Graves病患者甲状腺激素水平正常后sTSH长期抑制机制的探讨

目的 探讨临床上部分Graves病(GD)患者经抗甲状腺药物(ATD)治疗后甲状腺激素水平达到正常,但促甲状腺素(TSH)仍长期处于被抑制状态的机制.方法 入选初发122例GD甲亢患者,予以初始等效剂量的ATD治疗,每月随访时根据甲状腺功能测定的结果酌情减量,并适时添加左旋甲状腺素(L-T4).当甲状腺激素(FT3、FT4)水平持续正常3个月即达随访标准,复查FT3、FT4、sTSH、TSH受体抗体(TRAb),并根据TRAb是否阳性分组比较.结果 122例GD甲亢患者经(7.1±1.1)个月的ATD治疗后,甲状腺激素水平均已经达到正常3个月.随访时,58例TRAb转为阴性,64例TRAb持续阳性.两组甲状腺激素水平无差异, TRAb阳性组的sTSH水平明显低于阴性组[0.044 mIU/L(0.001～4.163 mIU/L) vs 1.749 mIU/L(0.079～4.646 mIU/L),P＜0.01];血清sTSH水平与TRAb呈明显负相关(r=-0.539,P＜0.01),与FT3、FT4、年龄、病程、治疗时间、L-T4剂量、L-T4添加时间等均无相关性.结论 药物治疗过程中,甲状腺激素水平正常的GD患者,其TSH水平长期受抑制的原因与高水平TRAb相关,可能由于TRAb直接与垂体内TSH受体结合,通过超短环反馈抑制TSH的分泌所致.     

小剂量甲状腺素治疗能减少Graves病的复发吗?

观察单用抗甲状腺药物 (ATD)治疗组与ATD联合小剂量甲状腺素治疗组之间Graves病(GD)复发率。结果显示两组治疗结束时临床表现、甲状腺功能、TSH受体抗体 (TRAb)阳性率均相似 ,停药 1年GD复发率差异无显著性 ,但复发者甲状腺肿较严重、突眼率较高以及TRAb阳性率较高 (均P <0 .0 1)。     

甲状腺上动脉峰值血流速度在自身免疫性甲状腺毒症鉴别中的应用

目的探讨甲状腺上动脉峰值血流速度(STA-PSV)对自身免疫性甲状腺毒症病因鉴别诊断的临床应用价值。方法收集2015年1月至2018年10月北京大学人民医院内分泌科新诊断的未用抗甲状腺药物治疗的自身免疫性甲状腺毒症患者301例,其中Grave病(GD)患者241例,自身免疫性甲状腺炎(AIT)患者60例,比较两组患者STA-PSV、甲状腺功能、促甲状腺激素受体抗体(TRAb)等相关指标。通过多元线性回归分析影响STA-PSV的相关因素。通过受试者工作特征(ROC)曲线下面积(AUC)评价STA-PSV对GD的鉴别能力。结果GD组STA-PSV明显高于AIT组[61.00(41.00,86.50)cm/s比34.50(25.25,46.00)cm/s,P<0.001],ROC曲线分析,AUC为0.790(95%CI 0.734~0.845,P<0.001),当STA-PSV切点值≥49.5 cm/s时,诊断GD的敏感性为64.3%,特异性为83.3%。在所有甲状腺毒症患者中,以STA-PSV(对数转换后)为因变量,以游离甲状腺素(FT4)和TRAb为自变量进行多因素回归分析,结果显示STA-PSV与FT4(β=0.371,95%CI 0.005~0.010,P<0.001)和TRAb(β=0.138,95%CI 0.001~0.014,P=0.035)独立相关。结论STA-PSV对GD和AIT具有一定的鉴别诊断意义,且与甲状腺素水平和TRAb相关。     

