Showing papers on "Propylthiouracil published in 2006"

Evaluation of the antithyroid, antioxidative and antihyperglycemic activity of scopoletin from Aegle marmelos leaves in hyperthyroid rats.

Abstract: Scopoletin (7-hydroxy-6-methoxy coumarin) was isolated from the leaves of Aegle marmelos and evaluated for its potential to regulate hyperthyroidism, lipid peroxidation and hyperglycemia in levo-thyroxine-induced hyperthyroid rats. Scopoletin (1.00 mg/kg, p.o.) administered daily for 7 days to levo-thyroxine-treated animals decreased the levels of serum thyroid hormones and glucose as well as hepatic glucose-6-phosphatase activity, demonstrating its potential to regulate hyperthyroidism and hyperglycemia. Scopoletin also inhibited hepatic lipid peroxidation and increased the activity of antioxidants, superoxide dismutase and catalase. Compared with the standard antithyroid drug, propylthiouracil, scopoletin exhibited a superior therapeutic activity, since unlike propylthiouracil, it also inhibited hepatic lipid peroxidation. These findings indicate that scopoletin has the potential to inhibit thyroid function and hyperglycemia without hepatotoxicity.

Dynamic nongenomic actions of thyroid hormone in the developing rat brain.

Abstract: Two well-characterized nongenomic actions of thyroid hormone in cultured brain tissues are: 1) regulation of type 2 iodothyronine 5'deiodinase (D2) activity and 2) regulation of actin polymerization. In particular, the latter is likely to have profound effects on neuronal migration in the developing brain. In this study, we determined whether these nongenomic actions also occurred in vivo during brain development. Neonatal hypothyroidism was induced by propylthiouracil given to pregnant dams beginning on d17 of gestation and continued throughout the neonatal period. On postnatal d 14, rats were injected with either cold or [(125)I]-labeled iodothyronines and killed sequentially after injection. In contrast to reports in the adult rat, all three iodothyronines readily and equally entered developing brain tissues. As expected, cerebrocortical D2 activity was markedly elevated in the hypothyroid brain and both reverse T(3) (rT(3)) and T(4) rapidly decreased D2 to euthyroid levels within 3 h. Furthermore, cerebellar G-actin content in the hypothyroid rat was approximately 5-fold higher than in the euthyroid rat. Again, both rT(3) and T(4) rapidly decreased the G-actin content by approximately 50%, with a reciprocal increase in F-actin content to euthyroid levels without altering total actin. Neither T(3) nor vehicle had any effect on D2 activity in the cortex or G- or F-actin content in the cerebellum. The thyroid hormone-dependent regulation of actin polymerization in the rat brain provides a mechanism by which this morphogenic hormone can influence neuronal migration independent of the need for altered gene transcription. Furthermore, these data suggest a prominent role for rT(3) during brain development.

Effects of the antithyroid agent propylthiouracil in a partial life cycle assay with zebrafish.

Abstract: Some ubiquitous pollutants of the aquatic environment, such as PCBs or other polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In a partial life cycle assay with zebrafish (Danio rerio), we studied the effects of the reference compound propylthiouracil (PTU) on reproduction, growth and development, histopathology of some target tissues, and plasma thyroid hormone levels. PTU induced a concentration-dependent increase of egg production with a concomitant decrease of mature oocyte size but had no effect on fertilization rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time, there was also a decreased scale thickness, suggesting inhibited metamorphosis, detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid follicles in a concentration-dependent way, in juveniles associated with hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults were associated with decreased circulating levels of the thyroid hormones T3 and T4. These observations indicate that disruption of the thyroid hormone system may affect the fitness of these aquatic organisms. The zebrafish model may contribute to the identification of thyroid hormone disrupting activity in water samples and also in the interpretation of histological observations in free-ranging fish species.

Pancytopenia in untreated patients with Graves' disease.

