三维斑点追踪成像评价亚临床甲状腺功能减退患者左心室收缩功能

目的 评价三维斑点追踪成像(3D-STE)技术对亚临床甲状腺功能减退(SCH)患者左心室心肌功能减低的预测价值。方法 对32例SCH患者(SCH组)和30名健康志愿者(对照组)行3D-STE检查,获得左心室收缩期整体面积应变(GAS)、整体纵向应变(GLS)和整体环向应变(GCS)。比较对照组和SCH组治疗前后左心室三维应变参数差异,以左心室射血分数<65%为诊断左心室收缩功能减低金标准,采用ROC曲线评价左心室三维应变参数诊断SCH左心室收缩功能减低的效能。结果 SCH组治疗前后GAS、GLS和GCS绝对值均低于对照组(P均<0.05),治疗后GAS、GLS和GCS绝对值均高于治疗前(P均<0.05)。ROC曲线显示GAS、GLS和GCS的AUC分别为0.805、0.723和0.614,分别以-40.5%、-29.3%和-32.6%作为GAS、GLS和GCS诊断左心室功能减低界值,其敏感度分别为85.7%、77.8%和71.1%,特异度分别为72.2%、71.3%和60.1%。结论 3D-STE中GAS诊断SCH患者左心室收缩功能减低效能较高,具有一定的临床预测价值。     

Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: A 4-year retrospective cohort study

Background/Aims

Hypothyroidism is reported to contribute to the development of nonalcoholic fatty liver disease (NAFLD). We compared the risk of the development of NAFLD among three groups with different thyroid hormonal statuses (control, subclinical hypothyroidism, and overt hypothyroidism) in a 4-year retrospective cohort of Korean subjects.

Methods

Apparently healthy Korean subjects without NAFLD and aged 20-65 years were recruited (n=18,544) at health checkups performed in 2008. Annual health checkups were applied to the cohort for 4 consecutive years until December 2012. Based on their initial serum-free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, they were classified into control, subclinical hypothyroidism (TSH >4.2 mIU/L, normal fT4), and overt hypothyroidism (TSH >4.2 mIU/L, fT4 <0.97 ng/dL) groups. NAFLD was diagnosed on the basis of ultrasonography findings.

Results

NAFLD developed in 2,348 of the 18,544 subjects, representing an overall incidence of 12.7%: 12.8%, 11.0%, 12.7% in the control, subclinical hypothyroidism, and overt hypothyroidism groups, respectively. The incidence of NAFLD did not differ significantly with the baseline thyroid hormonal status, even after multivariate adjustment (subclinical hypothyroidism group: hazard ratio [HR]=0.965, 95% confidence interval [CI]=0.814-1.143, P=0.67; overt hypothyroidism group: HR=1.255, 95% CI=0.830-1.899, P=0.28).

Conclusions

Our results suggest that the subclinical and overt types of hypothyroidism are not related to an increased incidence of NAFLD.     

老年亚临床甲状腺功能减退对代谢综合征及颅内动脉粥样硬化的影响

目的 探讨老年人亚临床甲状腺功能减退（SCH）对代谢综合征（MS）、颅内动脉粥样硬化的影响。方法 从2013年1月至2014年4月于我科住院的老年患者中随机选取416例,其中甲状腺功能正常者298例,亚临床甲状腺功能减退者118例,比较两组MS相关指标、尿酸、同型半胱氨酸（Hcy）水平的差异。以颅内动脉粥样硬化、MS分别为应变量做Logistic回归分析,并分析促甲状腺激素（TSH）与各观察指标的相关性。结果 与甲状腺功能正常组比较,亚临床甲状腺功能减退组颅内动脉粥样硬化的比例增多,MS患病比例增加,收缩压、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDLC）、尿酸、Hcy水平明显升高,高密度脂蛋白胆固醇（HDLC）、空腹血糖（FBG）水平显著减少（P<0.05或P<0.01）。经多元逐步Logistic回归分析发现,高TSH、MS、年龄、收缩压、LDLC、Hcy是颅内大动脉粥样硬化独立的危险因素,TSH、尿酸是MS独立的危险因素,且TSH与TG、尿酸、Hcy呈正相关,与HDLC呈负相关（P均<0.05）。结论 高TSH与MS及颅内动脉粥样硬化的发生发展明显相关,亚临床甲状腺功能减退可能通过改变血脂谱,使血尿酸、血Hcy升高等途径参与MS的发生发展,并进一步增加颅内动脉粥样硬化发生的危险。     

Turner综合征合并糖尿病、甲状腺功能减退症、骨质疏松症一例并文献复习

通过对1例42岁患有糖尿病合并先天性性征缺陷的女性患者进行系统的检查,了解Turner综合征的临床特征及其合并症,确定合适的治疗方案.该患者因口干、多饮、多尿12年,呕吐腹泻2d就诊.B超显示小子宫,双侧卵巢未见.糖化血红蛋白12.66％,口服葡萄糖耐量试验（OGTT）达到糖尿病诊断标准,同时C肽释放试验呈低平曲线.骨密度检查：腰椎骨质疏松,T值：-3.25,Z值：-3.01.外周血染色体核型分析示：45,X/46,XX.肾上腺皮质功能正常.确诊为Turner综合征（嵌合型）合并糖尿病及骨质疏松症.本研究表明当糖尿病合并先天性躯体发育异常时,临床医师应尽早注意全面检查,以便及早确诊Turner综合征并作相应治疗.     

