蔣寧一共識(shí)解讀.ppt

1、131I治療Graves甲亢專家共識(shí),解讀,中山大學(xué)孫逸仙紀(jì)念醫(yī)院核醫(yī)學(xué)科 蔣寧一,內(nèi)容提要,共識(shí)形成的背景 共識(shí)導(dǎo)讀要點(diǎn) 臨床基礎(chǔ) 療效評(píng)價(jià)與隨訪 安全性評(píng)價(jià) 合并癥處理原則 幾個(gè)主要觀點(diǎn) 131I治療甲亢的目的 對(duì)甲減的認(rèn)識(shí) 關(guān)于預(yù)處理問(wèn)題,20101019,同時(shí)配發(fā)“編寫(xiě)說(shuō)明”,中華核醫(yī)學(xué)雜志2010，30（5）：346-351,2010年10月,參編專家,（按姓氏筆畫(huà)排名） 丁 虹 王 鐵 王 輝 石洪成 包建東 馮 玨 匡安仁 安 銳 李 林 李亞明 李思進(jìn) 汪 靜 張永學(xué) 陸漢魁 陳 啟 林巖松 袁衛(wèi)紅 高再榮 蔣寧一 覃偉武 管 樑 譚 建 顏 兵 （共23位專家，18家單位）,

2、一、“共識(shí)”形成背景,我國(guó)131I治療甲亢的現(xiàn)狀： 1958年開(kāi)始131I治療甲亢，已有50余年歷史 全國(guó)多數(shù)核醫(yī)學(xué)科均已常規(guī)開(kāi)展 積累了豐富的經(jīng)驗(yàn)，有一定的影響 取得了一定的成績(jī)，但存在許多的不足 科學(xué)在發(fā)展，觀念在更新，需要進(jìn)一步規(guī)范,中華醫(yī)學(xué)會(huì)核醫(yī)學(xué)分會(huì)普查結(jié)果,甲亢年治療量超過(guò)萬(wàn)人次以上的省份有： 廣東 25110， 四川 15526， 廣西 12629， 湖北 11691， 吉林 10650，,甲亢年治療量較多的單位有： 核工業(yè)416醫(yī)院 8235 解放軍321醫(yī)院 5000 枝江市人民醫(yī)院 3778 梅州市人民醫(yī)院 3714 解放軍303醫(yī)院 3260 哈爾濱醫(yī)大二院 3260,李

3、亞明教授提供,“共識(shí)”形成背景,目前存在的問(wèn)題（131I治療甲亢）,全國(guó)發(fā)展不平衡，存在地區(qū)差異； 臨床路徑（治療方案）不規(guī)范（某些基層單位）； 有許多問(wèn)題存在爭(zhēng)議（甲減的認(rèn)識(shí)）； 某些治療環(huán)節(jié)與措施各地差距較大（治療前用藥）； 醫(yī)患溝通內(nèi)容偏差大（無(wú)統(tǒng)一模式）； 相關(guān)科普工作及兄弟學(xué)科交流不足。,“共識(shí)”形成背景,“共識(shí)”形成,在中華醫(yī)學(xué)會(huì)核醫(yī)學(xué)分會(huì)的指導(dǎo)下 由 20余位核醫(yī)學(xué)專家經(jīng)多次共同商討，數(shù)易其稿，歷時(shí)2年，就有關(guān)131I治療Graves甲亢臨床相關(guān)問(wèn)題形成此“共識(shí)”。 “共識(shí)”立足甲狀腺核醫(yī)學(xué)，參考國(guó)內(nèi)外多年來(lái)相關(guān)文獻(xiàn)和臨床應(yīng)用情況，遵循先進(jìn)性、實(shí)用性、公認(rèn)性和時(shí)效性原則，重點(diǎn)闡述

