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Graves病(Graves disease,GD)的发生与机体自身免疫失衡有关。有研究者发现,GD患者体内存在特征性促甲状腺素受体抗体(thyrotrophin receptor antibody,TRAb)[1]。近年来的研究结果显示,活性维生素D不仅能调节体内钙、磷等物质的代谢过程,而且还具有多重细胞免疫调节功能[2],通过影响各种免疫细胞的分化增殖及细胞因子的分泌等多种途径来调节机体免疫功能,抑制自身免疫疾病的发展。研究结果显示,体内偏低的维生素D水平会导致GD的患病率升高[3]。目前,GD的治疗方案主要包括内科药物治疗、外科手术治疗、131I治疗和中医药治疗。2016年美国甲状腺协会(ATA)调查结果显示,在美国约59.7%的GD患者选择131I治疗;在我国大陆约32%的医师首选131I治疗,在核医学科就诊的患者中有68%倾向选择131I治疗[4]。131I治疗是目前GD的有效治疗手段,患者在接受131I治疗的同时补充阿法骨化醇能否提高治疗的有效率,临床少有报道。本研究旨在探讨维生素D缺乏是否参与GD的发生发展,以及补充维生素D能否提高131I治疗GD的疗效。
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治疗前, GD患者组的FT3、 FT4、 TgAb、 TPOAb、TRAb水平较正常对照组明显升高,且差异有统计学意义(t=28.912~59.351,均P<0.01);而TSH、25-(OH)D3水平较正常对照组明显降低,且差异有统计学意义(t=−51.208、−18.106,均P<0.01)(表1)。
组别 例数 TSH(mIU/L) FT3(pmol/L) FT4(pmol/L) TgAb(IU/mL) TPOAb(IU/mL) TRAb(IU/L) 25-(OH)D3(nmol/L) GD患者组 200 0.016±0.001 31.02±12.39 43.29±11.56 243.73±186.23 152.36±87.26 9.62±6.82 29.32±12.43 正常对照组 200 2.160±0.980 5.39±0.51 15.26±1.09 20.15±16.28 7.23±5.06 1.06±0.51 51.46±25.92 t值 −51.208 51.847 59.351 28.912 41.265 30.996 −18.106 P值 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 注:表中,25-(OH)D3:25-羟维生素D3;GD:Graves病;TSH:促甲状腺激素;FT3:游离三碘甲腺原氨酸;FT4:游离甲状腺素;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;TRAb:促甲状腺素受体抗体 表 1 131I治疗前2组受检者血清甲状腺功能指标和自身抗体及25-(OH)D3水平的比较(
)$\bar x \pm s$ Table 1. Comparison of serum indices of thyroid function, thyroid autoimmune antibody, and 25-(OH)D3 in GD group and healthy control group before 131I treatment (
)$\bar x \pm s$ -
治疗前,GD患者组血清25-(OH)D3水平与TRAb、FT3、FT4、TgAb、TPOAb水平均呈负相关(r=−0.688~−0.219,均P<0.05),与TSH水平呈正相关(r=0.259,P<0.05)。
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治疗后12个月,GD2组血清25-(OH)D3水平高于GD1组,两组治疗前后差值的差异有统计学意义(t=−7.920,P<0.01);而血清TRAb、TgAb、TPOAb水平均低于GD1组,两组治疗前后差值的差异有统计学意义(t=−8.767、−4.106、−7.259,均P<0.01)(表2)。
组别 例数 25-(OH)D3(nmol/L) TRAb(IU/L) TgAb(IU/mL) TPOAb(IU/mL) 治疗前 GD1组 100 28.97±11.98 9.58±5.93 247.02±191.28 151.98±86.80 GD2组 100 29.68±12.11 9.67±6.91 242.38±185.97 153.29±88.67 治疗后 GD1组 100 29.86±12.78 3.12±1.80 146.33±103.81 100.41±63.11 GD2组 100 44.68±17.45 1.96±1.52 106.78±76.37 59.74±37.26 治疗前后差值 GD1组 100 7.71±5.82 6.45±3.86 117.79±83.84 57.59±42.23 GD2组 100 18.36±11.67 7.59±3.88 142.91±98.64 87.17±53.33 t值 −7.920 −8.767 −4.106 −7.259 P值 <0.01 <0.01 <0.01 <0.01 注:表中,GD:Graves病;25-(OH)D3:25-羟维生素D3;TRAb:促甲状腺素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体 表 2 GD1组与GD2组血清25-(OH)D3和甲状腺自身抗体水平在治疗前后差值的比较(
)$\bar x \pm s$ Table 2. Comparison of serum 25-(OH)D3, thyroid autoimmune antibody between GD1 and GD2 before and after treatment (
)$\bar x \pm s$ -
治疗后12个月,GD1组和GD2组的治疗有效率分别为63%(63/100)和78%(78/100),GD2组高于GD1组, 且差异有统计学意义(χ2=5.409, P=0.020)。
阿法骨化醇与131I治疗Graves病疗效的相关性研究
Study on the relationship between alfacalcidol and 131I in the treatment of Graves disease