初发Graves病患者血清促甲状腺激素受体抗体水平的影响因素分析

目的分析初发Graves病(GD)患者体内促甲状腺激素受体抗体(TRAb)水平的影响因素。方法初发GD患者378例,采用酶联免疫吸附测定法检测患者血清TRAb,化学发光法检测血清甲状腺过氧化酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)和促甲状腺激素(TSH)。采用多元逐步回归分析法,以TRAb为应变量,以患者年龄、性别、病程、甲状腺质量、TGAb、TPOAb、是否突眼、FT3、FT4和TSH为自变量建立回归方程。结果甲状腺质量及合并Graves眼病(GO)与初发GD患者体内TRAb水平相关。结论甲状腺质量及合并GO是初发Graves病患者体内TRAb水平的影响因素。     

Graves病459例5年追踪研究

目的　研究抗甲状腺药物 (ATD)或甲状腺次全切除术、加碘盐 (AIS)和甲状腺自身抗体对Graves病(GD)的影响。方法　每 3个月观察接受ATD或手术治疗的GD病人复发率、甲状腺自身抗体 ,第 1次复发病例的甲状腺激素和再次ATD治疗的缓解需时及维持ATD用量等 ;比较手术治疗和ATD治疗、AIS饮食或无碘盐(NIS)饮食、自身抗体 (TM -Ab和TG -Ab)增高和自身抗体正常病人的甲亢症状缓解需时、复发率、维持ATD用量、甲状腺激素和甲状腺大小等。结果　手术治疗组病人的TM -Ab水平、甲减发生率、第 1次复发后再次接受ATD治疗缓解后TSH水平明显高于ATD治疗组 (P均 <0 0 5 ) ;而 5年复发率、第 1次复发后的FT3 和FT4 及再次接受ATD治疗的缓解需时和维持ATD用量则明显低于ATD治疗组 (P均 <0 0 5 )。AIS饮食的ATD治疗病人的甲亢缓解需时、1年和 5年复发率、维持ATD用量和FT4 及甲状腺重量明显高于NIS饮食者 (P均 <0 0 5 ) ;而缓解期TSH则明显低于NIS饮食者 (P <0 0 5 )。自身抗体升高病人的 1年和 5年复发率、维持ATD用量和甲减发生率明显高于自身抗体正常者 (P <0 0 5 ) ;而TSH则明显低于自身抗体正常者 (P <0 0 5 )。结论　手术治疗甲亢症的缓解率较高 ,复发时病情较轻 ,再次ATD治疗较易 ;AIS饮食可增加GD病人的ATD治     

甲状腺功能亢进性心脏病危险因素分析

目的 探讨甲状腺功能亢进(简称甲亢)性心脏病发生的危险因素,为控制甲亢性心脏病的发生提供科学依据.方法 2010年3月选择自2000年以来在山东省甲状腺疾病防治中心住院的982例甲亢患者,依据是否并发心脏病分为单纯甲亢组和甲亢性心脏病组,就病因、性别、年龄、病程及游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)、促甲状腺激素受体抗体(TRAb)等因素进行比较,并采用Logistic回归方法对甲亢性心脏病发病相关因素进行分析.结果 甲亢患者并发甲亢性心脏病的患病率为7.7%(76/982),甲亢性心脏病组在年龄、病程、FT3和TRAb水平上分别为[(51.4±11.5)岁、(6.3±2.1)年、21.6pmol/L、71.6 U/L],单纯甲亢组为[(37.9±9.8)岁、(2.6±1.3)年、14.9 pmol/L、49.6 U/L],组间比较,差异有统计学意义(u=9.93、15.23,T=44954、48792.5,P均＜0.05).年龄大、FT3,和TRAb水平高、病程长、毒性弥漫性甲状腺肿(相对危险度值分别为1.751、1.470、1.483、1.445、1.234)并发甲亢性心脏病的危险性大.结论 毒性弥漫性甲状腺肿、高龄、病程长、FT3和TRAb水平高是甲亢性心脏病的危险因素,及时预防和控制甲亢性心脏病的危险因素,减少甲亢性心脏病的发生与死亡.

