碘盐防治后新发地方性克汀病的病因探讨

在贵州省地克病流行区两个乡碘盐防治后出生的５２２名儿童中，临床检出４例新发地克病患者。对新发病患者３例和非地克病儿童４８人作尿碘、Ｔ３、Ｔ４、ＴＳＨ检验和头发硒、锌、铜、铁四种微量元素测定，并测两地的水和大米的四种微量元素含量。检测结果提示，新发地克病患者出现的原因，可能仍为碘供给量不足。     

2007年陕西省黄陵县克山病病情监测报告

目的 了解2007年陕西省黄陵县克山病发病情况.方法 将陕西省黄陵县克山病重病区店头镇3个村村民和腰坪乡中心小学学生作为监测对象进行心电图等检查,用以筛检克山病患者,并对全县已知潜在型克山病(简称潜克)和慢型克山病(简称慢克)患者进行X线胸片检查.荧光分光光度法检测病区患者、病区健康人群(内对照)、非病区健康人群(外对照)血硒及儿童发硒水平.结果 店头镇和腰坪乡无急型、亚急型克山病发生,潜、慢克总检出率为3.92%(35/893),新发潜克1例,克山病患者心电图异常改变主要表现为ST-T改变.对全县潜、慢克患者83例进行X线胸片检查,心胸比例正常者27例,轻、中度增大者各20例.显著增大者16例.病区患者及内对照、外对照人群血清含硒量分别为(38.67±19.58)、(48.55±22.36)、(67.29±17.32)μg/L,组间比较差异有统计学意义(F=16.291,P<0.01);病区患者和内对照血硒明显低于外对照(P<0.01).病区患者血硒明显低于内对照(P<0.01).店头镇、腰坪乡中心小学儿童和非病区儿童发硒水平分别为(0.376±0.101)、(0.372±0.085)、(0.436±0.085)μg/L,组间比较差异有统计学意义(F=17.032,P<0.01);病区儿童发硒均明显低于非病区(P<0.01).结论 2007年陕西省黄陵县克山病检出率有所下降,而潜克仍有新发,可能与病区居民仍处于低硒状态有关.     

大骨节病患者红细胞免疫功能与血硒水平的关系

本文报道了大骨节病患者红细胞免疫功能和血清红细胞免疫调节因子以及血硒含量的检测结果。发现大骨节病患者和病区健康人红细胞Ｃ３ｂ受体花环率和血硒含量明显低于非病区健康人（Ｐ〈０．０１），而血清红细胞免疫粘附抑制率却明显增高（Ｐ〈０．０１），但免疫复合物花环率和血清红细胞免疫粘附促进率则无明显差异（Ｐ〉０．０５），提示大骨节病患者和病区健康人红细胞免疫功能低下，可能与缺硒和血清红细胞免疫粘附抑制因子增…     

硒在克山病防治中的作用

１９７５年Ａｗａｓｔｈｉ证明硒是人体的必需微量元素之后，关于硒的生物学效应研究，有关硒在人体营养和健康方面的作用，有了更进一步的深入了解。已知缺硒与心血管病、肿瘤、肝脏疾病、恶性营养不良等多种疾病有关，在我国已证实和地方病（克山病、大骨节病）的发生有密切的关系。 大量的流行病学调查结果表明，克山病具有明显的地区性分布、季节性高发和人群多发等特点，但克山病的病因至今不明。１９７９年我国证实克山病病区粮中及病区人体内（血、发）硒的含量明显低于非病区；用口服亚硒酸钠的方法对急型及亚急型克山病的发病有明…     

陕西省克山病病区低硒居民发锌和铜含量测定

用原子吸收光谱法测定了陕西省彬县克山病病区病户、非病户和非病区礼泉县对照户人发锌和铜含量。表明：病区病户和非病户低硒居民发锌和铜含量无显著差异，两者与非病区对照户的差异也不显著；３组儿童或成人发锌和发铜含量分别比较也均无显著差异。研究提示，克山病病区低硒居民发锌和铜含量与非病区相似，并达到文献报道的我国农村居民的水平。     

