甲状腺疾病的放射性核素治疗

1、 第三军医大学一院第三军医大学一院 内分泌科内分泌科131碘 到 病 除131I治疗后治疗后前位前位后位后位治疗前治疗前前位前位后位后位中华医学会核医学分会普查结果中华医学会核医学分会普查结果甲亢年治疗量超过万人甲亢年治疗量超过万人次以上的省份有：次以上的省份有：广东广东 25110，四川四川 15526，广西广西 12629，湖北湖北 11691，吉林吉林 10650，甲亢年治疗量较多的单甲亢年治疗量较多的单位有：位有：核工业核工业416医院医院 8235解放军解放军321医院医院 5000枝江市人民医院枝江市人民医院 3778梅州市人民医院梅州市人民医院 3714解放军解放军303医院医院

2、 3260哈尔滨医大二院哈尔滨医大二院 3260李亚明教授提供李亚明教授提供按我国甲亢患病率按我国甲亢患病率1%计算，接受计算，接受131I治疗的患者为治疗的患者为3.62%。153Sm/89Sr治疗骨转移癌治疗骨转移癌125I/ 103Pd粒子治疗恶性肿瘤粒子治疗恶性肿瘤32P胶体腔内治疗胶体腔内治疗原发性骨髓原发性骨髓增生性疾病增生性疾病放射免疫治疗放射免疫治疗冠脉内照射治冠脉内照射治疗血管再狭窄疗血管再狭窄 核素放射治疗 治好了我治好了我老爸的甲亢！老爸的甲亢！具体使用剂量可根据甲状腺摄碘率、甲状腺具体使用剂量可根据甲状腺摄碘率、甲状腺估重、病情等因素，按经验公式加以计算。估重、病情等因

3、素，按经验公式加以计算。 计划甲状腺吸收剂量（计划甲状腺吸收剂量（Gy）131I ITp（d）甲状腺重（甲状腺重（g）37 131I治疗量（治疗量（Bq）= 1.2131I ITeff（d）甲状腺甲状腺131I I最高摄取率（最高摄取率（%） 按甲状腺吸收剂量计算按甲状腺吸收剂量计算: : 一般为一般为6080Gy(600015000rad) TpTp物理半衰期物理半衰期 TeffTeff有效半衰期有效半衰期 1.21.2为为37KBq(137KBq(1 Ci)Ci)131131I I给予甲状腺组织的辐射吸收剂量（给予甲状腺组织的辐射吸收剂量（GyGy）具体使用剂量可根据甲状腺摄碘率、甲状腺具

4、体使用剂量可根据甲状腺摄碘率、甲状腺估重、病情等因素，按经验公式加以计算。估重、病情等因素，按经验公式加以计算。 计划每克甲状腺摄取计划每克甲状腺摄取131I I活度（活度（Bq或或 Ci ）甲状腺重（甲状腺重（g） 131I治疗量（治疗量（Bq）= 甲状腺甲状腺131I I最高摄取率（最高摄取率（%） 按每克甲状腺摄取活度计算按每克甲状腺摄取活度计算: 一般为一般为70120 Ci 131I /g 该公式假设该公式假设TeffTeff（有效半衰期）按有效半衰期）按5 5天计算；天计算； 若若TeffTeff与此差别太大，可将计算结果乘以与此差别太大，可将计算结果乘以5/Teff 5/Teff

5、 加以矫正。加以矫正。131I治疗甲亢安全性良好治疗甲亢安全性良好恶性肿瘤恶性肿瘤总发病率总发病率低于普通人群低于普通人群恶性肿瘤标化发病率（SIR）注：SIR, Standardised Incidence Ratio，标化发病率 P=0.0001Jayne A Franklyn, et al. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet 1999; 353: 211115.74177417例应用例

