高灵敏度测定人血清促甲状腺素的临床意义

本文随机抽取１００人次１９９８年住院治疗的甲状腺疾病患者的甲状腺功能测定结果,探讨高灵敏度测定促甲状腺素（ＨＳ－ＴＳＨ）的临床意义。１材料与方法１．１试剂 中美合资天津九鼎医学生物工程有限公司生产的免疫放射试剂盒。１．２测定方法１．２．１向编号各管加入包被珠１粒,固相管直接加样。加样顺序见表１。１．２．２摇动数次后,置于３７℃下温育３．５ｈ。吸出各管的反应液并加入蒸馏水３ｍｌ,反复洗３次。用吸水纸吸于干,倒入测量管。因相管按上述方法洗后直接测量。１．２．３γ计数器测量,求得待测标本的ＨＳ－ＴＳＨ…     

促甲状腺素受体抗体检测的临床意义

促甲状腺素受体抗体(TRAb)与多种自身免疫性甲状腺疾病的发病密切相关,是临床诊断这些疾病的重要指标.TRAb在功能上可分为甲状腺刺激性抗体(TSAb)和甲状腺刺激阻断性抗体(TSBAb),可与促甲状腺素受体分子上不同位点结合产生不同生物学效应.其中TSAb可引起Graves病(GD)患者甲状腺功能亢进和弥漫性甲状腺肿的发生,而TSBAb则可导致自身免疫性甲状腺功能减退症(甲减)患者甲减的发生.本文将对TRAb检测在GD鉴别诊断、辅助制定GD治疗方案、抗甲状腺药物疗效及预测复发、筛查自身免疫性甲减等方面的临床价值作一全面综述.     

促甲状腺素受体抗体检测的临床意义

促甲状腺素受体抗体 (TRAb)与多种自身免疫性甲状腺疾病的发病密切相关 ,是临床诊断这些疾病的重要指标。TRAb在功能上可分为甲状腺刺激性抗体 (TSAb)和甲状腺刺激阻断性抗体(TSBAb) ,可与促甲状腺素受体分子上不同位点结合产生不同生物学效应。其中TSAb可引起Graves病 (GD)患者甲状腺功能亢进和弥漫性甲状腺肿的发生 ,而TSBAb则可导致自身免疫性甲状腺功能减退症 (甲减 )患者甲减的发生。本文将对TRAb检测在GD鉴别诊断、辅助制定GD治疗方案、抗甲状腺药物疗效及预测复发、筛查自身免疫性甲减等方面的临床价值作一全面综述。     

促甲状腺素测定方法的进展及其在评价甲状腺功能中的作用

重点综述促甲状腺素测定的发展及其不同灵敏度的测定方法在确定甲状腺功能状态中的作用。     

肝硬化患者血清促甲状腺激素和甲状腺素水平变化及其临床意义*

目的分析血清TSH、FT3、FT4水平与肝硬化肝功能损害程度的相关性。方法对我院于2013年7月至2015年6月收治的肝硬化患者120例和门诊体检为无异常的健康者120例的临床资料进行回顾性分析。对比健康人和肝硬化组患者血清促甲状腺激素（TSH）、血清游离三碘甲状腺原氨酸（FT3）和血清游离甲状腺素（FT4）水平和肝功能指标白蛋白（ALB）、总胆红素（TBIL）水平,将肝硬化组患者按照Child-Pugh改良分级法分为A、B、C三组,对比三组患者血清TSH、FT3和FT4水平以及肝功能指标ALB和TBIL水平。结果肝硬化组患者血清TSH水平为（8.64±1.22） mIU/L,高于健康人（3.96±0.67） mIU/L（t=36.833,P=0.000）,FT3和FT4水平分别（3.16±0.51pmol/L、10.29±1.43pmol/L）,均低于健康人（6.09±0.94 pmol/L、19.20±3.42 pmol/L）（t值分别为30.013、26.330,均P=0.000）。肝硬化组患者血清ALB水平为（29.64±3.61） g/L,低于健康人（45.62±5.40） g/L（t=26.950,P=0.000）,血清TBIL水平为（45.96±4.19）μmol/L,高于健康人（13.52±2.16） μmol/L（t=75.385,P=0.000）。肝功能分级越高,患者血清TSH随之升高,但组间相比,差异无显著性（F=2.262,P=0.159）,FT3和FT4水平随肝功能分级升高而降低,组间相比,差异具有显著性（F值分别为7.737和5.286,P值分别为0.029和0.037）。肝功能分级越高,患者血清ALB越低,组间相比差异具有显著性（F=8.629,P=0.025）,血清TBIL水平随肝功能分级升高而升高,组间相比差异具有显著性（F=8.854,P=0.024）。TSH、FT3和FT4水平与血清ALB和TBIL水平的Pearson相关分析显示TSH水平和肝硬化组肝功能指标ALB和TBIL无相关性（r=-0.096,P=0.296;r=0.115,P=0.159）,FT3和FT4水平与肝功能指标ALB呈正相关（r=-0.468,P=0.031;r=0.391,P=0.045）,和TBIL水平呈负相关（r=-0.491,P=0.029;r=-0.435,P=0.036）。结论肝硬化患者肝功能损害程度越高,血清甲状腺激素FT3和FT4的水平越低,且与FT3和FT4水平呈负相关,肝功能受损会影响患者血清TSH水平,但无线性相关性。     

