促甲状腺素抑制治疗甲状腺癌患者的膳食调查分析

目的 对促甲状腺素(TSH) 抑制治疗期间的分化型甲状腺癌(DTC)患者进行膳食调查，为对患者进行个性化膳食指导及营养干预研究提供参考依据。方法 从湖南省肿瘤医院甲状腺内科的门诊患者中收集行TSH抑制治疗的DTC患者，根据抑制治疗副作用危险分层标准，收集低、中、高危患者各200例，共600例患者作为研究对象。对所有入选病例进行膳食调查:一年食物摄入频率和3天24小时回顾法膳食调查。结果 TSH抑制治疗的DTC患者整体人群膳食摄入不足且膳食结构不合理；整体人群畜肉类摄入过多，鱼类及水产品、蛋、奶、豆、蔬菜、水果则摄入过少；整体人群脂类、碳水化合物、维生素E摄入量基本达到要求；蛋白质、膳食纤维、钙、铁、锌、硒、维生素A、维生素B1、维生素B2、维生素C、烟酸摄入明显不足；碘摄入基本符合要求；低、中、高危组膳食摄入不足率分别是21.0%、8.0%、11.5%；中危组畜肉类摄入最多，碘摄入有0.5%的患者超标；高危组牛奶摄入最少。结论 TSH抑制治疗的DTC患者膳食结构不合理及多种营养素摄入不足，在临床工作中应加强对整体人群的营养教育及针对性的干预，以降低TSH抑制治疗对心血管系统及影响骨代谢的风险。     

Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease

Thyrotropin releasing hormone (TRH) was administered intravenously to ten patients with Alzheimer's Disease (AD) in a high-dose paradigm, thought to maximize central nervous system effects and potentially produce facilitation of cholinergic function, a known property of the neuropeptide. Acute effects of TRH on behavioral, cognitive and physiologic measures were assessed after patients received 0.1 mg/kg TRH, 0.3 mg/kg TRH and placebo, the higher TRH dose and placebo being given in a randomized, double-blind fashion. Patients showed statistically significant increases in arousal and improvement in affect, as well as a modest improvement in semantic memory, all after receiving the higher TRH dose. Both TRH doses produced transient rises in systolic blood pressure, with no effect on diastolic blood pressure, heart rate or temperature. This study suggests that high-dose TRH can be safely administered to AD patients and is neurobehaviorally active; further studies are needed to determine the extent and mechanism of the cognitive and psychobiological properties of this peptide in AD and other neuropsychiatric disorders.     

Mutations of thyrotropin receptor gene

 Thyrotropin is the primary pituitary hor- mone which stimulates the growth and differentiation of thyroid cells. TSH binds a specific receptor present in the plasma membrane of thyroid cells and signals the G protein transducers, which activate different effec- tors, mainly adenyl cyclase and phospholipase C. The TSH receptor belongs to a broad class of receptors known as seven-loop receptors because they contain a long stretch of amino acids which cross the plasma membrane seven times. Mutations in the TSH receptor gene have been found in hyperfunctioning thyroid adenomas. These mutations are: (a) somatic (present only in the tumor), (b) dominant (only one copy of the gene is affected), and (c) lead to the constitutive activation of the cAMP signaling cascade. Most mutations which have been identified occur in the intracellular loop III and in the transmembrane domain VI. Germline mutations in the same regions of the receptor have been found in congenital nonautoimmune hyperthyroidism. In addition, germ line mutations have been described in the extracellular domain of the receptor leading to increased TSH levels. The clinical implications of these findings are discussed. Received: 15 January 1996 / Accepted: 8 March 1996     

