Antithyroid drugs-induced antineutrophil cytoplasmic antibody-associated vasculitis in children: report of three cases and literature review / 中华肾脏病杂志

Objective:To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs.Methods:The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed.Results:(1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions:PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.

Vasculitis ANCA positiva inducida por Propiltiouracilo. Reporte de caso

La vasculitis asociada a propiltiouracilo (PTU) y ANCA es una enfermedad rara con una incidencia de 0,47-0,71 casos por cada 10 000 pacientes. Afecta principalmente a los vasos de menor calibre. Piel, riñones y pulmones son los más afectados. El diagnóstico requiere alta sospecha clínica y se apoya en estudios histopatológicos de las lesiones en piel y serología positiva para ANCA. La suspensión del medicamento suele bastar como manejo de la enfermedad. Mujer de 45 años de edad, con historia de consumo de PTU durante 2 años, desde su diagnóstico de hipertiroidismo; presentando placas purpúricas dolorosas en ambos miembros inferiores.

SUMMARY ANCA vasculitis associated to propylthiouracil (PTU) is a rare condition with an incidence of 0.47-0.71 cases per 100,000 patients. It affects mainly minor caliber blood vessels. The skin, kidneys and lungs are the organs most affected. To make the diagnosis it is necessary to have a high index of suspicion and rely on histopathologic findings of skin lesions plus a positive ANCA test. Stopping the inducing drug is usually necessary to manage this condition. We report the case of a 45-year-old woman who consumed PTU for two years for the treatment of hyperthyroidism presenting with painful purpuric plaques in the lower limbs.

Determining caries risk susceptibility in children of Udaipur city with genetic taste sensitivity and hormonal fingerprint

Background: Propylthiouracil (PROP) (a medicated tool) and hormonal fingerprint (second to fourth digits [2D:4D]) ratio can be used for detection of caries which is most prevalent oral health disease. Aim: This study aims to determine the role of genetic taste sensitivity and hormonal fingerprint (2D:4D ratio) on caries risk susceptibility. Materials and Methods: The present study was an observational and cross-sectional study. It was conducted on 570 children aged 6–12 years. PROP sensitivity test was done by PROP impregnated filter paper strips and subjects were divided accordingly into supertasters, medium-tasters, and nontasters. 2D:4D ratio was obtained by measuring length ratio of index to ring finger using Vernier caliper. Dietary preferences of the subjects were recorded. The evaluation of decayed, missing, and filled teeth/deft indices was done. Statistical Analysis: Intergroup comparisons were performed using One-way ANOVA test, independent t-test and Chi-square test at 5% significance level. Results: Positive correlation between nontasters, low digit ratio, sweet likers, and high caries index was found with a high significant difference. Conclusion: Genetic taste sensitivity and hormonal fingerprint (biological marker) can be used for detection of caries as the present research confirmed impact of hormones on taste perception.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism

SUMMARY OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

RESUMO ANTECEDENTES O objetivo deste estudo foi investigar o efeito do tratamento com propiltiouracil nas moléculas de adesão em pacientes com hipertireoidismo subclínico. MÉTODOS Neste estudo, 168 pacientes diagnosticados com hipertireoidismo subclínico foram tratados com propiltiouracil por um ano. Os níveis de moléculas de adesão, especificamente sICAM-1, sVCAM-1 e sE-Selectina, antes e após o tratamento foram medidos e comparados. Esses resultados foram comparados com os níveis de 148 indivíduos saudáveis no grupo de controle que receberam um placebo. RESULTADOS Os níveis de sICAM-1 foram significativamente maiores em pacientes com hipertireoidismo subclínico do que nos controles saudáveis (*pa=0,000). Os níveis de sICAM-1 diminuíram significativamente após o tratamento (**pb=0,000). Apesar dessa diminuição em pacientes com hipertireoidismo subclínico, ela não diminuiu para o nível do grupo controle. O sVCAM-1 não se alterou antes e após o tratamento com propiltiouracil. O nível de sE-Selectina foi semelhante ao do grupo de controle pré-tratamento, mas não apresentou significância estatística, embora tenha aumentado após o tratamento (** pb = 0,004). CONCLUSÃO O nível de sICAM foi significativamente superior aos valores pré-tratamento e diminuiu após o tratamento com propilciliouracil. No entanto, mais estudos são necessários para reduzir o risco de aterosclerose e câncer em pacientes com hipertireoidismo subclínico.