Abstract：

Objective To study the risk factors of hyperthyroid heart diseases(HHD) by analyzing clinical features of patients in order to provide a scientific basis for prevention and treatment of HHD. Methods Nine hundred and eighty two cases were selected as objective from in-patient data of Thyroid Disease Treatment Centre of Shandong Province. The cases were divided into hyperthyroidism group and HHD group. The variables of etiology,sex, age, duration of disease, TSH, FT3, FT4 and TRAb were analyzed by comparative analysis. The risk factors were analyzed by logistic regression. Results The prevalence of hyperthyroidism complicated hyperthyroid heart disease was 7.7%(76/982), age, duration of diseases, FT3, TRAb in the HHD group were [(51.4 ± 11.5), (6.3 ±2.1) years, 21.6 pmol/L, 71.6 U/L], in hyperthyroidism group were [(37.9 ± 9.8), (2.6 ± 1.3) years, 14.9pmol/L, 49.6 U/L]. The differences were statistically significant(u = 9.93,15.23, T = 44954,48792.5, P ＜ 0.05)between the two groups. The factors of the older, higher FT3 and TRAb, longer duration, Graves disease (OR =1.751,1.470,1.483,1.445,1.234) increased the risk of HHD. Conclusions Graves disease, longer duration, old age, higher FT3 and TRAb are the risk factors of HHD. Timely prevention and control of risk factors is necessary to reduce the incidence of HHD.     

稳心颗粒联合普萘洛尔对甲亢合并房颤患者相关激素水平及心脏功能的影响

目的:观察稳心颗粒联合普萘洛尔对甲状腺功能亢进合并房颤患者相关激素水平及心脏功能的影响。方法:选择我院确诊的甲状腺功能亢进合并房颤患者136例,随机分为普萘洛尔组和联合治疗组(普萘洛尔联合稳心颗粒治疗),各68例,两组均接受常规治疗,治疗8周,观察治疗前后两组患者血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)等激素水平变化及SBP、DBP、HR、LVEF等血压、心功能指标变化。结果:与治疗前比较,治疗后两组患者血清FT3、FT4水平及SBP、DBP、HR均显著降低,血清TSH水平及LVEF值均显著升高(P0.05或0.01);且与普萘洛尔组比较,联合治疗组FT3 [(6.68±1.94)pmol/L比(4.39±1.34)pmol/L]、FT4 [(28.67±5.17)pmol/L比(22.67±4.86)pmol/L]水平及SBP [(127.79±10.86)mmHg比(121.76±9.43)mmHg]、DBP [(81.65±8.41)mmHg比(75.12±8.16)mmHg]、HR [(85.67±7.64)次/min比(80.79±6.47)次/min]降低更显著,血清TSH [(1.28±0.26)mU/L比(1.81±0.34)mU/L]水平及LVEF [(56.28±5.12)%比(59.76±4.25)%]值升高更显著(P0.05或0.01);联合治疗组总有效率明显高于普萘洛尔组(95.59%比82.35%,P=0.014);两组不良反应无显著差异(P=1.000)。结论:稳心颗粒配合普萘洛尔,能显著改善甲状腺功能亢进患者甲状腺相关激素水平和心脏功能,值得临床推广。     

急性冠状动脉综合征患者游离三碘甲状腺原氨酸水平降低与预后的关系研究

目的探讨急性冠状动脉综合征(ACS)患者游离三碘甲状腺原氨酸(FT3)水平与预后的关系。方法选取2012—2014年ACS住院患者489例,测定血清甲状腺激素水平,根据FT3水平将患者分为正常FT3组和低FT3组,随访1年,比较两组患者死亡率及主要不良心血管事件(MACE)发生率。结果低FT3组患者的总胆固醇、载脂蛋白E、空腹血糖及肌酐水平均高于正常FT3组[(6.79±3.17)mmol/L比(4.57±2.92)mmol/L,P0.01;(4.53±1.47)mmol/L比(4.03±1.06)mmol/L,P0.01;(6.64±3.82)mmol/L比(5.88±2.24)mmol/L,P0.01;(116.64±43.20)μmol/L比(97.99±30.85)μmol/L,P0.01],高密度脂蛋白胆固醇低于正常FT3组[(0.98±0.17)mmol/L比(1.03±0.26)mmol/L,P=0.04]。与正常FT3组患者相比,低FT3组患者左心室射血分数更低(54.74%±10.03%比58.71%±7.96%,P0.01),脑利钠肽水平更高[739(304,4 922)pg/ml比140(62,462)pg/ml,P0.01],三支病变的患者比例高(73.3%比43.8%,P0.01)。1年随访结果显示,低FT3患者的总死亡率(13.1%比5.9%,P=0.03)、再次血运重建率(15.4%比7.6%,P=0.02)及MACE发生率(27.4%比14.0%,P0.01)均高于FT3正常组。Kaplan-Meier分析显示,低FT3组1年无MACE累积生存率明显低于正常FT3组(72.6%比86%,log rank P0.01)。Cox比例风险回归模型分析显示,低FT3是MACE的预测因素(HR=0.010,P=0.01)。结论血清FT3水平降低在ACS患者中常见,FT3降低的ACS患者预后更差。     