常温和中低温体外循环对甲状腺素变化的影响

目的探讨常温及低温体外循环心脏直视手术对甲状腺素的影响。方法选择先天性心脏病患者80例,随机分为常温组及低温组,各40例,分别于术晨、体外循环结束时及术后6、12、24、48h抽取患者动脉血,测定血浆T3、T4和TSH。结果两组术前各项检查指标差异无统计学意义。常温体外循环下甲状腺素T3升高水平低于中低温,恢复时间比中低温明显缩短。结论常温体外循环心脏直视手术对甲状腺素的影响显著轻于低温组,因而术后机体的恢复优于低温方法。     

二甲双胍对促甲状腺素影响的初步研究

目的 观察二甲双胍对血清促甲状腺素(TSH)的影响.方法从2型糖尿病患者中,入选原发性甲状腺功能减退症(甲减)患者48例,组1单用二甲双胍而未予左旋甲状腺素(L-T4)替代治疗(n=17),组2给予L-T4稳定替代量的同时加用二甲双胍(n=19),组3用L-T4稳定替代量和非二甲双胍的其他降糖药(n=12).另外20例甲状腺功能正常的其他甲状腺疾病患者(组4)和30例无甲状腺疾病的患者(组5)作为对照.各组患者均定期检测血清TSH、FT3、FT4、TT3、TT4及血糖等主要指标的变化.结果 治疗12个月与基线时比较,组1为(5.05±1.07)对(2.61±0.91)mU/L(P＜0.01),组2为(2.67±1.03)对(1.35±0.74)mU/L(P＜0.01),两组的FT3及FT4均无明显变化.15例TSH显著降低的患者中有13例(87%)在停用二甲双胍后8～12周内TSH由(1.30±0.71)回升至(2.58±1.02)mU/L(P＜0.01).组3、组4及组5的血清TSH和甲状腺激素的水平均无明显改变.结论 服用二甲双胍可使TSH下降.

Abstract：

Objective To evaluate the effects of metformin on thyrotropin(TSH)levels. Methods From the patients with type 2 diabetes mellitus or metabolic syndrome, 48 patients with primary hypothyroidism were enrolled and grouped. 17 patients were treated only with metformin(group A), 19 patients with metformin and stable L-T4substitution(group B), and the remaining 12 patients with antidiabetic drugs(other than metformin)and L-T4(group C). Meanwhile, 20 euthyroid patients with other thyroid abnormalities(group D)and 30 patients without thyroid diseases(group E)served as control. TSH, FT3, FT4, TT3, TT4, and blood glucose were determined regularly in all these subjects. Results After administration of metformin for 12 months, serum TSH were decreased in group A [(5.05±1.07 vs 2.61±0.91)mU/L, P＜0.01] and group B [(2.67±1.03 vs 1.35±0.74)mU/L, P＜0.01]. No difference was found in FT3and FT4in both groups. TSH levels were raised from(1.30±0.71)to(2.58±1.02)mU/L(P＜0.01)within 8～12 weeks in 13 out of 15 patients after metformin withdrawal. Serum TSH and thyroid hormones in the other 3 groups were not significantly changed. Conclusion Administration of metformin may lead to reduction of serum TSH level.     