液相人血清TSH免疫放射分析的建立

本文利用兔抗人ＴＳＨ（ｈＴＳＨ）多克隆抗体、（１２５）~Ｉ－鼠抗ｈＴＳＨ单克隆抗体、固相驴抗兔二抗建立了液相高灵敏度人血清ＴＳＨ免疫放射分析。方法学考核显示，灵敏度为０．００８ｍＩＵ／Ｌ，批内和批间变异系数分别为１．６％～４．１％和２．７％～８．６％，回收率为９５．２％～１０１．４％，与ｈＦＳＨ和ｈＨＣＧ的交叉反应率分别为４．４１×１０~（－５）和５．０８×１０~（－７）．用本法测定了３４名正常人、２７例甲亢和９例甲低患者血清值，结果与临床相符。     

Controlled trial of thyrotropin releasing hormone tartrate in ataxia of spinocerebellar degenerations

The clinical efficacy, dose-response relationship, and safety of TRH-T (thyrotropin releasing hormone tartrate) were assessed in 290 patients with spinocerebellar degeneration (SCD) in a 2-week, double-blind study using placebo as control. 254 patients satisfied the criteria for inclusion in evaluation of the drug efficacy. The patients were treated with TRH-T in an intramuscular dose of 2 mg, 0.5 mg or 0 mg (placebo) as TRH once a day for 2 weeks. Clinical responses to these treatments were evaluated 3 times: at the end of weeks 1 and 2 of treatment and a week after the end of treatment. The results of "global improvement rating" as well as those of "ataxia improvement rating" showed that both 2 mg and 0.5 mg TRH-T treatments were significantly superior to placebo treatment in patients with predominantly cerebellar form of SCD. The effect was well maintained a week after the end of the 2-week treatment in the patients who were given TRH-T in daily dose of 2 mg and showed improvement at the end of treatment. The results of "improvement rating of each symptom" revealed that 2 mg treatment was significantly more effective than placebo for disorders of standing, gait, speech and writing. In the patients who had no pyramidal involvement or disorder of deep sensation, the drug efficacy and dose-response relationship were evident. Adverse reactions to the drug such as headache, feeling febrile and nausea were observed in 50% of the patients on 2 mg treatment, in 38% of those on 0.5 mg treatment and in 21% of those on placebo patient, however, discontinued treatment because of adverse reactions.     

甲状腺癌术后妊娠期甲状腺素水平的调控

目的分析甲状腺癌术后妊娠期甲状腺素水平的调控过程，旨在降低母体甲状腺功能减退继发的胎儿异常发生率。方法回顾性分析20例甲状腺癌术后妊娠妇女甲状腺激素水平的调控过程，通过每月监测其甲状腺功能，了解左旋甲状腺激素（优甲乐）增加剂量和目标TSH水平。结果20例妊娠妇女孕21次，1例妊娠2次，第1次孕早期流产，20例优甲乐的基础剂量均为100μg，以12．5μg为调整增量，目标TSH水平设为0．10—0．25mU／ml。20例优甲乐剂量平均增加50μg，即增加了基础剂量的50％。在孕16周左右TSH水平达到平衡，直至分娩。所有胎儿均健康，发育良好；所有20位妇女产后均规律随访，时间平均5年（6个月～10年），无复发。结论甲状腺癌术后妊娠，应定期监测甲状腺功能，优甲乐以12．5μg为调整剂量，将母体TSH水平控制在0．10—0．25mU／ml，既保证胎儿健康发育，又抑制母体肿瘤生长。     

TSHR第三胞内袢基因突变与毒性多结节性甲状腺肿发病的相关研究

目的探讨促甲状腺激素受体(TSHR)第三胞内袢基因突变在毒性多结节性甲状腺肿(TMG)自主高功能性形成中的作用。方法将16例TMG患者手术切除标本及其作为对照的甲状腺正常组织,用酚-氯仿-异戊醇法提取基因组DNA,对目的基因片断进行聚合酶链反应(PCR)及行DNA测序。结果在16例TMG 标本中,发现3例为622位密码子的点突变。异亮氨酸被苯丙氨酸置换(I622F,ATT→TTT),2例为单碱基插入性突变,在1928位和1929位核酸之间播入了一个鸟嘌呤核苷酸(G),使该密码子609位以后氨基酸发生了移码突变。在对照组中,未发现TSHR基因突变。结论 TSHR第三胞内袢基因突变,可能在TMG发病中起重要作用。     

