ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The detection of autoantibodies to the TSH receptor is a useful tool for the diagnosis of Graves’ disease. Historically, there are two established methods for this purpose. One is the radioreceptor assay based on the porcine TSH-R, where autoantibodies and labelled bovine TSH compete for the binding sites of the receptor. The other method is based on the ability of some autoantibodies similar to TSH to induce the second messenger cAMP in certain cell lines. These so-called bioassays are able to distinguish between stimulating or blocking autoantibodies, based on their biologic activity, to either enhance or inhibit the cAMP production. Ten years after the cloning of the human TSH-R, these two basic detection principles were finally improved. In this article, the author summarizes the latest developments in TSH-R autoantibody assay technology and outlines the current research on alternative approaches, such as direct-binding assays. Controversies related to autoantibody terminology and assay interpretation are also addressed.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Pendred syndrome (OMIM 274600) is an autosomal, recessive disorder defined by the triad of congenital deafness, goiter, and positive perchlorate test. After the cloning of the Pendred syndrome (PDS) gene in 1997, a century after the recognition of the curious association of goiter and deaf-mutism by Vaugham Pendred in 1896, the elucidation of the molecular basis of Pendred syndrome has resulted in fascinating and surprising observations. It has become apparent that mutations in this gene are not only associated with PDS, but they form the molecular basis ofnonsyndromic autosomal recessive deafness DFNB4(OMIM 600791) andnonsyndromic familial enlarged vestibular aqueduct(OMIM 603545). These nonsyndromic forms of hearing impairment are therefore allelic variants of the syndromic deafness characterizing Pendred syndrome. The recent functional characterization of pendrin, the protein encoded by the PDS gene, as a transporter of iodide and chloride is a key step in further elucidating its role in the pathophysiology of both the inner ear and thyroid follicular cells.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Graves’ disease clusters in families, and higher concordance rates in monozygotic compared with dizygotic twins support a genetic basis to the disease. It seems likely that not only are a collection of small genetic effects contributing to this multifactorial complex disease but that susceptibility alleles are common in the general population and are not rare mutations. A combination of population-based case control and family-based studies is required to elucidate the genetic basis to Graves’ disease. The author reviews the size and nature of the genetic contribution to disease, the methods used for the detection of susceptibility loci, and the results currently available.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Congenital hypothyroidism is characterized by reduced thyroid hormone levels produced by the follicular cells of the thyroid gland in response to elevated levels of the thyroid stimulating hormone. In the great majority of the cases, congenital hypothyroidism is a consequence of thyroid dysgenesis (TD). Recently, it has been demonstrated that mutations in genes involved in the differentiation process of thyroid follicular cells cause, both in humans and in mouse models, alterations in the formation of the thyroid gland during embryogenesis (TD). The pathogenesis of TD is still largely unknown, although a genetic component has been suggested. The data presented in this review clearly underline that TD is a complex disease. However, they provide the first evidence in favor of the existence of a genetic basis of this condition.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Thyroid hormone is generally accepted in the treatment of patients with well-differentiated thyroid cancer, a tumor that is known to be capable of growth in the presence of high thyroid-stimulating hormone (TSH) levels. Using “TSH suppression” as the endpoint in treatment, the dosage of levothyroxine (L-T4) is often adjusted to achieve subnormal or undetectable TSH levels. Still, the effect of this therapy on the cancer and the health maintenance of the individual patient remains inadequately defined. This is confounded by the fact that advances in TSH measurement technology have made widely available commercial assays that can detect TSH from 1–3 orders of magnitude below normal euthyroid levels. As such, an “undetectable” TSH from one laboratory or study may not be the same as an “undetectable” TSH from another laboratory. It therefore behooves the clinician to understand the risks in the individual patient for progression or death from the cancer, the expected cancer response to thyroid hormone therapy, and the potential complications resulting from different levels of thyroid hormone treatment. Further study is needed to precisely establish the effects of TSH “suppression” on different parameters of thyroid cancer response.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The thyroid hormone receptor (TR) acts like a molecular switch. In the absence of ligand, TR binds to specific DNA sequences and actively represses transcription via interactions with other proteins, termed corepressors. The binding of ligand results in a conformational change in the TR that leads to transcriptional activation via the release of corepressors and the recruitment of coactivator proteins. The recent identification of some of the components of TR corepressor and coactivator complexes, and the discovery of respectively associated histone deacetylase and acetylase activity, has led to a greater understanding of how TR might accomplish its dual role. Additionally, several cofactors have been found to interact with TR and modulate transcription via mechanisms unrelated to histone acetylation or deacetylation.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Thyroid hormone receptors are encoded by two genes: TR&agr; and TRβ. Germline mutations in TRβ are responsible for a heterogenous genetic disease called resistance to thyroid hormone. This disease can be observed in mice after the transfer of a mutated human TRβ gene or after TRβ knockout. TR&agr; knockouts lead to different phenotypes, depending on which isoforms have been eliminated, but not to thyroid hormone resistance. Therefore, the function of the two types of receptors appears to be only partially redundant. These mice, and other knockouts altering thyroid function, also promise to be valuable tools for a better understanding of the pleiotropic intervention of the thyroid hormone in development and homeostasis.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

During the last two decades, insights into the pathophysiologic mechanism of maternal and fetal thyroid function during pregnancy have shown that the developing brain is strongly dependent on the thyroid hormone. Fetal thyroid function is totally dependent on maternal supply until 16–20 weeks of gestation, until which time the fetus does not produce the thyroid hormone. The negative impacts of maternal thyroid dysfunction on fetal development during pregnancy — hypothyroidism, Graves disease, endemic iodine deficiency, for example — have long been described. Very recently, several articles have been published about the possible harmful effects of subnormal fluctuations (i.e., generally considered normal or, more specifically, not considered to have negative effects) of maternal thyroid hormone levels during early pregnancy and subsequent impaired development of the offspring. Although an explanation is still lacking, the impact of these findings could be far-reaching: low “normal” maternal thyroid function appears to refer to thyroid hormone levels at or below the 10th percentile, suggesting that a substantial number of apparently healthy pregnant women could be at risk for impaired development of their offspring. Further research is needed to evaluate the consequences of these findings on a population-based level.

ISSN:1068-3097    

出版商:OVID    

年代:1999

数据来源: OVID