Determination of propylthiouracil in human plasma by UPLC-MS/MS / 药学实践杂志

Objective To establish a method for the determination of propylthiouracil in human plasma by UPLC-MS/MS and provide methodological basis for therapeutic drug monitoring (TDM) and bioequivalence test (BE) in clinical. Methods The chromatographic separation was performed on an Agilent SB-C18 column (4.6 mm×150 mm, 5 μm), the mobile phase was methanol and water containing 0.1% formic acid (80∶20, V/V), isocratic elution. MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent JetStream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were m/z 171.1→112.1 for propylthiouracil and m/z 176.1→117.0 for the internal standard (IS). Results The calibration curve was linear in the range of 10−5 000 ng/ml for propylthiouracil in human plasma, r=0.999 3. The intra-day and inter-day precision and accuracy were good (RSD<10%，RE<±10%). The matrix effect of different concentrations was less than 110% and the coefficient of variation was less than 5%. The average recovery of different concentrations was 101.60%−113.56%, which conformed with the requirement of methodological validation. Conclusion The method is rapid, sensitive and accurate, which can be used for the determination of propylthiouracil in human plasma.

Propylthiouracil-induced agranulocytosis as a rare complication of antithyroid drugs in a patient with Graves' disease

SUMMARY INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management. CASE: RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression. DISCUSSION: We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications. CONCLUSION: Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

RESUMO INTRODUÇÃO: A doença de Graves (DG) é uma doença autoimune caracterizada por hipertireoidismo. As drogas antitireoidianas (DAT) são opções terapêuticas disponíveis. A agranulocitose é uma complicação rara, potencialmente fatal desta terapia. Neste estudo, relatamos um caso de agranulocitose induzida por propiltiouracil (PTU) em paciente com DG e as dificuldades do manejo clínico. RELATO DE CASO: RNBA, sexo masculino, 30 anos, com DG, tratado com PTU. Evoluiu com faringoamigdalite, sendo o PTU suspenso e antibióticos, filgrastim, propranolol e prednisona, iniciados. Devido à descompensação do hipertireoidismo, iniciou carbonato de lítio (CL), dexametasona e a solução de Lugol. A tireoidectomia total (TT) foi realizada com boa evolução pós-operatória. DISCUSSÃO: Descrevemos caso de paciente jovem, sexo masculino, com DG. Para o tratamento do hipertireoidismo, as tionamidas são opções efetivas. A agranulocitose induzida por DATs é uma complicação rara, definida como a ocorrência de contagem de granulócitos <500/mm3 após uso de dats. PTU foi suspenso e foram prescritos filgrastim e antibiótico. O radioiodo (RAI) ou a cirurgia são alternativas terapêuticas. Devido a problemas com o uso de DAT, a TT foi proposta. A preparação pré-operatória foi realizada com betabloqueador, glicocorticoide, CL e solução de Lugol. A colestiramina também é uma opção para controlar o hipertireoidismo. A TT foi realizada sem complicações pós-operatórias. CONCLUSÃO: A agranulocitose induzida por drogas antitireoidianas é uma complicação rara. Com a contraindicação às DATs, RAI e cirurgia são opções terapêuticas definitivas para DG. Os betabloqueadores, glicocorticoides, CL, iodo e a colestiramina podem ser uma terapia adjuvante para o hipertireoidismo.

Thyroid function among women with gestational trophoblastic diseases. A cross-sectional study

