碘缺乏对人体的危害

人体一旦摄入的碘不足,甲状腺激素合成减少,机体就会出现一系列的障碍。我们将缺碘而造成的障碍统称为碘缺乏病。它不是单一的一种疾病,而是一系列疾病、障碍的总称,对人类健康造成极大的危害。主要有：（1）地方性甲状腺肿：在缺碘地区,不分性别、年龄都可能发生。人体缺碘造成甲状腺激素合成不足。由于体内甲状腺激素分泌减少,使脑垂体促甲状腺激素分泌增多,刺激甲状腺增强作业,久而久之,甲状腺细胞呈现活跃性的增生和肥大,从而导致了甲状腺肿的发生。目前全国约有70O万病人。（2）地方性克汀病：医学上叫呆小症,是由于母体严…     

钠/碘同向转运体的研究进展

甲状腺对I^-的摄取是甲状腺激素合成的第一步,而调节这一过程的重要物质是位于甲状腺滤泡细胞基底膜上的钠／碘同向转运体(sodium/iodide symporter,NIS)。NIS主要存在于甲状腺组织,其调节I^-摄取要依赖Na^ 的存在,摄取过程可被SCN^-、ClO4^-等一价阴离子所抑制。人和大鼠NIS的基因都已经被克隆,对其基因表达调控的研究也逐渐兴起。促甲状腺激素(TSH)对NIS的基因的表达及I^-摄取具有很强的刺激作用。研究人员在一些自身免疫性甲状腺疾病患的血清中发现了针对NIS的抗体,而且,认识到NIS的基因突变是先天性甲状腺功能低下的一个重要原因。此外,人们利用NIS的基因,进行基因治疗肿瘤的研究也已逐步展开。     

浅谈几种内分泌腺疾病

《生理卫生》课本“内分泌系统”一章中,讲了几种内分泌腺疾病。本文仅就这些疾病作一些介绍。地方性甲状腺肿甲状腺是体内最大的内分泌腺体,重约20—25克,女性甲状腺体积较男性稍大。地方性甲状腺肿主要是由于有些地区的土壤和饮食中长期缺碘所致的地方病。甲状腺的正常机能受高级神经中枢控制,经过垂体前叶所分泌的促甲状腺激素来促使甲状腺的增长和分泌甲状腺激素。甲状腺合成和分泌甲状腺激素是经过腺体摄取无机碘、酪氨酸的碘化、缩合等一系列的酶促反应来完成。正     

LATS对离体正常小鼠甲状腺合成和释放甲状腺激素的影响

本文研究了长效甲状腺刺激物(简称LATS)对离体正常小鼠甲状腺合成和释放甲状腺激素的影响。用配对实验法,将小鼠甲状腺两叶分别放入两个培养瓶内,一组加LATS-IgG,另一组加正常人IgG作对照,在其他条件相同的情况下,实验组的摄碘率、碘的有机化作用和甲状腺激素的合成,分别增加37.5%、85%和150%。在相同的培养条件下,大鼠甲状腺过氧化物酶(简称TPO)活性,实验组比对照组增高了约三倍。说明LATS可能通过促进摄碘和活化TPO酶,促进甲状腺激素的合成。用离体培养和放射免疫测定方法证明,每毫升培养液中加50μILATS血清(McKenzie活性为4,000%),正常小鼠甲状腺释放T_4和T_3均可增加十多倍。如果先用~(125)I体内标记2小时,再将甲状腺摘出体外培养,则LATS组不仅总的释放率增加,而且释放物的组成成分,也有所不同,激素碘占16.6%,无机碘占83.4%;而对照组分别为2.1%和97.9%。     

