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Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.


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Journal ArticleDOI
TL;DR: How pregnancy changes the risk of developing Graves' disease, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD are described.
Abstract: Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.

30 citations

Journal ArticleDOI
TL;DR: These studies may be relevant to the practice of administering propylthiouracil, propranolol, and iopanoic acid to pregnant women and the effects of drugs and other compounds on human and rat PT4ase.
Abstract: Human and rat placental homogenates contain inner ring deiodinase activity (PT4ase) towards T4 and T3. This activity may decrease the transfer of T4 and T3 across the placenta and influence thyroid hormone disposal in the fetal circulation. Data are now presented on human PT4ase in subcellular fractions, the Km of human PT4ase, and the effects of drugs and other compounds on human and rat PT4ase. The specific activity (nanograms of rT3 produced per min/ mg protein) of each fraction of human placenta was as follows: nuclear, 0.07; mitochondrial, 0.15; lysosomal, 0.19; microsomal, 1.30; and cytosol, 0.01. The apparent Michaelis-Menton (Km) for PT4ase in human placental microsomes was 1.2 × 10-7 M. T3, 3,3′-diiodothyronine, iopanoic acid, iodoacetic acid, diamide, and propranolol all exhibited dose-dependent inhibition of human and rat PT4ase when tested in the presence of 10 mM dithiothreitol (DTT). Propylthiouracil did not inhibit PT4ase at 10 mM DTT, but when the DTT concentration was lowered to 0.25 mM, ...

30 citations

Journal ArticleDOI
TL;DR: The mere presence of electrodes in the hypothalamus without electrical stimulation had no significant effect on TSH secretion and histology of the thyroid, but caused adrenal hypertrophy and elevation of plasma corticosteroid levels in sham-stimulated rats.
Abstract: Electrical stimulation of various sites in the medial ventral hypothalami of adult female rats was done through chronically implanted electrodes in order to determine simultaneous effects on the pituitaryadrenal and thyroid systems. A series of stimulations (10 min daily, 4–9 days) delivered to preoptic, suprachiasmatic and anterior hypothalamic areas induced cytological activation of pars distalis basophils, markedly reduced pituitary thyrotrophin (TSH) stores, increased plasma TSH concentrations 4- to 5-fold, and resulted in histological stimulation of the thyroid gland. Comparable excitation of the posterior median eminence and arcuate nuclear regions of the tuberal hypothalamus produced effects of similar magnitude. The mere presence of electrodes in the hypothalamus without electrical stimulation had no significant effect on TSH secretion and histology of the thyroid, but caused adrenal hypertrophy and elevation of plasma corticosteroid levels in sham-stimulated rats. Excitation of the rostral or cau...

30 citations

Journal ArticleDOI
TL;DR: Agranulocytosis developed in a patient who was receiving propylthiouracil and Cytotoxicity was shown to be mediated by a complement-dependent IgM antibody.
Abstract: Agranulocytosis developed in a patient who was receiving propylthiouracil. Using a microgranulocytotoxicity assay, serum taken from the patient was shown to be strongly granulocytotoxic when tested against the patients granulocytes and those obtained from two of eight normal subjects. Tests for granulocyte agglutinins and for lymphocytotoxicity were negative. Granulocytotoxic activity decreased as the patient's peripheral granulocyte count recovered. Cytotoxicity was shown to be mediated by a complement-dependent IgM antibody.

30 citations

Journal ArticleDOI
TL;DR: It is shown that the growth inhibitory effect was restricted to delta-iodolactones when delta-IL was compared to 6-iodo-8,11,14,17-eicosatetraenoic delta-lactone and 5-iodi-7,10,13,16,19-docosapentaenoic gamma-lactsone, suggesting that deiodination and a different iodide action is unlikely.
Abstract: delta-Iodolactone (6-iodo-8,11,14-eicosatrienoic delta-lactone, delta-IL), an iodinated derivative of arachidonic acid, has been shown to be synthesized in thyroid tissue and to inhibit thyroid cell proliferation. It is discussed as a potential mediator of the autoregulatory pathway of iodide in cyclic adenosine-3',5'-monophosphate (cAMP)- and thyrotropin (TSH)-independent growth. We therefore further localized the action of iodide and of delta-IL in isolated porcine thyroid follicles. Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) dose dependently stimulated thyroid cell proliferation, which could be inhibited by staurosporin (0.1-10 nmol/l). Iodide (2.5-40 mumol/l) as well as delta-IL (0.5-2 mumol/l) also dose dependently inhibited EGF- and TPA-induced proliferation. As the calcium ionophor A23187 (100 pmol/l) completely abolished the inhibitory effects of iodide and of delta-IL, this may indicate a mechanism of delta-IL at or proximal to the calcium-dependent activation of protein kinase C. The growth inhibitory effect was restricted to delta-iodolactones when delta-IL was compared to 6-iodo-8,11,14,17-eicosatetraenoic delta-lactone and 5-iodo-7,10,13,16,19-docosapentaenoic gamma-lactone. It could not be prevented with propylthiouracil and therefore deiodination and a different iodide action is unlikely. Inositol-1,4,5-trisphosphate (IP3) and cAMP were measured in extracts from isolated porcine thyroid follicles stimulated with EGF (10 ng/ml) or TSH (1.0 U/l) revealing comparable kinetics in IP3 generation, while cAMP formation was only stimulated by TSH. delta-Iodolactone (2 mumol/l) only decreased EGF-induced IP3 formation, whereas TSH-induced IP3 and cAMP formation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

30 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202342
202276
202138
202032
201934
201829