6、应用131I131I治疗的甲亢患者（治疗的甲亢患者（7207372073人人* *年随访）年随访）131I治疗甲亢安全性良好治疗甲亢安全性良好恶性肿瘤恶性肿瘤死亡率死亡率与普通人群无异与普通人群无异标化恶性肿瘤死亡率（SMR ）回顾性研究，35593例甲亢患者，分别接受131I、手术、抗甲状腺药物治疗。其中65%的患者接受131I治疗。评估这些甲亢患者尤其是应用131I治疗后的癌症死亡率。 特殊情况特殊情况 甲状腺危象甲状腺危象 Graves眼病眼病治疗转归治疗转归 多数甲亢性心脏病患者经131I治疗，甲状腺功能正常后，其心脏功能完全或部分恢复正常； 如甲亢性心脏病病程长、甲状腺肿大明显者，1

7、31I缓解甲亢性心脏病的疗效较差。强调131I治疗后终生随诊的重要！及时纠正甲减！研究报道：并发有甲状腺功能亢研究报道：并发有甲状腺功能亢进性心脏病的患者应用放射碘治进性心脏病的患者应用放射碘治疗作为单一方案治疗后并不使心疗作为单一方案治疗后并不使心脏症状加重。脏症状加重。Thyrocardiac Disease and Its Management with Radioactive Iodine I131Clement Delit;Solomon Silver;Stephen B. Yohalem;Robert L. Segal.AbstractHyperthyroidism was tre

8、ated with I131 in 1,603 cases. These included cases of diffuse toxic goiter and nodular goiter with hyperthyroidism. There were 187 patients with congestive heart failure, 30 with angina pectoris, and 32 with combined angina pectoris and congestive failure. In addition, there were 107 patients with

9、atrial fibrillation but without congestive failure or angina. Radioiodine was the only treatment used for the hyperthyroid state. The cardiac status was strikingly improved in all groups studied. The number of treatments and incidence of myxedema was almost the same for the cardiac and noncardiac pa

10、tients. The total administered dose averaged 7.0 millicuries for the entire series and 11.5 for the cardiac patients. The recurrence rate was less than 1%. The authors believe that I131 is the treatment choice for thyrocardiac disease.ATA316-317甲亢治疗方法 例数 改善% 无变化无变化% 恶化% 甲巯咪唑 148 2 95 3 131I 150 0 85

11、 15 131I + 泼尼松 145 35 65 0GO恶化率恶化率Bartalena et al N Engl J Med 1989, 321:1349Bartalena L, Baldeschi L, Dickinson A, et al. Consensus statement of the European Group on Graves orbitopathy(EUGOGO) on management of GO. Eur J Endocrinol, 2008, 158: 273-285. 2.Pinchera A 1998 Relation between therapy for

12、 hyperthyroidism and the course of Graves ophthalmopathy. N Engl J Med. 338:73-78338:73-783.Thyroid-associated ophthalmopathy after treatment for Graves hyperthyroidismwith antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009;94:3700-7一项大型的随机对照研究显示放射碘治疗一项大型的随机对照研究显示放射碘治疗GD与与GO进展进展的风险升高相关（与的

13、风险升高相关（与ATDs相比相比RR=5.8），且这种风险），且这种风险能够被能够被糖皮质激素糖皮质激素联合治疗抵销联合治疗抵销2 。研究提示主动吸烟者接受放射碘治疗后研究提示主动吸烟者接受放射碘治疗后1年随访中年随访中GO发生或恶化的发生率最高发生或恶化的发生率最高(23-40%) 2 。多项研究都一致认为：吸烟对放射碘治疗患者多项研究都一致认为：吸烟对放射碘治疗患者GO存在存在有害的影响。这种风险是与每日吸烟数量成比例的，有害的影响。这种风险是与每日吸烟数量成比例的，既往吸烟患者的风险仍明显低于目前吸烟患者。既往吸烟患者的风险仍明显低于目前吸烟患者。1.Pfeilschifter J, Z

14、iegler R 1996 Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf). 45:477-48145:477-481文献报道文献报道131I治疗加重突眼病情在吸烟者中更明显治疗加重突眼病情在吸烟者中更明显3Tallstedt L, Lundell G, Blomgren H, Bring J 1994 Does early administration of thyroxin

15、e reduce the development of Graves ophthalmopathy after radioiodine treatment? Eur J Endocrinol. 130:494-497. Perros P, Kendall-Taylor P, Neoh C, Frewin S, Dickinson J 2005 A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves ophthalm

