本文選題：甲狀腺激素抵抗綜合征 + TRβ受體　； 參考：《山東大學》2017年碩士論文

【摘要】：目的觀察3例甲狀腺激素抵抗綜合征(thyroid hormone resistance syndrome,THRS)先證者臨床特點及家族史,檢測甲狀腺功能和甲狀腺激素受體β基因突變情況,通過隨訪異常甲狀腺功能發(fā)現(xiàn)THRS的可能,總結回顧該疾病診斷治療方法,分析與其他甲狀腺疾病的鑒別,探討基因檢測的重要性,提高臨床醫(yī)師對該病的認識,防止漏診誤診誤治。方法對山東省立醫(yī)院內分泌科門診2011-2016年收治的3例先證者進行回顧性分析,收集病史資料(性別、年齡、癥狀、體征、既往史、家族史等)及包括其中1例先證者父母在內的外周血標本。通過檢測并隨訪甲狀腺功能包括游離甲狀腺素(FT4)、游離三碘甲腺原氨酸(FT3)、促甲狀腺激素(TSH)發(fā)現(xiàn)特征性甲狀腺激素抵抗表現(xiàn),甲狀腺自身抗體抗甲狀腺過氧化物酶抗體(TPOAb)、抗甲狀腺球蛋白(TGAb)、抗促甲狀腺激素受體抗體(TRAb)的檢測幫助排除自身免疫疾病,行垂體MRI檢查排除垂體瘤,通過復習文獻、調整治療、反復論證,逐步接近THRS的診斷,最后通過提取外周血DNA,對甲狀腺激素受體(thyroid hormone receptor,TR)β基因第7-10外顯子進行PCR擴增,對PCR產(chǎn)物測序檢測基因突變位點協(xié)助明確診斷。結果3例先證者發(fā)病年齡分別為6歲、15歲、32歲,均有甲狀腺腫大,以及多次甲狀腺激素升高伴促甲狀腺激素正�；蛏叩膶嶒炇覚z查特點,均已排除垂體TSH瘤。臨床表現(xiàn)為無癥狀,服用甲狀腺激素或抗甲狀腺藥物后甲功均未見明顯改善。先證者1 THRβ基因第803位點堿基C突變?yōu)镚,為雜合錯義突變,該突變導致TRβ基因編碼的第268位氨基酸由丙氨酸(Alanine,Ala)變?yōu)楦拾彼?Glycine,Gly),診斷為THRS,其父母未發(fā)現(xiàn)基因突變。先證者2基因檢測無陽性結果,臨床診斷為THRS。先證者3甲狀腺自身抗體TPOAb、TGAb陽性,基因檢測未發(fā)現(xiàn)THRβ基因突變,臨床診斷為THRS合并橋本氏甲狀腺炎。隨訪3位先證者均無不適癥狀,先證者1和2停藥后甲狀腺激素、促甲狀腺激素水平趨于下降;先證者3 TSH持續(xù)高水平。結論甲狀腺激素抵抗綜合征是一種罕見的家族遺傳病,絕大多數(shù)為常染色體顯性遺傳,A268G突變可能是該先證者致病原因,未檢測到THRβ基因突變者可能為其他原因所致THRS包括THRα基因突變、甲狀腺激素轉運、代謝過程異常。甲狀腺腫大同時伴有促甲狀腺激素不被抑制、垂體MR未見垂體瘤的青少年、幼兒患者需警惕甲狀腺激素抵抗綜合癥�；驒z測可為該病診斷提供線索。
[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 偽 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.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R581

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相關期刊論文 前3條

1 趙甜;朱惠娟;龔鳳英;李乃適;班博;潘慧;;1例甲狀腺激素抵抗綜合征患者THRβ基因突變的研究[J];中國衛(wèi)生檢驗雜志;2015年02期

2 童艷;涂梅;魏雯;陳陽;陳彤;;甲狀腺激素受體β基因H435Y突變所致甲狀腺激素抵抗綜合征:一家系研究[J];中華內分泌代謝雜志;2015年01期

3 張倩;梁軍;竇連軍;鄒彩艷;楊曼青;潘春明;占明;宋懷東;;TRβ基因突變致甲狀腺激素抵抗綜合征[J];中華內分泌代謝雜志;2012年06期

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