Abstract: Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this report, we describe four patients with Graves' disease who presented with pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400 mg/d) restored normal hematopoiesis in three of the patients. The remaining patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but had an increased peripheral blood count that almost reached normal values after radioiodinetherapy and standard immunosuppressive treatment with antithymocyte globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400 mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150 microg subcutaneous injection, 3 times per week). We conclude that: (1) a hematologic evaluation of all patients with Graves' disease should be performed before administering antithyroid drugs, (2) antithyroid drugs may be administered to patients with pancytopenia and bone marrow hypercellularity but a reevaluation of the bone marrow must be done if there is no recovery of the peripheral blood cell count when euthyroidism state is achieved, (3) standard immunosuppressive treatment of aplastic anemia caused by antithyroid drugs restores normal hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should be done, even though no related symptoms are found.

Effects of Soyasaponins on Lipid Peroxidation through the Secretion of Thyroid Hormones

Abstract: We investigated how soyasaponins (SS), which had been isolated from soybeans (Glycine max Merrill, seeds), influenced lipid peroxidation. The in vivo reduction in hepatic lipid peroxidation in mice intraperitoneally injected with total soyasaponins (TSS) was comparable to that which has been observed for alpha-tocopherol (VE). However, TSS and its five main constituent saponins (I, II, III, A1, and A2) had a much weaker in vitro inhibitory effect on lipid peroxidation induced by NADPH in mouse liver microsomes than VE. Therefore, we were not able to explain the in vivo effect of SS on lipid peroxidation level through direct antioxidative effects. We also demonstrated that TSS increased the levels of serum thyroid hormones. The effect of serum thyroid hormones on in vitro lipid peroxidation was much stronger than that observed for VE. Furthermore, the effects of TSS on levels of serum thyroid hormones and LPO were markedly decreased by propylthiouracil, an antithyroid drug. These results indicate that the effects of SS on lipid peroxidation levels appear to be mediated through the secretion of thyroid hormones.

Bioinorganic Chemistry in Thyroid Gland: Effect of Antithyroid Drugs on Peroxidase-Catalyzed Oxidation and Iodination Reactions

Abstract: Propylthiouracil (PTU) and methimazole (MMI) are the most commonly used antithyroid drugs. The available data suggest that these drugs may block the thyroid hormone synthesis by inhibiting the thyroid peroxidase (TPO) or diverting oxidized iodides away from thyroglobulin. It is also known that PTU inhibits the selenocysteine-containing enzyme ID-1 by reacting with the selenenyl iodide intermediate (E-SeI). In view of the current interest in antithyroid drugs, we have recently carried out biomimetic studies to understand the mechanism by which the antithyroid drugs inhibit the thyroid hormone synthesis and found that the replacement of sulfur with selenium in MMI leads to an interesting compound that may reversibly block the thyroid hormone synthesis. Our recent results on the inhibition of lactoperoxidase (LPO)-catalyzed oxidation and iodination reactions by antithyroid drugs are described.

Pharmacokinetics and pharmacotherapy of thionamides in pregnancy.

Abstract: Hyperthyroidism occurs in approximately 1 in every 1000 to 2000 pregnancies. Although the signs and symptoms of the disease are similar in the pregnant and nonpregnant patient, the complications of hyperthyroidism can have even more profound consequences for the mother and fetus during gestation. These include maternal heart failure, preeclampsia, miscarriage, and preterm labor; as well as fetal loss and low birth weight. Furthermore, thyroid function and laboratory testing for hyperthyroidism are altered in pregnancy. The gestational increase in thyroid size, increased thyroid-binding globulin levels, increased serum total T4 and total T3 levels, and decreased thyroid stimulating hormone levels often confuses the evaluation of the thyroid status in pregnancy. Worldwide, the thionamides-propylthiouracil, methimazole, and carbimazole-have been used in pregnancy for the treatment of hyperthyroidism. However, propylthiouracil has been the drug of choice in the United States because it is believed to have less potential to induce fetal/neonatal hypothyrodism, to cross the placenta and into breast milk to a lesser degree, and to be less teratogenic than methimazole or carbimazole. None of the above have been substantiated in more recent studies. The pharmacokinetics of the thionamides in the pregnant and nonpregnant states, as well as the pharmacotherapeutic recommendation for hyperthyroidism will be reviewed.

HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by modulating the ras-MAPK pathway

Abstract: The aim of this study was to evaluate in vivo the antiproliferative effect of an inhibitor of isoprenoids metabolism, lovastatin, in an experimental model of propylthiouracil-induced goiter. In thyroid cells, thyrotropin (TSH)-induced proliferation requires active isoprenoid synthesis, and the HMG-CoA reductase inhibitors have antiproliferative effects in vitro. Propylthiouracil treatment (PTU) of rats led to thyroid hypertrophy and hyperplasia by TSH-induced activation of the mitogen-activated protein kinase (MAPK) pathway. Immunohistochemistry showed an increased number of proliferating cell nuclear antigen (PCNA)-positive cells in the thyroid gland of PTU-treated rats. Moreover, the phosphorylation of ERK1 and ERK2 was increased in the extract from goiter tissue as compared with the thyroid tissue of untreated rats. To determine whether the inhibition of selected pro-survival pathways (i.e., p21ras-MAPK) was sufficient to affect goitrogenesis, thyroids from 12 PTU-treated rats were injected in vivo with an adenovirus transducing a dominant-negative ras gene (Rad-L61.S186) and another set of 12 rats were injected with a pharmacological inhibitor of MAPK (PD98059). Both Rad-L61.S186 and PD98059 were able to inhibit the PTU-induced goiter. It is interesting to note that lovastatin, when administered in drinking water, significantly prevented the thyroid gland enlargement. Therefore, lovastatin-treated thyroid glands were significantly smaller than those treated with PTU alone. In addition, the lovastatin-treated glands also showed a decreased expression of phosphorylated ERK1/2 and a number of PCNA-positive cells. Our data suggest that lovastatin is an efficient inhibitor of goitrogenesis and provide a rationale for innovative therapeutic strategies employing statins in the treatment of nodular goiter in humans.

Diffuse alveolar hemorrhage associated with antineutrophil cytoplasmic antibody levels in a pregnant woman taking propylthiouracil.

Abstract: Propylthiouracil (PTU) is known to be a potential cause of antineutrophil cytoplasmic antibody (ANCA) positive small vessel vasculitis, resulting in glomerulonephritis and diffuse alveolar hemorrhage (DAH). Herein, we describe a 25-year-old pregnant woman who developed a perinulcear ANCA (p-ANCA) and myeloperoxidase ANCA (MPO-ANCA) positive DAH during PTU therapy. The patient improved after corticosteroid therapy and discontinuation of the PTU. Methimazole was prescribed in spite of the risk of recurrence of DAH because of the pregnancy. The patient is currently free from pulmonary problems. Our case shows that the alternative agent, methimazole, can be used to treat hyperthyroidism in a pregnant patient with PTU associated DAH.

Influence of thyroxine and n-propylthiouracil on nephro-toxicity of inorganic arsenic in rat.

Abstract: The effect of hyper or hypoactive thyroid on the renal toxicity of arsenic trioxide has been studied in rats. It was observed that pre-treatment of rats with thyroxine stimulates arsenic excretion in urine. The anti-thyroid drug n-propylthiouracil (PTU), inhibits the accumulation of arsenic in renal tissue. Both treatments affect the renal pathology. Histopathological lesions are less severe in PTU and arsenic-treated rats in comparison to thyroxine and arsenic-treated rats. Ultrastructural studies support light microscopical observations. An adaptive response was noticed against arsenic in PTU pre-treated rats. We attribute this response to decreased glutathione-S-transferase (GSH) activity and increased GSH synthesis in the kidney. A relationship between thyroidal activity and arsenic toxicity is suggested by present observations.