16、opathy. J Clin Endocrinol Metab. 90:5321-5323.Saara Metso, et al. Long-term follow-up study of radioiodine treatment of Hyperthyroidism. Clinical Endocrinology (2004) 61, 641648.Joyce Sy, et al. Usage of a fixed dose of radioactive iodine for the treatment of hyperthyroidism: one-year outcome in a r

17、egional hospital in Hong Kong. Hong Kong Med J 2009;15:267-73.Robert A, et al. Optimal iodine-131 dose for eliminating hyperthyroidism in Graves disease. J Nucl Med 1991,32:411-416.大剂量131I比小剂量131I治疗能更快实现甲亢治愈更快实现甲亢治愈，从而降低甲亢相关的死亡率。131I治疗是安全的，但是大多数患者会发生治疗后甲减，需要个体化剂量的甲状腺激素终生替代治疗。这种疗法既解决了甲亢的治疗问题，也最大限度降低了

18、甲减相关性疾病发生率6 美国内分泌医师学会（AACE）甲亢及甲减临床指南甲亢并发症严重危害患者健康甲亢并发症严重危害患者健康131I治疗甲亢疗效好治疗甲亢疗效好P0.01发生率（%）治愈时间（月）Chen DY, et al. Comparison of the long-term efficacy of low dose 131I versus antithyroid drugs in the treatment of hyperthyroidism. Nucl Med Commun. 2009 Feb;30(2):160-8.前瞻性、随机研究，纳入前瞻性、随机研究，纳入2021例甲亢患者，

19、分别接受抗甲状腺药物或例甲亢患者，分别接受抗甲状腺药物或131I治疗，平均随访治疗，平均随访98个月。个月。*#131131I I治疗甲亢疗效显著治疗甲亢疗效显著131131I I治疗甲亢治愈时间快治疗甲亢治愈时间快*P=0.000#P=0.001几个主要观点几个主要观点过去认为：甲减是过去认为：甲减是131I治疗的并发症或副作用等。治疗的并发症或副作用等。现在观点：甲减是治疗的一种转归或是期望的结局。现在观点：甲减是治疗的一种转归或是期望的结局。131I治疗甲亢后治疗甲亢后甲减发生率高，甲减发生率高，早发晚发早发晚发有所不同有所不同1.131I治疗Graves甲亢专家共识2.Aftab M

20、Ahmad, et al. Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment ofThyrotoxicosis. European Journal of Endocrinology (2002) 146 767775.3.131I治疗甲状腺功能亢进症远期观察。中华核医学杂志，1984，4：7-11国外资料国外资料国内资料国内资料晚发甲减晚发甲减发生率与发生率与131I治疗剂量无关治疗剂量无关晚期甲减发生率（%）Leslie, W.D

21、,(2003) A randomized comparison of radioiodine doses in Graves hyperthyroidism. Journal of Clinical Endocrinology and Metabolism, 88, 978983.低固定剂量：235 MBq高固定剂量：350 MBq低调节剂量：2.96 MBq (80Ci)/g 甲状腺，经24h131I摄取率调节高调节剂量：4.44 MBq(120Ci)/g 甲状腺，经24h131I摄取率调节 甲亢治疗后发生甲低甲亢治疗后发生甲低与甲状腺细与甲状腺细胞转换速度和甲胞转换速度和甲状腺的增殖能力状

22、腺的增殖能力有关。而不是有关。而不是131131I I剂量。剂量。永久性甲低永久性甲低不同于早发甲不同于早发甲低，它低，它不是辐射不是辐射的直接结的直接结果果与自身与自身免疫过程免疫过程有关有关与甲亢与甲亢的自然病的自然病程有关程有关相比甲亢相比甲亢甲减的治疗更容易，危害程度更轻甲减的治疗更容易，危害程度更轻陈汉华. 131 碘治疗甲状腺功能亢进症7170例疗效总结.柳州医学.2008 年第21 卷第3 期廖学权等.甲状腺功能减退症的内分泌治疗.中国医药导报. 2010 年5 月第7 卷第13 期郭根武等. 碘-131治疗甲状腺功能亢进症治疗效果分析. 中国辐射卫生,2009,18(3)优甲乐

