亚临床甲状腺功能减退症

亚临床甲状腺功能减退症(甲减)是一种业临床甲状腺疾病.诊断标准是血清促甲状腺激素(TSH)水平高于正常上限而游离T4水平尚在正常范围.目前全世界业临床甲减的平均患病率为4%～10%,主要发生在女性和老年人群.桥本甲状腺炎是最常见的病因.其卡要的临床危害包括引起血脂异常、导致动脉粥样硬化和,冠心病、影响认知功能,还可导致不孕和流产.治疗主要针对血清TSH10 mIU/L的患者,应用左旋-T4替代治疗.对于血清TSH 4～10 mIU/L,特别是甲状腺自身抗体阳性者需密切监测.此外,对妊娠期亚临床甲减患者的治疗要求控制TSH<2.5 mlU/L.     

亚临床甲状腺功能减退症

亚临床甲状腺功能减退症(亚甲减)是依靠实验室诊断的一种亚临床疾病,其诊断标准是血清促甲状腺激素(TSH)水平增高,血清游离T4(FT4)正常。亚甲减的患病率为3％～15％,主要发生在女性和老年人群。碘摄人量增加是亚甲减发生的重要环境因素之一。亚甲减的主要危害是发展为临床甲减和引起血脂增高,导致缺血性心脏病。亚甲减对妊娠妇女后代的智力影响也不容忽视。针对亚甲减的治疗包括①对易感人群的筛查。②对血清TSH>10 mU/L,且甲状腺自身抗体阳性的患者给予左旋甲状腺素替代治疗。③未达到上述标准的亚甲减患者定期随访。     

左甲状腺素钠对亚临床甲状腺功能减退患者颈动脉内膜厚度的影响

亚临床甲状腺功能减退（甲减）是临床的常见疾病,具体的表现是血中TSH水平偏高,而血TT3,TT4,FT3、FT4水平正常。文献认为,亚临床甲减患者,如果有高胆固醇血症、血TSH〉10mIU／L、甲状腺自身抗体强阳性,可进行替代治疗,以阻止其发展为临床甲减和防止动脉粥样硬化。早期评估亚临床甲减患者的甲状腺素靶器官的功能很重要。我们以高分辨率超声测定的颈动脉内膜-中膜厚度（IMT）可以作为动脉粥样硬化的指标,观察应用左甲状腺素钠对亚临床甲减患者颈动脉内膜厚度的影响。     

亚临床甲状腺功能减退症患者血清hsCRP与TSH的相关性研究

目的探讨亚临床甲状腺功能减退症（简称甲减）患者血清高敏C反应蛋白（hsCRP）的变化及与促甲状腺激素（TSH）的关系。方法实验组为亚临床甲减患者30例,对照组为同期门诊查甲状腺功能正常的健康体检者30例,均测定血清hsCRP水平,并对亚临床甲减患者血清hsCRP和TSH水平进行相关性分析。结果实验组血清hsCRP水平高于对照组;亚临床甲减患者血清hsCRP与TSH无相关性。结论亚临床甲减可引起血清hsCRP增高,有促进动脉粥样硬化发生的可能。     

亚临床甲状腺功能减退对心血管系统的影响

亚临床甲状腺功能减退症（亚甲减）诊断主要依赖于实验室的生化结果,是指以临床无症状或症状轻微、患者血清中促甲状腺激素（TSH）水平升高而游离甲状腺素（FT4）水平正常为基本特征的临床状态。我国人口普查显示[1],随着血清促甲状腺激素放射免疫测定TSH技术的不断改进,亚临床甲减的检出率随年龄增加呈现明显上升趋势,一般在1%～6%,老年人与女性多见。     

亚临床甲状腺功能减退症

亚临床甲状腺功能减退症（简称亚临床甲减，subclinical hypothyroidism），以往也称轻度甲状腺功能减退症或临床前甲状腺功能减退症。一般是指血清游离甲状腺素（FT4）在正常范围，而血清促甲状腺激素（thyroid—stimulating hormone，TSH）水平升高，患者没有明显的甲状腺功能减退（甲减）的临床症状和体征，是甲状腺功能减退症的早期阶段，诊断必须依靠血清学检查。国内外对亚临床甲减的治疗和处理尚无统一的意见和观点，本文就有关亚临床甲减研究的现状进行复习，以供临床诊疗参考。     