不同程度冠状动脉病变的冠心病患者血清促甲状腺激素水平变化及其临床意义

目的观察不同程度冠状动脉病变的冠心病患者血清促甲状腺激素(TSH)水平变化及其临床意义。方法选择169例冠心病患者,依据冠状动脉病变程度分为单支病变组(55例)、双支病变组(58例)和多支病变组(56例),选择同期61例冠状动脉造影正常受试者作为正常对照组。检测各组入院时血清TSH水平,并进行组间比较。结果正常对照组、单支病变组、双支病变组、多支病变组血清TSH水平依次升高,两两比较差异有统计学意义(P<0.05)。结论血清TSH水平是冠心病发生、发展中重要的检测指标,血清TSH水平对预测冠心病患者冠状动脉病变严重程度有一定意义。     

心力衰竭病人血甲状腺激素、促甲状腺素的测定及其意义

目的:探讨充血性心力衰竭(CHF)病人血清游离甲状腺激素(FT3、FT4)、促甲状腺激素(TSH)浓度的变化及其意义。方法:用放免法测定77例CHF病人及30例正常人血清FT3、FT4、TSH的浓度,并对11例Ⅲ或Ⅳ级CHF病人治疗前、后及各种原发病致CHF时的FT3、FT4、TSH浓度进行比较。结果:CHF组FT3降低(P<0.01),FT4及TSH正常。严重CHF可伴有FT4降低(P<0.01)。心衰越重,FT3降低越明显(P<0.05)。结论:FT3、FT4可作为CHF病情程度判断的一个指标。     

血清促甲状腺素水平与急性缺血性卒中患者转归的相关性

目的 探讨血清促甲状腺素(thyroid-stimulating hormone,TSH)水平与急性缺血性卒中转归的相关性.方法 前瞻性纳入急性缺血性卒中患者,收集一般临床资料、血管危险因素和甲状腺.激素等生化指标.应用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评估基线神经功能缺损程度.在发病后90 d时采用改良Rankin量表(modified Rankin Scale,mRS)评估神经功能转归,0～2分定义为转归良好.采用多变量logistic回归分析确定急性缺血性卒中患者转归不良的独立影响因素.结果 共纳入140例急性缺血性卒中患者,其中男性95例(67.86％),女性45例(32.14％),年龄35 ～94岁.亚临床甲状腺功能减退13例(9.29％),亚临床甲状腺功能亢进17例(12.14％).98例(70.00％)转归良好,42例(30.00％)转归不良.转归良好组男性(x2=4.717,P=0.047)和小动脉闭塞性卒中(r=5.564,P=0.018)患者构成比以及尿酸(t=2.602,P=0.010)、FT3(归2.406,P=0.017)和TSH(t=2.302,P=0.023)水平显著高于转归不良组,年龄(泞-3.489,P=0.001)、空腹血糖(Z=-2.178,P=0.031)和基线NIHSS评分(归-8.009,P＜0.001)显著低于转归不良组.转归良好组TSH位于第1四分位数(＜0.805 mU/L)的患者构成比显著低于转归不良组(17.35％对42.86％;x2=10.204,P=0.003),而位于第4四分位数(＞2.476 mU/L)的患者构成比显著高于转归不良组(30.61％对11.90％;x2=5.488,P=0.020).多变量logistic回归分析显示,在校正各种混杂因素后,基线NIHSS评分较高是发病后90 d时转归不良的独立危险因素(优势比1.690,95％可信区间1.317 ～2.168;P＜0.001),而基线TSH水平较高与转归良好独立相关(优势比0.520,95％可信区间0.408 ～0.867;P =0.007).结论 血清TSH水平较高与急性缺血性卒中患者发病后90 d时神经功能转归良好独立相关.     

Leptin, thyrotropin, and thyroid hormones in obese/overweight women before and after two levels of energy deficit

The aim of our study was to compare serum concentration of leptin and pituitary-thyroid axis hormones in obese/overweight women before and after two levels of energy deficit with those parameters in lean women on adequate energy intake. Additionally, we attempted to elucidate if the effect of weight reduction could be related to anthropometric and hormonal parameters before treatment. Anthropometric and hormonal parameters—serum leptin, TSH, T4, fT4, T3 and leptin to fat mass (Lep/fm), T3/T4, fT4/T4, T4/TSH, fT4/TSH—were compared in two groups of women (n=18 each)—lean women (C: BMI 22.0±1.2) and overweight/obese (Ov/Ob: BMI 29.9±3.3). Ov/Ob women were subjected to weight-reducing treatment consisting of energy intake equal to 80% of calculated total energy expenditure for the first 4 wk and to 50% for subsequent 4 wk. All baseline hormone concentrations, Lep/fm, and fT4/T4 were higher in overweight/obese group. After 20% energy deficit decrease in BMI, percent body fat (fm%), leptin, T3, and TSH serum concentrations as well as in Lep/fm and T3/T4 was observed; T4/TSH increased, fT4, fT4/T4 and fT4/TSH did not change significantly. Increase in energy deficit from 20% to 50% resulted in normalization of Lep/fm, on the other hand, it provoked greater decline in thyroid hormone plasma concentration, which could hinder further mass reduction. Leptin and TSH levels were positively correlated after 50% energy deficit treatment. Changes in fm% were directly related to baseline T4/TSH, fT4/TSH, and log TSH. In conclusion, TSH serum concentration and its ratio to T4 and fT4 before weight reduction could be a good predictor of successful weight loss.     

