甲亢宁胶囊对Graves病减毒增效作用的临床观察

发布时间：2018-05-13 02:33

本文选题：Graves病 + 甲亢宁胶囊　；参考：《北京中医药大学》2017年硕士论文

【摘要】：Graves病(GD)也称毒性弥漫性甲状腺肿伴甲状腺功能亢进症,临床表现并不限于甲状腺,而是一种多系统的综合征,包括高代谢症候群,弥漫性甲状腺肿,眼征,皮损和甲状腺肢端病。目前,西医治疗Graves病的方法主要有3种:①抗甲状腺药物治疗,停药复发率高,改善症状与体征困难,有加重肝损伤、造血系统功能障碍、小血管炎和周期性麻痹等副作用;②1311治疗后甲减比例较高;③手术治疗并非人人皆宜。中医药在本病的治疗方面积累了丰富的经验,在改善症状与体征、抗复发、缩短疗程等方面具有显著的优势。本研究依托北京市科技计划课题"甲状腺功能亢进症病证结合诊疗方案推广验证"(编号:Z121107001012010)。本研究对广安门医院应用于临床38年的院内制剂甲亢宁胶囊治疗Graves病的减毒增效、缩短疗程作用,进行了系统临床观察。本论文分为文献综述和临床研究两部分:第一部分文献综述通过查阅古代文献、检索中外数据库,回顾总结近年中西医治疗甲状腺功能亢进症的现状。Graves病是甲亢的常见类型,以甲状腺毒症、甲状腺肿、突眼等为主要临床表现。中医认为甲亢属本虚标实证,本虚主要为气虚、阴虚,标实主要为气滞、火旺、痰凝、血瘀。阴虚阳亢是甲亢早期的主要证型,痰瘀、热毒是主要兼证。中医治疗以辨证论治、分期论治、专方专药及对症治疗为主,滋阴潜阳,软坚散结,活血解毒是最常用治法。中药可达到"减毒增效"的作用,即改善症状和体征、减少西药用量、减少并发症、降低复发率、缩短疗程等。西医治疗方式有3种,包括抗甲状腺药物治疗、1311治疗、手术治疗等,但是这些治疗手段均存在一些不良反应和局限性。第二部分临床观察.目的:观察甲亢宁胶囊治疗Graves病的减毒增效作用。方法:采用随机、盲法、对照的方法,共纳入332例Graves病(GD)患者,治疗组270例,对照组62例,观察24周,每4周随访一次,观察结束后,跟踪随访2年。治疗组:甲亢宁胶囊+标准剂量1/2的抗甲状腺药物;对照组:安慰剂+标准剂量抗甲状腺药物。主要观察比较:(1)增效作用:两组症状和体征的改善时间和改善率、两组甲状腺功能主要指标改善比例和恢复正常率、两组6个月、12个月、24个月复发情况和复发率。(2)减毒作用:两组抗甲状腺药物剂量、两组肝损害指标变化情况和恢复正常率、两组造血功能变化情况和改善正常率、两组安全性指标变化情况等。研究病例以Excel 2010建立数据库,进行数据分析采用SPSS 22.0软件。计量资料用±S表示,计量资料两组间比较各指标比较采用t检验,率的比较用χ2检验。结果:1增效作用(1)中医症状:治疗组改善症状快,4周内即改善,对照组8周～12周才达到治疗组4周的改善水平。治疗组多个时间节点优于对照组(P0.05)。(2)甲状腺肿大:两组以轻度甲状腺肿大恢复快,治疗组8周内即改善,对照组24周尚未达到治疗组4周的改善水平,治疗组在16周～24周优于对照组(P0.05)。中度甲状腺肿占比例最高,治疗组8周即改善,对照组24周才达到16周改善水平,治疗组在16周～24周优于对照组(P0.05)。重度甲状腺肿变化不大,两组无显著性差异(P0.05)。(3)突眼度:治疗组4周内即改善,对照组12周以后才达到治疗组4周的改善水平。治疗组各时间节点均优于对照组(P0.05)。(4)甲亢指数:甲亢指数4周即有改善,对照组8周～12周才达到治疗组4周的改善水平。治疗组在8周～12周均优于对照组(P0.05),16周～24周两组没有显著性差异(P0.05)。(5)甲状腺功能:两组各指标4周内均改善,对照组TSH水平8周～12周才达到治疗组4周的改善水平,8周以后各时间节点均优于对照组(P0.05);两组TT3、TT4指标的均数变化在各时间节点均没有显著性差异(P0.05);FT3指标4周时治疗组低于对照组,对照组在4周～8周达到治疗组4周水平,4周～16周两组没有显著性差异(P0.05),20周、24周时治疗组高于对照组,两组有统计学差异(P0.05);FT4指标均数在8周后两组存在统计学差异(P0.05),治疗组高于对照组;治疗组a-TG均数4周内即下降,对照组20周～24周才达到治疗组4周的改善水平,治疗组各时间节点(除24周)均优于对照组(P0.05);治疗组a-TP04周内即指标下降,对照组24周才达到治疗组4周的改善水平,治疗组各时间节点均优于对照组(P0.05)。(6)甲状腺功能恢复情况甲状腺功能主要指标:治疗8周时,FT3、FT4均正常例数者,两组均超过50.00%,两组无显著性差异(P0.05);FT3、FT4、TSH均正常例数者,治疗组4周即增多,且治疗组在4周优于对照组(P0.05),16周～24周对照组优于治疗组(P0.05)。(7)复发情况和复发率:6个月两组复发率无差异(P0.05),随访12个月、24个月治疗组复发率均低于对照组(P0.05)。2减毒作用(1)抗甲状腺药物用量:治疗组甲巯咪唑的剂量低于对照组,且对照组12周～16周才降至治疗组4周的剂量水平。治疗组各时间节点剂量均低于对照组(P0.05)。治疗组丙基硫氧嘧啶的剂量低于对照组,且对照组12周才降至治疗组4周的剂量水平。治疗组各时间节点剂量均低于对照组(P0.05)。(2)肝损害:治疗组ALT异常率低,4周内即降低,对照组24周尚未达到治疗组4周的改善水平。治疗组各时间节点均优于对照组(P0.05)。(3)白细胞减少症:治疗组白细胞减少例数少,4周内即改善,对照组8周～12周才达到治疗组4周的改善水平。治疗组4周～8周白细胞减少例数优于对照组(P0.05),8周～24周低于对照组(P0.05)。(4)不良反应:治疗组不良反应发生率低于对照组(P0.05)。结论:甲亢宁胶囊对Graves病的治疗优势主要表现在改善症状、改善甲功;可减少西药剂量、减少肝损害、改善造血功能;有抗复发作用。具有显著的减毒增效作用。
[Abstract]:Graves's disease (GD), also known as toxic diffuse goiter with hyperthyroidism, is not limited to thyroid, but a multisystem syndrome, including high metabolic syndrome, diffuse goiter, eye sign, skin lesions and acromegaly. Currently, there are 3 main methods for treating Graves disease in western medicine: (1) antithyroid drug treatment Relapse rate is high, symptoms and signs are difficult to improve, liver injury, hematopoietic system dysfunction, small vasculitis and periodic paralysis and other side effects; (2) the proportion of hypothyroidism after 1311 treatment is higher; (3) surgical treatment is not suitable for everyone. Chinese medicine has accumulated rich experience in the treatment of this disease, in improving symptoms and signs, anti recurrence This study is based on the Beijing science and technology program "hyperthyroidism syndrome combined diagnosis and treatment scheme" (number: Z121107001012010). This study was used in the hospital for 38 years in Guanganmen hospital for the treatment of Graves's disease with hyperthyroidism capsule to reduce the effect and shorten the course of treatment. This paper is divided into two parts: literature review and clinical research: the first part of the literature review, through consulting ancient literature, retrieving Chinese and foreign databases, review and summarize the