Graves病甲状腺功能亢进症性肝损害的相关因素分析

目的 探讨影响Graves病甲状腺功能亢进症(甲亢)性肝功能损害的相关因素.方法 回顾性分析天津医科大学总医院2013年1月至2015年12月收治的Graves病住院患者254例,根据肝功能将患者分为Graves病甲亢性肝损害组(A组,n=159)和甲亢肝功能正常组(B组,n=95),比较两组的基础代谢率(BMR)、甲状腺重量、FT3、FT4、促甲状腺激素(TSH)、TSH受体抗体(TRAb)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb).采用Pearson相关性分析甲状腺重量、BMR、FT3、FT4、TRAb与甲亢性肝损害的相关性,应用Logistic回归分析甲亢性肝损害的独立危险因素.结果 A组的甲状腺重量、BMR、FT3、FT4、TRAb、TPOAb均高于B组,而TSH低于B组(t或z=-4.720～-2.276,P均＜0.05).Pearson相关性分析显示,甲状腺重量、BMR、FT3、FT4、TRAb与甲亢性肝损害的发生呈正相关(r=0.157～ 0.270,P均＜0.05).Logistic回归分析显示,FT3(OR=1.052,95％ CI:1.001～1.105)、BMR(OR=1.019,9.5％ CI:1.006 ～ 1,033)是Graves病甲亢性肝损害发生的独立危险因素(P均＜0.05).结论 Graves病甲亢性肝损害与FT3、FT4、TRAb、BMR、甲状腺重量有关.其中FT3、BMR为甲亢性肝损害发生的独立危险因素.     

老年甲亢性肝损害患者炎症因子的变化及意义

目的探讨老年甲亢性肝损害患者炎症因子的变化及意义。方法选取40例老年甲亢性肝损害患者(老年组),40例中青年甲亢性肝损害患者(中青年组),40例健康体检老年人组(正常组)作为研究对象。采用化学发光法测定血浆中降钙素原(PCT)水平,放射免疫法测定IL-2、IL-6,ELISA法测定血清TNF-α,电化学发光法测定血清FT3、FT4,全自动生化分析仪测定血清ALT、AST、ALP、γ-GT和TBIL。结果老年组及中青年组IL-2、IL-6、TNF-α、FT3、FT4、ALT、AST、ALP、γ-GT、TBIL水平均高于正常组(P0.05或P0.01),PCT水平较正常组比较偏高但差异无统计学意义(P0.05);老年组IL-2、TNF-α、FT3、FT4水平和中青年组比较无显著差异(P0.05),但老年组IL-6、ALT、AST、ALP水平高于中青年组(P0.05);血清IL-6与TNF-α、ALT、AST、ALP呈正相关(r=0.45,0.32,0.39,0.28,P0.05)。结论老年甲亢易伴发更严重的肝功能损害,IL-6、TNF-α水平升高可能是老年甲亢性肝损害发生的重要机制。     

甲状腺功能亢进症合并肝损害给予复方甲亢片治疗的效果观察

目的探讨复方甲亢片治疗甲状腺功能亢进症合并肝损害对改善患者肝功能、甲状腺功能及临床症状的效果。方法纳入2015年6月至2017年3月我院收治的甲状腺功能亢进症合并肝损害患者104例,随机分为两组。患者入院后均行常规治疗,对照组在常规治疗的基础上给予常规西药治疗,治疗组在常规治疗的基础上给予复方甲亢片治疗。观察两组患者治疗前后甲状腺功能、肝功能及症状改善情况。结果治疗前,两组肝功能(AST、ALT、ALP、γ-GT、TBi L)、甲状腺功能(TSH、FT3、FT4)评分比较均无明显差异(P0.05)。治疗后,两组肝功能指标AST、ALT、ALP、γ-GT、TBi L水平均有所下降,但两组AST、ALT水平比较无显著差异(P0.05),且治疗组ALP、γ-GT、TBi L水平显著低于对照组(P0.001);两组甲状腺功能指标TSH水平均明显提高,FT3、FT4水平均明显降低,且观察组TSH水平提高及FT3、FT4水平降低较对照组更为显著(P0.001)。观察组治疗后恶热、心悸、肋痛、乏力、食欲亢进等临床症状改善程度明显优于对照组(P0.001)。结论复方甲亢片治疗甲状腺功能亢进症合并肝损害患者,能有效保护患者肝功能及甲状腺功能,改善患者临床症状,可作为临床治疗甲状腺功能亢进症合并肝损害的常用药物。     