Secretion rates of thyroxine, triiodothyronine, and reverse triiodothyronine in man during surgery

The secretion rates of T4, T3, and rT3 were studied in experiments of short duration by a new method based on determinations of the hormone difference across the thyroid combined with simultaneous electromagnetic thyroid blood flowmetry during surgery in 70 euthyroid patients. The secretion rate of T3 was similar in normal thyroid tissue and nodular goitre, but those of T4 and rT3 were lower in nodular goitre and solitary adenoma (P less than 0.05). In 61 patients with normal thyroid tissue or nodular goitre the secretion rates during surgery (mean +/- SEM) were for T4 222 +/- 28 nmol/day, for T3 27.4 +/- 3.1 nmol/day, and for rT3 3.5 +/- 0.5 nmol/day. In relation to the individual T4 secretion rate, the secretion rate of T3 was 12.5 +/- 3.0% and that of rT3 1.2 +/- 0.9%. In these short-term experiments we found a secretion rate for T4 during operation about 50% greater than in earlier long-term kinetic studies, but which tallied with a recent report using a 4-compartment model. For T3 and rT3 it was 2-3 times greater than earlier estimates. The secretion was estimated to be 50% of the total production rate for T3 and 6% for rT3. If proportional adjustment were performed to yield a T4 secretion of about 130 nmol/day. T3 and rT3 secretion rates would still be greater than earlier reported.     

Separation and analysis of two plasma membrane fractions from bovine thyroid which differ in TSH binding and TSH activation of adenylate cyclase

A tissue disruption technique leading to the separation of thyroid epithelial cell components from interfollicular material has been used to study the distribution and the properties of membrane adenylate cyclase originating from intraglandular thyroid and non-thyroid cells. Bovine thyroid fragments were forced through a metallic sieve. The material which filtrates was composed of open cells and cell debris (fraction A); the material remaining on the sieve contained the basal lamina and the interfollicular material as shown by photon and electron microscopic observations (fraction B). Homogenates (HA and HB) were prepared from fractions A and B and centrifuged on a 41% sucrose layer to prepare membrane fractions: MA and MB, which were tested for the presence of adenylate cyclase, TSH-responsive adenylate cyclase and 125I-labelled TSH binding activity. HA and HB contained respectively 70% and 30% of the total thyroid adenylate cyclase activity. MA and MB were similarly enriched in 5'-nucleotidase and adenylate cyclase: 8- to 10-fold as compared to the corresponding homogenates. MA and MB exhibited a marked difference in the response to TSH: TSH either alone or in the presence of Gpp(NH)p stimulated the adenylate cyclase of MA and did not have any effect on MB. Fractionation of MA by isopycnic centrifugation on Percoll gradients yielded a membrane peak exhibiting a TSH-responsive adenylate cyclase activity and a 125I-labelled TSH binding activity displaceable by an excess of unlabelled TSH. A membrane peak at the same density was obtained from MB but its adenylate cyclase did not respond to TSH and there was no specific binding of labelled TSH. Our data indicate that an important fraction of membrane adenylate cyclase of the thyroid does not seem to be coupled with TSH receptor; the major part of this fraction (MB) likely originates from intraglandular non-thyroid epithelial cells. The separation of this membrane fraction from the thyroid cell plasma membrane fraction (MA) allows to increase the response of this latter fraction to TSH.     

The growth hormone, prolactin and TSH response to TRH and L-dopa in patients with hyperprolactinaemia and a normal-sized sella turcica may denote a pituitary adenoma

Forty-one patients with hyperprolactinaemia and suspected prolactinomas were studied. Growth hormone (GH) and thyrotropin (TSH) secretory patterns after thyrotropin releasing hormone (TRH) were affected in the majority of patients. The disturbances were observed regardless of tumour size as indicated by the radiological sella size. In patients with hyperprolactinaemia and normal-sized sella turcica, an abnormal GH and TSH response to TRH can be helpful in the diagnosis of a microadenoma. The hyperprolactinaemia per se and its effect on dopaminergic hypothalamic neurones may be the cause of the GH and TSH response. By contrast, many patients with macroprolactinomas showed insufficient GH secretory capacity.     