4、131I治療Graves甲亢相關(guān)問(wèn)題。而對(duì)其他有關(guān)內(nèi)容主要參考中國(guó)甲狀腺疾病診治指南（內(nèi)分泌學(xué)會(huì)2007版）。,“共識(shí)”形成背景,“共識(shí)”目的： 集思廣益 行業(yè)規(guī)范 指導(dǎo)臨床 “解讀”目的： 進(jìn)一步廣泛征求意見(jiàn)，修訂為指南,“指南”,兄弟學(xué)科 本專業(yè)專家,共識(shí),已經(jīng)收到許多兄弟學(xué)科及本專業(yè)專家的建設(shè)性意見(jiàn),“共識(shí)”主要內(nèi)容,簡(jiǎn)要介紹： Graves甲亢的臨床表現(xiàn)、實(shí)驗(yàn)室檢查、甲亢危象處理和抗甲狀腺藥物治療等內(nèi)容。 重點(diǎn)介紹： 131I治療Graves甲亢方法、療效評(píng)價(jià)、隨訪和安全性及Graves甲亢合并癥的處理。,二、“共識(shí)”解讀要點(diǎn),臨床基礎(chǔ) 療效評(píng)價(jià)與隨訪 安全性評(píng)價(jià) 合并癥處理原則,（一

5、）131I治療Graves甲亢臨床基礎(chǔ),1.主要參照中國(guó)甲狀腺疾病診治指南。 2. 在診斷標(biāo)準(zhǔn)中增加了甲狀腺攝131I率增高，作為輔助條件之一。（與指南的區(qū)別） 攝131I率是決定能否使用和制定131I劑量的重要指標(biāo)，同時(shí)也是治療前基本檢查項(xiàng)目之一。 臨床表現(xiàn)為甲亢而不能診斷為Graves甲亢時(shí)應(yīng)進(jìn)行131I攝取試驗(yàn)。還可以評(píng)價(jià)治療效果。,1.“共識(shí)”專家討論意見(jiàn) 2. A practical method for the estimation of therapeutic activity in the treatment of Graves hyperthyroidism Q J Nucl

6、 Med Mol Imaging. 2010 Nov 11 3.影響131I 治療甲狀腺功能亢進(jìn)療效的因素。解放軍醫(yī)學(xué)雜志2003，28(2):180-181,3.關(guān)于適應(yīng)證與禁忌證,適應(yīng)證： Graves甲亢患者均適用131I治療。 特別提出: 抗甲狀腺藥物療效差或多次復(fù)發(fā)者; 病程較長(zhǎng)或中老年患者; 對(duì)抗甲狀腺藥物過(guò)敏或出現(xiàn)其他不良反應(yīng); 甲亢合并肝功能損傷; 甲亢合并白細(xì)胞或血小板減少; 甲亢合并心臟病; 其他特殊類型甲亢 。,適應(yīng)證解讀,比較內(nèi)分泌指南及核醫(yī)學(xué)以往規(guī)范等 特點(diǎn)：1.不提相對(duì)適應(yīng)證。 2.不設(shè)限：如年齡限制、突眼限制、甲狀腺腫大程度限制、甲亢病情的限制等。 目的：開(kāi)放患者

7、與醫(yī)生的選擇范圍。 理念：ATD、131I和手術(shù)治療都是有效方法，在醫(yī)患溝通的前提下，都可以選擇，不需要對(duì)某種方法設(shè)限。,近期N Engl J Med 2011;364:542-50，及多篇相關(guān)報(bào)道 即將發(fā)表的ATA-AACE指南，及1993ATA指南均沒(méi)有明確提出適應(yīng)證具體細(xì)則，而共同表達(dá)了以上觀點(diǎn)。,Radioiodine Therapy for Hyperthyroidism Douglas S. Ross, M.D. N Engl J Med 2011;364:542-50 A 37-year-old woman presented with palpitations, tremulo

8、usness, shortness of breath, and a 9-kg (20-lb) weight loss, and received a diagnosis of Graves hyperthyroidism. At the time of diagnosis, she had mild proptosis, no diplopia, and no signs of eye inflammation. Her thyroid gland was two times the normal size and nonnodular. Her initial serum triiodot

