An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter

Radioiodine ((131)I) treatment for nontoxic and toxic multinodular goiter (MNG) is an alternative therapeutic procedure used especially for patients with contraindication for surgery. Several studies have been conducted in recent years assessing the use of recombinant human TSH (rhTSH) in increasing (131)I uptake in MNGs. This procedure also decreases the activity level of the administered (131)I, changes the distribution of (131)I in the thyroid, lowers the absorption dose, and dramatically reduces the volume of the goiter (50-75% of the baseline volume). A major disadvantage, however, is the induction of hypothyroidism in a relatively large number of patients. A transient increase in thyroid volume and tenderness was noted in the first week of treatment. Also a short period (2-4 weeks) of hyperthyroidism was observed in most patients with potential consequences particularly for the elderly. Still, there has been no evidence to date that the adverse effects outweigh the positive results of using rhTSH. The use of rhTSH in benign goiter disease has not yet been approved worldwide, but its positive activity in MNG is remarkable and promising.     

Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding

Objective

GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression.

Materials/Methods

Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4 h after spontaneous refeeding; ii) 2–4 h after T3 injection, without refeeding; and iii) 0.5–2 h after intravenous infusion of insulin, insulin + glucose and insulin + amino acids, without refeeding.

Results

Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~ 20%, P < 0.05 vs. fasting), but T3 injection induced a ~ 2-fold increase in Slc2a4 mRNA, 2–4 h later (P < 0.001). Moreover, T3 increased glycemia and insulinemia to the 2 h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding.

Conclusions

Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.     

甲亢患者手术前后TSH受容体抗体的变化及临床意义

目的探讨作为甲状腺机能亢进症（甲亢）主要发病因子的ＴＳＨ受容体抗体（ＴＲＡｂ）在甲状腺切除手术前、后的变化及其临床意义。方法对９１例甲亢患者进行ＴＲＡｂ追踪测定，并根据术前ＴＲＡｂ值将其分为正常组，弱阳性组，中度阳性组和强阳性组，分别讨论其变化特点。结果术前ＴＲＡｂ阳性例术后１２～１８月间大部分转为正常或呈明显下降趋势；而甲状腺机能则全部转为正常或潜在性低下及低下状态。阳性组ＴＲＡｂ术后恢复正常的例数所占比率分别为２５／２７、１０／１７和２／８。结论外科手术治疗甲亢可以使ＴＲＡｂ转为阴性，因此，不但在临床上而且针对病因治疗也都有效，但目前尚无法治愈所有甲亢患者。     

TSHR基因内含子1区域多态性与Graves病的关联研究

目的 探讨中国江苏徐州地区汉族人群促甲状腺素受体(TSHR)基因内含子1 上单核苷酸多态性位点(SNP)rs179247和rs12101261与Graves病的关系.方法应用TaqMan探针技术,在Fluidigm EP1平台上对1 066例Graves病患者和1 107名健康对照者进行基因分型;同时检测样本血清甲状腺激素和TSH受体抗体(TRAb)水平.结果 rs179247_A、rs12101261_T与Graves病易感性关联(分别为OR=1.35,95%CI 1.19～1.54,P=5.92×10-6;OR=1.32,95%CI 1.16～1.50,P=2.22×10-5);Logistic回归提示rs179247是独立的易感位点.在rs179247_GG、AG、AA 3种基因型之间相比,血清TRAb水平具有统计学差异(P=0.015);其他临床表现其差异均无统计学意义(P＞0.05).结论 TSHR基因内含子1区域rs179247、rs12101261与徐州地区汉族人群Graves病相关联,并且rs179247是一个独立易感位点;该多态性与血清TRAb水平有关,与血清甲状腺激素水平、发病年龄、甲状腺肿大程度、Graves病眼征分级、复发与否无明显关联.