LATS对离体正常小鼠甲状腺合成和释放甲状腺激素的影响

本文研究了长效甲状腺刺激物(简称LATS)对离体正常小鼠甲状腺合成和释放甲状腺激素的影响。用配对实验法,将小鼠甲状腺两叶分别放入两个培养瓶内,一组加LATS-IgG,另一组加正常人IgG作对照,在其他条件相同的情况下,实验组的摄碘率、碘的有机化作用和甲状腺激素的合成,分别增加37.5%、85%和150%。在相同的培养条件下,大鼠甲状腺过氧化物酶(简称TPO)活性,实验组比对照组增高了约三倍。说明LATS可能通过促进摄碘和活化TPO酶,促进甲状腺激素的合成。用离体培养和放射免疫测定方法证明,每毫升培养液中加50μlLATS血清(McKenzie活性为4,000%),正常小鼠甲状腺释放T_4和T_3均可增加十多倍。如果先用~(125)Ⅰ体内标记2小时,再将甲状腺摘出体外培养,则LATS组不仅总的释放率增加,而且释放物的组成成分,也有所不同,激素碘占16.6%,无机碘占83.4%;而对照组分别为2.1%和97.9%。     

地方性克汀病遗传— 缺碘病因的探讨

克汀病（cretinism）有地方性和散发性之 分,前者系由Platter^[1]于1614年首先报告;后 者系由Curling^[2]于1850年首先报告,1871年又 由Fagge等详加描述。近年来对散发性克汀病 的病因及发病机理已有了比较清楚的认识。它 可分为两大类型：一类为先天性甲状腺发育障 碍,其病因系由自身免疫所致^[3.4].另一类由甲 状腺激素合成障碍所致,系一种遗传代谢病[5]. 根据此类患者甲状腺激素合成障碍发生的环节 不同,又可分为酪氨酸碘化障碍,碘酪氨酸脱碘 障碍,碘酪氨酸结合为碘甲状腺原氨酸障碍,甲 状腺球蛋白降解障碍（碘蛋白质分泌异常和甲 状腺球蛋白缺陷）,碘化物摄取障碍和甲状腺对 TSH（垂体促甲状腺激素）无反应及对毛（甲状 腺素）耐受性增高等不同类型［[610地方性克汀病 的病因及发病机理至今尚未完全阐明,归纳起 来有三种假说,即（1)胚胎期缺碘病因假说;(2) 遗传病因假说,和（3）自身免疫病因假说,其中 以胚胎期缺碘病因假说在目前被较多的作者所 承认。本病的缺碘也醒有较多的证据,但本文 作者认为此假说尚不能满意地解释地方性克汀 病的一切方面,包括：     

甲状腺过氧化物酶抗体对妊娠结局及后代智力影响的研究进展

甲状腺过氧化物酶(TPO)在甲状腺激素合成过程中催化碘离子氧化、酪氨酸碘化及碘化酪氨酸偶联,是甲状腺激素合成的关键酶.TPOAb是TPO的特异性抗体,TPOAb与TPO结合后可抑制TPO活性,减少甲状腺激素的合成,甚至导致甲状腺疾病发生.国外文献报道,妊娠期妇女TPOAb阳性率为15.3%～16%[1];国内研究显示,妊娠前半期TPOAb阳性率为9.17%[2].目前有大量研究证实,甲状腺功能异常的TPOAb(+)孕妇自然流产、早产、胎儿宫内发育迟缓、子痫前期及后代智力减低等发病率较阴性者明显增高,但TPOAb对甲状腺功能正常的孕妇及后代智力的影响还存在较大的争议.现就近年来国内外学者对甲状腺过氧化物酶抗体对妊娠、妊娠不良结局及后代智力发育影响的相关研究综述如下.     