ABSTRACT BACKGROUND: Gestational trophoblastic diseases (GTDs) are treatable rare tumors with wide distribution. The estimated incidence of GTDs varies dramatically between different regions globally. In early pregnancy, there may be high human chorionic gonadotropin (HCG) concentrations, normal or slightly increased free T4 (fT4) and subnormal thyroid-stimulating hormone (TSH), causing hyperthyroidism ranging from subclinical to severe. Beta-HCG causes thyrotoxicosis through thyroid stimulation in patients with trophoblastic tumors. OBJECTIVE: To assess thyroid function among patients diagnosed with complete or partial hydatidiform mole, within the GTD spectrum. DESIGN AND SETTING: Cross-sectional study based on patients' medical records at Van University Hospital, Van, Turkey. METHODS: 50 patients monitored due to diagnoses of hydatidiform mole were included and were examined regarding thyroid function. Thyroid gland size and volume were measured using thyroid ultrasonography. Beta-HCG, TSH, fT4, free T3 (fT3), total T4 (TT4), total T3 (TT3), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and thyroglobulin levels were measured. RESULTS: Among these patients, 15 (30%) were diagnosed with complete hydatidiform mole and 35 (70%) with partial hydatidiform mole, according to pathology results. Those with complete hydatidiform mole were older (P = 0.003), with higher number of pregnancies (P = 0.032), lower TSH level (P = 0.011) and higher fT4 and TT4 levels (P = 0.04; P = 0.028), compared with partial hydatidiform mole patients. CONCLUSION: In hydatidiform mole patients, thyroid disease severity increases with age, parity, beta-HCG level and mole size. However, prospective multicenter studies on this topic are needed, with larger numbers of patients and closer monitoring.

Comparison of effects of propylthiouracil and methimazole on pregnancy outcomes and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy / 国际检验医学杂志

Objective To compare the effects of propylthiouracil and methimazole on pregnancy outcomes and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy, and to analyze the security.Methods Totally 92patients with hyperthyroidism in pregnancy were divided into the observation group (46cases) and control group (46cases).Patients in both groups were given routine adjuvant therapy, such asβ-blocker, liver protection, increasing white blood cells.The patients in observation group were treated with propylthiouracil while the patients in control group were treated with methimazole.The thyroxine levels (TSH, T3, T4, FT3, FT4), pregnancy outcomes, glucose and lipid metabolism (FPG, FINS, TC, TG), liver function indicators (ALT, ALP, AST) and maternal complications of two groups were compared after treatment for 3months.Results The TSH level of the observation group was significantly higher than that of the control group, and the T3, T4, FT3, FT4levels of the observation group were significantly lower than those of the control group (P＜0.05).The incidence of premature birth, miscarriage, intrauterine fetal death, fetal distress and gestational hypertension of observation group were significantly lower than those of the control group, but the incidence of full-term production of observation group was significantly higher than that of the control group (P＜0.05).The FPG, FINS, TC and TG levels of the observation group were significantly lower than those of the control group (P＜0.05).The increased amplitude of ALT, ALP, AST of the observation group were significantly lower than those of the control group (P＜0.05).There were puerperal infection, hyperthyroid heart disease, diabetes, oligohydramnios, placental abruption, pregnancy-induced hypertension and other complications occurred in both two groups, but the incidence of the observation group were significantly lower than those of the control group (P＜0.05).Conclusion Compared with methimazole, propylthiouracil is more beneficial to improve thyroid function, pregnancy outcome and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy, and has higher security.

Aframomum melegueta prevents the ejaculatory complications of propylthiouracil-induced hypothyroidism in sexually experienced male rats: Evidence from intravaginal and fictive ejaculations / 中西医结合学报

OBJECTIVE@#Hypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract (AE) and methanolic extract (ME) of A. melegueta on the ejaculatory function of hypothyroid male rats.@*METHODS@#Forty sexually experienced male rats were partitioned into 8 groups (5 rats per group) and treated for 28 d as follows: Group 1, Control; Group 2, propylthiouracil (PTU, 10 mg/kg) + distilled water (DW, 10 mL/kg); Group 3, PTU + 5% Tween 80 (10 mL/kg); Group 4, PTU + bromocriptine (6 mg/kg); Group 5, PTU + AE (20 mg/kg); Group 6, PTU + AE (100 mg/kg); Group 7, PTU + ME (20 mg/kg), and Group 8, PTU + ME (100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time (ELT) and post-ejaculatory interval (PEI) for 1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected. Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings, blood was collected through the catheterization of abdominal artery and plasma was used for thyroid-stimulating hormone (TSH), prolactin and testosterone assays.@*RESULTS@#PTU-induced hypothyroidism was characterized by a significant elevation (P < 0.001) of plasmatic TSH and prolactin levels, but a decline (P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone (AE, 100 mg/kg, P < 0.01; ME, 100 mg/kg, P < 0.05) and decreased prolactin (AE, 100 mg/kg, P < 0.05; ME, 20 mg/kg, P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered (P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT (P < 0.05) and PEI (P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly (P < 0.05) alleviated in plant extract-treated groups.@*CONCLUSION@#This study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.