潜在型克山病患者红细胞免疫功能及其与硒水平的关系

本报道了潜在型克山病患红细胞免疫功能和血清免疫调节因子及血硒含量的检测结果，发现克山病患和病区健康人群红细胞Ｃ３ｂ受体花环率及全血硒含量明显低于非病区健康人群（Ｐ〈０．０１），红细胞免疫粘附抑制率却明显高于非病区健康人群（Ｐ〈０．０１），但免疫复合物花环率和免疫粘附促进率则无明显差异（Ｐ〉０．０５）。提示克山病患和病区健康人群红细胞免疫功能低下，可能与缺硒和血清免疫粘附抑制因子增加有关。     

补硒对克山病病区居民血小板聚集性和βTG释放反应的影响

探讨补硒对克山病病区居民血小板聚集和释放反应的影响，应用比浊法和ＥＬＩＳＡ地比测定病区补硒（２００μｇＳｅ／ｄ，亚硒酸钠，１２周）和未补硒居民血小板聚集率和β－血小板球蛋白（βＴＧ），用２，３＝二氨基萘荧光法和谷胱甘学原酶偶联法测定硒信号是和ＧＳＨ－Ｐｘ活性。结果表明：（１）补硒组红细胞硒含量和（Ｐ〈０．０５或０．０５）：（３）补硒组血浆ミＴＧ水平以及血以βＴＧ含量和释放率与对照组无显著差异（Ｐ〉     

克山病病因实验病理学研究Ⅳ (1)人工半合成低硒饲料饲养大白鼠光镜和初步的电镜观察 (2)低硒大鼠附加条件因素之心肌病理学改变

流行病学调查研究表明,克山病区水、土、粮中硒含量,病区居民血硒、发硒含量均低于非病区,硒预防急型、亚急型克山病取得了肯定的效果,但对硒参与克山病病理过程中的环节以及硒预防克山病的作用机制,还不清楚。本实验在以前工作的基础上,用人工半合成低硒饲料喂养大白鼠,通过心肌的光镜、电镜观察,并附加于低硒大鼠冰水泳条件因素,检查心肌的病理改变,以期进一步阐明缺硒在克山病发病中的作用及我们对克山病病因的认识。     

克山病病区居民血小板血栓素,聚集性和形态的改变及补…

对比研究了克山病病区和非病区居民的硒状态、血栓素（ＴＸＡ２）水平以及血小板聚集性形态，并观察了补硒的影响。发现：（１）血硒水平低的病区居民血小板ＧＳＨ－Ｐｘ活性也低；血浆ＴＸＡ２、血小板ＴＸＡ２生成和聚集性均显著高于非病区；血小板形态有异常，出现变形和团聚血小板。（２）给病区居民补硒（亚硒酸钠，２００μｇＳｅ／ｄ）１２周后，红细胞硒和ＧＳＨ－Ｐｘ活性显著增高，血浆ＴＸＡ２、血小板ＴＸＡ２生成和聚集     

补硒对低硒克山病病区居民血浆甲状腺激素水平的影响

给低硒克山病病区居民每日口服２００μｇ亚硒酸钠１２周，测定红细胞硒含量，谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性的血浆Ｔ３、Ｔ４及ｒＴ３水平，探讨硒对甲状腺激光水平的影响。结果表明：补硒显提高红细胞硒含量和ＧＳＨ－Ｐｘ活性；补硒组血浆Ｔ３明显升高，ｒＴ２明显降低，而Ｔ４无明显改变。红细胞硒含量与血浆Ｔ３呈明显正相关（ｒ＝０．５４７，ｎ＝３８，Ｐ〈０．００１）和血浆ｒＴ３呈显负相关（ｒ＝－０．４２     

地方性克汀病人甲状腺功能的临床研究及对分型的探讨

对新疆阿克苏地区４０名地方性克汀病患者及１５名当地正常人进行了Ｂ超法甲状腺体积测量，血清激素（ＴＳＨ，Ｔ４，Ｔ３）测定及皮肤组织粘液物质检查，以期了解该区地克病人的甲状腺功能水平。结果表明，４０名克汀病人的平均ＴＳＨ水平（３０．８５ｍＵ／Ｌ）明显高于当地正常人（３．２５ｍＵ／Ｌ）按ＴＳＨ不同水平将地克病人分为３组，则发现血清Ｔ４，Ｔ３水平随着ＴＳＨ升高而逐渐下降，甲状腺体积逐渐减小，皮肤粘液物质检     

A comparative study of neurological and myxedematous endemic cretinism in western China

Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.     