参与下丘脑-垂体-甲状腺轴负反馈调控的分子元件研究进展

下丘脑-垂体-甲状腺(hypothalamic-pituitary-thyroid,HPT)轴负反馈调节是维持血清甲状腺激素(thyroid hormone,TH)水平稳定的最重要的机制。目前,普遍认为位于下丘脑室旁核(paraventricular nuclei,PVN)的促垂体区的促甲状腺激素释放激素(thyrotropin-releasing hormone,TRH)神经元是HPT轴的核心调节区域。研究认为在血液循环中,不仅三碘甲状腺原氨酸(T3)参与HPT轴的负反馈调节,甲状腺素(T4)也可通过中枢神经系统伸长细胞的脱碘酶2(Dio2)催化脱碘来影响细胞中T3的可用性,从而参与其中。促垂体区的TRH神经元通过甲状腺激素转运体摄取循环中的TH,而TH进入PVN的TRH神经元或垂体促甲状腺区细胞核与甲状腺激素受体(TRs)(特别是TRβ2)结合后,可招募辅因子,共同参与相应靶基因的调控。此外,中枢神经系统伸长细胞表达的焦谷氨酰肽酶Ⅱ(PPⅡ)可降解释放的TRH,从而影响不同甲状腺功能状态下到达垂体门静脉的TRH水平。综述了参与HPT轴调节的分子元件,以期为甲状腺功能或甲状腺轴异常疾病的科学研究及临床治疗提供参考。     

碘的吸收和转化

提到碘必然联系到人体进行碘代谢的甲状腺,甲状腺是参与人体生长发育和代谢的重要腺体,它位于颈部咽喉前下方,分左右两叶,中间由峡部相连,约20～259,一般人被皮下脂肪和肌肉覆盖着,看不见摸不着,主要由大量大小不等的囊状腺泡组成,腺泡腔中充满胶状的甲状腺球蛋白。甲状腺分泌两种含碘的激素,三碘甲腺原氨酸飞和四碘甲腺原氨酸T。,合成甲状腺激素的主要原料是甲状腺球蛋白（包括其中的酪氨酸）和碘。甲状腺球蛋白在腺泡细胞内合成并贮存在腺泡腔中。碘有2种来源;体内甲状腺激素代谢过程中脱下的碘可以再利用,但食物供应是碘的…     

原发性肾病综合征合并甲状腺功能减退的发病机制及治疗

甲状腺功能减退(hypothyroidism)是临床上常见的内分泌疾病,是由于机体甲状腺素合成和分泌不足或组织作用减弱而导致的全身代谢减低综合征。甲状腺激素具有重要的生理功能,包括影响肾脏的发育、血流动力学、肾小球滤过率(glomerular filtration rate,GFR)等。甲状腺功能减退症与原发性肾病综合征的发病密切相关。甲状腺功能减退会增加原发性肾病综合征的风险。同时,甲状腺功能减退也是原发性肾病综合征的并发症之一。本综述主要介绍了原发性肾病综合征合并甲状腺功能减退症的相关发病机制的新进展以及寻找在治疗上的新思路。     

Scintigraphic imaging of paediatric thyroid dysfunction

Imaging of thyroid dysfunction is safe and clinically relevant in children. In congenital hypothyroidism (CH), thyroid imaging permits a precise characterization of the aetiology, which is important for genetic counselling and clinical management. CH may be due to thyroid dysgenesis (ectopia, hypoplasia and athyrosis) or occurs in eutopic glands. In the latter, hypothyroidism may be either transient, especially after iodine overload, or due to permanent autosomal recessive dyshormonogenesis. Thyroid scintigraphy (TS) with either 99mTcO4 or 123I will identify ectopic thyroid tissue, which is the commonest cause of CH. However, recent reports favour the use of 123I, which enhances the accuracy of the aetiological classification. In cases of eutopic thyroid, the measurement of 123I uptake before and after perchlorate administration evaluates the organification process. At all ages, colour Doppler ultrasound scanning (CDU) is helpful in assessing thyroid volume, in identifying nodules and in characterizing tissue vascularization. TS and CDU images of most paediatric thyroid dysfunctions are presented.     

Recent advances in understanding the molecular basis of primary congenital hypothyroidism

Primary congenital hypothyroidism is characterized by low levels of circulating thyroid hormones and raised levels of thyrotropin at birth. It can be either permanent or transitory. Most permanent cases (80-85%) result from alterations in the formation of the thyroid gland during embryogenesis (thyroid dysgenesis), and several were shown recently to be produced by mutations in genes responsible for the development of thyroid follicular cells (TITF1, TITF2, PAX8 and TSHR). Less frequently, congenital hypothyroidism is determined by defects in thyroid hormone synthesis (hormonogenesis defects). The latter are usually associated with goiter. Recently, the molecular mechanisms of two forms of hormonogenesis defects (iodine transport defects and Pendred syndrome) were elucidated.     

