甲状腺激素水平与冠状动脉粥样硬化性心脏病的回顾性研究

目的:观察冠状动脉粥样硬化性心脏病(冠心病,coronary heart disease,CHD)患者甲状腺激素水平的变化规律.方法:选取2010年至2011年在我院住院患者共299例,入选标准:年龄30岁～80岁之间;心功能Ⅰ-Ⅱ级;入选前未接受甲状腺激素及胺碘酮治疗.根据冠状动脉造影结果分为:对照组91例,实验组208例,实验组根据血管病变数量再分为单支血管病变组72例,双支血管病变组87例,及三支血管病变组49例,用放射免疫方法于造影前检测甲状腺激素水平,比较各组间FT3、FT4、TT3、TT4及TSH水平.结果:与对照组相比,实验组血清FT3水平下降,差异有显著统计学意义(P＜0.05);其中三支血管病变组患者血浆FT3水平显著低于双支血管病变组,双支血管病变组患者血浆FT3水平显著低于单支血管病变组,差异均有统计学意义(P＜0.05);各组间血清TT4、TT3、FT4、TSH水平比较无统计学差异(P＞0.05).结论:冠心病患者FT3呈低水平状态,且随着血管病变加重FT3下降越明显,检查甲状腺激素水平具有重要临床意义.     

术前血清促甲状腺激素水平与甲状腺结节相关性的研究

目的:探讨术前血清促甲状腺激素(TSH)水平与甲状腺结节良恶性的关系。方法:回顾性分析了1499例甲状腺结节手术切除患者术前血清TSH、甲状腺B超,手术记录、术后病理诊断报告。根据术后病理报告判定甲状腺结节良恶性,分析术前血清TSH水平在甲状腺良恶性结节中的不同分布。结果:分化型甲状腺癌(DTC)患者术前血清TSH水平明显高于甲状腺良性结节组(2.179±2.017vs1.259±0.884μIU/mL),P<0.001;在DTC患者中,有淋巴结转移较无淋巴结转移、TNM分期III、IV期较I、II期以及肿瘤直径≥1cm较<1cm的患者术前血清TSH明显升高(均P<0.001)。结论:术前血清TSH水平是预测甲状腺结节良恶性的重要指标。     

超声弹性成像联合血清TSH、TT3、TT4在甲状腺结节良恶性诊断的临床价值研究

目的:探讨超声弹性成像联合血清促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)在甲状腺结节良恶性诊断的临床价值。方法:选择2018年1月至2019年12月我院收治的甲状腺结节患者80例,根据病理检查结果分为良性结节组(48例),恶性结节组(32例),所有患者术前进行血清TSH、TT3、TT4及超声弹性成像检查,比较各组血清TSH、TT3、TT4水平及超声弹性成像评分,分析甲状腺结节患者血清TSH、TT3、TT4水平与超声弹性成像评分的相关性,超声弹性成像联合血清TSH、TT3、TT4在甲状腺恶性结节诊断的临床价值。结果:恶性结节组血清TSH、TT3、TT4水平显著高于良性结节组,超声弹性成像评分高分比例显著高于良性结节组(P<0.05),经Pearson相关分析显示,甲状腺结节患者血清TSH、TT3、TT4水平与超声弹性成像评分呈正相关(P<0.05)。以病理诊断为金标准,超声弹性成像联合血清TSH、TT3、TT4诊断甲状腺恶性结节的灵敏度为96.88%,特异度为93.75%,准确度为95.00%,灵敏度、特异度和准确度优于单独血清TSH、TT3、TT4检测和单独超声弹性成像检测。结论:超声弹性成像联合血清TSH、TT3、TT4对甲状腺结节良恶性的鉴别诊断具有较好的临床价值。     

