge (mean +/- SD, 65.0 +/- 15.8%), as did the 6 patients treated with PTU (57.6 +/- 26.6%). The mean values for the percent discharge 12 and 24 h after drug administration were 34.9 +/- 31.9% (4 patients) and 36.5 +/- 26.9% (69 patients), respectively, in the MMI group and 19.1 +/- 11.7% (11 patients) and 8.6 +/- 10.5% (7 patients) in the PTU group, indicating that the effect of MMI lasted longer. Secondly, the clinical effects of long term administration of the drugs were compared in a different group of patients with Graves' hyperthyroidism. Within 5 weeks after the onset of treatment, 34 (52%) of 66 patients treated with MMI (10 mg, 3 times daily) were euthyroid, while only 1 of 17 patients treated with PTU (100 mg, 3 times daily) was euthyroid. The average time required to achieve euthyroidism, namely normal serum T3 and T4 levels, was significantly shorter in the MMI group [6.7 +/- 4.6 (+/-SD) weeks] than in the PTU group (16.8 +/- 13.7). In spite of the well known effect of PTU on the extrathyroidal conversion of iodothyronines, the serum T3 level normalized much faster with MMI than with PTU. These results indicate that in our patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.
70 citations
TL;DR: A primordial role for thyroid hormones is suggested in directly regulating the appearance of myosin and fiber adult types and in modulating directly or indirectly the disappearance of the neonatal types.
65 citations
TL;DR: The effects of dietary cholesterol and hypothyroidism on the mRNA levels of rat apolipoproteins A-I, A-IV, and E were measured in extracts of rat liver and rat intestine by hybridization to specific cDNA and imply a role for thyroid hormones in regulating the RNA levels for these apoliproteins in rat liver.
63 citations
TL;DR: It is concluded that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.
Abstract: Goitre growth was investigated in rats receiving a low iodine diet (less than 0.1 microgram iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/1 T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 microgram T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 micrograms KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was highly significant correlation between goitre weight and TSH serum level (r = 0.93, P less than 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 micrograms KI/day (95 +/- 18 micrograms DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 +/- 21 micrograms DNA/gland) and under 0.5 microgram KI/day (161 +/- 19 micrograms DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.
57 citations
Journal Article•
TL;DR: Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described, and the clinical evidence suggests that an immunologic mechanism is involved, do not represent a true drug-induced lupus syndrome.
Abstract: Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described A review of the literature revealed 53 similar cases over a 35-year period Rash, fever, arthralgias and granulocytopenia were the most common manifestations Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal The clinical evidence suggests that an immunologic mechanism is involved A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus Thus, the reactions do not represent a true drug-induced lupus syndrome Current hypotheses and experimental data regarding the cause of the reactions are reviewed No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy Cross-reactivity between the two antithyroid drugs can be expected Except for minor symptoms (eg, mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful
54 citations
TL;DR: Propylthiouracil is the drug of choice in this situation, since it does not cross membranes readily, and milk concentrations are therefore quite low, however, methimazole in low dosages might be used if the infant's thyroid status was monitored at frequent intervals.
50 citations
TL;DR: Thyroxine 5'-deiodinase activity was studied in male rat Harderian gland homogenates and exhibited a nyctohemeral rhythmicity with a maximal activity at 03.00 h but this increase is totally prevented by the in vivo iopanoic acid treatment.
48 citations
TL;DR: It is concluded that interspecies variations in ventricular electrophysiological properties can be correlated with the thyroid state, which may be an important determinant of these properties.