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摘要:
目的 探讨维生素D缺乏是否参与Graves病(GD)的发生发展,以及补充维生素D能否提高131I治疗GD的疗效。 方法 回顾性分析2017年1月至2018年6月在青岛市市立医院就诊的GD患者200例,其中,男性60例、女性140例,年龄13~78(42.1±12.1)岁。将200例GD患者用随机数余数分组法分为GD1组(100例)和GD2组(100例),另选取正常健康者200名作为对照(正常对照组)。GD1组接受单纯131I治疗,GD2组接受131I治疗+阿法骨化醇治疗。检测治疗前GD患者组(GD1组+GD2组)和正常对照组的促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素受体抗体(TRAb)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)和25-羟维生素D3[25-(OH)D3]水平。治疗后12个月,复查2组GD患者的TRAb、TgAb、TPOAb和25-(OH)D3水平。采用两独立样本t检验行组间比较,配对样本t检验行组内差异比较;采用斯皮尔曼等级相关法进行相关性分析;采用χ2检验比较2组GD患者的治疗有效率。 结果 治疗前GD患者组的血清25-(OH)D3水平为(29.32±12.43) nmol/L,正常对照组为(51.46±25.92) nmol/L,GD患者组的维生素D水平较正常对照组低,且差异有统计学意义(t=−18.106,P<0.01)。GD患者组血清25-(OH)D3水平与TRAb、FT3、FT4、TgAb和TPOAb水平均呈负相关(r=−0.688~−0.219,均P<0.05),与TSH水平呈正相关(r=0.259,P<0.05)。治疗后12个月,GD2组血清25-(OH)D3水平[(44.68±17.45) nmol/L]高于GD1组[(29.86±12.78)nmol/L],两组治疗前后差值的差异有统计学意义(t=−7.920,P<0.01);GD2组血清TRAb、TgAb、TPOAb水平[(1.96±1.52) IU/L、(106.78±76.37) IU/mL、(59.74±37.26) IU/mL]均低于GD1组[(3.12±1.80) IU/L、(146.33±103.81) IU/mL、(100.41±63.11) IU/mL],两组治疗前后差值的差异有统计学意义(t=−8.767、−4.106、−7.259,均P<0.01)。治疗后12个月,GD1组的治疗有效率为63%(63/100)、GD2组为78%(78/100),两组间差异有统计学意义(χ2=5.409,P=0.020)。 结论 维生素D缺乏可能参与GD的发生发展,补充维生素D可能提高131I治疗GD的疗效。 Abstract:Objective To investigate whether vitamin D deficiency is involved in Graves disease (GD) occurrence and development and whether vitamin D supplementation can improve the efficacy of 131I in GD treatment. Methods A retrospective analysis was conducted on 200 GD patients in the nuclear medicine department of Qingdao Municipal Hospital from January 2017 to June 2018. The study included 60 males and 140 females aged 13–78 (42.1±12.1) years old. Two hundred patients with GD were divided into two groups, namely, GD1 group (100 cases) and GD2 group (100 cases) by random remainder grouping method, and 200 normal healthy people were selected to serve as the control. The levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyrotrophin receptor antibody (TRAb), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and 25-(OH)D3 in GD group and control group were detected before treatment. After 12 months, the levels of TRAb, TgAb, TPOAb and 25-(OH)D3 were reexamined. Two independent samples were compared by t-test. Paired samples were compared by t-test. Spearman rank correlation analysis was used. The effective rates of GD1 and GD2 groups were compared by χ2 test. Results Before treatment, the level of 25-(OH)D3 in GD group was (29.32±12.43) nmol/L, and that of normal control group was (51.46±25.92) nmol/L. The vitamin D level of GD group was lower than that of normal control group, and the difference was statistically significant (t=−18.106, P<0.01). Serum 25-(OH)D3 level was negatively correlated with TRAb, FT3, FT4, TgAb, and TPOAb levels (r=−0.688~−0.219, all