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131I治疗Graves甲状腺功能亢进症(甲亢)是一个已为人们所接受的方法,其疗效除与病程的长短、131I剂量、个体的放射敏感性和甲状腺肿的大小有关外,还取决于131I在甲状腺内的滞留量、有效半衰期、治疗前抗甲状腺药物(antithyroid drugs,ATD)的使用等因素。碳酸锂可阻断有机碘和甲状腺激素从甲状腺的释放而不影响甲状腺的放射性碘摄取[1]。因此,对于131I治疗前不能停用ATD的患者,在治疗前后短期服用碳酸锂,是否可防止131I治疗后甲亢病情的短暂恶化同时又提高疗效成为临床关注的焦点。为此,我们进行了一个随机对照的研究,分析了已随访半年以上的100例甲亢患者的临床资料,以对碳酸锂在131I治疗中的辅助作用作出一个初步的评估。
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131I +碳酸锂组治疗后15 d生化检测结果显示,所有患者血肌酐和尿素氮水平均正常。
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131I治疗前131I治疗组和131I+碳酸锂治疗组的甲状腺最大摄131I率分别为87.2%和89.5%,差异无统计学意义(t=0.89,P>0.05)。两组131I治疗后颈前放射性吸收剂量率均随时间的推移逐渐降低,同组不同监测时段总体差异有统计学意义(H=132.46、132.47,P均<0.01),治疗后15、30、45 d两两间的差异均有统计学意义(131I组:t=88.51、113.70、59.42,P均<0.01;131I+碳酸锂组:t=83.44、112.76、70.18,P均<0.01),但两组相同监测时段的放射性吸收剂量率比较,131I+碳酸锂组均明显高于131I治疗组(t=8.81、15.18、10.10,P均<0.01)(表 1)。
组别 例数 不同时间的放射性吸收剂量率 Ha值 P值 15d 30d 45d A组 50 1769.9±107.8 344.2±36.6 35.6±4.0 132.46 < 0.01 B组 50 1971.3±120.8 464.7±41.8 47.8±5.3 132.47 < 0.01 tb值 8.81 15.18 10.10 P值 < 0.01 < 0.01 < 0.01 注:表中,A组:131I治疗组;B组:131I+碳酸锂治疗组;a:同组不同时段放射性吸收剂量率总体差异性比较;b:两组相同时段放射性吸收剂量率总体差异性比较。 表 1 131I治疗后颈前放射性吸收剂量率测定结果(x±s,μGy/h)
Table 1. The radioactive absorbed dose rate of the anterior portion of neck after 131I treatment(x±s, μGy/h)
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两组治疗前和治疗后不同时段血清甲状腺激素水平见表 2。
组别 例数 检测时间(d) fT3(pmol/L) fT4(pmol/L) TSH(mIU/L) A组 50 治疗前 14.60±0.78 29.38±2.40 0.00 治疗后 30 d 19.28±1.31 45.53±2.32 0.00 45d 6.05±0.53 19.84±1.80 0.09 90d 4.64±0.70 16.95±2.64 0.12 180d 4.03±0.42 13.63±1.99 0.10 B组 50 治疗前 10.28±0.55 30.12±5.40 0.00 治疗后 30 d 14.38±1.36 38.21±4.21 0.00 45d 5.85±1.50 18.95±0.80 0.07 90d 4.04±0.70 16.45±1.64 0.17 180d 3.33±0.42 12.36±1.99 0.14 Fa值 9.65 22.45 1.23 P值 < 0.01 < 0.01 >0.05 注:表中,A组:131I治疗组;B组:131I+碳酸锂治疗组;a:两组血清甲状腺激素水平的总体差异性比较;fT3:游离三碘甲状腺原氨酸;fT4:游离甲状腺素。 表 2 两组治疗前后不同时段的血清甲状腺激素水平(x±s)
Table 2. Serum thyroid hormone levels of the two groups at different times, before and after treatment(x±s)
治疗前和治疗后不同时段,两组的血清TSH平均水平均低于正常参考值范围(0.55~4.78 mIU/L),总体差异无统计学意义(F=1.23,P>0.05)。两组的血清fT3和fT4水平总体差异有统计学意义(F=9.65、22.45,P均<0.01):治疗前两组血清fT3、fT4水平的差异均无统计学意义(t=0.99、1.01,P均>0.05);治疗后30 d两组的血清fT3、fT4水平均明显高于治疗前(131I组:tfT3=5.23,tfT4=10.14;131I+碳酸锂组:tfT3=5.12,tfT4=9.98,P均<0.01),此后逐渐下降至正常;各组治疗后45、90和180 d的血清fT3、fT4水平均明显低于治疗前(131I组:tfT3=9.89、12.34、13.12,tfT4=16.45、21.54、23.45,P均<0.01;131I+碳酸锂组:tfT3=10.11、11.24、9.78,tfT4=13.65、19.45、18.24,P均<0.01);各组治疗后45 d的血清fT3、fT4水平均高于治疗后90、180 d(131I组:tfT3=7.95、9.21,tfT4=15.21、8.45;131I+碳酸锂组:tfT3=13.26、10.22,tfT4=20.12、7.85,P均<0.01);各组治疗后90 d与180 d的血清fT3、fT4水平相当,其差异均无统计学意义(tfT3=2.13、2.04,tfT4= 1.24、1.28,P均>0.05)。
治疗后30 d,131I+碳酸锂组的血清fT3和fT4水平明显低于131I治疗组(tfT3=8.22,tfT4=19.18,P均<0.01);两组治疗后45、90、180 d同期血清fT3、fT4水平的差异均无统计学意义(tfT3= 1.28、2.01、0.99,P均>0.05;tfT4=1.11、1.99、1.13,P均>0.05)。