Abstract: Whereas action potential (AP) duration, area, and repolarization vary considerably, ventricular AP characteristics such as resting membrane potential, AP amplitude, and maximal upstroke velocity of phase 0 depolarization appear similar in a variety of mammalian species As it has been shown that modifications of the thyroid state are associated with alterations in ventricular electrophysiological properties, we hypothesized that some variations in transmembrane potentials among mammalian species result in part from differences in the individual thyroid states To test this hypothesis, we used standard microelectrode techniques to study ventricular APs in the dog, mole-rat, guinea pig, rat, mouse, and shrew, which encompass a wide range of thyroid states In these species O2 consumption ranges from 038 (in the shrew) to 405 ml O2 X g-1 X h-1 (in the dog) We found that resting membrane potential and AP amplitude, duration, and area were inversely correlated with O2 consumption The correlation coefficients between these parameters with O2 consumption were -092, -078, -091, and -092, respectively We further tested the hypothesis in guinea pigs in which we modified the thyroid state in opposite directions by thyroxine administration and by propylthiouracil treatment In the hypothyroid myocardium, AP duration (cycle length = 2,000 ms) markedly increased (P less than 0001), whereas in the hyperthyroid myocardium, resting membrane potential and AP amplitude (P less than 001) and duration (P less than 0001) decreased We conclude that interspecies variations in ventricular electrophysiological properties can be correlated with the thyroid state, which may be an important determinant of these properties
44 citations
TL;DR: It was concluded that physiological levels of thyroid hormones are needed to maintain normal weights of thymus and spleen and a normal level of circulating lymphocytes and lower than physiological levels might be sufficient to maintainnormal cell-mediated immunity.
Abstract: The objective of this experiment was to examine the relationship between circulating triiodothyronine (T3), thryoxine (T4) and cell-mediated immunity in immature male chickens. Three week old Single Comb White Leghorn male chicks were used as the experimental animals. In order to produce a wide range of circulating thyroid hormone concentrations, birds were divided into groups and received one of nine treatments including surgical thyroidectomy; 0.1% propylthiouracil (PTU) in the feed; 1 ppm T3 and 10 ppm T4 in the feed. The graft versus host (GvH) response and response to phytohemagglutinin (PHA) were measured at 6 weeks of age. Total and differential white blood cells were counted. Birds were bled, weighed, sacrificed, and the lymphoid organs were removed and weighed. Concentrations of T3 and T4 were measured in the birds from all treatment groups. There were positive correlations between thyroid hormones, mainly T3, and weights of thymus and spleen. T4 but not T3 was positively correlated with number of circulating lymphocytes. There were no significant correlations between circulating T3 and T4 and either PHA or GvH responses. It was concluded that physiological levels of thyroid hormones are needed to maintain normal weights of thymus and spleen and a normal level of circulating lymphocytes. Furthermore, we conclude
40 citations
TL;DR: It is demonstrated that in the male rat reproductive system the levels of TRH and its immediate biosynthetic precursor, TRH-Gly, are regulated by thyroid hormones.
Abstract: Thyrotrophin-releasing hormone (TRH) occurs in high concentrations in the rat ventral prostate and its concentrations is regulated in a positive dose-response manner by testosterone in castrated rats. alpha-Amidation of the tetrapeptide precursor, TRH-Gly, is a rate-limiting step in TRH biosynthesis. To investigate further the hormonal regulation of TRH biosynthesis in prostatic tissue, Sprague-Dawley rats of approximately 250 g were injected s.c. with either physiological saline or 3 mg propylthiouracil (PTU) daily for 5 days. The reproductive tissues were boiled in acetic acid (l mol/l), dried and extracted with methanol. The methanol extracts were measured for TRH immunoreactivity (TRH-IR) and TRH-Gly-IR by radioimmunoassay. Hypothyroidism induced by PTU significantly increased TRH-IR and TRH-Gly-IR levels in prostate and testis and reduced these levels in epididymis but did not affect the serum concentrations of testosterone compared with those of controls. Corresponding changes in TRH and TRH-Gly in the rat prostate were established by high-pressure liquid chromatography. To control for possible pharmacological effects of PTU on TRH biosynthesis, additional experiments were carried out on castrated rats receiving testosterone replacement and treatment with PTU plus methimazole. Treatment with thyroxine (T4) significantly reduced the increase in prostatic TRH levels due to hypothyroidism, despite the drug-induced blockade of the conversion of T4 to tri-iodothyronine. These effects parallel similar observations made in rat spinal cord and pancreas. This study demonstrates that in the male rat reproductive system the levels of TRH and its immediate biosynthetic precursor, TRH-Gly, are regulated by thyroid hormones.
Journal Article•
TL;DR: A fatal case of acute submassive hepatic necrosis occurring in a 42-yr-old black woman treated for hyperthyroidism with propylthiouracil for 1 yr is presented.
TL;DR: T3S is an important intermediate in the in vivo metabolism of T3 in rats and accumulates in plasma if type I deiodination is inhibited and is examined in rats after intravenous administration of radiolabeled T3 or T3S.