骨钙素在老年2型糖尿病患者中的血糖调控作用及其影响因素研究

背景　骨钙素是骨基质中含量最丰富的非胶原蛋白,由成骨细胞特异性合成并分泌,在骨基质矿化中起调节作用,但越来越多的研究发现骨钙素在调节糖代谢方面也起着重要作用。目的　探讨骨钙素在老年2型糖尿病（T2DM）患者中的血糖调节作用,同时讨论骨钙素血糖调节作用的影响因素。方法　本研究采用随机抽样方法,选取2017-2018年在兰州大学第一医院因T2DM住院的60岁及以上患者329例作为研究对象。入院时记录患者的一般资料,包括：性别、年龄、体质指数（BMI）、T2DM病程;收集患者的实验室检查指标,包括：同型半胱氨酸（Hcy）、尿酸（UA）、血肌酐（Scr）、25-羟基维生素D（25-OH-VD）、骨钙素、糖化血红蛋白（HbA1c）、促甲状腺激素（TSH）、血清总甲状腺素（TT4）、空腹血糖（FPG）、餐后2 h血糖（2 hPG）;采用Spearman秩相关分析评估不同临床指标之间的相关性。收集患者糖耐量+胰岛素释放试验检测指标,包括：餐后0、30、60、120、180 min时静脉血葡萄糖和胰岛素水平,基础状态下胰岛素敏感性采用稳态模型胰岛素抵抗指数（HOMA-IR）评估,基础状态下胰岛素分泌功能由稳态模型胰岛β细胞功能（HOMA-β）反映,糖负荷状态下胰岛素分泌功能由0~120 min胰岛素曲线下面积（AUCINS120）和0~120 min葡萄糖曲线下面积（AUCGLU120）的比值反映,即AUCINS120/AUCGLU120。根据患者骨钙素水平中位数（11.73 μg/L）,将患者分为两组：低骨钙素水平组（OL组,165例）与高骨钙素水平组（OH组,164例）。结果　Spearman秩相关性分析显示,老年T2DM患者骨钙素与HbA1c、FPG、2 hPG呈负相关,与TSH呈正相关（P<0.05）。OL组患者TSH水平低于OH组,男性比例、FPG与2 hPG水平高于OH组（P<0.05）。OL组患者HbA1c、HOMA-IR高于OH组（P<0.05）;不同骨钙素水平患者HOMA-β、AUCINS120/AUCGLU120比较,差异均无统计学意义（P>0.05）。根据患者是否合并亚临床甲状腺功能减退症（简称甲减）,分为亚临床甲减患者139例和甲状腺功能正常患者190例。亚临床甲减患者中,OL组HOMA-IR高于OH组（P<0.05）;OL组与OH组HbA1c、HOMA-β、AUCINS120/AUCGLU120比较,差异均无统计学意义（P>0.05）。甲状腺功能正常患者中,OL组HbA1c、HOMA-IR高于OH组（P<0.05）;OL组与OH组HOMA-β、AUCINS120/AUCGLU120比较,差异均无统计学意义（P>0.05）。根据患者是否合并超重,分为超重患者187例和非超重患者142例。超重患者中,OL组与OH组HbA1c、HOMA-IR、HOMA-β、AUCINS120/AUCGLU120比较,差异均无统计学意义（P>0.05）。非超重患者中,OL组患者的HOMA-IR高于OH组（P<0.05）;OL组与OH组HbA1c、HOMA-β、AUCINS120/AUCGLU120比较,差异均无统计学意义（P>0.05）。结论　骨钙素对老年T2DM患者的胰岛素敏感性、胰岛素分泌功能具有积极的调控作用,为进一步研究骨钙素相关的治疗糖尿病的药物提供了依据。当合并亚临床甲减及超重时,老年T2DM患者骨钙素调控糖代谢的作用减弱,提示临床治疗T2DM应重视亚临床甲减及超重对胰岛素敏感性的影响。     