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放射性碘治疗后半年,131I治疗组治愈36例、好转11例、无效3例,治愈率、好转率分别为72%(36/50)和22%(11/50);131I +碳酸锂组治愈38例、好转10例、无效2例,治愈率、好转率分别为76%(38/50)和20%(10/50)。两组的疗效比较,差异无统计学意义(χ2=0.21,P>0.05)。
131I辅以短期小剂量碳酸锂治疗Graves甲亢的研究
Clinical research on radioiodine addition of low-doses of lithium carbonate in short-term treatment of Graves hyperthyroidism
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摘要:
目的 探讨碳酸锂在131I治疗Graves甲亢中的辅助疗效。 方法 选取Graves甲亢患者100例,随机分为131I治疗组和131I+碳酸锂治疗组,每组患者各50例,两组间的平均年龄差异无统计学意义。131I+碳酸锂治疗组服131I前后15 d内分别给予碳酸锂治疗(2次/d,每次0.25 g);131I治疗前采用超声和触诊的方法估算甲状腺质量,两组甲状腺质量差异无统计学意义;两组患者均一次性服131I口服液并于治疗后15、30、45 d监测颈前放射性吸收剂量率;治疗前和治疗后30、45、90、180 d分别检测血清游离三碘甲状腺原氨酸(fT3)、游离甲状腺素(fT4)和TSH水平,治疗后半年对其疗效进行评价。 结果 两组131I治疗后颈前放射性吸收剂量率均随时间的推移逐渐降低,不同监测时段总体差异有统计学意义(H=132.46、132.47,P均<0.01);治疗后15、30、45 d放射性吸收剂量率两两间的差异均有统计学意义(131I组:t=88.51、113.70、59.42,P均<0.01;131I+碳酸锂组:t=83.44、112.76、70.18,P均<0.01);但两组相同监测时段的放射性吸收剂量率比较,131I+碳酸锂组均明显高于131I治疗组(t=8.81、15.18、10.10,P均<0.01)。治疗前和治疗后不同时段,两组的血清TSH平均水平均低于正常参考值范围(0.55~4.78 mIU/L),总体差异无统计学意义(F=1.23,P > 0.05)。两组间治疗前和治疗后不同时段的血清fT3和fT4水平总体差异有统计学意义(F=9.65、22.45,P均<0.01):治疗前两组血清fT3、fT4水平的差异均无统计学意义;各组治疗后30 d的血清fT3、fT4水平均明显高于同组治疗前(131I组:tfT3=5.23,tfT4=10.14;131I +碳酸锂组:tfT3=5.12,tfT4=9.98,P均<0.01),此后逐渐下降,治疗后90 d基本恢复正常;两组治疗后同期fT3、fT4水平比较,仅治疗后30 d 131I+碳酸锂治疗组明显低于131I治疗组(t=8.22、19.18,P均<0.01),其余各期两组的fT3、fT4水平差异无统计学意义;131I治疗后半年疗效评价,131I治疗组与131I+碳酸锂治疗组的治愈率分别为72%(36/50)和76%(38/50)。两组疗效比较,差异无统计学意义(χ2=0.21, P > 0.05)。 结论 碳酸锂可延长131I的有效半衰期、预防131I治疗后一个月内血清甲状腺激素浓度反应性升高、加强甲状腺毒症的控制,对于131I治疗前停服抗甲状腺药物、不能耐受或无效和有效半衰期短的患者,Graves甲亢辅以碳酸锂治疗有助于131I治疗短期疗效的提高和避免131I治疗后短期甲状腺毒症的恶化。本研究尚未观察到碳酸锂有助于提高Graves甲亢131I治疗的远期治愈率。 Abstract:Objective To explore the effect of lithium carbonate plus 131I in the treatment of Graves hyperthyroidism. Methods One hundred patients with Graves hyperthyroidism were enrolled in this study. All of them were randomly divided in to 2 groups: groupⅠwith 50 patients treated with 131I and groupⅡwith 50 patients treated with lithium carbonate plus 131I. Patients in groupⅡwere treated with a dose of 0.5 g per day(2×0.25 g) of lithium carbonate for 15 days before and after the administration of 131I. Thyroid weight was estimated by ultrasonography and careful palpation of the thyroid before treatment, and no significance were found between this two groups. Radiation absorbed dose rate in the front of neck was measured respectively 15, 30 and 45 d after the administration of 131I. Serum concentrations of TSH, free triiodothyrosine (fT3) and free thyroxine (fT4) were tested respectively before and 30, 45, 90, 180 days after administration of 131I. Results The radiation absorbed dose rate in the front of neck were decreased gradually as time went on after 131I therapy in each group. In general, the difference of radiation absorbed dose rate among different monitor term were significant (H=132.46, and 132.47, all P < 0.01)in same group. The difference of radiation absorbed