甲状腺激素抵抗综合征3例及文献复习

发布时间：2018-05-18 21:30

本文选题：甲状腺激素抵抗综合征 + TRβ受体　；参考：《山东大学》2017年硕士论文

【摘要】：目的观察3例甲状腺激素抵抗综合征(thyroid hormone resistance syndrome,THRS)先证者临床特点及家族史,检测甲状腺功能和甲状腺激素受体β基因突变情况,通过随访异常甲状腺功能发现THRS的可能,总结回顾该疾病诊断治疗方法,分析与其他甲状腺疾病的鉴别,探讨基因检测的重要性,提高临床医师对该病的认识,防止漏诊误诊误治。方法对山东省立医院内分泌科门诊2011-2016年收治的3例先证者进行回顾性分析,收集病史资料(性别、年龄、症状、体征、既往史、家族史等)及包括其中1例先证者父母在内的外周血标本。通过检测并随访甲状腺功能包括游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)、促甲状腺激素(TSH)发现特征性甲状腺激素抵抗表现,甲状腺自身抗体抗甲状腺过氧化物酶抗体(TPOAb)、抗甲状腺球蛋白(TGAb)、抗促甲状腺激素受体抗体(TRAb)的检测帮助排除自身免疫疾病,行垂体MRI检查排除垂体瘤,通过复习文献、调整治疗、反复论证,逐步接近THRS的诊断,最后通过提取外周血DNA,对甲状腺激素受体(thyroid hormone receptor,TR)β基因第7-10外显子进行PCR扩增,对PCR产物测序检测基因突变位点协助明确诊断。结果3例先证者发病年龄分别为6岁、15岁、32岁,均有甲状腺肿大,以及多次甲状腺激素升高伴促甲状腺激素正常或升高的实验室检查特点,均已排除垂体TSH瘤。临床表现为无症状,服用甲状腺激素或抗甲状腺药物后甲功均未见明显改善。先证者1 THRβ基因第803位点碱基C突变为G,为杂合错义突变,该突变导致TRβ基因编码的第268位氨基酸由丙氨酸(Alanine,Ala)变为甘氨酸(Glycine,Gly),诊断为THRS,其父母未发现基因突变。先证者2基因检测无阳性结果,临床诊断为THRS。先证者3甲状腺自身抗体TPOAb、TGAb阳性,基因检测未发现THRβ基因突变,临床诊断为THRS合并桥本氏甲状腺炎。随访3位先证者均无不适症状,先证者1和2停药后甲状腺激素、促甲状腺激素水平趋于下降;先证者3 TSH持续高水平。结论甲状腺激素抵抗综合征是一种罕见的家族遗传病,绝大多数为常染色体显性遗传,A268G突变可能是该先证者致病原因,未检测到THRβ基因突变者可能为其他原因所致THRS包括THRα基因突变、甲状腺激素转运、代谢过程异常。甲状腺肿大同时伴有促甲状腺激素不被抑制、垂体MR未见垂体瘤的青少年、幼儿患者需警惕甲状腺激素抵抗综合症。基因检测可为该病诊断提供线索。
[Abstract]:Objective to observe the clinical characteristics and family history of 3 cases of thyroid hormone resistance syndrome (thyroid hormone resistance syndrome) probands, to detect thyroid function and the mutation of thyroid hormone receptor 尾 gene, and to find out the possibility of THRS by following up abnormal thyroid function. The diagnosis and treatment methods of this disease were summarized and reviewed, the differential diagnosis from other thyroid diseases was analyzed, the importance of gene detection was discussed, the understanding of the disease was improved by clinicians, and the misdiagnosis and mistreatment were prevented. Methods A retrospective analysis of 3 proband patients admitted to the Department of Endocrinology Department of Shandong Provincial Hospital from 2011 to 2016 was carried out to collect the historical data (sex, age, symptoms, signs, past history). Family history, etc.) and peripheral blood samples including the parents of one of the proband. Thyroid function including free thyroxine FT4, free triiodothyronine FT3, thyroid stimulating hormone (TSHs), and characteristic thyroid hormone resistance were detected and followed up. The detection of anti-thyroid peroxidase antibody, anti-thyroglobulin antibody, anti-thyrotropin receptor antibody, and anti-thyrotropin receptor antibody can help to exclude autoimmune diseases. Pituitary MRI examination was performed to exclude pituitary adenoma. The treatment was adjusted by reviewing the literature. It was proved repeatedly that it was close to the diagnosis of THRS step by step. Finally, by extracting the peripheral blood DNA, the exon 7-10 of thyroid hormone receptor (TRT) 尾 gene was amplified by PCR, and the PCR product sequencing was used to detect the mutation site of the gene. Results the onset age of the three proband patients was 6 years old, 15 years old and 32 years old respectively. All of them had thyroid enlargement, and the laboratory examination of thyroid hormone elevation accompanied by thyroid stimulating hormone (TSH) was normal or elevated. Pituitary TSH's tumor was excluded. The clinical manifestations were asymptomatic and no significant improvement of thyroid function was found after taking thyroid hormone or antithyroid drugs. Base C at locus 803 of the 1 THR 尾 gene was transformed into G, which was a heterozygous missense mutation. The mutation resulted in the conversion of the amino acid encoding tr 尾 from alanine Alanine Ala to Glycine Glycine Glycine, which was diagnosed as THRS.The gene mutation was not found in the parents. No positive results were found in proband 2 gene, and the clinical diagnosis was THRS. THR 尾 gene mutation was not found in Provost 3 thyroid autoantibody TPO Ab TGAb. The clinical diagnosis was THRS combined with Hashimoto's thyroiditis (Hashimoto's thyroiditis). All the 3 proband patients were followed up with no symptoms. Thyroid hormone and thyrotropin levels tended to decrease after 1 and 2 discontinuation of the drug, and the probands had a high level for 3 TSH. Conclusion thyroid hormone resistance syndrome is a rare familial hereditary disease, most of which are autosomal dominant genetic mutation A268G, which may be the cause of the disease. THR 尾 gene mutations may be caused by other causes, including THR 伪 gene mutations, thyroid hormone transport, and abnormal metabolic processes. Thyroid enlargement accompanied by uninhibited thyrotropin, pituitary Mr no pituitary adenoma in adolescents, young children should be on guard against thyroid hormone resistance syndrome. Gene detection can provide clues for diagnosis of the disease.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R581

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