桥本氏病合并甲状腺乳头状癌患者血清甲状腺相关激素水平的变化及意义

目的:探究桥本氏病(HT)合并甲状腺乳头状癌(PTC)患者血清甲状腺相关激素水平的变化及意义。方法:对我院148例HT患者的临床资料进行回顾性分析,根据其是否合并PTC分为HT合并PTC组(n=68)和单纯HT组(n=80)。比较两组患者性别、年龄及血清促甲状腺激素(TSH)、甲状腺功能指标[游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)]、抗甲状腺抗体[甲状腺球蛋白抗体(TGAb)、甲状腺过氧物酶抗体(TPOAb)]水平等临床资料差异,分析血清TSH水平变化及意义。结果:HT合并PTC组患者男性比例、年龄、病程及血清TSH水平均大于单纯HT组,血清TGAb、TPOAb水平则均小于单纯HT组(P0.05);血清FT3、FT4水平比较差异无统计学意义(P0.05)。HT合并PTC患者组血清TSH4.2 m IU/L患者占比高于血清TSH正常组(P0.05)。血清TSH4.2 m IU/L患者中HT合并PTC患者的占比大于血清TSH水平正常的患者(P0.05)。HT合并PTC患者中,血清TSH水平4.2 m IU/L患者中央区淋巴结转移发生率高于血清TSH水平正常患者(P0.05);血清TSH4.2 m IU/L与血清TSH正常患者多灶癌发生率比较差异无统计学意义(P0.05)。结论:HT患者血清TSH水平升高可能促进其甲状腺组织癌变,HT合并PTC患者血清TSH水平升高可能促进其中央区淋巴结转移。     

术前血清促甲状腺激素水平与甲状腺结节相关性的研究

目的：探讨术前血清促甲状腺激素（TSH）水平与甲状腺结节良恶性的关系。方法：回顾性分析了1499例甲状腺结节手术切除患者术前血清TSH、甲状腺B超,手术记录、术后病理诊断报告。根据术后病理报告判定甲状腺结节良恶性,分析术前血清TSH水平在甲状腺良恶性结节中的不同分布。结果：分化型甲状腺癌（DTC）患者术前血清TSH水平明显高于甲状腺良性结节组（2．179±2．017vsl．259±0．884μIU／mL）,P〈0．001;在DTC患者中,有淋巴结转移较无淋巴结转移、TNM分期Ⅲ、Ⅳ期较Ⅰ、Ⅱ期以及肿瘤直径≥1cm较〈1cm的患者术前血清TSH明显升高（均P〈0．001）。结论：术前血清TSH水平是预测甲状腺结节良恶性的重要指标。     

自身免疫性甲状腺功能紊乱孕妇血清TPOAb 检测的临床价值

目的:探讨血清甲状腺过氧化物酶抗体(TPOAb)对于患有自身免疫性甲状腺功能紊乱的孕妇的临床诊断价值。方法:筛选2009年9月至2013年1月我院收治的205例孕妇,其中甲状腺功能紊乱孕妇55例(紊乱组),非甲状腺功能紊乱孕妇150例(非紊乱组);非紊乱组中,年龄30岁的高龄孕妇50例(高龄组),年龄≤30岁的孕妇100例(正常组)。采用化学发光法,测定所有孕妇血清中游离甲状腺三碘原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)和TPOAb水平。结果:紊乱组患者血清中TSH、TPOAb及TPOAb阳性率水平显著高于非紊乱组,且存在统计学意义(均P0.05),而两组患者血清中FT3和FT4水平无统计学意义(均P0.05);高龄组和正常组血清中TSH、FT3、FT4及TPOAb水平均无统计学意义(均P0.05);与TSH正常组相比,TSH异常组中约有超过半数TPOAb表现为阳性,有统计学意义(P0.05);孕妇体内的TSH水平正常与否,均有出现TPOAb阳性的可能,在TSH水平较高(4.67 m IU/L)中,TPOAb阳性概率更高。结论:TSH、FT3、FT4水平正常而TPOAb呈阳性的孕妇依然存在自身免疫性甲状腺功能紊乱的可能性,监测TPOAb的水平对于妊娠期孕妇功能紊乱的诊断与治疗具有重要意义。     

