Abstract：
OBJECTIVE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.
METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.
RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).
CONCLUSIONS: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.
METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.
RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).
CONCLUSIONS: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.
摘要：
目的：甲状腺过氧化物酶（TPOAb）和甲状腺球蛋白（TgAb）自身抗体定义了临床前自身免疫性甲状腺疾病（AITD），可发展为临床甲状腺功能减退或甲状腺功能亢进。我们确定了遗传上有1型糖尿病风险的儿童血清转换的年龄。
方法：在青年糖尿病环境决定因素（TEDDY）研究中，对5066名含有HLADR3或DR4单倍体基因型的健康儿童进行了TPOAb和TgAb血清阳性测定。在8-13岁的横断面初始筛查中血清阳性的儿童进行了纵向收集的样本（来自3.5个月大），回顾性和前瞻性地筛查了甲状腺自身抗体，以确定血清转换时的年龄。首次出现的自身抗体与性别有关，HLA基因型,AITD家族史,以及随后的甲状腺功能障碍和疾病。
结果：TPOAb和TgAb的最年轻外观为10和15个月，分别。女孩两种自身抗体的发病率较高。AITD家族史与TPOAb风险比[HR]1.90，95％置信区间[CI]1.17，3.08和TgAbHR2.55，95％CI1.91，3.41的较高风险相关。TgAb和TPOAb进展为甲状腺功能减退或甲状腺功能亢进的风险没有差异，但与首次出现TPOAb相比,在同一访视中出现两种自身抗体的儿童的风险更高(HR6.34,95%CI2.72,14.76).
结论：甲状腺自身抗体可能出现在生命的最初几年，尤其是女孩,以及有AITD家族史的儿童。同时出现两种自身抗体会增加甲状腺功能减退或甲状腺功能亢进的风险。
方法：在青年糖尿病环境决定因素（TEDDY）研究中，对5066名含有HLADR3或DR4单倍体基因型的健康儿童进行了TPOAb和TgAb血清阳性测定。在8-13岁的横断面初始筛查中血清阳性的儿童进行了纵向收集的样本（来自3.5个月大），回顾性和前瞻性地筛查了甲状腺自身抗体，以确定血清转换时的年龄。首次出现的自身抗体与性别有关，HLA基因型,AITD家族史,以及随后的甲状腺功能障碍和疾病。
结果：TPOAb和TgAb的最年轻外观为10和15个月，分别。女孩两种自身抗体的发病率较高。AITD家族史与TPOAb风险比[HR]1.90，95％置信区间[CI]1.17，3.08和TgAbHR2.55，95％CI1.91，3.41的较高风险相关。TgAb和TPOAb进展为甲状腺功能减退或甲状腺功能亢进的风险没有差异，但与首次出现TPOAb相比,在同一访视中出现两种自身抗体的儿童的风险更高(HR6.34,95%CI2.72,14.76).
结论：甲状腺自身抗体可能出现在生命的最初几年，尤其是女孩,以及有AITD家族史的儿童。同时出现两种自身抗体会增加甲状腺功能减退或甲状腺功能亢进的风险。