9、hyronine (T3) concentration was 655 ng per deciliter (9.2 nmol per liter), and her free thyroxine (T4) concentration was 5.7 ng per deciliter (73 pmol per liter). She was treated with methimazole for a year, and her thyroid tests became normal. She discontinued the methimazole 10 weeks before the cu

10、rrent presentation with recurrent palpitations and tremulousness. Her serum T3 concentration is 345 ng per deciliter (5.4 nmol per liter), and her free T4 concentration is 2.8 ng per deciliter (36.0 pmol per liter). The patient does not smoke. She has a 3-year-old daughter and wishes to become pregn

11、ant again. Her endocrinologist recommends radioiodine ablation of her thyroid.,泛指Graves甲亢患者均可選用131I治療,禁忌證問(wèn)題,妊娠和哺乳期患者。 與內(nèi)分泌指南及核醫(yī)學(xué)規(guī)范基本一致。 近來(lái)國(guó)外學(xué)者提出：合并或懷疑甲狀腺癌； 不能遵循放射安全指引的患者； 計(jì)劃在4-6月內(nèi)懷孕的女性患者。 （以上情況，可以靈活處理，不是絕對(duì)禁忌證） 原規(guī)范有：急性心梗及嚴(yán)重腎功能障礙， “共識(shí)”沒(méi)有表達(dá)。 理由：沒(méi)有大量文獻(xiàn)支撐；臨床上實(shí)施標(biāo)準(zhǔn)難掌握,界定模糊。,（二）治療前診斷,特指在使用131I治療前，意在規(guī)范； 提出了基

12、本檢查項(xiàng)目與針對(duì)性檢查項(xiàng)目。 基本項(xiàng)目中提出攝131I率和核素顯像與B超； 專家強(qiáng)烈推薦 理由：排除非Graves甲亢；了解有無(wú)結(jié)節(jié)及結(jié)節(jié)功能；提供制定131I治療劑量依據(jù)。 針對(duì)性項(xiàng)目，不作強(qiáng)求，因人而定； 其他：特殊檢查類，如育齡婦女要注意排除孕娠。,（三）治療劑量,介紹3種劑量法，不具體推薦，適宜選擇； 提出劑量調(diào)整因素： 4點(diǎn)減少劑量的因素； 5點(diǎn)增加劑量的因素。,在我國(guó)，計(jì)算法是目前是最常用的方法，符合個(gè)體化治療。 半固定劑量法和固定劑量法，方法簡(jiǎn)單，個(gè)別醫(yī)院使用。 無(wú)論是使用哪種方法，均會(huì)發(fā)生治療后甲減，使用固定劑量法，甲減的發(fā)生幾率高于其他方法。,減少131I劑量降低了甲亢治愈率

13、,N=443,P0.0001,患者治愈比例（%）,Amit Allahabadia, et al. Radioiodine Treatment of HyperthyroidismPrognostic Factors for Outcome. J. Clin. Endocrinol. Metab. 2001 86: 3611-3617.,單一固定劑量131I(185MBq,370MBq)治療甲亢，1年內(nèi)患者轉(zhuǎn)歸,N=370,131I治療的劑量,治愈率降低18%,注：131I治愈包括治療為甲減及正常甲功者,同理：加大131I劑量提高了甲減發(fā)生率,Alexander EK, Larsen PR.

14、High dose of (131)I therapy for the treatment of hyperthyroidism caused by Graves disease.J Clin Endocrinol Metab 2002;87:1073-7,國(guó)外學(xué)者有主張個(gè)體劑量：一項(xiàng)隨機(jī)對(duì)照研究認(rèn)為，根據(jù)患者個(gè)體化準(zhǔn)確計(jì)算的攝入量能達(dá)到更好的效果。,Eur J Clin Invest. 1995 Mar;25(3):186-93. Radioiodine therapy of Graves hyperthyroidism: standard vs. calculated 131iodine

15、activity. Results from a prospective, randomized, multicentre study. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H. Abstract The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq 131io