体外循环围术期血清FT_3,FT_4及TSH含量的测定及意义

应用放射免疫法测定40例心脏病患者围术期血清FT_3,FT_4及TSH的含量,结果发现FT_3含量于术中,术后明显降低,与术前比较有非常显著差异(P<0.001).而FT_4无明显变化,TSH则稍有降低,与术前比较差异不显著(P>O.05).本文对FT_3降低的原因及FT-3变化的临床意义进行了讨论.旨在为进一步研究T_3的心血管作用及T_3替代治疗提供有利的依据.     

TSH, theophylline and cyclic AMP: in vitro thyroid activity in aging rats.

In vitro thyroid accumulation of cyclic 3',5'-adenosine monophosphate (cyclic AMP) and release of triiodothyronine (T₃) and thyroxine (T₄) in response to TSH, theophylline or cyclic AMP treatment was assessed in 60- and 340-day-old male rats. Plasma levels of T₃ and T₄ at the time of sacrifice were determined. Mature animals exhibited significantly lower plasma T₃ and T₄ levels but slightly elevated in vitro secretory rates of T₃ and T₄. TSH stimulation elicited little effect in the mature gland in terms of cyclic AMP accumulation or thyroid hormone release. Conversely, cyclic AMP enhanced in vitro thyroid hormone release in both age groups. The data suggest an age-related alteration in thyroid responsiveness to TSH which in turn may be a function of changes in the thyroidal adenylate cyclase-cyclic AMP-phosphodiesterase system. Evidence is also presented which suggests either cyclic AMP-mediated T₄ to T₃ conversion or a differential action of the nucleotide upon T₃ as compared to T₄ synthesis.     

TSH受体基因SNP与Graves病、桥本甲状腺炎和结节性甲状腺肿之间的相关性研究

目的　探讨TSH受体基因单核苷酸多态性 (SNP)与甲状腺疾病〔包括Graves病 (GD) ,结节性甲状腺肿 ,桥本甲状腺炎 (HT)〕有无相关性。方法　以 60例有甲状腺疾病家族史患者 (其中 3 0例GD、10例HT、2 0例结节性甲状腺肿患者 ) ,48例散发Graves病患者及 96名健康对照者作为研究对象 ,采用外周血白细胞抽提DNA ,设计引物 ,PCR扩增 ,对扩增产物纯化后测序。结果患者中共发现 8个多态位点 ,其中第8外显子上的多态位点 (E8A 40C)在SNP库中未见报道 ,为首次发现 ;将这些多态位点基因型变化与正常组比较 ,无明显统计学差异。结论　本研究提示汉族人TSH受体基因与这几种甲状腺疾病无相关性 ;该基因的多态位点在不同的人种间存在明显差异。     

Five‐year incidence and progression of thyroid dysfunction in an older population

Background: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population‐based cohort. In this study, we aimed to assess the 5‐year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population. Methods: The Blue Mountains Eye Study is a longitudinal population‐based cohort study. During 1997–1999, 1768 participants (≥55 years) had thyroid function assessed. After excluding participants reporting any form of treatment for their thyroid condition at baseline, 951 participants (91.4%) without thyroid dysfunction and 54 (5.4%) with thyroid dysfunction were re‐examined 5 years later. Thyroid dysfunction was defined using serum thyrotropin (thyroid stimulating hormone (TSH)) screen, followed by serum free T4 assessment. Results: The overall 5‐year incidence of thyroid dysfunction was 4.7% (95% confidence interval (CI) 3.4–6.1). Obesity (body mass index ≥ 30 kg/m²) and serum TSH > 2 mIU/L at baseline predicted incident overt hypothyroidism (odds ratio (OR) 4.05, CI 1.74–9.41) and (OR 5.46, CI 1.16–25.67) respectively. The 5‐year incidence of subclinical hypothyroidism was significantly higher in women than in men, 2.5% versus 0.7% (P= 0.03). Progression to overt hypothyroidism was observed in 17.9% of subjects with subclinical hypothyroidism over 5 years. Conclusions: The 5‐year incidence of thyroid dysfunction in this older population was relatively low, and was associated with obesity and serum TSH level > 2 mIU/L at baseline. Over one in six persons with subclinical hypothyroidism progressed to overt thyroid dysfunction over the 5‐year period. Our findings highlight the need for appropriate management of subclinical hypothyroidism among older people.