Abstract: Triiodothyronine sulfate (T3S) is rapidly deiodinated by the propylthiouracil (PTU)-sensitive type I deiodinase. Here we examined the effects of PTU on plasma T3S levels in rats after intravenous administration of radiolabeled T3 or T3S. Sephadex LH-20 chromatography and high-performance liquid chromatography were used to quantify conjugated and nonconjugated iodothyronines, and iodide was measured as the TCA-soluble radioactivity. In control rats, radioiodide was the main metabolite of both T3 and T3S. Plasma T3S was cleared more rapidly than plasma T3 despite increased binding to plasma proteins. PTU reduced plasma iodide levels by 66 and 78% after T3 and T3S, respectively, and decreased plasma clearance of T3S by 81%. However, PTU had no effect on plasma T3 clearance but increased plasma T3S from injected T3 4.2 times. Biliary excretion of injected T3S was less than 20% in normal rats, in contrast to 70% within 4 h in PTU-treated rats. In conclusion, T3S is an important intermediate in the in vivo metabolism of T3 in rats and accumulates in plasma if type I deiodination is inhibited.
TL;DR: Graves disease with ophthalmopathy was diagnosed in a 37-year-old woman and treatment consisted of propranolol, 20 mg three times a day, propylthiouracil, 100 mg three once a day.
Abstract: Excerpt To the editor: Graves disease with ophthalmopathy was diagnosed in a 37-year-old woman. Treatment consisted of propranolol, 20 mg three times a day, propylthiouracil, 100 mg three times a d...
TL;DR: The hypothesis that capillary growth during thyroid enlargement occurs, at least in part, as a result of a parenchymal-stromal (epithelial-mesenchymal) paracrine interaction mediated by specific endotheliotropic (angiogenic) factors released by follicular epithelial cells and distinct from T3, T4, and thyroglobulin is supported.
Abstract: Thyroid enlargement in response to chronic hypersecretion of TSH reflects the coordinated growth of both parenchyma and stroma. Because Wollman et al. observed in propylthiouracil-fed rats that enlargement and remodeling of thyroid capillaries were strictly localized around follicles, they hypothesized that growth of perifollicular blood vessels is stimulated by angiogenic factors secreted by neighboring follicular epithelial cells. In support of this hypothesis, we report that media conditioned by rat thyroid cells were very active in an in uitro angiogenesis bioassay that measures stimulation of endothelial cell migration through chemotaxis membranes in microwell Boyden chamber assemblies. Primary cultures of thyroid cells from collagenase-dispersed glands from male or female Holtzman rats fed 0.01% propylthiouracil in the drinking water released activity that produced up to 5-fold increases in endothelial cell migration rates relative to those in identical unconditioned medium. Thyroid-derived activity...
TL;DR: It was found that the triiodothyronine level took significantly longer than the thyroxine (T4) level to return to normal, and treatment may have been stopped prematurely in some patients, causing the relapse rate to be falsely high.
Abstract: • We treated 69 hyperthyroid children with propylthiouracil, of whom 53 remained under surveillance. Of these children, 34 (64%) had an Initial remission, but relapses were frequent (47%). At this writing, 24 patients (45%) were in remission, with a mean duration of remission of 55 months (range, ten to 132 months). We found that the triiodothyronine level took significantly longer than the thyroxine (T 4 ) level to return to normal. Thus, based on the T 4 level alone, treatment may have been stopped prematurely in some patients, causing the relapse rate to be falsely high. The response to therapy did not depend on the size of the goiter nor on the Initial levels of T 4 or triiodothyronine. Six patients had adverse reactions, which were serious in two patients. ( AJDC 1987;141:1084-1086)
TL;DR: It is concluded that hyperthyroidism and hypothyroidism in man are not associated with significantly altered plasma AP concentrations and the higher plasma AP levels in T4-treated rats may reflect the relatively shorter duration or greater severity of thyroid dysfunction or thyroid hormone-induced myocardial hypertrophy in the animals.