β型甲状腺激素抵抗综合征患者临床特点分析

背景　β型甲状腺激素抵抗综合征（RTHβ）属于罕见内分泌疾病,临床极易误诊、误治。目的　总结RTHβ患者的临床特点,为临床医师了解本病提供帮助。方法　选取2013-2016年于中国医科大学附属第一医院内分泌与代谢病科诊断为RTHβ的患者6例。回顾性分析6例RTHβ患者的临床资料,包括性别、诊断年龄、发病年龄、家族史、主诉、心电图检查结果、甲状腺触诊结果、甲状腺超声检查结果、甲状腺核素静态显像结果、甲状腺功能指标〔游离三碘甲腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）〕、促甲状腺素受体抗体（TRAb）、性激素结合蛋白（SHBG）、血清铁蛋白、脂代谢指标、骨代谢指标、骨密度、基因测序情况等。结果　6例RTHβ患者的诊断年龄均高于发病年龄,患者在确诊RTHβ之前均被误诊为甲状腺功能亢进症,长期服用抗甲状腺药物治疗。患者主诉均存在心悸、多汗,3例伴心房颤动。6例患者甲状腺核素静态显像均显示甲状腺双叶摄取率增高。5例RTHβ患者甲状腺超声显示有甲状腺肿大,4例显示多发结节。6例RTHβ患者血清FT3、FT4水平升高,TSH水平在参考范围,且TRAb均为阴性;血清SHBG和血清铁蛋白均在参考范围;甲状腺激素受体（TR）β基因测序均存在点突变。结论　RTHβ的临床表现存在高度异质性,临床诊断时需注意与甲状腺功能亢进症和甲状腺功能减退症区分,同时注意并非所有的RTHβ患者能检测出TRβ基因突变。对于高度怀疑为RTHβ的患者,可以采用促甲状腺素释放激素（TRH）兴奋试验、左旋-三碘甲腺原氨酸（L-T3）抑制试验或TRH兴奋试验联合L-T3抑制试验进行临床诊断。     

成年期甲状腺功能异常对患者空间记忆和物体记忆的影响

目的 探索成年期甲状腺功能异常对患者空间记忆和物体记忆的影响。方法 选择2013年3至11月在安徽医科大学第一附属医院内分泌科门诊就诊的甲状腺功能异常的患者,按甲状腺素水平将患者分为甲状腺功能亢进组（甲亢组,42例）和甲状腺功能减退组（甲减组,16例）,并按是否存在甲状腺相关抗体分为抗体阳性和抗体阴性亚组,收集患者背景资料,采用九盒迷宫实验检测空间记忆和物体记忆,以27例健康体检者为对照。采用SPSS 17.0进行统计学分析,组间差异比较采用t检验、单因素方差分析、秩和检验或χ2检验。结果 与对照组相比,甲亢患者的空间参考（z=2.407,P=0.016）和物体再认（z=7.553,P〈0.001）错误分值和甲减患者的物体再认（z=6.221,P〈0.001）错误分值显著增高;甲亢抗体阳性者的空间参考（z=3.695,P〈0.001）、空间工作（z=2.693,P=0.007）和物体再认（z=6.415,P〈0.001）及甲减抗体阳性者的空间工作（z=2.574,P=0.010）、物体再认（z=5.655,P〈0.001）错误分值显著增加,甲亢和甲减抗体阴性者的物体再认错误分值也显著增加（z=6.699、5.422,均P〈0.001）。结论 甲状腺功能障碍患者（尤其是甲状腺相关抗体阳性者）存在一定程度的认知功能损害,自身免疫因素可能参与其中。     

Effects of levothyroxine treatment on insulin sensitivity,endothelial function and risk factors of atherosclerosis in hypothyroid women

Objectives

Contradictory results are encountered in literature regarding the effects of hypothyroidism on the risk factors of atherosclerosis. We aimed to explore the changes in atherosclerotic risk factors and insulin sensitivity before and after levothyroxine replacement therapy in women with primary hypothyroidism and compare with that of healthy controls.

Patients and methods

Twelve patients (mean age of 34 ± 11.7 years) without an evident disease except for primary hypothyroidism (TSH ≥ 20 mIU/L) and eleven euthyroid, age-matched (33.8 ± 8.4 years) female volunteers as controls were included. Baseline thyroid hormones, lipid parameters, homocysteine, fibrinogen levels were measured in both groups. Flow-mediated endothelial-dependent vasodilatation (FMD) method was used to evaluate endothelial dysfunction. Insulin sensitivity was assessed by M values based on euglycemic hyperinsulinemic clamp technique. The same measurements were performed after 6 months of levothyroxine treatment and recovery of euthyroid state in hypothyroid patients.