碘盐对药物治疗Graves病疗效的影响

目的：探讨碘盐对抗甲状腺药物（ATD）治疗Graves病（GD）疗效的影响，从而为临床上碘盐的合理应用提供依据。方法：将49例GD患者随机分为食非碘盐组和食用碘盐组，予ATD治疗并定期测定心率、体重、甲状腺肿大程度、Graves眼病分级、血清T3、T4、FT3、FT4、TSH、TGA、MSA、TRAb，连续观察6个月后，分析比较两组检查结果。结果：（1）非碘盐组与碘盐组患者比较，甲状腺肿大和Graves眼病非碘盐组患者好转更明显，差异有显著意义（P＜0．05）；（2）非碘盐组患者治疗后6个月血清TRAb下降，与治疗前比较差异有显著意义（P＜0．05），而碘盐组患者治疗前后血清TRAb差异无显著意义（P＞0．05）；（3）非碘盐组患者血清TGA、MSA有降低趋势，但与碘盐组与比较差异无显著意义（P＞0．05）；（4）碘盐对GD患者血清甲状腺激素影响不大，对心率、体重变化无影响。结论：食用非碘盐有利于控制GD患者的病情，提示GD患者ATD治疗过程中应食用非碘盐。     

血清TRAb水平与Graves病患者131I治疗后早发甲减的关系

目的探讨血清促甲状腺激素受体抗体(TRAb)水平在Graves病(GD)患者131I治疗后早发甲状腺功能减低(甲减)发生中的作用,为临床随访监测提供依据。方法将123例GD患者按治疗前血清TRAb水平分为TRAb阳性组(TRAb>15 IU/mL)和TRAb阴性组(TRAb≤15 IU/mL),分别于131I治疗前及治疗后3、6、12个月测定血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、促甲状腺激素(TSH)水平,并判定早发甲减发生情况。结果 TRAb阳性组和TRAb阴性组早发甲减率分别为54.72%(29/53)、31.43%(22/70),两组比较P<0.05。结论血清TRAb水平在GD患者131I治疗后早发甲减发生中起重要作用,临床可据此采取相关防治措施。     

Standardized grey scale ultrasonography in Graves' disease: correlation to autoimmune activity.

OBJECTIVE: Graves' disease leads to thyroid enlargement and to reduction of tissue echogenicity. Our purpose was to correlate grey scale ultrasonography of the thyroid gland with clinical and laboratory findings in patients with Graves' disease. DESIGN: Fifty-three patients with Graves'disease were included in our study, 100 euthyroid volunteers served as control group. Free thyroxine (FT(4)), TSH and TRAb (TSH receptor antibodies) values were measured and correlated with sonographic echogenicity of the thyroid gland. METHODS: All patients and control persons underwent ultrasonographical histogram analyses under standardized conditions. Mean densities of the thyroid tissues were determined in grey scales (GWE). RESULTS: Compared with controls with homogeneous thyroid lobes of normal size (25.6 +/- 2.0GWE, mean +/- S.D.) echogenicity in patients with Graves' disease was significantly lower (21.3 +/- 3. 3GWE, mean +/- S.D., P < 0.0001). Among the patients with Graves' disease significant differences of thyroid echo levels were revealed for patients with suppressed (20.4 +/- 3.1 GWE, mean +/- S.D., n=34) and normalized TSH values (22.5 +/- 3.6GWE, mean +/- S.D., n=19, P < 0.02). Significantly lower echogenicities were also measured in cases of persistent elevated TRAb levels (19.9 +/- 2.9GWE, mean +/- S.D., n=31) in comparison with normal TRAb levels (22.9 +/- 3.5 GWE, mean +/- S.D., n=22, P < 0.0015). No correlation could be verified between echogenicity and either still elevated or already normalized FT(4) values or the thyroid volume. In coincidence of hyperthyroidism and Graves' ophthalmopathy (19.7 +/- 3.5GWE, mean +/- S.D., n=23) significantly lower echogenicity was measured than in the absence of ophthalmological symptoms (22.3 +/- 3.3GWE, mean +/- S.D., n=30, P < 0.016). Patients needing active antithyroid drug treatment revealed significantly lower thyroid echogenicity (20.3 +/- 3.1 GWE, mean +/- S.D., n=40) than patients in remission (23.7 +/- 3.4 GWE, mean +/- S.D., n=13, P < 0.001). Statistical evaluation was carried out using Student's t-test. CONCLUSIONS: Standardized grey scale histogram analysis allows for supplementary judgements of thyroid function and degree of autoimmune activity in Graves' disease. Whether these values help to estimate the risk of recurrence of hyperthyroidism after withdrawal of antithyroid medication should be evaluated in a prospective study.     