亚临床甲状腺功能减退症的治疗

亚临床甲状腺功能减退症(亚甲减)以基线促甲状腺激素(TSH)水平升高和血清游离甲状腺素水平正常为特征,亚临床或隐匿性甲减常常反映甲状腺激素分泌的缺陷。甲状腺破坏性治疗(甲状腺次全切除术或放射碘治疗)或颈部广泛放射治疗后的亚临床甲减应开始使用左甲状腺素(L-T4)治疗;妊娠和哺乳期的亚甲减也应使用L-T4治疗。其他早期使用甲状腺激素替代治疗的指征包括TSH水平升高以及抗甲状腺过氧化物酶(TPO)抗体阳性,因为这些患者的亚甲减很可能进展为临床甲减。提示存在甲状腺激素相对缺乏的临床体征和症状的所有患者都应该试用L-T4替代治疗,这些患者包括亚临床甲减并发不孕、抑郁症或其他神经心理异常。单纯血清TSH水平升高或高胆固醇血症不是L-T4治疗的适应症,除非患者有甲状腺疾病史以及提示甲状腺激素缺乏的临床症状。     

老年亚临床甲状腺功能减退症的诊治特点

亚临床甲状腺功能减退症(甲减)是老年人群常见的疾病.诊断标准为血清促甲状腺激素(TSH)水平升高伴游离甲状腺素(FT4)水平正常.TSH正常值上限随年龄增长而升高,但临床上尚缺乏根据年龄调整的TSH正常值范围.老年亚临床甲减与老龄化症状极为相似,易于被忽视.持续性亚临床甲减可对老年人心血管、认知、肌肉骨骼等方面带来负面影响,而TSH小于10 mIU/L的轻度亚临床甲减可能与75岁以上老人长寿相关.老年亚临床甲减的治疗应该强调个体化,TSH大于10 mIU/L或存在其他危险因素时,应给予左旋甲状腺素(L-T4)治疗.初始剂量推荐25～75μg/d,每4～6周根据TSH水平和临床表现调整剂量,至维持剂量后每6～12个月监测甲状腺功能.     

老年人亚临床甲减和甲亢的诊断与治疗

亚临床甲状腺疾病是临床上常见的问题。亚临床甲减是指患者血清TSH水平升高，而总或游离T4和T3水平正常。文献报道存总人群中亚临床甲减的患病率为4％～10％不等，在年龄≥60岁的老年妇女中可高达20％。亚临床甲亢则是指患者血清TSH水平降低，     

老年亚临床甲状腺机能减退患者血清促甲状腺素对血脂水平的影响

目的探讨老年亚临床甲状腺机能减退（以下称亚临床甲减）患者促甲状腺素（TSH）与血脂水平的关系。方法 126例老年（年龄〉60岁）亚临床甲减患者,TSH〉10.0 mIU/L 62例（A组）,TSH 5.0～10.0 mIU/L 64例（B组）,分析两组血脂水平;对A组左旋甲状腺素治疗前后血脂变化进行分析。结果 A组血清总胆固醇（TC）及低密度脂蛋白胆固醇水平（LDL-C）明显高于B组（P〈0.05）,两组甘油三酯（TG）水平无统计学差异;A组口服左旋甲状腺素钠片治疗后（TSH正常）TC及LDL-C低于治疗前（P〈0.05）。结论 TSH可使老年亚临床甲减患者血脂水平增高,而应用左旋甲状腺素钠治疗血脂可获改善。     

Subclinical hypothyroidism,lipid metabolism and cardiovascular disease

Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10 mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.     