23、优甲乐支持放射性碘治疗甲亢导致甲减支持放射性碘治疗甲亢导致甲减Thyroid Function and Mortality in Patients Treated for HyperthyroidismJayne A. Franklyn, Michael C. Sheppard, Patrick MaisonneuveJAMA. 2005 Jul 6;294(1):71-80RESULTS: In 15,968 person-years of follow-up, 554 died vs 487 expected deaths (standardized mortality ratio SMR

24、, 1.14; 95% confidence interval CI, 1.04-1.24, P=.002). Increased risks of all-cause and circulatory deaths vs age- and period-specific mortality were observed in follow-up in those not requiring, or prior to, T(4) therapy. These increased risks were not observed during follow-up on T(4) therapy (ci

25、rculatory disease SMR prior to T(4), 1.33; 95% CI, 1.14-1.53 vs SMR, 0.91; 95% CI, 0.70-1.17 during T(4). Patients receiving T(4) had decreased risk of mortality vs risk in the period not requiring, or prior to, T(4) therapy (all-cause mortality hazard ratio HR, 0.65; 95% CI, 0.54-0.79; circulatory

26、mortality HR, 0.65; 95% CI, 0.48-0.87). Increased all-cause mortality vs the background population was observed in the period prior to T(4) therapy in follow-up associated with low, normal, and high serum thyrotropin. The SMR for ischemic heart disease increased slightly when analyzed by serum thyro

27、tropin, high serum thyrotropin being the highest SMR (low thyrotropin SMR, 1.06; 95% CI, 0.75-1.45; normal thyrotropin SMR, 1.17; 95% CI, 0.76-1.71; high thyrotropin SMR, 1.48; 95% CI, 0.86-2.37). Comparison within the cohort showed that mild hypothyroidism prior to T(4) therapy was associated with

28、increased risk of mortality from ischemic heart disease vs biochemical euthyroidism (HR, 2.08; 95% CI, 1.04-4.19).CONCLUSIONS: Patients treated with radioiodine for hyperthyroidism had increased mortality vs age- and period-specific mortality in England and Wales, a finding no longer evident during

29、T(4) therapy. This supports treating hyperthyroidism with doses of radioiodine sufficient to induce overt hypothyroidism. The association within the cohort of mortality from ischemic heart disease with subclinical hypothyroidism suggests T(4) replacement should be considered should this biochemical

30、abnormality develop after radioiodine therapy.结果认为放射性碘治疗后甲减结果认为放射性碘治疗后甲减接受接受T4治疗的患者死亡率与背治疗的患者死亡率与背景人群相似。景人群相似。131I治疗治疗GD出现出现甲减，替代治疗甲减，替代治疗对存活无影响。对存活无影响。甲减的替代治疗是安全、简便的。甲减的替代治疗是安全、简便的。但在内科学界尚不能完全接受此观点，但在内科学界尚不能完全接受此观点，有些内科医生经常有些内科医生经常“告诫告诫”患者，患者，“不不要接受要接受131I治疗，甲减比甲亢更难治治疗，甲减比甲亢更难治”等。等。在有关在有关131I治疗后甲减引

31、起的医疗纠纷治疗后甲减引起的医疗纠纷中，有些就是因为内科医生的中，有些就是因为内科医生的“忠告忠告”而引发的。而引发的。应该沟通，达成共识。应该沟通，达成共识。一般情况下，一般情况下，131I治疗前停服治疗前停服MMI27d, PTU 24周周。Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials.Walter MA,et al. BMJ. 2007 Mar 10;334(7592):514 Abstra

32、ct OBJECTIVE: To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment.DESIGN: Meta-analysis.DATA SOURCES: Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched t

33、o August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects

34、model.RESULTS: We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroid

35、ism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment.CONCLUSIONS: Antithyroid drugs potentially increase rates of failure and re

36、duce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.Pretreatment with propylthiouracil but not methimazole reduces the therapeutic efficacy of iodine-131 in hyperthyroidism.Imseis RE, Vanmiddlesworth L, Massie JD, Bush AJ, Vanmiddlesworth NR