16、dine vs. an activity calculated to deliver 100 Gy for treatment of Graves thyrotoxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radioiodine application (range 4.5-8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for

17、 both approaches, but only in retrospective investigations. Investigated prospectively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic suc

18、cess was inversely related to thyroid size. The rate was 100% for thyroid volumes or = 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume or = 15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%

19、, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11% for a target dose of 50 Gy, 50% for 100 Gy, 67% for 150 Gy, 80% for 200 Gy, 84% for 250 Gy, 88% for 300 Gy

20、, 90% for 350 Gy and 93% for 400 Gy.,也有學(xué)者主張采用相對(duì)固定劑量法，認(rèn)為固定劑量與計(jì)算劑量效果一樣 1.Leslie, W.D,(2003) A randomized comparison of radioiodine doses in Graves hyperthyroidism. Journal of Clinical Endocrinology and Metabolism, 88, 978983.,（四）治療前醫(yī)患溝通要點(diǎn),1.治療前常規(guī)準(zhǔn)備：停藥、戒碘。 一般情況下囑患者停服MMI27d,PTU24周,特殊情況需作針對(duì)性處理。 囑患者禁食海帶、紫

21、菜、深海魚(yú)油、含碘復(fù)合維生素類等2周左右。 提出8點(diǎn)溝通要點(diǎn)。 要求簽署知情同意書(shū)（文件）。 (患者教育內(nèi)容，不在此展開(kāi)),（五）治療后特殊情況處理,1.重癥Graves甲亢。可考慮先用抗甲狀腺藥物短程治療,病情緩解后再行 治療。也可在給予 后48 h加抗甲狀腺藥物短程治療。采取住院治療或密切隨訪。 2.甲亢危象. (參照中華醫(yī)學(xué)會(huì)內(nèi)分泌學(xué)分會(huì)中國(guó)甲狀腺疾病診治指南)。 3.甲減。 處理甲減的關(guān)鍵在于早發(fā)現(xiàn),及時(shí)進(jìn)行甲狀腺激素替代治療。,（六）療效評(píng)價(jià)與隨訪,療效評(píng)價(jià)分為 臨床治愈、好轉(zhuǎn)、無(wú)效、復(fù)發(fā)、甲減。 甲減可作為臨床治愈的指標(biāo)之一。 隨訪 輕中度Graves甲亢且無(wú)嚴(yán)重合并癥者,可在治療

22、后13個(gè)月內(nèi)復(fù)診,以初步評(píng)價(jià)療效。治療后6個(gè)月再?gòu)?fù)診,如確定已臨床治愈,隨訪間隔時(shí)間可延長(zhǎng),每年隨訪復(fù)查1次。 重復(fù)治療： 再次 治療,建議與初次治療時(shí)間間隔36個(gè)月。,鑒于TSH受抑制的情況可能在治療成功后繼續(xù)存在，故治療后數(shù)月內(nèi)FT4和FT3的監(jiān)測(cè)尤為重要。 臨床出現(xiàn)甲減癥狀，僅甲狀腺激素水平低于正常范圍,即使TSH仍處于受抑狀態(tài),應(yīng)考慮早發(fā)甲減，及時(shí)替代治療。,共識(shí)已有表達(dá),特別指出,Uy HL, Reasner CA, Samuels MH. Pattern of recovery of the hypothalamic-pituitary-thyroid axis following

23、 radioactive iodine therapy in patients with Gravesdisease. Am J Med 1995;99:173-9.,（七）安全性評(píng)價(jià),131I治療Graves甲亢 不影響生育能力； 不會(huì)導(dǎo)致遺傳損害； 不會(huì)增加甲狀腺癌、白血病及其他癌癥的發(fā)病率； 兒童和青少年其生育能力和后代生長(zhǎng)情況與普通人群比較無(wú)明顯差別。,131I治療甲亢安全性良好惡性腫瘤總發(fā)病率低于普通人群,惡性腫瘤標(biāo)化發(fā)病率（SIR）,注：SIR, Standardised Incidence Ratio，標(biāo)化發(fā)病率,P=0.0001,Jayne A Franklyn, et al.

