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格雷夫斯病(Graves disease,GD)是甲状腺功能亢进症(hyperthyroidism)最常见的原因之一。青少年及儿童格雷夫斯甲状腺功能亢进症(以下简称Graves甲亢)也并不少见,其治疗方式主要有手术、内科抗甲状腺药物(antithyroid drug,ATD)和131I治疗。手术治疗风险大、创伤大;ATD治疗时间长且易复发;131I治疗方法简便、一次性治愈率高。国际上将青少年及儿童Graves甲亢一直列为131I治疗的适应证[1],但国内对于青少年及儿童Graves甲亢是否采用131I治疗仍然存有诸多顾虑。为了探讨131I治疗青少年及儿童Graves甲亢的疗效及安全性,笔者收集了1995年1月1日至1999年12月31日ATD治疗无效或效果差的青少年及儿童Graves甲亢行131I治疗,对此进行前瞻性随访研究,现报道如下。
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89例青少年及儿童Graves甲亢患者中,行131I治疗并随访至今的患者80例,其中,男性30例、女性50例,年龄6~19岁,平均年龄(12.2±2.3)岁,失访9例(10.1%)。随访142~221个月,平均(183±23)个月,到2013年12月31日统计截止。患者服用131I治疗次数为:服1次者71例(88.75%),服2次者8例(10%),服3次者1例(1.25%)。第1次131I治疗的剂量范围为177.6~555.0 MBq,平均剂量为203.5 MBq,以后再次服131I间隔时间均大于3个月。患者初次行131I治疗时,有6例患者在3 d内出现轻度头晕、食欲下降、颈部不适等症状,未经特殊处理后好转。
治疗后3个月随访时,57例痊愈,痊愈率为71.25%(57/80);18例好转,好转率为22.50%(18/80);2例无效(2.50%);3例甲减(3.75%),有效率为97.50%(78/80)。2例无效患者及18例好转患者中6例再次行131I治疗,其余好转患者给予ATD治疗,3例甲减患者给予甲状腺激素替代治疗。治疗后6个月随访时65例痊愈,痊愈率为81.25%(65/80),15例好转,好转率为18.75%(15/80),无无效及甲减患者,有效率达100%(80/80)。15例好转患者采用ATD治疗。随访至第12个月,有1例患者Graves甲亢治疗无效(因未按医嘱服药),5例患者Graves甲亢好转,66例患者痊愈,8例患者发生甲减,甲减发生率为10.00%(8/80),131I治疗Graves甲亢有效率为98.75%(79/80),1例无效患者再次行131I治疗。随访至5年,12例发生甲减,5年甲减累计发生率为15.00%(12/80)。随访至10年,19例患者发生甲减,10年甲减累计发生率为23.75%(19/80)。随访至15年,28例患者发生甲减,15年甲减累计发生率为35.00%(28/80)(表 1)。所有甲减患者均给予甲状腺激素替代治疗,无不良反应发生。治愈病例中无复发病例,未见不良反应发生,生长发育均正常。有1例女性患者患甲状腺右叶结节(手术后病理证实),随访病例中无甲状腺癌、白血病等疾病发生。
随访时间 痊愈 好转 无效 甲减 有效率 3个月 57(71.25%) 18(22.50%) 2(2.50%) 3(3.75%) 97.50% 6个月 65(81.25%) 15(18.75%) 0 0 100% 12个月 66(82.50%) 5(6.25%) 1(1.25%) 8(10.00%) 98.75% 5年 68(85.00%) 0 0 12(15.00%) 100% 10年 61(76.25%) 0 0 19(23.75%) 100% 15年 52(65.00%) 0 0 28(35.00%) 100% 注:表中,痊愈率+好转率+甲减率=有效率。 表 1 80例青少年及儿童Graves甲亢患者131I治疗后随访结果(例)
Table 1. The follow-up results of 80 adolescents and children with Graves hyperthyroidism after 131I treatment(case)
截至2013年12月31日,所有治疗患者均育有后代,共计生育92个小孩,其中,男性52人、女性40人,年龄1~17岁,平均年龄(12±3.2)岁,智力及发育未见确切异常,无死婴。有2例甲减女性患者分别有1次自然流产史,流产期前患者未按时服用甲状腺激素处于甲减状态。随访后代中甲状腺功能暂未发现异常,亦无甲状腺癌、白血病等疾病发生。
131I治疗青少年及儿童格雷夫斯甲亢的临床应用随访研究
Follow-up study on children and adolescents with Graves hyperthyroidism after 131I treatment
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摘要:
目的探讨131I治疗青少年及儿童格雷夫斯甲状腺功能亢进症(Graves甲亢)的疗效及安全性。 方法89例青少年及儿童Graves甲亢患者行131I治疗。给药剂量采用公式法计算(2.59~4.44 MBq/g),参考病程、甲状腺质量和最高摄碘率进行修正。均采用一次性空腹口服,有合并症的给予相应处理。治疗后3、6、12个月随访,以后每年随访1次。前瞻性随访观察所有患者131I治疗后的治愈率、甲减率、甲状腺良恶性肿瘤发生情况、生长发育情况及后代健康情况。 结果随访至今的患者共80例,失访9例(10.1%)。131I治疗剂量范围为177.6~555.0 MBq,平均剂量为203.5 MBq。随访至12个月,131I治疗青少年及儿童Graves甲亢痊愈率82.50%,有效率98.75%,无效率1.25%;随着时间的推移甲减发生率逐渐升高,15年甲减累计发生率为35%。所有治疗患者生长发育均正常,均育有后代,后代智力及发育均正常。随访病例中无甲状腺癌、白血病等疾病发生。 结论131I治疗青少年及儿童Graves甲亢安全且疗效好,不良反应少,值得临床推广应用。 Abstract:ObjectiveTo investigate the therapeutic effects and safety of 131I treatment on children and adolescents with Graves disease. MethodsIn this study, 89 children and adolescents with Graves hyperthyroidism cases were treated using 131I. 131I was given at a dosage of 2.59 to 4.44 MBq per gram of thyroid tissue and calibrated according to the course of disease, thyroid weight, and the highest iodine rate. The treatment was via oral medication on an empty stomach once a day. All cases were required to undergo a proper medical follow-up at the end of 3, 6, and 12 months after treatment and once a year later. The cure, hypothyroidism rates and incidence rates of benign and malignant thyroid tumors and the health of their offspring were studied. The safety of radioiodine treatment for children and adolescents'growth, development were also evaluated. ResultsFollow-up was conducted on 80 cases, with 30 males and 50 females, aged from 6 to 19(12.2±2.3) years; nine patients were lost to follow-up(10.1%). The maximum dose of 131I ranged from 177.6 to 555 MBq per patient; the mean dose was 203.5 MBq. After one year of radioiodine treatment, the cure rate was 82.50%, and the effective rate was 98.75%; no efficiency is very low(1.25%). As time passed, the incidence of hypothyroidism increased, reaching 35% within 15 years. All cured patients had normal growth and produced offspring whose intelligence and development were normal. No one was diagnosed with thyroid carcinoma or leukemia in his/her medical follow-ups. ConclusionsUsing 131I for treating children and adolescents with Graves hyperthyroidism was effective and safe. The minimal side effects make it worthy of wide application in clinics. -
Key words:
- Graves disease /
- Adolescent /
- Child /
- Brachytherapy /
- Iodine radioisotopes
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表 1 80例青少年及儿童Graves甲亢患者131I治疗后随访结果(例)
Table 1. The follow-up results of 80 adolescents and children with Graves hyperthyroidism after 131I treatment(case)
随访时间 痊愈 好转 无效 甲减 有效率 3个月 57(71.25%) 18(22.50%) 2(2.50%) 3(3.75%) 97.50% 6个月 65(81.25%) 15(18.75%) 0 0 100% 12个月 66(82.50%) 5(6.25%) 1(1.25%) 8(10.00%) 98.75% 5年 68(85.00%) 0 0 12(15.00%) 100% 10年 61(76.25%) 0 0 19(23.75%) 100% 15年 52(65.00%) 0 0 28(35.00%) 100% 注:表中,痊愈率+好转率+甲减率=有效率。 -
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