甲状腺素对仔鼠脑NAPOR基因表达的影响

目的研究甲状腺素对仔鼠脑成纤维母细胞瘤凋亡相关的RNA结合蛋白(neuroblastoma apoptosis-related RNA-binding protein,NAPOR)基因表达的影响。方法以丙基硫氧嘧啶灌胃复制孕鼠甲状腺功能低下模型,采用逆转录-聚合酶链反应检测仔鼠出生后第1、5、10天仔鼠皮层NAPOR的表达,年龄匹配的正常仔鼠为对照组。结果NAPOR在甲状腺功能低下孕鼠所产仔鼠表达均高于正常对照组;在出生后一段时期内,随着鼠龄增长表达降低。结论转录后水平的调节机制可能参与甲状腺素对脑基因表达的影响。     

地塞米松联合甲巯咪唑治疗自身免疫性甲状腺炎效果及对T细胞免疫功能、炎性因子影响观察

目的观察地塞米松联合甲巯咪唑治疗自身免疫性甲状腺炎的效果及对T细胞免疫功能、炎性因子的影响。方法选取自身免疫性甲状腺炎79例,根据治疗方法不同将其分为观察组(41例)和对照组(38例)两组。观察组予地塞米松磷酸钠注射液联合甲巯咪唑片治疗,对照组予甲巯咪唑片治疗,疗程均为1个月。观察比较两组治疗后临床效果,治疗前后血清甲状腺功能相关指标、T细胞免疫功能相关指标和炎性因子水平,以及治疗期间不良反应发生情况。结果治疗后,观察组总有效率为90.24%高于对照组总有效率71.05%,差异有统计学意义(P<0.05)。治疗前,两组血清甲状腺功能相关指标、T细胞免疫功能相关指标和炎性因子水平比较差异均无统计学意义(P>0.05)。治疗后,血清游离三碘甲状腺原氨酸、甲状腺过氧化物酶抗体、甲状腺球蛋白抗体和肿瘤坏死因子-α、白细胞介素-17水平两组均较治疗前降低,且观察组低于对照组;两组血清CD4+水平及CD4+/CD8+值较治疗前升高,血清CD8+水平较治疗前降低,观察组血清CD4+水平及CD4+/CD8+值高于对照组,血清CD8+水平低于对照组,差异均有统计学意义(P<0.05或P<0.01)。治疗期间,观察组不良反应总发生率为34.15%高于对照组不良反应总发生率28.95%,但两组比较差异无统计学意义(P>0.05)。结论地塞米松联合甲巯咪唑治疗自身免疫性甲状腺炎可提高临床效果,降低自身抗体水平,改善机体免疫功能,减轻炎症反应程度,且安全性良好。     

The Putative Role of Fibroblasts in the Pathogenesis of Graves' Disease: Evidence for the Involvement of the Insulin-like Growth Factor-1 Receptor in Fibroblast Activation

Graves' disease when fully expressed affects the thyroid gland and connective tissues of the orbit and pretibium. While the glandular disease is relatively well-characterized, the pathogenesis of the orbital and dermal components remains enigmatic. In the following article, we review some of the evidence suggesting that fibroblast activation in Graves' disease might play an integral role in the tissue remodeling associated with ophthalmopathy. The thyrotropin receptor (TSHR) is expressed at low levels in several connective tissue depots and by their derivative fibroblasts, including those from the orbit. Little direct evidence currently links extra-thyroidal TSHR expression with Graves' disease. Very recent observations now implicate the insulin-like growth factor-1 receptor (IGF-1R) as a fibroblast activating antigen. When immunoglobulins from patients with the disease, with or without clinical ophthalmopathy, bind IGF-1R on the surface of fibroblasts, the receptor becomes activated and upregulates the expression of two T lymphocyte chemoattractants, IL-16 and RANTES. Thus, IGF-1R may represent a second self-antigen with a pathogenic role in extra-thyroidal Graves' disease.