肝病患者血清甲状腺相关物质的检测与意义

目的探讨不同程度肝病患者血清甲状腺激素水平的变化及其意义。方法应用放射免疫法分别检测114例慢性肝炎、130例肝硬化、96例重型肝炎、120例健康体检者的血清甲状腺激素水平(T3、T4、FT3、FT4、rT3、TSH),抗甲状腺过氧化物酶抗体(抗TPO)、抗甲状腺球蛋白抗体(抗TG)的含量变化。结果肝病患者较正常人血清甲状腺素水平(T3、T4、FT3、FT4)显著降低,而抗TPO、抗TG、rT3含量显著升高,差异有统计学意义;随着肝功能受损程度的加重,血清甲状腺素水平(T3、T4、FT3、FT4)降低程度差异有统计学意义。结论肝病患者血清甲状腺激素水平的检测对评估肝功能、判断病程及预测预后有一定的临床意义。     

葫芦岛地区育龄期女性甲状腺功能指标的调查研究

目的探讨葫芦岛地区育龄期女性甲状腺功能水平与孕前促甲状腺激素(TSH)、抗甲状腺过氧化物酶抗体(TPO-Ab)筛查对优生优育的意义。方法选择葫芦岛市1 540例育龄女性,采用罗氏电化学发光E602检测血清TSH、游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)和TPO-Ab。结果 1 540例育龄妇女中,TSH异常135例,总异常率为8.7%,不同年龄组间TSH的异常率差异有统计学意义(χ2=33.56,P0.05)。TPO-Ab总阳性率为8.2%,TSH正常与异常组间的比较差异有统计学意义(χ2=34.84,P0.05)。进一步分层分析,TSH异常者中,甲亢与甲减组TPO-Ab阳性率的比较组间差异无统计学意义(χ2=0.043,P0.05)。结论葫芦岛地区育龄期女性甲状腺功能异常率较高,应对孕产妇常规进行甲状腺功能检测。     

甲亢患者甲状腺激素水平与血脂代谢相关性分析及临床意义探讨

目的:探讨甲亢患者甲状腺激素水平与血脂代谢指标之间的关系。方法:对160例甲亢患者治疗前后的甲状腺激素(TH)水平、血脂水平进行对照分析。结果:甲亢治疗前后与健康对照组比较,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)明显增高,促甲状腺激素(TSH)明显降低,差异有统计学意义(P<0.01);总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(apoAΙ)、载脂蛋白B(apoB)均明显降低,且差异具有统计学意义(P<0.01);低密度脂蛋白胆固醇(HDL-C)无明显变化(P>0.05)。结论:甲状腺激素与脂类代谢密切相关,临床上在诊治甲亢患者时,应当加强血脂水平的监测,以便更好地指导临床诊治,为疾病的发生发展、判断预后提供有价值的实验室检测指标。     

甲状腺功能5 项检测在妊娠期妇女中的应用

目的:分析甲状腺功能5项检测在妊娠期妇女中的应用价值,为制定妊娠期妇女的甲状腺功能指标的参考值范围提供依据。方法:选取2013年8月~2014年12月我院收治的826例健康妊娠妇女(实验组)与794例非妊娠育龄妇女(对照组)为研究对象。采用电化学发光法检测甲状腺功能5项指标,即三碘甲腺原氨酸(TT3)、甲状腺素(TT4)、促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4),比较两组甲状腺功能异常率,并比较5项指标在妊娠早、中、晚期妇女与对照组中的差异。结果:(1)实验组甲状腺功能异常的发生率(39.10%)显著高于对照组(17.63%),差异有统计学意义(P0.05);(2)实验组FT4、TT4水平随着妊娠期的进展逐渐降低,TSH水平逐渐升高,且均低于对照组水平,差异有统计学意义(P0.05);而各妊娠期FT3、TT3水平比较差异无统计学意义,但均略低于对照组(P0.05)。结论:甲状腺功能5项指标检测应作为妊娠期妇女的孕期必查项目之一,且制定早、中、晚期妊娠期妇女的甲状腺功能5项指标参考值范围十分必要。     