P<0.05), and positively correlated with TSH level (r=0.259, P<0.05). Twelve months after treatment, the serum 25-(OH)D3 level in GD2 group [(44.68±17.45) nmol/L] was higher than that in GD1 group [(29.86±12.78) nmol/L], and the difference between the two groups before and after treatment was statistically significant (t=−7.920, P<0.01). The levels of TRAb, TgAb, and TPOAb in GD2 group were (1.96±1.52) IU/L, (106.78±76.37) IU/mL, and (59.74±37.26) IU/mL, while in GD1 group were (3.12±1.80) IU/L, (146.33±103.81) IU/mL, and (100.41±63.11) IU/mL, respectively. The difference between the two groups before and after treatment was statistically significant (t=−8.767, −4.106, −7.259, all P<0.01). Twelve months after treatment, the effective rate of GD1 group was 63% (63/100), whereas that of GD2 group was 78% (78/100). The difference between the two groups was statistically significant (χ2=5.409, P=0.020). Conclusion Vitamin D deficiency may be involved in GD development. Vitamin D supplementation may improve the efficacy of 131I in GD treatment. -
Key words:
- Graves disease /
- Thyroid hormones /
- Calcifediol /
- Iodine radioisotopes /
- Brachytherapy /
- Alfacalcidol
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表 1 131I治疗前2组受检者血清甲状腺功能指标和自身抗体及25-(OH)D3水平的比较(
)$\bar x \pm s$ Table 1. Comparison of serum indices of thyroid function, thyroid autoimmune antibody, and 25-(OH)D3 in GD group and healthy control group before 131I treatment (
)$\bar x \pm s$ 组别 例数 TSH(mIU/L) FT3(pmol/L) FT4(pmol/L) TgAb(IU/mL) TPOAb(IU/mL) TRAb(IU/L) 25-(OH)D3(nmol/L) GD患者组 200 0.016±0.001 31.02±12.39 43.29±11.56 243.73±186.23 152.36±87.26 9.62±6.82 29.32±12.43 正常对照组 200 2.160±0.980 5.39±0.51 15.26±1.09 20.15±16.28 7.23±5.06 1.06±0.51 51.46±25.92 t值 −51.208 51.847 59.351 28.912 41.265 30.996 −18.106 P值 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 注:表中,25-(OH)D3:25-羟维生素D3;GD:Graves病;TSH:促甲状腺激素;FT3:游离三碘甲腺原氨酸;FT4:游离甲状腺素;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;TRAb:促甲状腺素受体抗体 表 2 GD1组与GD2组血清25-(OH)D3和甲状腺自身抗体水平在治疗前后差值的比较(
)$\bar x \pm s$ Table 2. Comparison of serum 25-(OH)D3, thyroid autoimmune antibody between GD1 and GD2 before and after treatment (
)$\bar x \pm s$ 组别 例数 25-(OH)D3(nmol/L) TRAb(IU/L) TgAb(IU/mL) TPOAb(IU/mL) 治疗前 GD1组 100 28.97±11.98 9.58±5.93 247.02±191.28 151.98±86.80 GD2组 100 29.68±12.11 9.67±6.91 242.38±185.97 153.29±88.67 治疗后 GD1组 100 29.86±12.78 3.12±1.80 146.33±103.81 100.41±63.11 GD2组 100 44.68±17.45 1.96±1.52 106.78±76.37 59.74±37.26 治疗前后差值 GD1组 100 7.71±5.82 6.45±3.86 117.79±83.84 57.59±42.23 GD2组 100 18.36±11.67 7.59±3.88 142.91±98.64 87.17±53.33 t值 −7.920 −8.767 −4.106 −7.259 P值 <0.01 <0.01 <0.01 <0.01 注:表中,GD:Graves病;25-(OH)D3:25-羟维生素D3;TRAb:促甲状腺素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体 -
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