Plasma free triiodothyronine response to thyrotropin-releasing hormone to predict the remission of Graves' disease treated with antithyroid drugs.

The responses of both plasma TSH and free T3 (FT3) to TRH were examined in 31 patients with Graves' disease who were euthyroid after treatment with antithyroid drugs, 6 patients with primary hypothyroidism, and 14 control subjects. TSH was measured 0, 15, 30, 60, 90, and 120 min and FT3 was measured 0, 30, 60, 90, 120, 150, and 180 min after TRH injection (500 microgram, iv). The increment in FT3 above the basal level (delta FT3) in normal controls ranged from 1.2-3.7 pmol/L, with a mean +/- SD of 2.2 +/- 0.8 pmol/L. The mean (+/- SD) delta FT3 in patients with primary hypothyroidism was 0.3 +/- 0.2 pmol/L. After the TRH test, antithyroid drugs were stopped in patients with Graves' disease. Nine of 31 Graves' patients relapsed within 6 months after the TRH test. The other 22 patients with Graves' disease were followed while in remission during the observation period of up to 48 months. The mean (+/- SD) delta FT3 were significantly lower in 9 Graves' patients who relapsed than in those who achieved remission (0.5 +/- 0.3 vs. 2.6 +/- 1.1 pmol/L; P less than 0.01). Eight of 9 Graves' patients who relapsed showed lower delta FT3 values than the lowest value (1.1 pmol/L) in 22 Graves' patients in remission. Although the mean increment of TSH above the basal level (delta TSH) was also significantly different between the Graves' patients who relapsed and those in remission (1.4 vs. 12.3 mU/L; P less than 0.01), there was considerable overlap between the 2 groups. These findings suggest that delta FT3 reflects the endocrinological recovery of the pituitary-thyroid axis and is a beneficial indicator for the termination of antithyroid drugs in Graves' disease.     

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.     

EVALUATION OF TSH RECEPTOR ANTIBODY BY ''NATURAL IN VIVO HUMAN ASSAY'' IN NEONATES BORN TO MOTHERS WITH GRAVES'' DISEASE

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.     

Serum concentrations of adiponectin and resistin in hyperthyroid Graves' disease patients

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). CONCLUSIONS: Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.     