甲状腺功能亢进症316例肝功能某些指标变化的分析

目的探讨甲状腺功能亢进症（甲亢）患者与肝功能的一些指标变化关系。方法对316例甲亢患者行甲功、肝功能检测,指标包括丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、谷胺酰转肽酶（GGT）、碱性磷酸酶（ALP）、血清总胆红素（TBL）;比较分析甲亢性肝功能损害和甲亢无肝功能损害两组之间的游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）水平;并分析甲亢患者肝功能变化的情况。结果甲亢性肝损害组TSH、FT3、FT4比无肝损害甲亢组高（P〈0．05）,甲亢性肝功能损害时主要以ALP、ALT、AST的异常增高为主;并且FT3、FT4分别与ALP、ALT、AST存在正相关关系,P〈0．05。结论甲亢性肝功能损害（特别是ALP变化）与甲状腺激素水平有密切关系,能否用ALP来协助甲亢诊断和治疗观察值得探讨。     

甲状腺机能亢进性肝损害30例临床分析

甲状腺机能亢进症(甲亢)是由甲状腺激素分泌过多所引起的一种常见的内分泌疾病,过多的甲状腺激素作用于全身多个器官,引起一系列病理生理变化,并可累及肝脏导致肝功能异常,甚至发生黄疸。我院近3年来收治甲状腺机能亢进性肝损害(甲亢性肝损)患者30例。现将30例患者的临床资料分     

甲状腺功能亢进症与肝损害

甲状腺功能亢进症(甲亢)是内分泌系统的常见病、多发病,临床上甲亢并肝功能损害比较常见,可分类为:①甲状腺激素直接作用致肝损害;②抗甲状腺药物致肝损害;③合并病毒性肝炎致肝损害;④合并自身免疫性肝炎致肝损害.     

甲状腺功能亢进及抗甲状腺药物与肝损害

甲状腺功能亢进(甲亢)、抗甲状腺药物均可引起肝损害。甲亢引起肝损害比较常见,可分为肝酶的升高和黄疸,其对肝功能损害的原因是多方面的,与甲状腺激素的直接毒性作用、高代谢、心力衰竭及免疫等因素有关;治疗原则以控制甲亢为主,甲亢治愈后,肝功能大多数可恢复正常。抗甲状腺药物引起肝损害的诊断通常采用排除法,其发病机制目前主要认为与机体的异质性反应有关;亚临床肝损害时不需停用抗甲状腺药物,如果肝损害显著,立即停药是治疗的关键。     

甲状腺功能亢进症初诊患者肝功能异常的临床分析

探讨甲状腺功能亢进症(甲亢)初诊患者肝功能异常的发生率、临床特点及相关因素。将428例甲亢患者根据肝功能是否异常分为两组,分析其临床表现、肝功能指标与血清甲状腺激素水平以及甲状腺自身抗体的水平的关系。初诊甲亢患者肝功能异常的发生率为30．1％,肝功能损害最常见的是碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)增高,其甲状腺激素水平显著高于无肝功能异常者。而TSH、甲状腺微粒体抗体(TMA)、甲状腺球蛋白抗体(TGA)则无明显差异。甲亢初诊患者合并肝功能异常较常见,肝功能损害以ALP、ALT增高为最常见,且与甲状腺激素水平关系密切。     

复方甲亢片治疗甲状腺功能亢进症合并肝损害的临床研究

目的：探讨复方甲亢片治疗甲亢合并肝损害的临床疗效。方法：对明确诊断的40例甲亢合并肝损害患者随机分别采用复方甲亢片治疗（治疗组）、西药治疗（对照组）观察。结果：治疗组、对照组临床总有效率分别为85．00％、80．00％，经Ridit分析，差异无显著性意义（P〉0．05），两组患者经治疗后FT3。FT4、ALT、AST明显降低，TSH升高，但两组比较差异无显著性意义（P〉0．05）；治疗组在对γ-GT、ALP、TBil指标改善方面有明显优势（P〈0．05）；治疗组症状改善明显，多汗、乏力、口苦、胁痛等症状的改善与对照组比较差异有显著性意义（P〈0．05）。结论：甲亢患者合并肝损害时治疗甲亢是首要的，中药配合小剂量他巴唑（即复方甲亢片）同样能达到大剂量他巴唑配降酶护肝西药的效果，并在改善甲亢合并肝损害症状及综合治疗作用方面有明显优势。     

药物性肝损害41例临床分析

目的分析药物性肝损害(DILI)的病因及临床特点,提高对药物性肝损害的认识。方法对本院41例药物性肝损害患者的临床资料进行回顾性分析,根据服药时间及服用药物种类、临床表现、肝损害的分型进行综合评价,总结药物性肝损害的临床特点。结果引起肝损害的药物前3名依次为:中草药及中成药14例(32.6%),抗生素10例(23.3%),降压药5例(11.6%)。临床分型:肝细胞损伤型13例,占31.7%;胆汁淤积型15例,占36.6%;混合型12例,占39.3%。结论临床上多种药物可导致肝损害,因此在使用有肝损害副作用药物时,应及时检测肝功能,以求早发现、早治疗。     