Antineutrophil cytoplasmic antibody-positive cutaneous leukocytoclastic vasculitis associated with propylthiouracil therapy.

Abstract: Administration of propylthiouracil therapy has been associated with a hypersensitivity syndrome that typically manifests as vasculitis. 1 Most cases of propylthiouracil therapy-induced antineutrophil cytoplasmic antibody (ANCA) positivity react to perinuclear ANCA (p-ANCA). 1 We describe a patient who presented with cutaneous manifestations of propylthiouracil therapy hypersensitivity vasculitis with ANCA positivity.

Effect of propylthiouracil on the level of Schiff's bases in tissues of rats on diet with different doses of potassium iodide.

Abstract: Objectives Iodide administration to animals, living in iodine-deficient areas, can induce oxidative processes in the thyroid gland and increase concentration of lipid peroxidation (LPO). Propylthiouracil (PTU)--a well-known antithyroid drug--may also act as an antioxidant. There are some reports, which consider the protective ability of this drug against LPO. The goal of the study was to evaluate oxidative processes and the protective role of PTU in three rat organs during treatment with pharmacological doses of iodide. Material and methods Schiff's bases (SB) concentrations (a parameter of oxidative stress) were measured in liver, lung and kidney homogenates of male Wistar rats. For 2 weeks the animals received iodides in their diet in the following concentrations: Group 1--Controls (standard diet, approx. 0.7 mg of potassium iodide per kg; KI/kg); Group 2--diet containing 0.25 mg KI/kg; Group 3--diet with 4.0 mg KI/kg; Group 4--diet with 8.0 mg KI/kg. Group 5--standard diet with 0.1% of PTU in drinking water for two weeks. Subsequent tree groups (6-8) received KI in their diet in doses as above, respectively, together with PTU. Results We noted increased SB levels in the lungs and in the liver, compared to those observed in the control group. We also found decreased SB concentrations in liver and lung homogenates after the administration of PTU but, unexpectedly, the level of SB increased in kidney homogenates of all the groups. Conclusions The results of this study indicate that iodine is involved in oxidative processes in different organs and PTU protects against iodine-induced oxidative stress.

Comparison of enhancing effects of different goitrogen treatments in combination with β‐estradiol‐3‐benzoate for establishing a rat two‐stage thyroid carcinogenesis model to detect modifying effects of estrogenic compounds

Abstract: With the aim of establishing a sensitive model for the detection of weak effects of endocrine disrupting chemicals on thyroid carcinogenesis, thyrotrophic and tumor-promoting influences of beta-estradiol-3-benzoate (EB) in combination with representative antithyroidal agents (goitrogens), sulfadimethoxine (SDM), propylthiouracil (PTU), potassium perchlorate (PPC), iopanoic acid (IOP) or an iodine-deficient diet were evaluated in a short-term (7-day) experiment without N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation and a long-term (30-week) experiment with DHPN initiation in ovariectomized F344 rats. In the short-term experiment, the most remarkable thyrotrophic effects were found in the PTU-treated group, followed by the SDM and PPC cases. EB treatment alone caused slight increases in thyroidal weights but no apparent morphological changes. Concomitant treatment with EB and antithyroidal agents enhanced the changes in thyroid weights, histopathological findings and/or serum thyroid hormone levels in the SDM (30 and 100 p.p.m), PTU (5 and 30 p.p.m) and PPC (100 p.p.m), IOP (30 and 100 mg/kg) or iodine-deficient diet groups. In the long-term experiment after DHPN initiation, EB alone slightly increased small numbers of animals with follicular hyperplasias, adenomas and adenocarcinomas. Simultaneous treatment with antithyroidal chemicals was associated with an increase in the incidences of focal hyperplasias, adenomas and/or adenocarcinomas. The enhancement was most remarkable with PTU (5 p.p.m), followed by PTU (2 p.p.m), SDM (100 p.p.m) and PPC (100 p.p.m). The results showed that EB has only a marginal promoting effect on DHPN-induced rat thyroid carcinogenesis and that antithyroidal chemicals, particularly PTU, are effective as co-promoting agents.