current status of.Graves disease in the treatment of hyperthyroidism in Chinese and Western medicine, which is the common type of hyperthyroidism, with thyrotoxicosis, goiter, and exophthalmos. It is the main clinical manifestation. Traditional Chinese medicine believes that hyperthyroidism is a virtual standard. The deficiency is mainly Qi deficiency and yin deficiency. The main body is Qi stagnation, fire flourishing, phlegm coagulation and blood stasis. Yin deficiency and yang hyperactivity is the main syndrome type in the early stage of hyperthyroidism. Phlegm and stasis, heat toxin is the main syndrome. Traditional Chinese medicine can improve symptoms and signs, reduce the dosage of Western medicine, reduce complications, reduce the recurrence rate, and shorten the course of treatment. There are 3 kinds of treatment in western medicine, including anti thyroid medicine treatment, 1311 treatment and surgical treatment, but these treatments all have some bad methods. The second part of the clinical observation. Objective: To observe the attenuated and synergistic effect of hyperthyroidism capsule in the treatment of Graves's disease. Methods: a total of 332 cases of Graves's disease (GD) were randomly, blinded and controlled, 270 cases in the treatment group and 62 cases in the control group, followed up for 24 weeks, followed up for 2 years after the observation. The treatment group: Hyperthyroidism Ningxia capsule + standard dose 1/2 antithyroid drug; control group: placebo + standard dose antithyroid drugs. The main observation and comparison: (1) synergistic effect: two groups of symptoms and signs of improvement time and improvement rate, the two groups of main indicators of thyroid function improvement ratio and recovery of normal rate, two groups 6 months, 12 months, 24 months of recurrence and recurrence (2) antitoxic effect: two groups of anti thyroid drug dosage, two groups of liver damage indexes and recovery normal rate, two groups of hematopoietic function changes and improvement of normal rate, two groups of safety index changes, and so on. Study cases with Excel 2010 to establish a database, data analysis using SPSS 22 software. Measurement data in + S, to count Comparison of the two groups compared each index with t test, the comparison of the rate compared with the x 2 test. Results: 1 synergistic effect (1) of Chinese medicine symptoms: the treatment group improved the symptoms quickly, the improvement in 4 weeks, 8 weeks to 12 weeks in the control group to reach the improvement level of 4 weeks in the treatment group. The treatment group was better than the control group (P0.05). (2) the two groups were mild. The recovery of thyroid enlargement was faster, the treatment group was improved within 8 weeks, and the control group had not reached the improvement level of 4 weeks in the treatment group for 24 weeks. The treatment group was superior to the control group in 16 weeks to 24 weeks (P0.05). The moderate goiter accounted for the highest proportion, the treatment group was improved for 8 weeks, the control group reached 16 weeks for 24 weeks, and the treatment group was better than the control group for 16 weeks to 24 weeks (P0.05). There was no significant difference in severe goiter (P0.05). (P0.05) there was no significant difference (3) the degree of exophthalmos: the treatment group was improved within 4 weeks and the control group reached the level of improvement for 4 weeks after 12 weeks. All time nodes in the treatment group were better than the control group (P0.05). (4) hyperthyroidism index: the hyperthyroidism index was improved for 4 weeks, and the control group was 4 weeks from 8 to 12 weeks before the treatment group. The level of improvement in the treatment group was superior to the control group in 8 weeks to 12 weeks (P0.05), and there was no significant difference between the two groups in 16 weeks to 24 weeks (P0.05). (5) the thyroid function: the two groups of indexes were improved in 4 weeks, and the level of TSH in the control group was 8 weeks to 12 weeks to achieve the improvement of the group 4 weeks, after 8 weeks, the nodes were better than the control group (P0.05); two group TT3, TT4 There was no significant difference in the average number of indexes at all time nodes (P0.05), while the FT3 index was lower than the control group at 4 weeks, the control group reached the 4 week level in the treatment group from 4 weeks to 8 weeks, and there was no significant difference between the two groups in the 4 week to 16 weeks (P0.05), the treatment group was higher than the control group at 20 weeks and 24 weeks, and the two groups were statistically different (P0.05), and the FT4 index was in 8. There was a statistical difference between the two groups after the week (P0.05), and the treatment group was higher than the control group. The a-TG in the treatment group decreased within 4 weeks, and the control group reached the improvement level of the treatment group for 4 weeks for 20 weeks to 24 weeks. The treatment group was better than the control group (P0.05) at all time nodes (except 24 weeks). The treatment group was decreased in the a-TP04 week, and the control group was 24 weeks to reach 4 weeks in the treatment group. The time node of the treatment group was better than the control group (P0.05). (6) the thyroid function was the main index of thyroid function recovery: at 8 weeks, the normal cases of FT3 and FT4 were all normal, two groups were more than 50%, the two groups had no significant difference (P0.05); FT3, FT4, TSH were all normal cases, the treatment group increased for 4 weeks, and the treatment group was superior to the control in 4 weeks. Group (P0.05), 16 weeks to 24 weeks of control group was better than the treatment group (P0.05). (7) recurrence and recurrence rate: 6 months of two group recurrence rate no difference (P0.05), 12 months of follow-up, 24 months treatment group recurrence rate is lower than the control group (P0.05).2 antitoxic effect (1) antithyroid drug dosage: the treatment group is lower than the control group, and the control group is 12 weeks to 16. The dose level of the treatment group at 4 weeks was lower than that of the control group (P0.05). The dose of propyl sulfur in the treatment group was lower than the control group, and the control group was lower than the control group for 12 weeks. The dose of the treatment group was lower than the control group for 4 weeks. The dose of each node in the treatment group was lower than the control group (P0.05). (2) the liver damage: the ALT abnormality rate in the treatment group was low, 4 Within 24 weeks, the control group had not reached the improvement level of the treatment group for 4 weeks. All the time nodes in the treatment group were better than the control group (P0.05). (3) leuccytopenia: the number of leukocyte reduction in the treatment group was less, the treatment group was improved within 4 weeks, and the control group reached the improvement level of 4 weeks in the treatment group for 8 weeks to 12 weeks. The number of leukocyte reduction in the treatment group for 4 to 8 weeks was excellent. In the control group (P0.05), 8 to 24 weeks was lower than that of the control group (P0.05). (4) adverse reaction: the incidence of adverse reactions in the treatment group was lower than that of the control group (P0.05). Conclusion: the advantages of hyperthyroidism capsule for Graves disease are mainly manifested in improving the symptoms and improving the thyroid function; it can reduce the dose of Western medicine, reduce the liver damage and improve the hematopoiesis, and have the effect of anti recurrence. Attenuated and synergistic effects.

【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

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