24、 Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet 1999; 353: 211115.,7417例應(yīng)用131I治療的甲亢患者（72073人*年隨訪）,131I治療甲亢安全性良好惡性腫瘤死亡率與普通人群無(wú)異,標(biāo)化惡性腫瘤死亡率（SMR ）,注：SMR（ Standardized cancer mortality ratios），標(biāo)化惡性腫瘤死亡率,回顧性研究，35593例甲亢患者，分別接受131I、手術(shù)、抗

25、甲狀腺藥物治療。其中65%的患者接受131I治療。評(píng)估這些甲亢患者尤其是應(yīng)用131I治療后的癌癥死亡率。,Elaine Ron, et al. Cancer Mortality Following Treatment for Adult Hyperthyroidism. JAMA, 1998,280(4):347-355.,Graves甲亢合并癥的處理,1、甲亢性心臟病 進(jìn)行一定的預(yù)處理：如減慢心率、控制心衰、改善心功能、控制血壓等。 治療目標(biāo)：直接選擇甲減。 建議131I 治療時(shí)宜加強(qiáng)心臟動(dòng)態(tài)監(jiān)控,住院密切觀察。 推薦：甲亢性心臟病確診后,宜盡早采取 一次性決定性治療。（一次到位：甲減）,治

26、療轉(zhuǎn)歸,多數(shù)甲亢性心臟病患者經(jīng)131I治療，甲狀腺功能正常后，其心臟功能完全或部分恢復(fù)正常； 如甲亢性心臟病病程長(zhǎng)、甲狀腺腫大明顯者，131I緩解甲亢性心臟病的療效較差。,強(qiáng)調(diào)131I治療后終生隨診的重要！及時(shí)糾正甲減！,研究報(bào)道：并發(fā)有甲狀腺功能亢進(jìn)性心臟病的患者應(yīng)用放射碘治療作為單一方案治療后并不使心臟癥狀加重。,Thyrocardiac Disease and Its Management with Radioactive Iodine I131 Clement Delit;Solomon Silver;Stephen B. Yohalem;Robert L. Segal. Abstra

27、ct Hyperthyroidism was treated 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, the

28、re were 107 patients with 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

29、 cardiac and noncardiac patients. 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.,2、甲亢合并肝功能損害,治療原則：及時(shí)有效地控制甲亢,同時(shí)輔以保肝治療。 確

30、診甲亢伴肝損害時(shí),應(yīng)首選一次臨床治愈或甲減。 即使是肝損害嚴(yán)重者,在加強(qiáng)護(hù)肝保肝、拮抗應(yīng)激、抑制免疫的同時(shí),仍可考慮用 治療。 經(jīng)治療后,絕大多數(shù)Graves甲亢肝損害在甲狀腺激素水平恢復(fù)正常后肝功能可逐漸恢復(fù)。,3、甲亢合并白細(xì)胞、粒細(xì)胞或血小板減少,治療Graves甲亢所用的131I劑量水平不會(huì)導(dǎo)致白細(xì)胞、粒細(xì)胞或血小板減少； 應(yīng)積極進(jìn)行131I 治療,同時(shí)給予對(duì)癥、支持 、升白細(xì)胞藥物治療,定期檢查血常規(guī); 建議血液科醫(yī)生會(huì)診,聯(lián)合制定治療方案; 甲亢合并血白細(xì)胞、粒細(xì)胞或血小板減少及粒細(xì)胞缺乏癥者采用 治療明顯優(yōu)于抗甲狀腺藥物或手術(shù)治療 。 黃勤,鄒大進(jìn),潘文舟. 治療伴白細(xì)胞減少Gr