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??Abstract??Subclinical hypothyroidism is a common endocrine and metabolic disease??which characterized by elevated level of thyroid-stimulating hormone (TSH) with normal free thyroxine (FT??4) level.The incidence rate is 4% to 10% of the world’s population??and It is more common in women.The causes of subclinical hypothyroidism are much complicated.They could generally be divided into two categories??abnormal structure and/or dysfunction of thyroid gland itself or non-thyroid organs.Serum TSH is the most important mark to screen and diagnose the disease.80% patients are with positive anti-thyroid antibodies.Since subclinical hypothyroidism has certain clinical harm??it is recommended a screening in high-risk groups and a replacement therapy to patients with serum TSH>10 mU/L.Treatments should follow a principle of stratification and individuation.     

Lack of association between thyrotropin receptor gene polymorphisms and subclinical hypothyroidism in children

Subclinical hypothyroidism is defined as a serum TSH level above the statistically set reference range, associated to normal free thyroid hormone concentrations. Genetic and environmental factors contribute to the inter- and intra-individual biological variations of TSH levels, sometimes leading to uncertainty of treatment in the clinical practice, especially when moderate elevations above the upper limit of the reference range are considered (5< TSH <10 mIU/l). In this view, the study of association between subclinical hypothyroidism and possible molecular effectors, such as polymorphisms in the TSH receptor (TSHR) gene, could be interesting. In this paper, we analyzed the TSHR gene polymorphisms in 103 hyperthyrotropinemic infants. A control group of 120 newborns of the same ethnic background was used to evaluate the frequencies of each polymorphism in the population. We found a statistically significant difference in the allelic frequency of the P52T polymorphism, being that the T variant was more represented in the control group (p=0.03). However, no significant results have been obtained in the analysis of the association between genotypes and serum TSH levels. In conclusion, we analyzed 7 polymorphic variants of TSHR gene in subclinical hypothyroidism. The only significant result refers to the allelic frequency of A in the P52T polymorphism, which is statistically reduced when compared with that of a control group.     

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??Abstract??Hypothyroidism often results in the elevation of serum total cholesterol??low-density lipoprotein cholesterol and triglyceride??and is one of common causes for secondary dyslipidemia.This association is mainly attributed to the reduction of circulating thyroid hormones.Recently??results from epidemiological studies showed that subclinical hypothyroidism??defined as a serum thyroid stimulating hormone (TSH) concentration above the normal range with normal serum FT??4 and FT??3 concentration??was closely associated with dyslipidemia.Experimental studies confirmed the role of TSH per se in lipid metabolism.For overt hypothyroidism??replacement therapy with thyroid hormones can correct dyslipidemia.However??the beneficial effects of replacement therapy on dyslipidemia in subclinical hypothyroidism were not established by clinical trials??which warrants further intervention studies to answer it.     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

Subclinical thyroid dysfunction in the elderly.

Subclinical thyroid dysfunction is more common in older persons. By definition, these disorders are recognized by isolated elevation or suppression of the serum TSH concentration, in association with a normal serum free thyroxine level. Among individuals over 65 years old, subclinical hypothyroidism is found in approximately 10% of women and approximately 3% of men. It is most commonly due to autoimmune thyroiditis or previous treatment for hyperthyroidism. There may be three indications for L-thyroxine therapy: (a) presence of antithyroid antibodies, indicating substantial risk of progression to over hypothyroidism; (b) symptoms consistent with thyroid hormone deficiency; and (c) an elevated serum LDL-cholesterol. Subclinical hyperthyroidism is present in approximately 1%-2% of older persons. The most common cause is excessive thyroid hormone therapy, followed by mild endogenous hyperthyroidism due to Graves' disease or nodular goiter. These can be differentiated from other causes of low serum TSH concentration based on clinical and other laboratory and radionuclide scan criteria. The most serious consequences of subclinical hyperthyroidism are atrial fibrillation and osteoporosis, to which elderly patients are particularly predisposed.     