匹伐他汀对冠心病合并非酒精性脂肪肝患者肝功能的影响

目的:观察匹伐他汀对肝功能正常冠心病(CHD)合并非酒精性脂肪肝(NAFLD)患者肝功能的影响。方法:选择我院CHD合并NAFLD且肝功能正常的患者205例为CHD+NAFLD组,根据NAFLD严重程度患者被分为轻度组87例、中度组64例、重度组54例,另选择同期在我院就诊的单纯CHD患者70例(CHD组)作为对照。四组均在常规治疗的基础上给予匹伐他汀治疗,治疗15d。观察四组治疗前后血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转移酶(γ-GT)水平和严重肝功能损害发生率。结果:治疗后CHD组、CHD+NAFLD轻、中、重度组血清ALT、AST、γ-GT水平均显著升高(P均=0.001),且四组治疗后ALT[(45.89±11.36)U/L比(46.92±12.67)U/L比(46.35±11.95)U/L比(47.32±14.06)U/L]、AST[(46.32±12.13)U/L比(48.54±13.49)U/L比(47.63±12.57)U/L比(48.66±13.54)U/L]、γ-GT[(58.49±14.86)U/L比(57.62±11.38)U/L比(57.92±10.51)U/L比(58.52±13.8)U/L]水平及严重肝功能损害发生率(2.90%比3.57%比1.61%比3.92%)相比较差异均无统计学意义(P均>0.05)。结论:与单纯CHD患者比较,匹伐他汀用于肝功能正常CHD联合NAFLD患者未增加肝功能损害,具有良好的临床安全性。     

Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism

OBJECTIVE: The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.     

Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.

The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either hypothyroidism or TRAb-associated hyperthyroidism, were seen in 8 of 20 patients (40%) with anti-TPO before 131I treatment, compared to 9 of 129 (7%) without (p<0.005). In conclusion, TRAb and a Graves' like hyperthyroidism can be triggered by 131I treatment in patients with nodular toxic goiter. The presence of anti-TPO seem to be a marker of an increased risk of development of TRAb-associated hyperthyroidism as well as hypothyroidism, but both side effects can be seen despite the absence of anti-TPO autoantibodies.     

Thyroid-stimulating antibody is related to Graves' ophthalmopathy, but thyrotropin-binding inhibitor immunoglobulin is related to hyperthyroidism in patients with Graves' disease.

We investigated the relationship between thyroid function or ophthalmopathy of Graves' disease and thyrotropin receptor antibodies (TRAb) in 155 untreated patients with Graves' hyperthyroidism. All patients were examined by ophthalmologists, and underwent computed tomography of the orbit and measurement of serum free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin-binding inhibitor immunoglobulin (TBII), and thyroid stimulating antibodies (TSAb). Patients were divided into three groups according to the presence of orbital fat increase (OFI) and extraocular muscle enlargement (EME): 57 patients without OFI and EMO formed the no Graves' ophthalmopathy (NGO) group; 55 patients with OFI but without EMO formed the OF group; 43 patients with EME with or without OFI formed the EM group. The FT3, FT4, and thyroid weight increased in the order of the EME, NGO, and OFI groups. TSAb increased in the order of the NGO, OFI, and EME groups, and TSAb was significantly greater in the EME and OFI than in the NGO group. TBII was not significantly different among the three groups, but was lower in EME than NGO. There was a significant positive correlation between TBII and FT3 or FT4 in all patients combined as well as in all three groups, but correlation between TSAb and FT3 or FT4 was very weak in all groups, and that between TSAb and FT3 was not significant in the EM group In the relationship between ophthalmopathy and TRAb, the sum of the scores of eyelid swelling, proptosis, and extraocular muscle enlargement was taken as a measure of the overall severity of the Graves' ophthalmopathy (GO). TSAb was significantly correlated with the GO score, but there was no correlation between TBII and GO scores. In conclusion, TSAb was correlated with ophthalmopathy but TBII was related to hyperthyroidism.     

Radioiodine therapy in Graves' disease patients with large diffuse goiters treated with or without carbimazole at the time of radioiodine therapy.