Patrones de prescripción de medicamentos antitiroideos en una población de Colombia / Patterns of prescription of antithyroid drugs in a Colombian population

Resumen Introducción: en Colombia no se conoce la prevalência de los trastornos asociados a tirotoxicosis ni se dispone de estudios fármacoepidemiológicos acerca de la prescripción de los medicamentos antitiroideos. Objetivo: determinar los patrones de prescripción de los antitiroideos y variables asociadas a su uso en una población de pacientes en Colombia. Métodos: estudio de corte transversal, realizado entre enero 1 y marzo 30 de 2015 sobre los hábitos de prescripción de medicamentos antitiroideos en una población afiliada al sistema de salud colombiano. Se midieron variables sociodemográficas, farmacológicas y de comedicación. Se diseñó una base de datos sobre el consumo de medicamentos y se utilizaron pruebas t de student, X 2 y modelos de regresión logística. Resultados: un total de 327 pacientes en tratamiento con medicamentos antitiroideos fueron incluidos. La edad media fue de 53.7±18.1 años y 78.3% de pacientes correspondió a mujeres. El metimazol se prescribió en 95.4% de los pacientes, el propiltiouracilo en 4.6%. En 76.8% de pacientes se presentó comedicación; en particular con antihipertensivos (38.2%) y adicionalmente con propranolol (34.3%). Conclusiones: la tendencia de prescripción de medicamentos antitiroideos en Colombia es similar a lo reportado en diferentes estudios a nivel mundial. El principal medicamento antitiroideo es metimazol, con una tasa de uso mayor a la reportada en Norteamérica y en estudios europeos. Las dosis del metimazol y de propiltiouracilo reportadas en este estudio se ajustan a las recomendaciones de la Asociación Americana de Endocrinología Clínica.

Abstract Introduction: the prevalence of disorders associated with thyrotoxicosis is not known in Colombia, nor pharmacoepidemiological studies are available on the prescription of antithyroid drugs. Objective: to determine the prescription patterns of antithyroid drugs and variables associated with their use in a population of Colombian patients. Methods: cross-sectional study, conducted between January 1 and March 30, 2015 on the prescription habits of antithyroid drugs in a population affiliated with the Colombian Health System. Sociodemographic, pharmacological and comedication variables were measured. A database on drug consumption was designed and student t-tests, X 2 and logistic regression models were used. Results: a total of 327 patients in treatment with antithyroid drugs were included. The mean age was 53.7 ± 18.1 years and 78.3% of patients corresponded to women. Methimazole was prescribed in 95.4% of patients, propylthiouracil in 4.6%. In 76.8% of patients, comedication was present in particular with antihypertensive agents (38.2%) and additionally with propranolol (34.3%). Conclusions: the prescription tendency of antithyroid drugs in Colombia is similar to that reported in different studies worldwide. The main antithyroid drug is methimazole, with a rate of use higher than that reported in North America and in European studies. The doses of methimazole and propylthiouracil reported in this study are in accordance with the recommendations of the American Association of Clinical Endocrinology.

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats / Timoquinona protegeu contra deficiências de aprendizagem e memória e danos nos tecidos cerebrais em ratos hipotireoidais juvenis

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

Comparison of the effects of propylthiouracil and methimazole in the treatment of hyperthyroidism / 中国基层医药