Abstract: Atriopeptin (AP) is a polypeptide produced by atrial myocytes that is capable of inducing diuresis, natriuresis, and vasodilatation. Because thyroid dysfunction is known to be associated with alterations in both renal function and vasomotor control, we investigate the possible effects of varying thyroid function on AP in humans and rats. Plasma AP concentrations were determined in hyperthyroid and hypothyroid patients and normal subjects. Plasma AP was also measured in some patients after the iv infusion of 1 L 150 mmol/L NaCl and after treatment of hyperthyroidism or hypothyroidism. Plasma and atrial AP concentrations were measured in hyperthyroid, euthyroid, and hypothyroid rats. Plasma AP concentrations did not differ in the hyperthyroid (n = 22), euthyroid (n = 45), and hypothyroid (n = 16) subjects [47.1 ± 18.2 (mean ± sd), 45.1 ± 28.9, and 42.4 ± 20.0 pg/mL, respectively]. After NaCl infusion, mean plasma AP concentrations did not increase significantly in any of the three groups. Treatment of hyper...
TL;DR: Thyroid hormones may be involved in control of thyroidal function and body growth and pigmentary changes and Hypo-osmoregulatory competence is not further stimulated by exogenous T3 and PTU does not block T4 synthesis but may block T3, action by interfering with nuclear T3 binding.
Abstract: Yearling coho salmon (Oncorhynchus kisutch) were fed diets containing triiodothyronine (T3; 4 or 12gmg), propylthiouracil (PTU; 1.5 or 6.0 mg/g), or both T3 (12μg/g) and PTU (1.5 mg/g) from January 10 to May 29. Plasma T4 and T3, concentrations were maintained within normal physiological limits in all groups of treated fish. Increases in plasma thyroxine (T4) occurred in late April in groups receiving the high dose of T3 or PTU, or the combination of T3, and PTU. Peaks of plasma T4 occurred in May in the other groups. Thyroid follicle epithelial cell height was increased in the groups in the following order: highest; PTU (6.0 mg/g), PTU (1.5 mg/g), PTU + T3, control, T3 (4gmg/g), T3 (12μg/g); lowest. In March specific binding of T3 by liver nuclei was not affected by treatment with T3 (12μg/g) but was decreased 30% by treatment with PTU (6.0μg/g). Body growth, food conversion efficiency, and pigmentary changes were increased by T3 (12μg/g), decreased dose-dependently by PTU, and unaffected by the other dietary treatments. All treatments altered body proximate composition. Food consumption and the ability to osmoregulate in seawater were decreased in fish fed 6.0 mg/g PTU, but were unaffected by the other dietary treatments. These results suggest that during smoltification: 1) Thyroid hormones may be involved in control of thyroidal function and body growth and pigmentary changes, 2) Hypo-osmoregulatory competence is not further stimulated by exogenous T3 and 3) PTU does not block T4 synthesis but may block T3, action by interfering with nuclear T3 binding.
TL;DR: A perchlorate discharge test was developed for rats to detect changes in the thyroidal iodide accumulation and organification mechanisms and significantly reduced the thyroid: blood 125I ratio in propylthiouracil-treated rats but had no effect in those pretreated with SK&F 93479, indicating an iodide organification block in the former.
TL;DR: Using a monoclonal antibody (mabN210) that selectively recognizes an epitope associated with the 210-kDa neurofilament subunit, the relationship between thyroid hormone levels and basket cell maturation is explored and suggests either abnormal compensatory sprouting of axon collaterals by the remaining basket cells or the occurrence of competition between basket cell axons for a limited number of Purkinje cell targets followed by the elimination of the excess collateral.
TL;DR: The present study shows that the reversal of depressive-like behavior in rats was markedly attenuated in hypothyroid rats, which supports the notion of intricate thyroid/CNS interactions in the mechanisms of action of antidepressant drugs.
Abstract: Several investigations have suggested that a special relationship exists between thyroid function and affective disorders and/or therapeutic response to antidepressants. The present study shows that the reversal by clomipramine, desipramine, imipramine and nialamide of depressive-like behavior in rats (escape deficits produced by previous exposure to uncontrollable stress) was markedly attenuated in hypothyroid rats (propylthiouracil, 0.05% in the drinking water). Conversely, the effect of these same antidepressants was significantly hastened in euthyroid rats given daily triiodothyronine. This supports the notion of intricate thyroid/CNS interactions in the mechanisms of action of antidepressant drugs.
TL;DR: Thyroid epithelial cell kinetics were investigated in rats when a normal iodine diet was re-established after a long period of iodine deficiency supplemented with propylthiouracil (0.15%) for the last 2 months.