Selective modulation of thyroid hormone receptor action

Thyroid hormones have some actions that might be useful therapeutically, but others that are deleterious. Potential therapeutically useful actions include those to induce weight loss and lower plasma cholesterol levels. Potential deleterious actions are those on the heart to induce tachycardia and arrhythmia, on bone to decrease mineral density, and on muscle to induce wasting. There have been successes in selectively modulating the actions of other classes of hormones through various means, including the use of pharmaceuticals that have enhanced affinities for certain receptor isoforms. Thus, there is reason to pursue selective modulation of thyroid hormone receptor (TR) function, and several agents have been shown to have some β-selective, hepatic selective and/or cardiac sparring activities, although development of these was largely not based on detailed understanding of mechanisms for the specificity. The possibility of selectively targeting the TRβ was suggested by the findings that there are - and β-TR forms and that the TR-forms may preferentially regulate the heart rate, whereas many other actions of these hormones are mediated by the TRβ. We determined X-ray crystal structures of the TR and TRβ ligand-binding domains (LBDs) complexed with the thyroid hormone analog 3,5,3′-triiodithyroacetic acid (Triac). The data suggested that a single amino acid difference in the ligand-binding cavities of the two receptors could affect hydrogen bonding in the receptor region, where the ligand's 1-position substituent fits and might be exploited to generate β-selective ligands. The compound GC-1, with oxoacetate in the 1-position instead of acetate as in Triac, exhibited TRβ-selective binding and actions in cultured cells. An X-ray crystal structure of the GC-1-TRβ LBD complex suggests that the oxoacetate does participate in a network of hydrogen bonding in the TR LBD polar pocket. GC-1 displayed actions in tadpoles that were TRβ-selective. When administered to mice, GC-1 was as effective in lowering plasma cholesterol levels as T₃, and was more effective than T₃ in lowering plasma triglyceride levels. At these doses, GC-1 did not increase the heart rate. GC-1 was also less active than T₃ in modulating activities of several other cardiac parameters, and especially a cardiac pacemaker channel such as HCN-2, which may participate in regulation of the heart rate. GC-1 showed intermediate activity in suppressing plasma thyroid stimulating hormone (TSH) levels. The tissue/plasma ratio for GC-1 in heart was also less than for the liver. These data suggest that compounds can be generated that are TR-selective and that compounds with this property and/or that exhibit selective uptake, might have clinical utility as selective TR modulators.     

Design of thyroid hormone receptor antagonists from first principles

It is desirable to obtain TR antagonists for treatment of hyperthyroidism and other conditions. We have designed TR antagonists from first principles based on TR crystal structures. Since agonist ligands are buried in the fold of the TR ligand binding domain (LBD), we reasoned that ligands that resemble agonists with large extensions should bind the LBD, but would prevent its folding into an active conformation. In particular, we predicted that extensions at the 5′ aryl position of ligand should reposition helix (H) 12, which forms part of the co-activator binding surface, and thereby inhibit TR activity. We have found that some synthetic ligands with 5′ aryl ring extensions behave as antagonists (DIBRT, NH-3), or partial antagonists (GC-14, NH-4). Moreover, one compound (NH-3) represents the first potent TR antagonist with nanomolar affinity that also inhibits TR action in an animal model. However, the properties of the ligands also reveal unexpected aspects of TR behavior. While nuclear receptor antagonists generally promote binding of co-repressors, NH-3 blocks co-activator binding and also prevents co-repressor binding. More surprisingly, many compounds with extensions behave as full or partial agonists. We present hypotheses to explain both behaviors in terms of dynamic equilibrium of H12 position.     