Objective To compare the effects of propylthiouracil and methimazole in the treatment of hyperthyroidism.Methods From January 2014 to January 2015,100 patients with hyperthyroidism in Tengnan Hospital of Zaozhuang Mining Group were selected as study objects,and they were divided into control group and research group according to the digital table,with 50 cases in each group.The control group was treated with propylthiouracil,the research group was treated with methimazole.The clinical effects,thyroid associated antibody level,other relevant indicators and adverse reactions between two groups were compared.Results The total effective rate of the research group was higher than that of the control group(84％ vs.80％),the difference was not statistically significant (x2 =0.271,P ＞ 0.05).Before treatment,the thyrotropin receptor antibody(TRAb) and anti-thyroid peroxidase antibody (TPOAb) between the two groups had no statistically significant differences(t =0.141,0.199,all P ＞ 0.05).After treatment,TRAb of the research group was lower than that of the control group [(7.84 ± 4.26) U/L vs.(8.67 ±4.48) U/L],TPOAb of the research group was higher than that of the control group[(167.62 ± 45.53) IU/mL vs.(158.37 ± 49.40) IU/mL],but the differences were not statistically significant (t =0.949,0.974,all p ＞ 0.05).After treatment,FT3 [(7.34 ± 2.36) pmol/L vs.(13.78 ± 2.91) pmoL/L] and FT4 [(18.52 ± 6.79) pmol/L vs.(23.71 ±6.52) pmol/L] of the research group were lower than those of the control group,the differences were significantly significant (t =12.154,3.899,all P ＜0.05).In the 2 years follow-up,24 cases(48％) in the research group stopped taking medicine,and 14 cases(28％) in the control group,the rate between the two groups had statistically significant difference (x2 =4.244,P ＜ 0.05).The thyroid-stimulating hormone (TSH) recovery time,symptom control time,liver injury time of the research group were (7.45 ± 4.01) months,(6.86 ± 3.49) weeks,(20.85 ± 8.34) d,respectively,which were shorter than those of the control group [(10.36 ± 5.14) months,(9.75 ± 3.42)weeks,(39.21 ± 27.65) d],the differences were statistically significant(t =4.i82,3.156,4.495,all P ＜ 0.05).The incidence rate of liver injury and total incidence rate of adverse reaction of the research group were 8％,54％,which were significantly lower than those of the control group (22％,74％) (x2 =3.843,4.340,all P ＜ 0.05).Conclusion Both propylthiouracil and methimazole have good treatment effects in hyerthyroidism,but methimazole works rapidly,and with good safety.

Influence of discontinuance of methimazole and propylthiouracil on 24 h radioactive iodine uptake in normal rats / 中华核医学与分子影像杂志

Objective To investigate the influence of discontinuance of methimazole (MMI) and propylthiouracil (PTU) on 24 h radioactive iodine uptake(RAIU) in normal rats.Methods A total of 66 female SD rats were randomly divided into 3 groups by simple random sampling method.MMI group (30 rats) received MMI with a dose of 0.6 mg · ml-1 · d-1 orally for 2 weeks,PTU group (30 rats) received PTU with a dose of 6 mg · ml-1 · d-1 orally for 2 weeks.At 1,3,5,7 and 9 d after MMI or PTU was discontinued,6 rats were sacrificed to measure 24 h RAIU respectively.The control group (6 rats) received normal saline with a dose of 1 ml/d orally for 2 weeks,and then they were sacrificed to measure 24 h RAIU too.Data were analyzed with two-sample t test or t'test.Results Thyroid 24 h RAIU in normal rats was (14.6±4.3) ％.The 24 h RAIU on 1,3,5,7 and 9 d was (4.6±0.7) ％,(24.2±7.2) ％,(13.1 ±2.9) ％,(14.1±2.6) ％,(16.1 ±3.7)％ respectively after MMI withdrawal.The 24 h RAIU was significantly lower than that in control group at day 1 (t'=5.55,P＜0.01),higher at day 3 (t=-2.83,P＜0.05),and returned to the normal level at day 5,7,9 (t =0.68,0.24,-0.67,all P＞0.05).The 24 h RAIU on 1,3,5,7 and 9 d was (1.9±0.8)％,(3.3±1.2)％,(7.7±2.4)％,(29.0±4.0)％,(17.1±4.8)％ respectively after PTU withdrawal.It was lower than that in control group (t=7.01,6.10,3.40,all P＜0.05) at day 1,3,5,and higher at day 7 (t=-5.97,P＜0.01).The 24 h RAIU of 9 d showed no difference when compared with that in control group (t=-0.95,P＞0.05).Conclusions MMI and PTU can inhibit the iodine uptake of thyroid,the 24 h RAIU returns to normal level at day 5 after withdrawal of MMI and at day 9 after withdrawal of PTU in euthyroid rats.

