儿童及青少年Graves病131I治疗后的随访研究

目的 探讨儿童及青少年Graves病131I治疗的随访结果.方法 对161例8～17岁儿童及青少年Graves病患者(男43例,女118例)进行131I治疗.甲状腺按其质量1.85～3.70 MBq/g给药,全疗程剂量范围74～1221 MBq,首次给药剂量中位数为185 MBq.随访24～104个月,平均(62±22)个月.结果 失访14例(8.70%),治愈98例(60.87%),好转9例(5.59%),甲状腺功能亢进症(简称甲亢)复发3例(1.86%),甲状腺功能减退症(简称甲减)37例(22.98%).随访期内未见患者生长发育受影响,亦无致癌致畸.131I治疗对患者及其后代无影响,除甲亢复发和甲减外没有其他不良反应和并发症.结论 131I治疗儿童及青少年甲亢安全有效.     

265例精细个体化131I治疗Graves甲亢的疗效观察

目的 观察265例Graves甲亢患者精细个体化131I治疗后的疗效。 方法 回顾性分析265例应用131I治疗的Graves甲亢患者的临床资料,引入精细个体化治疗方案矫正系数,根据甲状腺大小、最高吸碘率、是否为毒性结节性或毒性弥漫性甲状腺肿等指标对矫正系数进行精细化,进而调整服131I的剂量,跟踪随访至少6个月。 结果 服药后3个月、6个月患者临床症状显著改善,TSH、血清游离三碘甲腺原氨酸、血清游离甲状腺素较治疗前明显降低,131I治疗后3个月和6个月的有效率分别为63.4%和81.5%,甲减率分别为24.9%和27.9%。 结论 精细个体化131I治疗Graves甲亢能够明显改善患者的临床症状,具有比较可靠的治疗效果。     

Graves病的131I治疗和抗甲状腺药物治疗:随机对照试验荟萃分析

目的通过荟萃分析比较131I治疗与抗甲状腺药物治疗对Graves病的临床治疗效果,包括眼病的发生或恶化、甲状腺功能亢进症（甲亢）的治愈率、甲状腺功能减退症（甲减）发生率、复发率和不良反应。 方法以"Graves病"、"放射性碘"、"抗甲状腺药物"、"治疗"等为关键词检索了1990年至2016年在PubMed检索系统、荷兰医学文摘数据库、科学网、中国生物医学文献服务系统（SinoMed）和中国国家知识基础设施（中国知网）等数据库中发表的关于Graves病131I和抗甲状腺药物治疗效果的随机对照试验（RCTs）研究文献,比较131I治疗与抗甲状腺药物治疗对Graves病患者的疗效。采用12.0版Stata软件进行荟萃分析。结果以置信区间95% CIs风险比表示。利用固定效应模型和随机效应模型,根据研究的异质性,进行综合分析。 结果最终纳入了1992年至2015年的17项RCTs,共4024例患者。综合分析结果表明:131I治疗组和抗甲状腺药物治疗组患新眼病率分别为23.3%和16.1%,甲亢的治愈率分别是77.8%和45.6%,甲减发病率分别是19.7%和9.3%,甲亢复发率分别是6.3%和35.0%。131I治疗会增加患者患眼病（RR=1.36,95% CI:[1.04,1.77];P=0.024）、眼病恶化（RR=1.76,95% CI:[1.30,2.38];P < 0.001）和甲减的风险（RR=1.99,95% CI:[1.34,2.98];P=0.001）。但是,与抗甲状腺药物治疗相比,131I治疗的甲亢治愈率高（RR=1.66,95% CI:[1.49,1.86];P < 0.001）、复发率低（RR=0.16,95% CI:[0.08,0.33];P < 0.001）,且不良反应的发生率相对较低（RR=0.22,95% CI:[0.10,0.49];P < 0.001）。 结论与抗甲状腺药物治疗相比,131I治疗的甲亢治愈率相对较高,复发率相对较低。但是,131I治疗同时也会增加患眼病和甲减的风险。因此,要采取更积极的干预措施,以减少和预防这些合并症的发生。     