We sought to ascertain how high the success rates of radioiodine therapy are for Graves' disease patients with large diffuse goiters when aiming for a constant absorbed dose of 250 Gy. Thirty-six patients with a thyroid volume of 50-110 mL were evaluated for changes in thyroid function and appearance 3, 6, and 12 months after radioiodine therapy. Success was defined as definitive elimination of hyperthyroidism following therapy (hypothyroidism corrected with thyroxine on diagnosis); failure as persistent/recurrent hyperthyroidism after 12 months. Overall success rate was 50%. However, a subgroup of 20 patients without simultaneous carbimazole (carbimazole-off) showed a highly significantly larger success rate (85%) than the 16 patients with simultaneous carbimazole (carbimazole-on) at the time of radioiodine therapy (6.3%, p < 0.000005). Successful cases showed a significantly higher volume reduction after radioiodine than failures (75.5% vs. 35.4%, p < 0.00005). Stepwise logistic regression showed that therapy failure was related to administration of carbimazole during radioiodine therapy (p < 0.0250 and absorbed dose (p < 0.05), but not thyroid function (free triiodothyronine [FT3] and free thyroxine [FT4]), initial thyroid volume or thyrotropin-receptor antibody (TRAb) value. However, a significant correlation of therapy success to absorbed dose (r = 0.69, p < 0.005) could be shown only for carbimazole-off patients, but not for the others. Finally, multivariate factor analysis consistently showed that therapy success was correlated only to absorbed dose and antithyroid drugs, not to initial thyroid volume, TRAb value, or thyroid function. Thyroid volume per se is not responsible for the lower success rate in Graves' disease patients with large goiters because even a comparable group of 32 Graves' disease patients with small thyroid glands (< or =20 mL) and without simultaneous carbimazole showed a success rate of 87.5%. The high failure rate in the carbimazole-on patients (absorbed dose comparable to carbimazole-off) is due to the simultaneous administration of carbimazole. Therefore, if clinically feasible, we recommend discontinuing carbimazole at least one day before beginning radioiodine therapy.     

Graves病患者药物治疗复发的相关因素分析

目的 回顾抗甲状腺药物(ATD)治疗的初发Graves病(GD)患者的临床资料,观察各临床特征对ATD治疗转归的影响,以评价GD复发的影响因素.方法 收集204例初发GD甲亢患者的临床资料.根据ATD治疗结果分为有效组和失败组,失败组包括停药复发和未能停药两个亚组,比较各因素对ATD治疗转归的影响.结果 204例初发GD患者中94例(46.1%)治疗有效,110例(53.9%)治疗失败.与有效组比较,失败组发病年龄小[(31.0±12.2)岁比(36.3±14.0)岁,P=0.004],发病初游离T3水平高[(25.60±9.52)pmol/L比(19.16±6.38)pmol/L,P=0.001],FT3/FT4比值大[(4.87±1.21)比(3.86±0.98),P=0.001],促甲状腺素受体抗体(TRAb)水平高[(57.3±18.4)%比(29.6±14.9)%,P=0.001].logistic分析显示,发病初甲状腺大小、FT3/FT4比值、TRAb水平是药物治疗失败的独立影响因素.复发亚组停药时,甲状腺明显肿大、伴有眼征的患者比率高.治疗过程中甲状腺激素正常3、6、9、12个月时,复发亚组中超敏促甲状腺素(TSH)受抑制患者的比率均明显多于有效组(P=0.001).结论 (1)治疗前甲状腺明显肿大、TRAb水平高、FT3/FT4比值大的患者,药物治疗反应差;(2)停药时甲状腺明显肿大、伴有眼病者,停药后复发率高;(3)经治疗甲状腺激素正常、TSH延迟恢复或仍受抑制者复发率高.     

The effect of combination therapy with propylthiouracil and cholestyramine in the treatment of Graves' hyperthyroidism

OBJECTIVE: The study aims to evaluate the efficacy of combination therapy with propylthiouracil (PTU) and cholestyramine in the treatment of Graves' hyperthyroidism. BACKGROUND: Thyroxine (T4) is metabolized mainly in the liver by conjugation to glucuronides and sulphates that enter the enterohepatic circulation. Thyrotoxic patients have an abnormal increase in thyroid hormone in their enterohepatic circulation. Previous studies on combination therapy with methimazole and cholestyramine for Graves' hyperthyroidism have shown it to be an effective adjunctive treatment. In this study, we examined the efficacy of combination therapy with PTU and cholestyramine in the treatment of Graves' hyperthyroidism. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups: group I (n = 15) received PTU 100 mg twice a day, propranolol 40 mg twice a day and cholestyramine 4 g twice a day for 4 weeks; group II (n = 15) received PTU 100 mg twice a day and propranolol 40 mg twice a day for 4 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), free thyroxine (FT4) and TRAb levels at baseline, and at the end of 2 and 4 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. At the end of 2 and 4 weeks of the study period, serum TT3 and FT4 levels of group I were significantly lower than those of group II. No significant differences in the TRAb level were found between the two groups. CONCLUSION: Cholestyramine contributed to a more rapid and complete decline in thyroid hormone levels in patients with Graves' hyperthyroidism. It was thus proved to be an effective and well-tolerated adjunctive therapy.