选择性垂体甲状腺激素抵抗综合征二例

例1 患者男，26岁。因甲状腺弥漫性肿大、心慌、气短、怕热、多汗、食多、便次多、手颤等症状，在外省县级医院诊为甲状腺功能亢进症（甲亢），经他巴唑（30mg／d）及中药治疗1年多，甲状腺未见缩小，当地检测血T3、T4、促甲状腺激素（TSH）多次均高于正常，甲亢症状缓解不明显，来我院要求^131I治疗。就诊时体检：甲状腺Ⅲ度弥漫性肿大，质地中硬、表面光滑，无压触痛、杂音及震颤；     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

垂体选择性甲状腺激素抵抗综合征1例

垂体选择性甲状腺激素抵抗(PRTH)综合征临床上极少见,主要表现为垂体对甲状腺激素不敏感,外周组织仍保留对T3的正常反应.因其临床表现与Graves病相似而常被误诊,并错误的长期用抗甲状腺药物治疗,甚至进行手术或131I治疗.     

选择性垂体甲状腺激素抵抗的新认识

选择性垂体甲状腺激素抵抗是甲状腺抵抗综合征中的一种少见类型,为一种常染色体显性遗传性疾病.主要由于甲状腺激素受体β亚基基因突变所致.它的临床特征为轻度甲状腺功能亢进,实验室检查提爪游离T3游离T4升高的同时伴有促甲状腺激素的不适当分泌.治疗可选用三碘甲状腺醋酸、右旋T4、溴隐亭等,目前尚无根治方法.     

Thyroid hormone resistance: the role of mutational analysis

The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a patient with normal or increased thyroid-stimulating hormone is unexpected and presents a differential diagnosis between a thyroid-stimulating hormone-secreting pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory artefact. Without careful clinical and biochemical evaluation, errors may occur in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid hormone receptor beta gene results in generalized tissue resistance to thyroid hormone. As the pituitary gland shares in this tissue resistance, euthyroidism with a normal thyroid-stimulating hormone is usually maintained by increased thyroid hormones. To date, we have identified eight pedigrees in New Zealand with mutations in the thyroid hormone receptor beta gene, including two novel mutations. Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing and imaging. Mutational analysis also enables family screening and may help to avoid potential misdiagnosis and inappropriate treatment.     

From the Cover: A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

Resistance to thyroid hormone (RTH) is most often due to point mutations in the β-isoform of the thyroid hormone (TH) receptor (TR-β). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-β locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic–pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T₃ replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T₃ treatment failed to normally suppress these levels. T₃ treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T₃ treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH.     

新生早期甲状腺功能减退大鼠心肌甲状腺激素受体mRNA表达的实验研究

目的探讨新生早期甲状腺功能减退（简称甲减）对大鼠心肌发育过程中甲状腺激素受体（TR）各亚型mRNA表达的影响。方法Wistar雌鼠从怀孕15d开始每天经胃灌注1％丙硫氧嘧啶2．5ml，复制甲减仔鼠动物模型，分别于各时间点称体质量后处死仔鼠，取心脏。放射免疫分析法（RIA）动态监测各组大鼠血清FT3、FT4水平，FQ—PCR方法检测各组心肌TR各亚型mRNA的表达差异。结果与对照组比较，甲减大鼠心肌TRα1 mRNA表达量在出生后0、21、45d分别下调90％、15％、36％（tod=8．33，t21d=2．58，t45d=3．25，P〈0．05），表达峰值于生后2周延迟出现。甲减大鼠心肌TRα2 mRNA表达量在出生后0、14、21、45d分别上调22％、72％、82％、36％（t0d=3．89，t14d=11．88，t21d=13．90，t45d=6．19，P〈0．05），表达峰值于生后2周延迟出现。甲减大鼠心肌TRβ1 mRNA表达量在出生后0、14、21、45d分别下调75％、62％、68％、60％（t0d=38．96，t14d=5．22，t21d=17．23，t45d=5．43，P〈0．05），表达变化趋势与对照组一致。结论新生早期甲减大鼠心肌上TR mRNA的异常表达可能与甲减性心脏病的发病机制密切相关。     

甲状腺激素抵抗综合征两例报道并文献回顾

对2例甲状腺激素抵抗综合征患者的临床表现、实验室检查及治疗效果进行分析.2例均表现出生长发育迟缓,血清TT_3、FT_3升高,吸碘率降低.其中1例患者存在先天性鸟脸畸形和神经性耳聋,血清TSH升高.超生理剂量外源性甲状腺素可抑制其促甲状腺素的合成与释放,2例患者均对甲状腺素治疗有效.甲状腺激素抵抗综合征是甲状腺激素受体基凶突变相关性疾病,基因诊断是确诊本病的根本手段.     

不同甲状腺功能状态下游离脂肪酸与胰岛素抵抗的关系

44例甲状腺功能亢进症(甲亢)、23例甲状腺功能减退症(甲减)和30例甲状腺功能正常人的研究显示,甲亢患者存在胰岛素抵抗,甲亢和甲减患者HOMA-IR与游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)正相关,甲状腺功能正常者HOMA-IR与游离脂肪酸正相关。     

甲状腺激素抵抗合并妊娠的临诊应对

女性先证者,14岁零10个月时因确诊甲状腺激素抵抗(RTH)而接受治疗.该患者为其母的第一胎,孕36周经阴道自然分娩,出生时母30岁,父35岁.拥有奥地利/德国血统,出生体重2.8 kg,身长59.7 cm.生后不久出现"腹绞痛"症状,频繁发作哭闹.6～14个月期间几乎每个月都会发生耳部感染而接受抗生索治疗.     

糖尿病患者合并甲状腺功能异常的机制及其影响

糖尿病患者甲状腺功能异常的发生率是非糖尿病患者的2～3倍.甲状腺激素与糖代谢多个环节密切相关.糖尿病患者合并甲状腺功能异常时不仅加重机体的糖代谢异常,而且可以增加心血管疾病的风险.早期发现糖尿病患者潜在的甲状腺功能异常并及时纠正,可避免患者出现血糖控制紊乱及严重的合并症.