31、aves病的臨床觀察. 中華內(nèi)分泌代謝雜志, 2006, 16: 184-185.,4、甲狀腺相關(guān)眼病,甲亢伴GO患者是否采用131I治療？ 學(xué)術(shù)界一直存在爭(zhēng)議。 大量文獻(xiàn)報(bào)道：可以采用131I治療。強(qiáng)烈推薦接受糖皮質(zhì)激素聯(lián)合治療。 內(nèi)分泌指南： 輕度、穩(wěn)定期的中-重度單獨(dú)應(yīng)用131I ； 進(jìn)展期加用潑尼松。(我們認(rèn)同此觀點(diǎn)),131I治療法對(duì)GO的影響,131I治療法是甲狀腺眼病的高危因素之一。 GO明確的危險(xiǎn)因素包括甲亢的131I治療、吸煙、治療前T3高水平、治療前TRAb高水平和放射碘治療后甲減。 （多篇文獻(xiàn)報(bào)道） 2. 131I治療后眼病的惡化往往是短暫的，可以采用糖皮質(zhì)激素抵銷。（

32、N Engl J Med. 1998 Jan 8;338(2):73-8.Relation between therapy for hyperthyroidism and the course of Graves ophthalmopathy.）,ATA316-317,甲亢治療方法 例數(shù) 改善% 無(wú)變化% 惡化% 甲巰咪唑 148 2 95 3 131I 150 0 85 15 131I + 潑尼松 145 35 65 0,GO惡化率,Bartalena et al N Engl J Med 1989, 321:1349,戒煙很重要,在激素聯(lián)合131I 治療期間宜輔以指導(dǎo)患者飲食和生活習(xí)慣,尤

33、其告知患者戒煙。,Bartalena 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 hyperthyroidism and the course of Graves ophthalmopathy. N Engl J M

34、ed. 338:73-78 3.Thyroid-associated ophthalmopathy after treatment for Graves hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009;94:3700-7,一項(xiàng)大型的隨機(jī)對(duì)照研究顯示放射碘治療GD與GO進(jìn)展的風(fēng)險(xiǎn)升高相關(guān)（與ATDs相比RR=5.8），且這種風(fēng)險(xiǎn)能夠被糖皮質(zhì)激素聯(lián)合治療抵銷2 。,研究提示主動(dòng)吸煙者接受放射碘治療后1年隨訪中GO發(fā)生或惡化的發(fā)生率最高(23-40%) 2,多項(xiàng)研究都一致認(rèn)為：吸煙對(duì)

35、放射碘治療患者GO存在有害的影響。這種風(fēng)險(xiǎn)是與每日吸煙數(shù)量成比例的，既往吸煙患者的風(fēng)險(xiǎn)仍明顯低于目前吸煙患者,1.Pfeilschifter J, Ziegler R 1996 Smoking and endocrine ophthalmopathy: impact of smoking severity and current vs lifetime cigarette consumption. Clin Endocrinol (Oxf). 45:477-481,文獻(xiàn)報(bào)道,131I治療加重突眼病情在吸煙者中更明顯3,高度關(guān)注甲減,眾多研究表明治療后出現(xiàn)的持續(xù)、未處理的甲狀腺功能減退癥是GO進(jìn)

36、展的有害因素。 131I治療后早期使用左旋甲狀腺素預(yù)防甲減發(fā)生（血清甲狀腺激素正常后即給予），這類患者GO極少出現(xiàn)惡化(0%-2%)。,Tallstedt L, Lundell G, Blomgren H, Bring J 1994 Does early administration of thyroxine reduce the development of Graves ophthalmopathy after radioiodine treatment? Eur J Endocrinol. 130:494-497.,Perros P, Kendall-Taylor P, Neoh C,

37、Frewin S, Dickinson J 2005 A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves ophthalmopathy. J Clin Endocrinol Metab. 90:5321-5323.,三、幾個(gè)主要觀點(diǎn),(一)131I治療甲亢的目的,盡早治愈甲亢（甲減或甲功正常）、縮短甲亢持續(xù)時(shí)間而不是避免甲減的發(fā)生，已成為公認(rèn)的131I治療目標(biāo)要求。,Saara Metso, et al. Lo

