4例甲状腺过氧化物酶基因突变患者的临床表现及预后分析  

Clinical manifestations and prognostic analysis of four patients with thyroid peroxidase gene mutations

作　　者：彭荣光 张洁[1] 董辰辰 韩如来 孟令扬 李浩榕 金磊 周文中[1] 沈力韵 周瑜琳[1] 严佶祺[2] 王曙[1] 叶蕾[1] Peng Rongguang;Zhang Jie;Dong Chenchen;Han Rulai;Meng Lingyang;Li Haorong;Jin Lei;Zhou Wenzhong;Shen Liyun;Zhou Yulin;Yan Jiqi;Wang Shu;Ye Lei(Department of Endocrine and Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Institute of Endocrine and Metabolic Diseases,Shanghai National Clinical Research Center for Metabolic Diseases,Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission,Shanghai Key Laboratory for Endocrine Tumor,Shanghai 200025,China;Department of General Surgery,Rujin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病研究所,国家代谢性疾病临床医学研究中心(上海),国家卫生健康委员会内分泌代谢病重点实验室,上海市内分泌肿瘤重点实验室,200025 [2]上海交通大学医学院附属瑞金医院普外科,200025

出　　处：《中华内分泌代谢杂志》2025年第1期46-53,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(82141115,82370790);中国医学科学院中央级公益性科研院所基本科研业务费(2023-PT320-05)。

摘　　要：目的探讨甲状腺过氧化物酶(TPO)基因突变患者的临床特点及基因表型,为临床医生提供识别和诊断TPO突变的依据。方法回顾性分析上海交通大学医学院附属瑞金医院2014年1月至2023年12月期间收治的4例TPO突变患者,分析患者人口学信息、临床表现、基因型、治疗、预后等特征。结果男性2例,女性2例,确诊年龄为13~27岁。4例患者均因甲状腺肿大起病,3例表现在青春期,血清促甲状腺素(TSH)轻度升高或接近参考范围上限,游离三碘甲腺原氨酸(FT3)/游离甲状腺素(FT4)比值及甲状腺球蛋白(TG)显著升高。4例患者检出TPO基因符合杂合变异,均为致病或可能致病性复合杂合变异。规律使用左旋甲状腺素(L-T4)治疗后,甲状腺肿大难以逆转。其中3例患者因外观或压迫症状行甲状腺切除术,病理提示甲状腺滤泡增生性病变。结论TPO基因突变患者的临床特征为迟发性甲状腺肿,青春期明显,FT3/FT4比值升高伴TSH正常或升高,可通过基因诊断确诊。L-T4对其甲状腺肿大治疗效果不明显,最终需要手术治疗。Objective:To examine the clinical features and genetic profiles of patients with thyroid peroxidase(TPO)gene mutations and provide diagnostic guidance for clinicians.Methods:A retrospective review of four patients with TPO mutations treated at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2023.Data on demographics,clinical manifestation,genotypes,treatment,and prognosis of these patients were analyzed.Results:Two males and two females,aged 13 to 27 years at diagnosis,presented with goiter as the initial symptom,with three cases menifesting during puberty.Laboratory findings showed mildly elevated or upper-limit-normal serum thyroid-stimulating hormone(TSH)levels,significantly increased free triiodothyronine/free thyroxine(FT 3/FT 4)ratios,and elevated thyroglobulin(TG)levels.Genetic testing revealed compound heterozygous pathogenic or likely pathogenic TPO mutations.Despite regular levothyroxine(L-T 4)therapy,goiter persisted.Three patients required thyroidectomy due to cosmetic or compressive symptoms,with pathology showing follicular hyperplasia.Conclusion:TPO mutations are characterized by adolescent-onset goiter,elevated FT 3/FT 4 ratios,and normal to high TSH.Genetic testing confirms the diagnosis.L-T 4 offers limited improvement,and surgery is often needed.

关 键 词：先天性甲状腺功能减退症 甲状腺过氧化物酶 基因突变 分子遗传学 诊断 预后 

分 类 号：R440[医药卫生—诊断学] R581.2[医药卫生—临床医学]