37、.J Clin Endocrinol Metab. 1998 Feb;83(2):685-7 AbstractNinety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were

38、discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-5

39、5 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used

40、as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one stud

41、y, the effects of pretreatment with PTU and MMI on 131I therapy. 抗甲状腺药物可能增抗甲状腺药物可能增加首次剂量放射碘治加首次剂量放射碘治疗失败的几率疗失败的几率这种现象发生在使这种现象发生在使用用PTU的患者中，的患者中，而在使用而在使用MMI治疗的治疗的患者中并未有此现患者中并未有此现象发生象发生u131I治疗前治疗前 过去认为：甲状腺激素水平降至正常。过去认为：甲状腺激素水平降至正常。 现在倾向：甲状腺激素水平偏高可用。摄现在倾向：甲状腺激素水平偏高可用。摄131I率保持率保持在较高水平，有利于在较高水平，有利于131I的摄

42、取。的摄取。u131I服药后服药后 过去观点：使用过去观点：使用131I治疗后，不再用治疗后，不再用ATD。 现在观点：服用现在观点：服用131I后，短期少量的后，短期少量的ATD辅助治疗效辅助治疗效果更好。果更好。uATD药物类中赛治对药物类中赛治对131I吸收、排泄的影响较小。吸收、排泄的影响较小。u提倡联合治疗，综合治疗。提倡联合治疗，综合治疗。观念更新观念更新适应证适应证对儿童应该用甲巯咪唑治疗对儿童应该用甲巯咪唑治疗1-2年，对年，对10岁以上的少岁以上的少年而言放射治疗、手术或抗甲状腺药物都可以选择。年而言放射治疗、手术或抗甲状腺药物都可以选择。Radioiodine Therap

43、y for HyperthyroidismRadioiodine Therapy for HyperthyroidismDouglas S. Ross, M.D. N Engl J Med 2011;364:542-50Douglas S. Ross, M.D. N Engl J Med 2011;364:542-50131131I I治疗在很小的治疗在很小的儿童儿童(5(5岁岁) )中应避免中应避免。131131I I剂量经剂量经计算所得计算所得10 mCi150 Ci150 Ci，可接受可接受131131I I 治疗。治疗。若恰当使用，放射碘在儿科若恰当使用，放射碘在儿科GD患者是有效的治

44、疗手患者是有效的治疗手段。段。Rivkees SA, Sklar C, Freemark M 1998 Clinical review 99: The management of Graves disease in children,with special emphasis on radioiodine treatment. J Clin Endocrinol Metab. 83:3767-3776Levy WJ, Schumacher OP, Gupta M 1988 Treatment of childhood Graves disease. A review with emphasis

45、 on radioiodine treatment. Cleve Clin J Med. 55:373-382.国外学者观点国外学者观点经经131I治疗的青少年患者，成年后生育情况与普通人群无异治疗的青少年患者，成年后生育情况与普通人群无异研究结论：接受高剂量131I治疗的青少年患者，其生育功能未受任何影响。Salil D. Sarkar, et al. Subsequent fertility and birth histories of children and adolescents treated with 131I for thyroid cancer. J Nuci Med,197

46、6,17:460-464.40例20岁及以下经131I治疗的青少年患者，电话随访成年后生育情况。A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves patients.Read CH Jr, Tansey MJ, Menda Y. J Clin Endocrinol Metab. 2004 Sep;89(9):4227-8. AbstractThis report details the 26- and 36-yr outcomes o

47、f 116 patients under the age of 20 yr with Graves disease who were treated with radioiodine between 1953 and 1973. Contacted by telephone and mail in 1991-1992, 107 of them supplied personal historical data, and their physicians furnished interval histories, physical examinations, and laboratory dat

48、a. This was repeated in 2001-2002, with 98 of them being contacted. At the time of treatment, the patients ages ranged between 3 yr, 7 months and 19 yr, 9 months. Six were less than 6 yr of age, 11 were between 6 and 11 yr, 45 were between 11 and 15 yr, and 45 were between 16 and 19 yr. The average length of fo