dose rate between each other at 15, 30 and 45 d were significant(t=88.51, 113.7, 59.42 in groupⅠ, and 83.44, 112.76, 70.18 in groupⅡ, all P < 0.01), all of which in same monitor term were significantly higher in group Ⅱ than those in groupⅠ(t=8.81, 15.18, 10.10, all P < 0.01). The mean serum TSH of each group before and all different time periods after treatment were below the normal range(0.55~4.78 mIU/L) without significant difference (F=1.23, P>0.05). In general, the differences of fT3 and fT4 values in all groups were significant(FfT3=9.65, FfT4=22.45, all P < 0.01)before and after treatment. The fT3 and fT4 values in both groups rose significantly 30 days after therapy (tfT3=5.23, tfT4=10.14 in groupⅠ, tfT3=5.12, tfT4=9.98 in groupⅡ, all P < 0.01), then decreased gradually to the normal ranges. The fT3 and fT4 values in groupⅡwere much lower than those in groupⅠ(tfT3=8.22, tfT4=19.18, all P < 0.01)30 days after therapy, no significance were found in other time periods. Cure rate of hyperthyroidism was achieved in 36 of the 50 patients (72%) in groupⅠand in 38 of the 50 patients (76%) in groupⅡwithout significant difference. There were no significant differences in curative effect of the two groups(χ2=0.21, P > 0.05). Conclusions For patients withdrawing of ATD and those with short effective half-time, as well as those intolerant or invalid, the short term addition of lithium to 131I allows for a better control of thyrotoxia and the completeness of treatment. But there have not been observed that lithium carbonate plus 131I can improve the long term cure rate of Graves hyperthyroidism. -
Key words:
- Graves disease /
- Iodine radioisotopes /
- Lithium carbonate /
- Chemotherapy, adjuvant
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表 1 131I治疗后颈前放射性吸收剂量率测定结果(x±s,μGy/h)
Table 1. The radioactive absorbed dose rate of the anterior portion of neck after 131I treatment(x±s, μGy/h)
组别 例数 不同时间的放射性吸收剂量率 Ha值 P值 15d 30d 45d A组 50 1769.9±107.8 344.2±36.6 35.6±4.0 132.46 < 0.01 B组 50 1971.3±120.8 464.7±41.8 47.8±5.3 132.47 < 0.01 tb值 8.81 15.18 10.10 P值 < 0.01 < 0.01 < 0.01 注:表中,A组:131I治疗组;B组:131I+碳酸锂治疗组;a:同组不同时段放射性吸收剂量率总体差异性比较;b:两组相同时段放射性吸收剂量率总体差异性比较。 表 2 两组治疗前后不同时段的血清甲状腺激素水平(x±s)
Table 2. Serum thyroid hormone levels of the two groups at different times, before and after treatment(x±s)
组别 例数 检测时间(d) fT3(pmol/L) fT4(pmol/L) TSH(mIU/L) A组 50 治疗前 14.60±0.78 29.38±2.40 0.00 治疗后 30 d 19.28±1.31 45.53±2.32 0.00 45d 6.05±0.53 19.84±1.80 0.09 90d 4.64±0.70 16.95±2.64 0.12 180d 4.03±0.42 13.63±1.99 0.10 B组 50 治疗前 10.28±0.55 30.12±5.40 0.00 治疗后 30 d 14.38±1.36 38.21±4.21 0.00 45d 5.85±1.50 18.95±0.80 0.07 90d 4.04±0.70 16.45±1.64 0.17 180d 3.33±0.42 12.36±1.99 0.14 Fa值 9.65 22.45 1.23 P值 < 0.01 < 0.01 >0.05 注:表中,A组:131I治疗组;B组:131I+碳酸锂治疗组;a:两组血清甲状腺激素水平的总体差异性比较;fT3:游离三碘甲状腺原氨酸;fT4:游离甲状腺素。 -
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