Propylthiouracil-induced hypersensitivity syndrome

Abstract: Propylthiouracil (PTU) is usually the first choice for the treatment of hyperthyroidism, but it has serious side effects such as hepatitis, cholestatic jaundice, splenomegaly and lupus-like syndrome, in addition to mild and common side effects like granulocytopenia, pruritus, urticaria and maculopapular or papular eruption. Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is another serious side effect. A 14-year-old female receiving PTU treatment for hyperthyroidism was referred to our clinic with fever, cough and dyspnea. The PTU dosage was first decreased but pericardial, dermal and joint involvement ascribed to PTU developed later and the drug was discontinued. ANCA-positive vasculitis due to PTU was considered when tests revealed an ANCA-positive state. We suggest that severe multisystemic vasculitis due to PTU should be considered during PTU usage.

Propylthiouracil-induced vasculitic oral ulcers with anti-neutrophil cytoplasmic antibody

Abstract: 1 Ellis CN, Krach KJ. Uses and complications of isotretinoin therapy. J Am Acad Dermatol 2001; 45: S150–S157. 2 De Raeve L, Willemsen M, De Coninck A, Roseeuw D. Paronychia and the formation of granulation tissue during isotretinoin therapy. Dermatologica 1986; 172: 278–280. 3 Önder M, Öztas MO, Öztas P. Isotretinoin-induced nail fragility and onycholysis. J Dermatol Treat 2001; 12: 115–116. 4 Zachariae H. Delayed wound healing and keloid formation following argon laser treatment or dermabrasion during isotretinoin treatment. Br J Dermatol 1988; 118: 703–706. 5 http://www.rocheusa.com/products/accutane/pi.pdf. (Last accessed: 17 October 2005). 6 Bigby M, Stern RS. Adverse reactions to isotretinoin. J Am Acad Dermatol 1988; 18: 543–552.

Antithyroid Drugs for the Treatment of Graves Disease A Randomized Clinical Trial

Abstract: Treatment of Graves disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least 6 months and the overall relapse rate is high. A few small prospective trials have considered methimazole (MMI) somewhat more effective and safer in lower doses than propylthiouracil (PTU), but the choice between the drugs has been a matter of personal preference. The aim of this clinical trial is to evaluate the effect of different ATD regimens on remission rates of GD and on the side effect profiles. The study included 55 previously untreated patients with GD who were randomized in 2 groups: 40 to 60 mg methimazole daily was prescribed to 30 patients and 200 to 300 mg propylthiouracil every 12 hours was prescribed to 25. The patients were treated for 12 months and followed for 12 to 38 months after drug withdrawal. Fifteen patients of 21 in the PTU group (71.4%) and 10 of 25 in the MMI group (40.0%) reached 1-year remission of GD (P 0.04), but there was no statistical difference between the drug regimes after adjusting for antithyroid- stimulating hormone receptor antibody (TRAb) levels. Among the 25 patients who reached 1-year remission, relapse occurred in one case at 18 months after drug withdrawal. All patients presented good compliance and only 2 patients developed minor side effects. During the treatment, both drug groups showed a significant fall in serum TRAb and thyroid peroxidase autoantibody titers, and the TRAb levels observed in the MMI group were consistently higher. There- fore, in our study, there were no significant differences between PTU and MMI groups in relation to remission rate, side effect profiles, and compliance rates. Furthermore, individuals with higher baseline antibody titers presented a lower probability of long term remission of GD.

Effects of propylthiouracil on testicular tissue in undescended testes of newborn rats.