甲状腺功能亢进性肝损害与甲巯咪唑继发性肝损害的临床比较研究

目的分析甲状腺功能亢进症(简称甲亢)性肝损害患者的肝功能与甲状腺功能的相关性,探讨抗甲亢药物甲巯咪唑所致肝损害患者的临床特征及其引起肝损害的相关因素。方法纳入甲亢性肝病患者54例(甲亢性肝损害组)和初诊未治的无肝损害甲亢患者33例(甲亢无肝损害组),收集两组患者用药前的一般资料和临床资料(甲状腺功能和肝功能),分析甲亢性肝损害的相关因素;将同期抗甲亢药物甲巯咪唑致肝损害患者(27例)根据肝功能指标分为肝细胞型组(7例)、胆汁淤积型组(12例)和混合型组(8例),收集其一般资料和临床资料(甲状腺功能和肝功能)并比较。结果甲亢性肝损害组患者治疗前的ALT、AST、碱性磷酸酶(ALP)、谷氨酰转肽酶(γ-GT)、总胆红素(TBIL)、游离三碘甲腺原氨酸(FT 3)、游离甲状腺激素(FT 4)和促甲状腺激素受体抗体(TRAb)水平明显高于甲亢无肝损害组(P<0.05),两组患者ALT、ALP、γ-GT水平均与FT 3、FT 4、TRAb水平呈明显正相关(P<0.05)。肝细胞型组、胆汁淤积型组和混合型组患者的年龄、用药时间、ALT、ALP比较差异均有统计学意义(P<0.05)。结论甲亢患者甲状腺功能异常的严重程度可能与其肝损害相关;抗甲亢药物甲巯咪唑引起的肝损害类型可能与患者年龄、病程及用药时间有关。     

Elevation of serum adiponectin levels in Basedow disease

The present study was undertaken to determine whether thyroid hormone affects serum adiponectin levels in the patients with Basedow disease. Sixty-four patients with Basedow disease were examined; 32 patients had hyperthyroid state and 32 patients had euthyroid state who had been treated with antithyroid drugs. In addition, 30 age- and sex-matched subjects served as a control. Serum adiponectin, free T4, free T3, thyroid-stimulating hormone, and thyroid-stimulating hormone receptor antibody (TRAb) were measured. Serum adiponectin levels were 12.9+/-1.6 microg/mL in the hyperthyroid state, a value significantly greater than that of 8.2 +/- 0.5 microg/mL in the euthyroid state (P<.05) and that of 8.6+/-0.7 microg/mL in the control subjects (P<.05). Serum adiponectin levels had positive correlations with either of serum free T4 (r=0.453, P<.001), free T3 (r=0.47, P< .001), or TRAb (r= 0.491, P<.001), but not with body mass index. Multiple regression analysis showed TRAb had the strongest contribution to serum adiponectin concentration in the patients with Basedow disease. The present findings indicate that hyper-adiponectinemia is closely associated with increases in serum thyroid hormone levels and TRAb in Basedow disease.     

Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves' hyperthyroidism

We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves' hyperthyroidism. The patients were randomly divided into 2 groups. In group A, 65 patients received either methimazole (MMI): 60 +/- 14.5 mg/day (mean +/- SD); range 40-100 mg/day, or propylthiouracil (PTU): 693 +/- 173 mg/day; range 500-1200 mg/day. These high doses were maintained throughout treatment with later addition of 50-75 micrograms T3 daily. Forty eight patients (group B) were treated with lower doses of MMI or PTU without thyroid hormone addition. The maintenance dose of MMI was 13.6 +/- 7 mg/day (range 5-25 mg/day) and that of PTU was 180 +/- 58 mg/day (range 100-300 mg/day). The treatment period was 15.1 +/- 4.2 (range 10-30) months for group A and 13.5 +/- 2.2 (range 12-20) months for group B. Remission occurred in 75.4% patients from group A and in 41.6% patients from group B (P less than 0.001). The mean follow-up was 42 +/- 14 months (17-81 months). The free T4 index (FT4I) in group A remained below the normal range during treatment. The mean FT4I, obtained during the course of treatment, of patients who went into remission from group A was significantly (P less than 0.001) lower than in relapsed patients (4.8 vs. 6.5). Moreover, there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI (r = -0.567; P less than 0.001), or PTU (r = -0.379; P less than 0.01). A fall in microsomal antibody (MCHA) titer occurred mainly in remission patients, and was more significant (P less than 0.05) in group A patients. In contrast, 11 (7 from group B) of the 16 patients with an increase of microsomal antibody levels relapsed. The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients (71%) than in group B (29%) at the end of therapy (P less than 0.01). No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment. Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen. These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens. Furthermore, a high dosage regimen could permit the restoration of the immune surveillance mechanisms and, thus, lasting remission of Graves' disease.