Abstract：

Objective To investigate the association between polymorphisms of thyroid-stimulating hormone receptor(TSHR)gene intron 1(rs179247, rs12101261)and Graves′ disease(GD)in the China Han population from Xuzhou city, Jiangsu Province. Methods Total 1 066 GD patients and 1 107 control subjects were recruited for genotyping by Taqman probe technique on Fluidigm EP1 platform. Meanwhile, serum concentrations of thyroid hormone and TSH receptor antibodies(TRAb)were determined. Results The rs179247_A, rs12101261_T were significantly associated with GD risk(OR=1.35, 95%CI 1.19-1.54, P=5.92×10-6; OR=1.32, 95%CI 1.16-1.50, P=2.22×10-5). Logistic regression identified that rs179247 was an independent susceptibility locus of GD. Serum TRAb concentration showed a significant difference(P=0.015)among rs179247_AA, AG, and GG genotypes. Conclusion rs179247 and rs12101261 in TSHR intron 1 are both associated with GD, and rs179247 may contribute risk to GD independently. The polymorphism is associated with TRAb, but not with serum concentration of thyroid hormones, age of onset, diffused thyroid goiter, ophthalmic signs, and relapse.     

Arterial hypertension and thyroid disorders: what is important to know in clinical practice?

This review describes the pathogenic mechanisms of blood pressure (BP) regulation and long-term control in thyroid disorders. Variations from the euthyroid status affect virtually all physiological systems but the effects on the cardiovascular system are particularly pronounced. Thyroid disorders induce several hemodynamic changes leading to elevated BP as a consequence of their interaction with endothelial function, vascular reactivity, renal hemodynamic and renin-angiotensin system. However, in thyroid disorders, the regulation of BP and the development and maintenance of variable forms of arterial hypertension (HT) are different. Hyperthyroidism results in an increased endothelium-dependent responsiveness secondary to the shear stress induced by the hyperdynamic circulation, and contributes to reduce vascular resistance. Conversely, hypothyroidism is accompanied by a marked decrease in sensitivity to sympathetic agonists with an increase of peripheral vascular resistance and arterial stiffness. Furthermore in animal models, hypothyroidism reduces the endothelium-dependent and nitric oxide-dependent vasodilatation. HT due to thyroid disorders is usually reversible with achievement of euthyroidism, but in some cases pharmacological treatment for BP control is required. In hyperthyroidism, β-blockers are the first-choice treatment to control BP but when they are contraindicated or not tolerated, ACE-inhibitors or calcium-channel blockers (CCB) are recommended. Hypothyroidism is a typical low rennin HT form showing a better antihypertensive response to CCB and diuretics; indeed in hypothyroidism a low-sodium diet seems further to improve BP control. Randomized clinical trials to compare the efficacy on BP control of the antihypertensive treatment in thyroid disorders are needed.     

计算方法在COBAS COREⅡ免疫分析仪测定TSH中的应用

目的　研究计算方法在 COBAS CORE 免疫分析仪测定 TSH中的应用。方法　用对比随机抽样的方法作 t检验 ,研究测得值与计算值之间的差异。结果　条件式自动稀释法测得值与计算值之间的 t检验 ,P>0 .0 5 ,无显著性差异。结论　在 TSH≥ 5 m IU/ L,A<3.5时 ,可用计算方法代替自动稀释方法。     

Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: A response associated with up-regulation of Akt/mTOR and AMPK activation

Objective

Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI).

Materials/Methods

AMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI + TH), while sham-operated animals served as control (DM-SHAM).

Results

TH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI + TH vs 37 (2.0) for DM-AMI, p < 0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI + TH vs DM-AMI respectively, p < 0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI + TH vs DM-AMI, p < 0.05.

Conclusion

TH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation.     

Hormones and health outcomes in aging men

Increasing age is a predictor of ill-health and mortality related to cardiovascular disease and to frailty, a syndrome characterized by deterioration of multiple organ systems leading to loss of physiological reserve, diminished capacity to cope with stressors, and increased risk of disability and death. As men grow older, their levels of testosterone decline while the prevalence of ill-health increases. Observational studies have linked lower testosterone levels with cardiovascular disease and mortality in middle-aged and older men. More recently, lower testosterone has been shown to predict reduced sexual activity and frailty in aging men. Additional studies are needed to determine whether lower testosterone is a biomarker or a potentially treatable risk factor for poorer health outcomes in older men. During aging, the response of the pituitary–thyroid axis alters to manifest higher thyrotropin levels. The presences of subclinical hypo- and hyper-thyroidism predict adverse cardiovascular outcomes. Newer results indicate that in euthyroid older men, differences in free thyroxine levels within the normal range predict specific health outcomes including frailty. Clarification of the roles of endogenous testosterone and thyroxine in the genesis of ill-health during male aging offers the prospect of future intervention to preserve health and well-being in this growing population.