Subclinical thyroid diseases

Subclinical thyroids disease (STD) is recently defined term in clinical thyroidology, which includes mainly functional disorders. Basic diagnostic signs are: normal values of thyroid hormones (fT4, fT3) and elevated TSH level (subclinical hypothyroidism) or suppresed TSH level (subclinical hyperthyroidism). In a category of STD may be included subclinical autoimunne thyroiditis (elevated level of thyroid antigens antibodies and/or hypoechogenity in sonographic screen, increased volume of the thyroid without clinical symptoms and/or autoimminity) and microscopic lesions of papillary thyroid carcinoma. Subclinical hypothyroidism may be dangerous for tendency to development of manifest hypothyroidism and for risk of disorders of lipid profile and development of atherosclerosis and its organ complication (esp. myocardial infarction). Subclinical hyperthyroidism is a risk factor of cardiac arythmias and probably can increase a risk of cardiovascular mortality) as well for osteoporosis (esp. in peri- and post-climacteric women), and last but not least for degenerative diseases of brain (?). Indication of treatment of STD is a matter of controversies. Recomendations of experts, varied from "no therapy, monitoring only" to "treat always". Treatment of risk groups (esp. pregnant women) is probably nowadays a most rationale recommendations since results of sofisticated prospective studies will be available.     

妊娠早期母体甲状腺功能及其抗体异常对妊娠结局的影响

目的 评估妊娠早期甲状腺疾病与产科并发症关系.方法 2 517名来自沈阳市10家医院妊娠12周内的妇女,测定血清TSH、FT4、甲状腺过氧化物酶抗体(TPOAb)水平.收集妊娠结局资料,评价妊娠早期TPOAb(+)、TSH升高或降低以及抗甲状腺药物或左旋甲状腺素钠(L-T4)治疗对产科并发症的影响.结果 妊娠早期TSH升高妇女自发性流产发生率增加(8.69％对6.38％.P=0.048),并且亚临床甲状腺功能减退即可显著增加自发性流产发生率(9.50％对6.38％,P=0.009).TPOAb(+)组与TPOAb(-)组相比自发性流产发生率无差别(5.22％对7.41％,P=0.204).Logistic回归分析显示,血清TSH水平升高、妊娠期间被动吸烟、年龄≥30岁均是妊娠期间自发性流产的独立危险因素(分别为OR=1.572,95％ CI1.120-2.208;OR=1.432,95％CI1.012～2.025;OR=1.904,95％CI1.245 ～2.914).甲状腺功能亢进或甲状腺功能减退药物治疗维持妊娠期间正常甲状腺功能可降低自发性流产的发生.血清TSH水平升高或降低、TPOAb(+)与其他产科并发症无关.结论 妊娠早期血清TSH水平升高是妊娠期自发性流产的危险因素;甲状腺功能亢进或甲状腺功能减退经药物治疗维持妊娠期间TSH在正常范围可降低自发性流产发生率.     

Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?

The relationship between overt hypothyroidism and cardiovascular risk has been well documented and some data also suggest an association between cardiovascular risk and subclinical hypothyroidism. The aim of our study was to investigate, in a large cohort of euthyroid women, the association of thyroid stimulating hormone (TSH) within the normal reference range with cardiovascular risk factors. The study was carried out on 744 women with normal thyroid function (TSH 0.3–4.9 μU/mL). Women with TSH above the median (≥2.1 μU/mL) were more obese, had greater waist girth, were more hypertensive and had higher levels of total cholesterol (TC), serum triglycerides (TG), blood sugar (BG) and lower levels of HDL-cholesterol (HDL-C) than women with TSH below the median. TSH was significantly correlated with body mass index (BMI), waist circumference, BG, TG, TC, HDL-C and hypertension. Multiple backward stepwise regression analysis with age, waist circumference and TSH as independent variables confirmed the strong association of TSH with BG, TG, HDL-C and hypertension. A total of 205 patients (28%) fulfilled the definition criteria of the metabolic syndrome and the prevalence of metabolic syndrome was significantly greater in patients with TSH above than in patients with TSH below the median. Results of logistic analysis, including age and TSH as predictor variables, confirmed the association of TSH with metabolic syndrome.The results of this study suggest that TSH in the upper limits of the reference range (above 2.1 μU/ml) is associated with a less favourable cardiometabolic profile and consequently with a higher risk of developing cardiovascular diseases.