Scintigraphy has the potential to replace thyroid stimulating hormone and ultrasonography in hyperthyroidism diagnosis

The value of thyroid scintigraphy in hyperthyroidism diagnosis has long been the subject of debate. Unresolved issue is whether scintigraphy should be performed routinely, selectively, or for all hyperthyroidism patients. So, this study is concerned with the evaluation of thyroid scintigraphy for identifying hyperthyroidism in comparison with thyroid stimulating hormone (TSH) and ultrasound. This is cross sectional study including convenient patients sample (n = 50, 15 males and 35 females) aged (20–50 years) with primary hyperthyroidism and were attending endocrine clinics at King Faisal Specialist Hospital and Research Centre. All patients performed clinical investigations (TSH, ultrasound and thyroid scintigraphy). Among these patients, 96%, 48/50, had positive findings for hyperthyroidism with thyroid SC (95% CI; 96.0–99.5%); 84%, 42/50, had positive findings for hyperthyroidism by US (95% CI; 70.9–92.8%); and 56%, 28/50, had positive findings for hyperthyroidism by TSH measurement (95% CI; 41.3.0–70.0%). There was very good agreement between scintigraphy diagnosis and ultrasonography (kappa score = 0.812 (P < 0.0001), 95% CI (0.77–0.85). In many cases, scintigraphy provides considerably more functioning and anatomic details than ultrasound. In conclusion, these findings bring forth practical aspects of thyroid scintigraphy utilization for hyperthyroidism. By combining functional and anatomical information in one step, scintigraphy provides non-invasive, simple, fast and cost effective hyperthyroidism diagnostic method and has the potential to replace TSH and ultrasonography in hyperthyroidism investigation.     

Resistance to thyroid hormone mediated by defective thyroid hormone receptor alpha

Background

Thyroid hormone acts via receptor subtypes (TRα1, TRβ1, TRβ2) with differing tissue distributions, encoded by distinct genes (THRA, THRB). THRB mutations cause a disorder with central (hypothalamic–pituitary) resistance to thyroid hormone action with markedly elevated thyroid hormone and normal TSH levels.

Scope of review

This review describes the clinical features, genetic and molecular pathogenesis of a homologous human disorder mediated by defective THRA. Clinical features include growth retardation, skeletal dysplasia and constipation associated with low-normal T4 and high-normal T3 levels and a low T4/T3 ratio, together with subnormal reverse T3 levels. Heterozygous TRa1 mutations in affected individuals generate defective mutant receptors which inhibit wild-type receptor action in a dominant negative manner.

Major conclusions

Mutations in human TRα1 mediate RTH with features of hypothyroidism in particular tissues (e.g. skeleton, gastrointestinal tract), but are not associated with a markedly dysregulated pituitary–thyroid axis.

General significance

Human THRA mutations could be more common but may have eluded discovery due to the absence of overt thyroid dysfunction. Nevertheless, in the appropriate clinical context, a thyroid biochemical signature (low T4/T3 ratio, subnormal reverse T3 levels), may enable future identification of cases.This article is part of a Special Issue entitled Thyroid hormone signalling.     

Influence of VIP on thyroid hormone secretion

Since VIP occurs in intrathyroidal nerves its role in thyroid hormone secretion has been investigated. It has been found that VIP is a stimulator of iodothyronine secretion in mice. In this respect VIP has a weaker potency than TSH, but shows a similar time characteristic. Also, VIP and TSH potentiate each others effects. In contrast to the effect of TSH, that of VIP is uninfluenced by alpha-adrenoceptor blockade. VIP, like TSH, stimulates thyroid cyclic AMP production. Thus, VIP nerves might, together with TSH, adrenergic and cholinergic nerves and other peptides such as somatostatin, participate in the complex regulation of iodothyronine secretion. Beside this, VIP has also been found to stimulate calcitonin secretion in rats. Other intrathyroidal neuropeptides, such as substance P and CCK-4, have been found to be without effects on iodothyronine secretion, but, like VIP, to stimulate calcitonin secretion.