Graves甲亢合并贫血患者的临床特征和 131I治疗效果的分析

目的 分析Graves甲状腺功能亢进症（简称甲亢）合并贫血患者的临床特征并评价131I治疗的效果。 方法 回顾性分析2018年1月至2019年12月在中国科学技术大学附属第一医院行131I治疗的164例[男性32例、女性132例,年龄（45.47±13.44）岁]Graves甲亢患者的临床资料,根据是否合并贫血将患者分为贫血组（77例）和普通组（87例）。分析贫血组患者的贫血严重程度和细胞学分类,分析和比较2组患者经131I治疗后血红蛋白浓度（HGB）的变化、临床特点及131I治疗甲亢的疗效。计量资料的比较采用两独立样本t检验,计数资料的比较采用卡方检验。 结果 在贫血组中,轻、中度贫血患者分别占92.21%（71/77）、7.79%（6/77）;正常细胞性、小细胞低色素性和大细胞性贫血分别占57.14%（44/77）、41.56%（32/77）、1.30%（1/77）。131I治疗后2~4周,贫血组的HGB恢复率为67.53%（52/77）,贫血组[（104.19±10.56） g/L对（120.90±16.20） g/L]和普通组的HGB[（126.28±10.09） g/L对（137.84±10.41） g/L]较治疗前均明显增高（t=?12.40、?12.57,均P<0.05）。2组Graves甲亢患者在年龄、性别比、甲状腺质量、131I治疗剂量及每克甲状腺组织131I剂量方面的差异均无统计学意义（t或χ2值分别为0.06、0.00、0.30、?0.62、?0.04,均P>0.05）。2组患者Graves甲亢总治愈率为87.20%（143/164）,贫血组和普通组的治愈率分别为87.01%（67/77）和87.36%（76/87）,且差异无统计学意义（χ2=0.00,P>0.05）。 结论 Graves甲亢合并贫血患者以轻度、正常细胞性贫血多见,其131I治疗效果与普通的Graves甲亢患者类似,大部分患者的HGB在131I治疗后短期内可恢复正常。     

131I合并小剂量碳酸锂治疗Graves病的临床探讨

目的探讨放射性核素131I合并小剂量碳酸锂治疗Graves病的临床疗效。方法治疗前口服碳酸锂250mg,1次/d,共5周。于第三周末给予Graves患者一次性口服131I,剂量为3.15MBq(80uCi)/g甲状腺组织的60%～70%。随访时间6～24个月(平均14个月),按随访结果分成痊愈、好转、无效三类。结果单次131I合并小剂量碳酸锂治疗Graves患者,痊愈率(106例)、好转率(28例)、无效率(8例)分别为74.6%、19.7%、5.6%,对23例Graves患者进行重复治疗(未再次服用碳酸锂)后痊愈为10例、好转8例、无效5例,分别占43.5%、34.8%、21.7%。其中,首次131I治疗后半年随访为甲状腺功能减退症(简称甲减)者25例,占17.6%。结论131I合并小剂量碳酸锂治疗Graves病疗效显著,同时可以减少131I的使用剂量,降低了药物的毒性反应。     