Abstract: Thyroid epithelial cell kinetics were investigated in rats when a normal iodine diet was re-established after a long period of iodine deficiency supplemented with propylthiouracil (0.15%) for the last 2 months. In the first (prelabelling) experiment, all rats were labelled with a single injection of [3H]thymidine 2 days before iodine refeeding in order to follow the fate of the prelabelled cells. In the second experiment, the pulse-labelling index at the time of killing was measured; for this purpose the rats received [3H]thymidine 1 h before death. In these two experiments autoradiography was performed on histological sections. Thyroids were excised on day 0 and then at various intervals up to day 73 of iodine refeeding. Plasma tri-iodothyronine (T3) and thyroxine (T4) were very low until day 4 and then increased to reach control values on day 30. Thyroid concentration of iodide rose to 20 times the value on day 0, remained at this high level until day 2, and then diminished on day 4 to reach the control value on day 16. Plasma TSH concentrations were very high in iodine-deficient rats and did not vary significantly until day 8, when they fell rapidly to reach the control value on day 30. Thyroid weight, raised on day 0, decreased relatively quickly until day 4, then more slowly until day 30. Total thyroid epithelial cell number, high on day 0 (30.7 x 10(6) cells) was constant until day 16, then decreased until day 30 at which time a plateau was reached.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The contention that the alteration of the BSP retention observed in hyperthyroidism could be due to a decreased availability of hepatic glutathione for conjugation is supported.
Abstract: 1. Sulphobromophthalein (BSP) retention and liver glutathione levels were studied in uncomplicated hyperthyroid patients. 2. BSP retention was increased in 52.5% of the subjects at admission (n = 40) and in 28% of the cases after 3 months of propylthiouracil treatment (300-400 mg/day) (n = 25). 3. Hepatic levels of glutathione were measured in six patients and significant inversed power correlation with BSP retention was observed (r = 0.968, P less than 0.001). 4. These data support the contention that the alteration of the BSP retention observed in hyperthyroidism could be due to a decreased availability of hepatic glutathione for conjugation.
TL;DR: A case of a 29-year-old man with hyperthyroidism associated with autoimmune hemolytic anemia and periodic paralysis is described, which may indicate that the hyperdynamic circulatory state secondary to hyperthy thyroidism plays an important role in the destruction of red blood cells which were coated by anti-red blood cell antibody.
Abstract: We describe a case of a 29-year-old man with hyperthyroidism associated with autoimmune hemolytic anemia and periodic paralysis. Euthyroidism, which was achieved by propylthiouracil, brought inhibition of hemolysis and amelioration of anemia in spite of continuously positive direct and indirect Coombs' tests. Neither adrenocortical steroid nor blood transfusion was administered. Since indirect monospecific Coombs' test was negative against anti-human complements serum, the membrane of red blood cells may be less fragile. This is one reason why hemolysis was inhibited by anti-hyperthyroid therapy only. This may indicate that the hyperdynamic circulatory state secondary to hyperthyroidism plays an important role in the destruction of red blood cells which were coated by anti-red blood cell antibody.
TL;DR: It is suggested that propylthiouracil can be administered in standard dosages to patients with thyrotoxicosis and renal failure and that the disappearance of the drug from the serum was normal after hemodialysis was completed.
Abstract: • The simultaneous occurrence of thyrotoxicosis and renal failure has rarely been reported in the literature, and data concerning appropriate antithyroid drug management in this circumstance are limited. We studied propylthiouracil pharmacokinetics in one such patient basally and while the patient was receiving hemodialysis. On a day when the patient was not receiving hemodialysis, propylthiouracil serum levels were high, but serum propylthiouracil half-life was not prolonged. During hemodialysis, serum propylthiouracil levels were normal, and the time to peak serum levels was delayed; the disappearance of the drug from the serum was normal after hemodialysis was completed. The amount of propylthiouracil that appeared in the dialysate was approximately 5% of the administered dose. These data suggest that propylthiouracil can be administered in standard dosages to patients with thyrotoxicosis and renal failure. ( Arch Intern Med 1987;147:785-786)
TL;DR: The results of this study show that while PTU causes a slight increase in pituitary gland weight and in PRL cell numbers, it inhibits estrogen-inducedPRL cell hyperplasia.