Results

Treatment reduced total cholesterol (P < 0.005), LDL-cholesterol (P < 0.005), lipoprotein(a) (P < 0.01), fibrinogen (P < 0.0001) and homocysteine (P < 0.0005) levels. Treatment significantly improved M values of hypothyroid patients (3.68 ± 1.53 mg/kg.min vs 6.02 ± 1.21 mg/kg.min, P < 0.0001) and FMD (9.1 ± 3.7% vs 16.4 ± 4.4%, hypothyroid vs euthyroid, P < 0.0001). Significant correlations were found between M values and TSH (r = −0.6, P < 0.005), fibrinogen (r = −0.53, P < 0.01) measurements, free T3 (r = 0.51, P < 0.02) and free T4 (r = 0.49, P < 0.02) levels. FMD was significantly correlated with fibrinogen levels (r = −0.49, P < 0.05).

Conclusion

Insulin resistance, endothelial dysfunction, atherosclerotic risk markers improves with treatment of hypothyroidism.     

Levothyroxine Dosage Is Associated with Stability of Thyroid-stimulating Hormone Values

Objective

In patients treated for hypothyroidism, the usual practice is to monitor thyroid-stimulating hormone values yearly once a therapeutic dosage of levothyroxine is determined. This study investigates whether there are any clinical predictors that could identify a subset of patients who might be monitored safely on a less frequent basis.

Methods

With the use of a retrospective study design, 715 patients treated for hypothyroidism who had a normal (ie, therapeutic) thyroid-stimulating hormone value in 2006 while taking levothyroxine were identified. All thyroid-stimulating hormone values were then obtained through December 31, 2012. By using a Cox proportional hazard model, gender, age, body mass index, history of chronic autoimmune thyroiditis, initial thyroid-stimulating hormone level, and levothyroxine dose were analyzed for time to first abnormal thyroid-stimulating hormone value.

Results

Age, gender, history of chronic autoimmune thyroiditis, and body mass index at the time of initial normal thyroid-stimulating hormone were not associated significantly with time to abnormal thyroid-stimulating hormone value. Levothyroxine dose >125 μg/day had an increased hazard ratio of 2.4 (95% confidence interval, 1.7-3.4; P < .0001) for time to first follow-up abnormal thyroid-stimulating hormone value, but dosages less than that did not increase the hazard ratio. One year after the initial normal thyroid-stimulating hormone value, 91.1% of patients taking ≤125 μg/day had a continued normal thyroid-stimulating hormone, whereas only 73.3% of patients taking >125 μg/day did. Transformed thyroid-stimulating hormone value (which represents a measure of how far the initial thyroid-stimulating hormone was from the midpoint of the normal range) also had an increased hazard ratio of 1.14 (95% confidence interval, 1.1-1.2; P < .0001) for time to first abnormal thyroid-stimulating hormone value.

Conclusions

For patients receiving ≤125 μg/day of levothyroxine, we propose that a testing interval up to 2 years may be acceptable if their thyroid-stimulating hormone is well within the normal range.     

左旋甲状腺素和维生素E干预对甲状腺功能减退大鼠心肌氧化应激和细胞凋亡的影响

目的 通过研究左旋甲状腺素(LT4)、维生素E(VitE)及二者联合治疗对甲状腺功能减退(甲减)大鼠氧化应激及心肌细胞凋亡的影响,进一步探讨甲减心肌损伤的发生机制及其治疗方法.方法 将SD雄性大鼠分为正常对照组、丙基硫氧嘧啶组(PTU)、LT4治疗组(PTU +LT4)、VitE治疗组(PTU+VitE)、LT4和VitE联合治疗组(PTU+LT4 +VitE).测定血清T3、T4、TSH水平以及血清、心肌组织超氧化物歧化酶(SOD)活性和丙二醛含量;用TUNEL法检测心肌细胞凋亡指数.结果 (1)与正常对照组比较,PTU组、PTU+VitE组T3、T4水平明显降低,TSH显著升高(P＜0.05);与PTU组比较,PTU+LT4组、PTU+LT4 +VitE组T3、T4水平明显升高,TSH显著降低(P＜0.05);PTU组与PTU+VitE组T3、T4、TSH水平差异无统计学意义(P＞0.05).(2)与正常对照组比较,PTU组血清及心肌组织丙二醛含量显著升高(P＜0.05),其他各组之间差异无统计学意义(P＞0.05);与正常对照组比较,PTU组血清SOD活性显著降低(P＜0.05),但心肌组织SOD活性各组之间差异无统计学意义(P＞0.05).(3)与正常对照组比较,PTU组、PTU+VitE组心肌细胞凋亡显著升高(P＜0.05);与PTU组比较PTU+LT4组、PTU+ LT4+ VitE组凋亡显著降低(P＜0.05).结论 LT4、VitE及二者联合治疗可降低甲减大鼠心肌细胞凋亡,其机制可能与甲状腺功能改善和氧化应激水平降低有关.