Clinical picture of endemic cretinism in central Apennines (Montefeltro).

Endemic cretinism is still present in an endemic goiter area of the central Apennines (Montefeltro) (goiter prevalence 55%; mean urinary iodine level 39 micrograms/g creatinine). Clinical and biochemical features of patients with myxedematous, neurologic, and mixed cretinism were studied. Also, in this area, as in most other, neurologic cretinism is more prevalent than myxedematous and mixed forms. The hormonal profiles of the three types of cretinism were clearly different. Nevertheless, all myxedematous cretins had some neurologic disorders (hyperreflexia, increased muscle tone, disorder of gait, Babinski sign, hypoacusia) that were similar to those present in neurologic cretins. These findings suggest that neurologic damage is very similar in all forms of endemic cretinism, reflecting a diffuse insult to the developing fetal nervous system. Furthermore, these data support the hypothesis that the primary pathophysiologic event in the different types of endemic cretinism is represented by maternal and fetal hypothyroidism, while differences may be explained by the extent and duration of postnatal hypothyroidism. All the cretins were over 35 of age, suggesting a severe iodine deficiency in the past decades, and a progressive improvement of nutritional status resulted in "silent iodine prophylaxis." However, recent studies have revealed the persistence of a moderate iodine deficiency, a high prevalence of neurologic hypoacusia, and reduction of mental performance in normal schoolchildren of this area. These findings constitute strong evidence in favor of adequate iodine prophylaxis.     

Epidemiology and clinical characteristics of endemic cretinism in Sicily

In this study we report the prevalence of endemic cretinism in the general population of two iodine deficient areas in Northeastern Sicily that were described more than 10 yr ago. In addition, the individual characteristics of endemic cretins are considered in order to define the typical expressions of this major iodine deficiency disorder in Sicily. Forty-three mental defectives were identified: 22 were living in an area with three bordering and closely connected municipalities within the province of Messina and with a population of 17,485 inhabitants (prevalence = 0.13%). Three out of the 22 were school-age children. The other community, in the province of Catania, was constituted by a unique and mostly agricultural hamlet, and showed a prevalence of cretinism that was 0.68% (21/3,100). Among the 43 mental defectives, 16 (37%) presented prominent neuromotor and neurosensorial disorders, including deafmutism and were euthyroid, thus conforming to the neurological type of cretinism; 13 (30%) were hypothyroid and exhibited stunted growth without significant neuromotor and neurosensorial impairment (myxedematous cretins). In the remaining 14 individuals (33%) neurological disorders were associated with stunted growth and clinical or biochemical hypothyroidism. These data indicate that also in Sicily endemic cretinism is a continuum of a variety of forms: among these the pure neurological and pure myxedematous forms represent the two extremes. Our observations also indicate that endemic cretinism still represents a major public health problem in Sicily. The finding of 3 endemic cretins younger than 13 yr suggests the persistence of this disorder even in the presence of improved economic, social and nutritional conditions.     

ENDEMIC CRETINISM IN EASTERN NEW GUINEA

A study has been carried out of the clinical features, epidemiology and thyroid function in 254 cases of endemic cretinism in Eastern New Guinea. The clinical picture resembles closely that described for Western New Guinea and other endemic goitre areas throughout the world. Goitre was encountered more commonly in mothers of cretins than in adult females of the studied population. Examination of thyroid function revealed a significantly lower serum PBI value and I uptake in cretins when compared with neurologically normal natives. No clinical evidence of hypothyroidism was encountered in endemic cretins, and no biosynthetic defect was isolated as shown by perchlorate discharge testing and chromatography of I131 labelled thyroid glands and serum. Mothers of 13 cretins, born since the introduction of iodized oil prophylaxis, were identified, and in only one instance was there a possibility that iodine therapy had been given. These findings suggest that the condition is related to iodine deficiency and may be prevented by correction of maternal iodine deficiency.     