Effect of integrated traditional chinese and western medicine on hyperthyroidism and on blood glucose metabolism disorder / 中国生化药物杂志

Objective To explorer effect of integrated traditional chinese and western medicine on hyperthyroidism and on blood glucose metabolism disorder. Methods 70 cases of patients with hyperthyroidism during March 2014 to March 2016 were randomly divided into two groups with 35 cases respectively ,and control group were treated with propylthiouracil,while observation group were treated with traditional chinese medicine on the basis of the control group.Before and after treatment,serum thyroid stimulating hormone(TSH), triiodothyronine(FT3), thyroxine(FT4 ) and fasting plasma glucose (FPG) , 2 hours postprandial blood glucose(2hPG)were detected respectively,the curative effect and adverse reactions were observed. Results After treatment,the levels of TSH,FT3 and FT4 of the both two groups were significantly ameliorative (P<0.05),and FT3 ,FT4 of the observation group were significantly more ameliorative than the control group (P<0.05).The levels of FPG,2hPG of two groups were significantly depressed (P<0.05),and those of the observation group were significantly lower than those of the control group (P<0.05).The clinical effective rate of the observation group was significantly higher than those of the control group (P<0.05).Adverse reactions of two groups were not significantly different. Conclusion The treatment of hyperthyroidism with traditional chinese and western medicine can significantly improve the clinical curative effect and regulate the blood glucose metabolism, and the safety is high.

Influence of discontinuance of methimazole and propylthiouracil on 24 h radioactive iodine uptake in normal rats / 中华核医学与分子影像杂志

Objective To investigate the influence of discontinuance of methimazole (MMI) and propylthiouracil (PTU) on 24 h radioactive iodine uptake(RAIU) in normal rats.Methods A total of 66 female SD rats were randomly divided into 3 groups by simple random sampling method.MMI group (30 rats) received MMI with a dose of 0.6 mg·ml-1·d-1 orally for 2 weeks, PTU group (30 rats) received PTU with a dose of 6 mg·ml-1·d-1 orally for 2 weeks.At 1, 3, 5, 7 and 9 d after MMI or PTU was discontinued, 6 rats were sacrificed to measure 24 h RAIU respectively.The control group (6 rats) received normal saline with a dose of 1 ml/d orally for 2 weeks, and then they were sacrificed to measure 24 h RAIU too.Data were analyzed with two-sample t test or t′ test.Results Thyroid 24 h RAIU in normal rats was (14.6±4.3)%.The 24 h RAIU on 1, 3, 5, 7 and 9 d was (4.6±0.7)%, (24.2±7.2)%, (13.1±2.9)%, (14.1±2.6)%, (16.1±3.7)% respectively after MMI withdrawal.The 24 h RAIU was significantly lower than that in control group at day 1 (t′=5.55, P0.05).The 24 h RAIU on 1, 3, 5, 7 and 9 d was (1.9±0.8)%, (3.3±1.2)%, (7.7±2.4)%, (29.0±4.0)%, (17.1±4.8)% respectively after PTU withdrawal.It was lower than that in control group (t=7.01, 6.10, 3.40, all P0.05).Conclusions MMI and PTU can inhibit the iodine uptake of thyroid, the 24 h RAIU returns to normal level at day 5 after withdrawal of MMI and at day 9 after withdrawal of PTU in euthyroid rats.

Literature Analysis of 118 Cases of Propylthiouracil-associated Small Vasculitis / 中国药房

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.

Effect of curcumin in prolonging survival timeof cryopreserved mice via promoting thyroid function / 中国药理学通报