Abstract: Aim: The most important goal in the treatment of cryptorchidism is to preserve the potential for fertility. This experimental study was performed to investigate the effect of propyl

Thyroid Hormone and Antithyroid Drugs

Abstract: Endogenous iodine-containing thyroid hormones L-thyroxine and L-triiodothyronine are produced by the thyroid gland, which exhibits pronounced metabolic control over practically every cell in the body using the two mentioned iodine-containing hormones. By controlling the rate of oxidative cellular processes, these hormones take part in regulation of growth and development of the organism, formation of bone marrow and bone tissue. They affect activity of the central nervous systems (CNS), cardiovascular system, gastrointestinal tract, metabolism of carbohydrates, fats, and proteins. Synthesis, storage, and release of thyroid hormones by the thyroid gland are primarily regulated by the thyrotropin hormone, while the iodides necessary for their synthesis are usually present in consumed foods. Diseases associated with thyroid glands are the result of either excess production of thyroid hormone (hyperthyroidism), or its insufficiency (hypothyroidism). This chapter focuses on drugs that are used for treating hyperthyroidism and hypothyroidism. Hypothyroidism is treated using thyroidin-dried thyroid, thyroglobulin and synthetic drugs such as synthetic drugs levothyroxine and lyothyronin, and lotrix. For treatment of hyperthyroidism, drugs are used that suppress production of thyrotropic hormones in the anterior lobe of the hypophysis (diiodotyrosine), in the thyroid gland (propylthiouracil, methylthiouracil, methimazole, and carbimazole), as well as drugs that destroy thyroid gland follicles (radioactive iodine).

Effect of abouthiouline, a novel drug with therapeutic potential as antithyroid, on some biochemical and hematologic parameters in mice and rats

Abstract: Abouthiouline (1-Cyclohexyl-3(3-quinolyl)-2-thiourea) is a novel compound with antithyroid activity. Abouthiouline (ABL) was designed based on structure-activity relationships (E-state indexes) aimed at reducing the antioxidant properties of the compound by modification of acyclic thiourylene moiety. Antioxidant effects of currently available treatments such as propylthiouracil (PTU), methimazole (MTM) are associated with an incidence of agranulocytosis and aplastic anemia. In the present study, the preclinical toxicology of ABL was determined in mice and rats and compared with two reference compounds, namely, propylthiouracil, methimazole. Following short-term administration (7 days) to mice, ABL had minimal effects on biochemical parameters, although significant reductions in both total protein and albumin were noted. Long-term studies (30 days) in rats revealed significant effects of Abouthiouline, propylthiouracil and methimazole on serum electrolyte and glucose levels. Abouthiouline had no detrimental effects on hematologic parameters. However, total WBC count (propylthiouracil) and neutrophil levels (propylthiouracil and methimazole) were significantly decreased among other treatment groups. The results of this investigation suggest that Abouthiouline is a promising new antithyroid therapy with a reduced risk of hematologic toxicity that is associated with PTU and MTM. Further studies are warranted to assess the safety and efficacy of Abouthiouline. אא אאאאאאאא

[Current problems in the treatment of Graves' disease in pregnancy and in lactation].

Abstract: In Graves' patients complicated by pregnancy, both maternal and fetal problems related to the disease can be reduced or avoided by controlling hyperthyroidism. However, optimal treatment for mothers may exert detrimental effects on fetuses. Methimazole may cause "methimazole embryopathy". Antithyroid drug doses that maintain mothers in euthyroid status are sometimes excessive fetuses. Furthermore, successful treatment with surgery or radioiodine occasionally may result in fetal hyperthyroidism due to TSH receptor antibody(TRAb). There are approaches to manage these problems. Propylthiouracil is chosen in treating Graves' disease in early pregnancy. In later pregnancy, maternal free thyroxine is maintained near or somewhat above normal. Ablative therapy is not recommended in women whose TRAb levels are extremely high from the standpoint of fetal thyroid state.

[Treatment with inorganic iodine for Graves' hyperthyroidism].