500例Graves病患者131I治疗后3年随访分析

目的 分析500例Graves病患者131I治疗后3年内不同时期甲状腺功能亢进症(简称甲亢)缓解率和甲状腺功能减退症(简称甲减)发生率,探讨早发甲减的发展规律以及影响131I治疗的因素.方法 500例131I治疗后3年的Graves病患者,平均年龄(39.3±12.6)岁,男女比例1∶5.收集每例患者资料,包括症状、体征、实验室检查、24h摄碘率、有效半衰期、131I剂量,治疗后3、6、9个月以及1、2、3年的甲亢缓解和甲减发生例数,并观察早发甲减者的甲状腺功能变化.用SPSS 15.0软件对数据行t检验、x2检验及多因素logistic逐步回归分析.结果 131I治疗后3个月甲亢缓解率63.8％(319/500),甲减发生率36.6％(183/500);6个月甲亢缓解率67.8％(339/500),甲减发生率43.4％(217/500);9个月甲亢缓解率70.0％(350/500),甲减发生率39.4％(197/500);1年甲亢缓解率72.6％(363/500),甲减发生率38.2％(191/500);2年甲亢缓解率79.6％(398/500),甲减发生率40.8％(204/500);3年甲亢缓解率90.8％(454/500),甲减发生率46.0％(230/500).84例(16.8％)首次治疗后疗效不佳,进行了第2次治疗.260例初次治疗后发生早发甲减,治疗后3年其中70例(26.9％)甲状腺功能恢复正常,178例(68.5％)持续甲减,12例(4.6％)甲亢复发.单次131I治疗后3年甲状腺功能正常192例,甲减200例,此392例为成功组,84例2次治疗者为失败组.对成功组与失败组数据进行单因素分析,筛选出ATD治疗(x2=16.758,P＜0.01)、TRAb(t=-2.074,P=0.039)、甲状腺摄碘率(t=-2.229,P=0.026)、有效半衰期(t=3.827,P＜0.01)、SPECT测定的甲状腺质量(t=-3.153,P =0.002)、每克甲状腺组织计划剂量(t=-2.154,P =0.032)和实际剂量(t=-1.985,P=0.048)为影响131I治疗的有关因素.将这些有关因素进行logistic逐步回归分析,得ATD治疗(Wald=14.227,P＜0.01)和有效半衰期(Wald=4.497,P=0.034)是影响131I成功治疗的因素.结论 131I治疗Graves病后3年,甲亢缓解率高,但甲减发生率也高.大部分早发甲减患者仍持续甲减,少数甲状腺功能恢复正常或甲亢复发.ATD治疗和有效半衰期是影响131I成功治疗的重要因素.     

131I治疗青少年Graves病58例临床分析

目的 研究131I治疗青少年Graves病的可行性和安全性.方法 回顾性分析58例经131I治疗的青少年Graves病患者,分别于131I(剂量:148～240.5MBq)治疗前和治疗6个月后,用化学发光免疫法检测血清游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平及用彩色多普勒超声测量甲状腺大小;随访2～7年,评价疗效.结果 治疗6个月后,血清FT3和FT4水平明显降低(t=12.43,t=21.21,P均＜0.01),TSH水平明显升高(t=10.34,P＜0.01),甲状腺体积明显缩小.58例患者中,治愈31例(53.45%),好转16例(27.59%),无效7例(12.07%),甲减3例(5.17%),复发1例(1.72%).结论 131I治疗青少年Graves病安全有效.     

131I治疗甲亢后61例早发甲状腺功能减低分析

目的分析131I治疗甲亢后发生早发甲状腺功能减低(甲减)的转归及与转归有关的因素.方法 61例甲亢经131I治疗后的早发甲减患者,随访1年以上,根据随访结果分为暂时性甲减组(包括转为正常或甲亢者)和永久性甲减组,比较了两组间早发甲减的出现时间、性别、TGA和TMA、甲状腺重量、131I治疗剂量、甲状腺摄碘率峰值.结果 61例患者中有一半以上为暂时性甲减(3.3%转为甲亢,50.4%转为正常).根据甲减出现的时间不同分为≤3个月、4～6个月、>6个月,131I治疗6个月后出现的甲减均为永久性甲减.其他参数与早发甲减的转归无关.结论早发甲减绝大多数为暂时性甲减,甲减出现的时间可能与其转归有关.     

Graves甲亢患者131I治疗后早期TRAb及TSAb变化的研究分析

目的 探讨和分析131I治疗Graves甲亢后早期促甲状腺素受体抗体(TRAb)和甲状腺刺激抗体(TSAb)的变化及其相关性。 方法 随机选择了89例Graves甲亢患者, 其中, 未行131I治疗的47例患者为对照组, 131I治疗后3个月的42例甲亢患者为观察组。两组患者均进行了血清游离三碘甲状腺原氨酸(FT₃)、血清游离甲状腺素(FT₄)、TSH、TRAb、TSAb和甲状腺刺激阻断性抗体(TSBAb)的测定。FT₃、FT₄、TSH采用化学发光法测定。TRAb采用放射受体分析法测定。TSAb、TSBAb采用酶联免疫法测定。 结果 观察组和对照组中的TRAb阳性率分别为78.6%(33/42)和36.2%(17/47);TSAb、TSBAb阳性率分别为38.1%(16/42)、0(0/42)和53.2%(25/47)、6.4%(3/47);TSAb与TRAb均为阳性的病例数分别为13例、15例; TSBAb为阳性的病例数分别为0例和3例, 其中3例TSBAb阳性的患者, 2例伴有TSAb和TRAb阳性, 1例伴有TSAb阳性和TRAb阴性。 结论 131I治疗后3个月时, 多数Graves甲亢患者的血清TRAb异常增高; 131I治疗后早期异常升高的TRAb只有部分(39.4%, 13/33)显示TSAb增高, 表明131I治疗后异常升高的TRAb多数并无TSAb功能。     