A comparative study of EEG in patients with neurological and myxedematous cretinism

A comparative study of EEG between neurological and myxedematous cretins was carried out in a total of 61 cases. The results were as follows: (1) The changes of EEG in myxedematous cretins appeared to be more obvious than those in neurological cretins; (2) The degree of mental retardation in cretins was not parallel to the degree of the abnormality of EEG; (3) with thyroid therapy, EEG in cretins was improved. The improvement rate in myxedematous cretins was higher than that in neurological cretins; (4) Brain CT scan was carried out in 50 cases of those cretins. It was found that the abnormality of certain intracerebral structure in myxedematous cretins appeared to be more obvious than that in neurological cretins. The change of EEG appeared in the same way as well. This is in contradiction to the traditional knowledge that the defect of neurological system in neurological cretinism was more severe than that in myxedematous cretinism. The current classification of cretins into neurological and myxedematous cretins does not reflect the changes of pathophysiology properly.     

NF、MBP、Synaptophysin、GFAP在地方性克汀病人和缺碘及甲低大鼠小脑中的分布

本文利用免疫组化技术,采用单克隆抗体分别对4种重要的神经物质(神经微丝NF,髓鞘基本蛋白MBP,突触蛋白Synaptophysin和胶质原纤维酸性蛋白GFAP)在地方性克汀病人和实验性缺碘及甲低大鼠小脑中的分布以及免疫反应强度进行了对比观察。观察结果证明,4种物质的分布数量及反应强度均较对照组明显减少和减弱,而且在克汀病人中的观察结果与在缺碘及甲低大鼠中所见相似,从而为人类地方性克汀病的病因及发病机理研究提供证据。     

Studies on hearing loss in a community with endemic cretinism in Central Java, Indonesia.

An audiometric study was carried out in a community of 642 subjects severly affected by endemic goitre and cretinism. Hearing loss was measured in 34 out of 41 subjects diagnosed as cretins, 92 normal subjects aged 5-20 years from the same community and 54 subjects (also of 5-20 years) living in a nearby control area without endemic goitre. The excess number of hearing defects in the endemic area seems to be entirely due to the process that leads to cretinism. There is no reason to describe deafness and deafmutism in an area with severe endemic goitre as a separate entity. The hearing defect showed a definite greater loss in the higher frequencies than in the lower frequencies and was found in 92% of the cretins. Deafmutism was present in 5, a loss of more than 60 db in 8, a loss of 40-60 db in 10 cretins. A loss of 20-30 db was found in 2.2% of normal subjects in the endemic area and 1.8% of those living in the control area. It is concluded that audiometry is a simple and significant test to establish the presence of the neurological form of endemic cretinism, which is the most prevalent form in most endemias. The differential diagnosis and pathogenesis of the described hearing defect are discussed.     

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.     

Selenium status in pregnant women of a rural population (Zaire) in relationship to iodine deficiency

Endemic myxoedematous cretinism has been associated with combined selenium and iodine deficiency in several areas of Zaire. To determine selenium and iodine status across the country, serum selenium and thyroid function parameters including urinary iodide were determined at prenatal clinics in 30 health centres of rural villages distributed over the whole country. Only in Bas-Zaire was the mean serum selenium level similar to that in non-deficient areas (80–120 ng/ml); in the regions of Bandundu and Kasai levels were marginally decreased (55–80 ng/ml), and in Kivu, Haut-Zaire, Equateur and Shaba they were marginally or moderately decreased (<55 ng/ml). The frequency of abnormally low urinary iodide (<5 μg/dl) varied from 20% in the region of Bas-Zaire to 50% in Kasai (P<0.001), and to still higher percentages in the 5 other regions of Zaire (Bandundu, 57%; Kivu, 63%; Equateur, 72%; Shaba, 76%; Haut-Zaire, 84%). With the exception of Bas-Zaire, biochemical maternal hypothyroidism (serum TSH >5mU/l) was present in every region, with a frequency ranging from 3% in Kivu to 12% in Equateur. Iodine deficiency affects most of the Zairean population and requires public health measures on a larger scale than previously estimated. Combined iodine and selenium deficiency affects Equateur, Haut-Zaire and Kivu, where endemic myxoedematous cretinism occurs, but also Shaba, where it was not previously described. Besides combined iodine and selenium deficiency which is permissive, another factor (thiocyanate?) must be taken into account to explain the peculiarly elevated prevalence of endemic myxoedematous cretinism in Central Africa.