Abstract: Nowadays, patients with Graves' hyperthyroidism are initially treated with methimazole or propylthiouracil. Several serious adverse reactions like agranulocytosis are caused by these drugs. Inorganic iodine decreases serum thyroid hormone concentrations in patients with Graves' hyperthyroidism without adverse reaction, but this effect usually continues only a limited time. However, a virtually complete remission or longstanding euthyroid state may be obtained with inorganic iodine therapy alone in patients with mild Graves' disease, who show small thyroid volume and low TRAb titers. Inorganic iodine therapy may become one of the treatment methods in the patients with mild Graves' hyperthyroidism.

Clinical analysis of 64 cases with propylthiouracil-induced granulocytopenia

Abstract: [Objective] To clarify the onset,development,clinical manifestations and management of propylthiouracil(PTU)-induced granulocytopenia.[Methods] 64 outpatients with PTU-induced granulocytopenia,who had complete medical records and were encountered during the past two years,were statistically analyzed in terms of their clinical features and treatment.[Results] In most cases the granulocytopenia occurred between 2 to 8 weeks after the drug administration and was related to the dose of PTU.Clinically the majority of the patients developed dizziness and weakness.All the subjects continued to use PTU and simultaneously received leukogenic agents or subcutaneous injection with granulocyte colony-stimulating factor(G-CSF).As a result granulocytes were restored to the normal in all the cases and none progressed into agranulocytosis.[Conclusions] The initial dose for PTU is proposed not to exceed 300 mg per day.And the peripheral leucocytes should be closely monitored especially within 1 to 2 months after PTU treatment.Either oral leukogenic agents or injectile G-CSF is effective for the leucocytes normalization,thus preventing the occurrence of agranulocytosis.

The effect of propylthiouracil on function of phagocytic peripheral blood cells in persons with thyroid hyperfunction

Abstract: Introduction It is known that hyperthyroidism as well as thyrosuppressive therapy can influence the cells of immunological system. Objective To examine the function of phagocyte cells in persons with hyperthyroidism and to examine if propylthiouracil (PTU) influences this function. Method The study included 15 patients with hyperthyroidism and 10 healthy persons. The parameters of phagocytic activity of mononuclear and polymorphonuclear leucocytes were tested by method of ingestion of particles of inactivated yeast labeled with neutral-red. Results It was demonstrated that patients with hyperthyroidism, before the onset of therapy as well as 14 days after introduction of PTU, had decreased number of leucocytes (before PTU: 6.7 +/- 3.2 x 10(9)/l, after PTU: 6.1 +/- 2.0 x 10(9)/l and control: 8.0 +/- 1.6 x 10(9)/l; p=0.039), PMN leucocytes (before PTU: 3.9 +/- 2,4 x 10(9)/l, after PTU: 3.5 +/- 1.6 x 10(9)/l and control: 4.8 +/- 0.9 x 10(9)/l; p=0.037) and number of phagocyte PMN cells (before PTU: 0.9 +/- 0.9 x 10(9)/l, after PTU: 0.9 +/- 0.7 x 10(9)/l and control: 1.3 +/- 0.6 x 10(9)/l; p 0.05). The number of mononuclear leucocytes and parameters of phagocytic activity of mononuclear phagocytes in persons with hyperthyroidism did not change significantly in comparison with the control group. Conclusion Patients with hyperthyroidism had decreased number of leucocytes, PMN leucocytes and number of phagocyte PMN cells, and increased index of phagocytosis, while capacity of phagocytosis remained unchanged. The number and parameters of phagocytic activity of mononuclear leucocytes did not change. PTU therapy had no effect on the examined parameters.

Clinical characteristics of nineteen vasculitis patients associated with propylthiouracil-induced antineutrophil cytoplasmic antibody

Abstract: 分析19例丙基硫氧嘧啶(PTU)引起抗中性粒细胞胞浆抗体相关小血管炎患者的临床资料,其中17例患Graves病,18例服用PTU超过2年.多表现为多系统受累,78.9%肾受累,42.1%肺受累,关节痛、皮疹及发热也很常见.所有患者均停用了PTU,内脏受累较重的患者应用了免疫抑制治疗。