1003例Graves病131I治疗临床分析

目的探讨个体化131I剂量治疗Graves病的效果.方法根据经验结合国内外文献,给予Graves病患者个体化的每克甲状腺组织剂量,范围为1.48～4.07 MBq/g.对治疗后甲状腺毒症、甲状腺肿(简称甲肿)、Graves眼病、甲状腺功能亢进(简称甲亢)性心脏病(简称甲心病)和周期性麻痹的转归进行临床随访,成功随访1003例(76.9%).131I使用剂量平均(329.3±307.1,44.4～3700)MBq,随访(16.4±10.0,3.0～44.7)个月.结果1次131I治疗后甲状腺功能(简称甲功)恢复正常593例(59.1%),甲状腺功能减退(简称甲低)200例(19.9%),甲亢部分缓解190例(18.9%),治疗无效20例(2.0%).259例(25.8%)发生了早发甲低,其中88例为一过性甲低,Logistic逐步回归分析示甲肿质硬者易发生早发甲低,而甲肿体积较大者早发甲低易转归为甲功正常或甲亢.等级偏相关分析示甲肿较大、病程较长和使用过抗甲状腺药物者对131I治疗反应较差.131I治疗后Graves眼病痊愈195例(41.7%),好转155例(33.1%),无效105例(22.4%),加重13例(2.8%).131I治疗后甲心病痊愈56例(77.8%),好转10例(13.9%),无效6例(8.3%).131I治疗后周期性麻痹痊愈60例(85.7%),好转2例(2.9%),无效8例(11.4%).131I治疗后249例巨大甲肿(≥90g)患者中88.0%(219例)甲状腺基本恢复正常.结论个体化131I剂量治疗Graves病疗效良好.131I对Graves眼病、甲心病和巨大甲肿性Graves病的治疗有效、安全.     

131I治疗Graves病后暂发性甲低的临床分析

目的：探讨^131I治疗后暂发性甲低的临床特点和转归。方法：对32例^131I治疗后出现暂发性甲低的患者进行临床分析和随访。结果：暂发性甲低出现在^131I治疗后2～6个月，有甲低症状者19例(59．38％)。甲低缓解后甲状腺功能正常者20例(62．5％)，又甲亢者12例(37．5％)。甲低时，T3和T4明显降低，TSH变化不一。结论：暂发性甲低多发生在低剂量^131I治疗的患者，甲低缓解后部分患者可再次出现甲亢。     

Iodine-131: optimal therapy for hyperthyroidism in children and adolescents?

To assess the medium- to long-term effects of I-131 therapy of hyperthyroidism in children and adolescents, we studied 51 patients (age range 6--18; boys, 43 girls) treated with I-131 for Graves' disease with hyperthyroidism at the University of Michigan Medical Center (1951--1972). Patients received total doses ranging from 3 to 81.6 mCi. The mean followup period was 14.6 +/- 7.9 yr. Hyperthyroidism was effectively treated in 49 within 1 to 12 mo. One patient failed to respond to three treatment doses, and hyperthyroidism recurred in two patients: 2 and 11 yr after initial therapy. Of these three patients, two were treated by thyroidectomy and one was retreated successfully with I-131. There were no cases of thyroid cancer, other malignancies or leukemia. The patients' reproductive histories and the health of their offspring were as in the general population. At the time of study, the prevalence of hypothyroidism was 92%, with no recurrent goiters or thyroid nodules. Iodine-131 is found to be safe and effective treatment of hyperthyroidism in children and adolescents and should be the preferred mode of therapy.     