Molecular pathogenesis of neonatal hypothyroidism

In patients with congenital hypothyroidism (CH), the autosomal recessive inheritance of mutations of thyroid peroxidase, thyroglobulin and the NIS and pendrin genes encoding for sodium iodide transporters has been identified. CH due to thyroid dysgenesis was considered to be a sporadic disease, but recently, inheritable defects of thyroid development have been described. The autosomal recessive inheritance of mutations of the thyroid-stimulating hormone receptor gene was recognized in patients with CH and thyroid hypoplasia, while autosomal dominant mutations of the Pax-8 gene were described in patients with thyroid dysgenesis. In addition, analysis of mutations of the beta-thyrotropin gene has resulted in a new understanding of the pathogenesis of central CH. Molecular genetic studies in patients with CH detected by newborn screening will provide the information necessary for genetic counselling and may help to explain the less favourable outcome present in 5-10% of the patients.     

Permanent and Transient Congenital Hypothyroidism in Fayoum,Egypt: A Descriptive Retrospective Study

Background

Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation. One important challenge in understanding the epidemiology of CH is that some newborns will have transient CH, a temporary depression of thyroid hormone concentrations that can last from several days to several months. Studies from other countries have reported that 10 to 15% of children treated for CH ultimately prove not to need treatment past 3 years of age to maintain normal hormone concentrations, and thus have transient hypothyroidism. The purpose of this study was to determine the prevalence of permanent and transient congenital hypothyroidism in Fayoum, Egypt.

Methods

Cases detected by Fayoum neonatal screening program (NSP) between January 2003 and December 2011, and followed up at health insurance center were included. Permanent or transient CH was determined using results of thyroid function tests.

Results

Of the 248 patients diagnosed primarily with CH by NSP; 204 (82.3%) patients were diagnosed to have permanent CH (prevalence 1/3587 live birth), and 44 (17.7%) patients were diagnosed to have transient CH (prevalence 1/16667 live birth). Initial TSH levels were higher in permanent CH cases than transient cases (p<0.004). Female to male ratio was 0.8 and 0.7 in permanent and transient CH respectively. 161 (65%) patients had thyroid dysgenesis (107 ectopic thyroid gland, 28 athyreosis and 26 thyroid hypoplasia). 87 (35%) patients had intact gland in thyroid scan and were considered to have dyshormonogenesis. Of these 87 patients 44 proved to have transient CH and 43 had permanent CH.

Conclusion

The preliminary data from our study revealed that the incidences of CH as well as the permanent form were similar to worldwide reports. Although the high incidence of transient CH in our study could be explained by iodine deficiency further studies are needed to confirm the etiology and plan the treatment strategies.     

Molecular mechanisms of thyroid dysgenesis

Thyroid dysgenesis (TD) is the most prevalent form of congenital hypothyroidism. Ttf-1, Ttf-2, Pax8 and the Tshr are expressed at early stages of thyroid development and are implicated in thyroid ontogeny. Mutations in these genes have been found in some cases of TD. The prevalence of familial forms of TD is significantly higher than expected if the disease was only sporadic, allowing to postulate a genetic basis of the disease. Linkage analysis and mutational screening of the four above-mentioned genes in familial forms of TD showed their exclusion as contributors to the disease in some families, implicating genetic heterogeneity and involving other genetic mechanisms. Strategies to uncover new genes involved in TD are therefore needed. We underscore differences in the temporal expression patterns during the human thyroid development with those in animal models. Further, the extrathyroid expression of these genes during human development enables to define the gene-specific malformations that may be present in patients bearing mutations. The data gathered on molecular thyroid development enable precise genetic counselling of affected families. By increasing our knowledge of thyroid development, we hope to uncover new perspectives of genetic screening and eventually of early in utero treatment.     

Multivariate analysis on factors affecting suppression of thyroid-stimulating hormone in treated congenital hypothyroidism

AIMS: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. METHODS: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.