38、ng-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 regional hospital in Hong Kong. Hong Kong Med J 2009;15:267-73. Robe

39、rt A, et al. Optimal iodine-131 dose for eliminating hyperthyroidism in Graves disease. J Nucl Med 1991,32:411-416.,大劑量131I比小劑量131I治療能更快實(shí)現(xiàn)甲亢治愈，從而降低甲亢相關(guān)的死亡率。131I治療是安全的，但是大多數(shù)患者會(huì)發(fā)生治療后甲減，需要個(gè)體化劑量的甲狀腺激素終生替代治療。這種療法既解決了甲亢的治療問(wèn)題，也最大限度降低了甲減相關(guān)性疾病發(fā)生率6 美國(guó)內(nèi)分泌醫(yī)師學(xué)會(huì)（AACE）甲亢及甲減臨床指南,甲亢不及時(shí)治愈可導(dǎo)致諸多并發(fā)癥,1. 放射性碘（131I）治療Grave

40、s甲亢專家共識(shí)討論稿 2.Luo Y，Jiang DYChanges in seFum interleukin-6 and high-sensitivity C-reactive protein levels in patients with acute coronary syndeome and their responses to sivastatinJHeart Vessels，2004，19(6)：257-262 3.WghgarrdenCecil Textbook of MedicineM19th edit1992：1257 4 葉任高內(nèi)科學(xué)第5版北京：人民衛(wèi)生出版社，2002：61

41、8，738,甲亢并發(fā)癥嚴(yán)重危害患者健康,131I治療甲亢療效好,P0.01,發(fā)生率（%）,治愈時(shí)間（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、隨機(jī)研究，納入2021例甲亢患者，分別接受抗甲狀腺藥物或131I治療，平均隨訪98個(gè)月。,*,*,*,#,131I治療甲亢療效顯著,131I治療

42、甲亢治愈時(shí)間快,*P=0.000 #P=0.001,(二)對(duì)甲減的認(rèn)識(shí),甲減是131I治療的必然轉(zhuǎn)歸之一，不是副作用，不是并發(fā)癥，更不是醫(yī)療事故。 “核醫(yī)學(xué)和內(nèi)分泌專家都一致認(rèn)為，甲減是131I治療甲亢難以避免的結(jié)果，選擇131I治療主要是要權(quán)衡甲亢與甲減后果的利弊關(guān)系。 中華醫(yī)學(xué)會(huì)內(nèi)分泌學(xué)會(huì)中國(guó)甲狀腺疾病診治指南，2007，4,幾個(gè)主要觀點(diǎn),過(guò)去認(rèn)為：甲減是131I治療的并發(fā)癥或副作用等。 現(xiàn)在觀點(diǎn)：甲減是治療的一種轉(zhuǎn)歸或是期望的結(jié)局。,131I治療甲亢后甲減發(fā)生率高，早發(fā)晚發(fā)有所不同,1.131I治療Graves甲亢專家共識(shí) 2.Aftab M Ahmad, et al. Objectiv

43、e estimates of the probability of developing hypothyroidism following radioactive iodine treatment of Thyrotoxicosis. European Journal of Endocrinology (2002) 146 767775. 3.131I治療甲狀腺功能亢進(jìn)癥遠(yuǎn)期觀察。中華核醫(yī)學(xué)雜志，1984，4：7-11,國(guó)外資料,國(guó)內(nèi)資料,晚發(fā)甲減發(fā)生率與131I治療劑量無(wú)關(guān),晚期甲減發(fā)生率（%）,Leslie, W.D,(2003) A randomized comparison of ra