Graves病药物治疗后TSH增高伴摄99Tcm增强患者131I治疗

目的：探讨甲状腺功能亢进症（甲亢）抗甲状腺药物（ATD）治疗后促甲状腺激素（TSH）增高伴摄99Tcm增强患者131I治疗的可能性和必要性。方法：27例经临床ATD治疗后TSH增高伴摄99Tcm增强患者分3组，治疗组15例，及时进行131I治疗；随访观察组12例，仅作随访观察，均随访年，结果：治疗组15例中9例血清游离三碘甲状腺原氨酸（FT3），游离甲状腺激素（FT4），TSH水平及甲状腺显像均恢复正常。有2例5－6个月复查甲亢复发，第2次治疗后恢复正常，1例为早发甲低，甲低发生率为6．7％，随访观察组12例在1－4个月内均复发为典型甲亢，复发率100％，结论：甲亢ATD治疗后TSH增高伴摄99Tcm增强患者宜及时进行131I治疗。     

Radioiodine treatment of solitary functioning thyroid nodules

Forty-eight patients with hyperthyroidism due to a single toxic nodule have been treated with radioiodine (131I). The mean follow-up period is 37 months. All patients were rendered euthyroid and no cases of hyperthyroidism have been observed. Forty patients required only one dose of 131I to render them euthyroid, six patients required more than one dose and two patients initially rendered euthyroid relapsed during follow-up and required further 131I treatment. It is concluded that a single fixed dose of 131I is a simple, effective treatment for a solitary toxic thyroid nodule and does not cause hypothyroidism.     

Radioiodine treatment of non-toxic multinodular goitre: effects of combination with lithium

Purpose This study aimed to evaluate the effects of radioiodine (¹³¹I), alone or in combination with lithium, on thyroid volume and the prevention of radioiodine-induced thyrotoxicosis. This is the first clinical trial including only patients with multinodular goitre, normal TSH values and negative anti-thyroid auto-antibodies at baseline.Methods Eighty consecutive patients were randomised to receive ¹³¹I plus lithium (group I+L) or ¹³¹I alone (group I). Thyroid ultrasonography and biochemical analyses were performed at baseline and at 1, 3, 6, 12 and 24 months after treatment.Results At 1–4 weeks after treatment, ¹³¹I-induced hyperthyroidism was observed in 58.8% of patients and was prevented by lithium administration. A low incidence of hypothyroidism (19%) was recorded at 24 months, whereas up to 44% of patients developed anti-thyroid antibodies. A significant reduction in thyroid volume was observed after ¹³¹I, with a mean decrease of 47.2% (median 48.2%) at 24 months, without differences between the groups. Moreover, it was shown that the decrease in thyroid volume after ¹³¹I was also due to the significant shrinkage of thyroid nodules.Conclusion This demonstrates that adjunctive lithium is able to reduce radioiodine-induced hyperthyroidism. Therefore, such treatment appears to be safe in older patients and those with underlying cardiovascular disease. In the present large series, ¹³¹I therapy was demonstrated to be highly effective in reducing thyroid and nodular volume even in patients treated with low ¹³¹I doses (2.5 MBq/ml of thyroid tissue), further supporting the view that radioiodine therapy represents a real alternative to surgery.     

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 (131I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule. The risk of development of hypothyroidism is low if extranodular uptake of 131I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.     

Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.     

Functional results of radioiodine therapy with a 300-GY absorbed dose in Graves' disease

The aim of this study was to assess the results of high-dose radioiodine therapy given to 43 patients with recurrent hyperthyroidism due to Graves' disease between 1986 and 1992. We chose an intrathyroidal absorbed dose of 300 Gy and determined the applied activity individually, which ranged from 240 to 3120 MBq with a median of 752 MBq. Hyperthyroidism was eliminated in 86% of cases after 3 months and in 100% after 12 months. No patient required a second radioiodine treatment. The incidence of hypothyroidism was 63% after 3 months and 93% after 18 months. Neither the pretherapeutic thyroid-stimulating immunoglobulin level nor the degree of co-existing endocrine ophthalmopathy was correlated with the time at which hypothyroidism developed. Patients with previous radioiodine therapy developed hypothyroidism earlier than patients with previous thyroid surgery. The results show that ablative radioiodine therapy with a 300-Gy absorbed dose is a very effective treatment of hyperthyroidism in Graves' disease, but it should be restricted to patients with recurrent hyperthyroidism combined with severe co-existing disorders or episodes of unfavourable reactions to antithyroid drugs. Correspondence to: U.F. Willemsen