Aim To look for cold-protective drugs treating cryogenic freezing that may bring great damage to animal physiological system.Methods The protective effect of curcumin on frozen damage and the changes of thyroid function in mice were studied in this study.Quantitative analysis of the changes in survival time and metabolic indexes in mice disposed at(-20±1)℃ was conducted.Mouse serum free triiodothyronine(FT3) and free thyroxine(FT4) contents were detected by ELISA kit.HE staining was used to observe thyroid tissue morphological items.The expression of genes related to thyroid function was assessed via real-time quantitative PCR.Results The intraperitoneal injection of curcumin(12.5~50 mg·kg-1) could remarkably prolong the survival time of mice when exposed to cryogenic freezing.HE staining results displayed a recovered thyroid injury in morphology in the curcumin group, further with a notably improved metabolic indexes and evidently increase in serum FT3 and FT4 levels.The real-time quantitative PCR results indicated that the expressions of sodium iodide symporter(Nis), thyroglobulin(Tg) and thyroid peroxidase(Tpo) were up-regulated, and the expression of thyroid-stimulating hormone receptor(Tshr) was down-regulated.Sodium levothyroxine collabrated with the promoting thyroid effects of curcumin, while propylthiouracil inhibited the effects.Conclusion Curcumin can prolong the survival time of the cryogenic freezing mice, which is closely related to its ability to promote thyroid function.

Effect of Methimazole and Propylthiouracil on beta-2 globulin and thyroid hormone levels in the treatment of hyperthyroidism / 中国生化药物杂志

Objective To compare the effects of methimazole and propylthiouracil on 2-beta globulin and thyroid hormone level in patients with hyperthyroidism.Methods90 cases of patients with hyperthyroidism were treated in our hospital from May 2013 to May 2015, and randomly divided into control group and observation group, 45 cases in each group, the control group was treated with propylthiouracil, the observation group was treated with methimazole, and the level of thyroid hormone, the blood and urine β2-globulin, the occurrence of adverse reactions were compared between the two groups during before&after treatment.ResultsCompared with before treatment, blood, urine β2-globulin content of two groups were significantly decreased, and the blood, urine beta β2-globulin content of the observation group significantly lower than the control group (P<0.05);compared with before treatment, FT3 and FT4 levels of two groups were significantly decreased during 1,2,3 months after treatment (P<0.05), TSH levels were significantly increased(P<0.05), and the observation group was better than the control group(P<0.05);During treatment, the incidence of adverse reactions in the two groups was no significant difference.ConclusionThere is significantly effect of methimazole in the treatment of hyperthyroidism with methimazole, it can effectively reduce the β2-globulin content, and regulating thyroid hormone levels in the body, it is safe worthy of promotion and application.

Clinical comparative study of methimazole and propylthiouracil affecting liver function by treating hyperthyroidism / 药物评价研究

Objective To compare methimazole and propylthiouracil affecting liver function by treating hyperthyroidism.Methods Total 80 patients with hyperthyroidism were randomly divided into two groups.Group A (41 cases) was given methimazole,group B (39 cases) was given propylthiouracil.The effect of methimazole and propylthiouracil affecting liver function by treating hyperthyroidism was evaluated by the indexes of thyroid function,liver function,liver damage,and adverse reaction during treatment.Results Before treatment,there were no statistical significance on FT3 and FT4 between two groups.After treatment,the FT3and FT4 were decreased and TSH was increased in two groups (P ＜ 0.05).But there were no statistical significance between two groups.Before treatment,there was no statistical significance on ALT,AST,and GGT between two groups.After treatment,the ALT,AST,and GGT increased in group B and higher than that of group A (P ＜ 0.05).The ALT,AST,and GGT had no change before and after treatment in the group A.During treatment,there were five cases of liver injury in group A and 14 cases in group B.The liver injury rate of group B was higher than that of group A (P ＜ 0.05) and injury time of group B was later than that of group A.During treatment,there was no statistical significance on adverse reaction rate between two groups.Conclusion The efficacy of methimazole was equal to propylthiouracil in treating hyperthyroidism.Compared with propylthiouracil,the methimazole had less injury on liver but induce the liver injury in earlier.It is suggested that the patients should check the liver function regularly during treatment.

Approach to the patient with propylthiouracil induced anti-neutrophil cytoplasmic antibodies positive vasculitis / 中华内分泌代谢杂志

[Summary] Propylthiouracil-induced anti-neutrophil cytoplasmic antibodies ( ANCA ) positive vasculitis ( APV) is an autoimmune diseases with multi-system damage. Its basic pathological lesions are characterized by necrotizing vasculitis. We present a case of propylthiouracil-induced APV, with regard to its pathogenesis, clinical manifestation, diagnosis, treatment, and outcomes for futher understanding this disease.