44、dioiodine doses in Graves hyperthyroidism. Journal of Clinical Endocrinology and Metabolism, 88, 978983.,低固定劑量：235 MBq 高固定劑量：350 MBq 低調(diào)節(jié)劑量：2.96 MBq (80Ci)/g 甲狀腺，經(jīng)24h131I攝取率調(diào)節(jié) 高調(diào)節(jié)劑量：4.44 MBq(120Ci)/g 甲狀腺，經(jīng)24h131I攝取率調(diào)節(jié),相比甲亢甲減的治療更容易，危害程度更輕,陳漢華. 131 碘治療甲狀腺功能亢進(jìn)癥7170例療效總結(jié).柳州醫(yī)學(xué).2008 年第21 卷第3 期 廖學(xué)權(quán)等.甲狀腺功能減退

45、癥的內(nèi)分泌治療.中國(guó)醫(yī)藥導(dǎo)報(bào). 2010 年5 月第7 卷第13 期 郭根武等. 碘-131治療甲狀腺功能亢進(jìn)癥治療效果分析. 中國(guó)輻射衛(wèi)生,2009,18(3),優(yōu)甲樂(lè),支持放射性碘治療甲亢導(dǎo)致甲減,Thyroid Function and Mortality in Patients Treated for Hyperthyroidism Jayne A. Franklyn, Michael C. Sheppard, Patrick Maisonneuve JAMA. 2005 Jul 6;294(1):71-80 RESULTS: In 15,968 person-years of fol

46、low-up, 554 died vs 487 expected deaths (standardized mortality ratio SMR, 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. The

47、se increased risks were not observed during follow-up on T(4) therapy (circulatory 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 (a

48、ll-cause mortality hazard ratio HR, 0.65; 95% CI, 0.54-0.79; circulatory 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 f

49、or ischemic heart disease increased slightly when analyzed by serum thyrotropin, 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 s

50、howed that mild hypothyroidism prior to T(4) therapy was associated with 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-sp

51、ecific mortality in England and Wales, a finding no longer evident during 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 hypothyroidi

52、sm suggests T(4) replacement should be considered should this biochemical abnormality develop after radioiodine therapy.,結(jié)果認(rèn)為放射性碘治療后甲減接受T4治療的患者死亡率與背景人群相似。,131I治療GD出現(xiàn)甲減，替代治療對(duì)存活無(wú)影響。,甲減的替代治療是安全、簡(jiǎn)便的。,但在內(nèi)科學(xué)界尚不能完全接受此觀點(diǎn)，有些內(nèi)科醫(yī)生經(jīng)?！案嬲]”患者，“不要接受131I治療，甲減比甲亢更難治”等。在有關(guān)131I治療后甲減引起的醫(yī)療糾紛中，有些就是因?yàn)閮?nèi)科醫(yī)生的“忠告”而引發(fā)的。 希望繼續(xù)溝通，

53、達(dá)成共識(shí)。,(三)關(guān)于預(yù)治療,對(duì)甲亢伴有并發(fā)癥患者，建議將并發(fā)癥控制在相對(duì)穩(wěn)定時(shí)，采用131I治療； 對(duì)重癥甲亢，可考慮先用抗甲狀腺藥物短程治療，病情緩解后再行131I治療；（指嚴(yán)重高代謝癥狀，而不包含嚴(yán)重并發(fā)癥“高?！被颊撸?對(duì)一般適應(yīng)證患者，沒(méi)有提及或強(qiáng)調(diào)在131I治療前需要預(yù)治療。,幾個(gè)主要觀點(diǎn),“共識(shí)”,一般情況下，131I治療前停服MMI27d, PTU 24周。,Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised contro

54、lled trials. Walter MA,et al. BMJ. 2007 Mar 10;334(7592):514 Abstract 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 (Cochra

55、ne central register of controlled trials, Medline, Embase) searched to 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 withou

56、t adjunctive antithyroid drugs were calculated with a random effects 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% confide

57、nce interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (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. CONC

58、LUSIONS: Antithyroid drugs potentially increase rates of failure and reduce 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 hyperthyroid

59、ism. Imseis RE, Vanmiddlesworth L, Massie JD, Bush AJ, Vanmiddlesworth NR. J Clin Endocrinol Metab. 1998 Feb;83(2):685-7 Abstract Ninety-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 discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months bef