Abstract: The effects of diethylstilbestrol [(DES) CAS: 56-53-1] and propylthiouracil [(PTU) CAS: 51-52-5] on the pituitary glands of female weanling F344 rats were studied by immunohistochemistry and electron microscopy. Six weeks of PTU treatment resulted in a significant increase in pituitary gland weight and in the percentage of pituitary prolactin (PRL) cells. The percentage of thyroid-stimulating hormone (TSH) cells was slightly increased in PTU-treated rats. DES treatment produced a thirteenfold increase in pituitary gland weight and a significant increase in the percentage of PRL cells as well as in serum PRL levels. Combined PTU-DES treatment increased pituitary gland weight and serum PRL levels, but this increase was less than that observed with only DES treatment. A relative decrease in the percentage of TSH cells was seen after both DES and PTU-DES treatment. Ultrastructural immunohistochemical studies showed two types of PRL cells in the pituitary of all groups. Classical PRL cells with granule diameters of 150-800 nm were most abundant in DES-treated groups, whereas cells with smaller granules, 100-350 nm in diameter, were equally prominent in control groups and after PTU treatment. The results of this study show that while PTU causes a slight increase in pituitary gland weight and in PRL cell numbers, it inhibits estrogen-induced PRL cell hyperplasia. This model can be used to study the effects of PTU on pituitary PRL cell morphology and on the regulation of PRL cell hyperplasia.
TL;DR: In deeeloping PTU-treated rats, the abnormalities completely disappeared after therapy with increasing physiological doses of thyroxine; consequently they were directly related to thyroid deficiency and not to toxic effects of PTU.
TL;DR: Only severe hypothyroidism produced by surgical thyroidectomy was able to partially prevent the effects of TCDD on hepatic MDA content and glutathione peroxidase activity.
Abstract: Thyroid hormones have been implicated in the toxicity of 2,3,7,8-tetrachloro-dibenzo- p -dioxin (TCDD). Therefore, the effects of methimazole (MMI) and propylthiouracil (PTU) induced
TL;DR: In vitro study shows that 3,4-DHP, like MMI and PTU, inhibits iodination of human thyroglobulin and interferes with mitogenic activation of human lymphocytes, which makes it a potential antithyroid drug.
Abstract: 3,4-Dihydroxypyridine (3,4-DHP), a goitrogenic derivative of the plant amino acid mimosine, has no SH-group, in contrast to conventional antithyroid agents such as methimazole (MMI) and propylthiouracil (PTU). The current in vitro study shows that 3,4-DHP, like MMI and PTU, inhibits iodination of human thyroglobulin and interferes with mitogenic activation of human lymphocytes. This, together with a very low murine bone marrow toxicity, probably related to the absence of an SH-group, makes 3,4-DHP a potential antithyroid drug.
TL;DR: It is suggested that PTU impairs thyroidal uptake of iodide, that endogenous TSH stimulates release from the thyroid of inorganic iodide as well as of thyroid hormones, and that in organic iodide released by the thyroid has a much shorter biological half-life than hormone-bound iodine.
Abstract: The kinetics of free and hormone bound blood iodine after stimulation with endogenous thyroid stimulating hormone (TSH) are not satisfactorily characterized We studied these kinetics in mice injected with 125I and thyroxine In control mice, the injected 125I is organified within the thyroid and incorporated into thyroid hormones, whereas in mice treated with the thyreostatic drug propylthiouracil (PTU), most 125I remains inorganic, since the thyroperoxidase activity is inhibited by PTU We found that during blockade of TSH secretion by means of thyroxine, blood 125I activity was significantly higher in PTU-treated animals than in controls, indicating that PTU impaired thyroidal uptake of 125I On the fourth day after the thyroxine load, the blockade of TSH secretion vanished This caused the blood 125I activity to increase markedly The increase of blood 125I was as high in PTU-treated animals as in controls After the peak, blood 125I was cleared according to first order kinetics, with a half-time of 072 days (= 173 hours) in PTU-treated animals and of 63 days in controls (P less than 0001) It is suggested (1) that PTU impairs thyroidal uptake of iodide, (2) that endogenous TSH stimulates release from the thyroid of inorganic iodide as well as of thyroid hormones, and (3) that inorganic iodide released by the thyroid has a much shorter biological half-life than hormone-bound iodine