促甲状腺激素参考范围的影响因素

促甲状腺激素(TSH)是反映下丘脑-垂体-甲状腺轴功能的敏感指标,也足临床诊断亚临床甲状腺疾病的唯一指标.近年来根据美国国家临床生化协会(NACB)指南制定的TSH参考范围存在争议.TSH分泌节律、年龄、性别、甲状腺自身抗体、超声、种族、碘营养状态、妊娠等可能影响TSH的检测.建议临床医生在NACB指南基础上,综合考虑TSH参考范围的多种影响因素,并根据实际情况建立符合当地标准的TSH参考范围.     

The evidence for a narrower thyrotropin reference range is compelling

Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. It has become clear that previously accepted reference ranges are no longer valid as a result of both the development of more highly sensitive TSH assays and the appreciation that reference populations previously considered normal were contaminated with individuals with various degrees of thyroid dysfunction that served to increase mean TSH levels for the group. Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter. The remainder with higher values are outliers, most of whom are likely to have underlying Hashimoto thyroiditis or other causes of elevated TSH. Importantly, data indicating that African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.     

对血清促甲状腺激素正常值范围的新认识

促甲状腺激素（TSH）是垂体前叶产生的主要激素之一。由于血清TSH水平与血清T4之间密切的负反馈关系,TSH成为诊断甲状腺功能亢进症（甲亢）和甲状腺功能减退症（甲减）的重要的第一线指标,已经在临床应用了20多年。随着TSH测定方法的不断改进,它的特异性、灵敏性和精确性显著提高,以固相化学发光酶免疫法（ICMA）为代表的第三代TSH检测技术（也称为敏感TSH,sTSH）,     

碘充足地区血清TSH正常值范围及其影响因素的流行病学研究

目的 分析血清TSH测定的影响因素,参考美国国家临床生化协会(NACB)指南,建立中国辽宁碘充足地区血清TSH的正常参考范围.方法 2007年,来自辽宁省3个碘充足地区的5 348人参加了甲状腺疾病的社区调查,进行了TSH、甲状腺自身抗体[甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)]的测定,并作了甲状腺超声检查和问卷调查.结果 正常人群的TSH分布向右偏斜,接近于对数正态分布.年龄在12～19岁血清TSH水平明显高于其他年龄段(P＜0.01),而其他年龄段之间无统计学差异.血清TSH水平女性[(1.68±1.90)mIU/L]明显高于男性[(1.45±1.92)mIU/L,P＜0.01].因此,年龄大于20岁的健康男性TSH的分布范围是0.43～4.74 mIU/L,健康女性TSH的分布范围是0.48～5.39 mIU/L.甲状腺疾病家族史、甲状腺超声异常、甲状腺抗体阳性均影响TSH的测定水平,非甲状腺疾病对TSH参考范围没有显著影响.结论建立了碘充足地区血清TSH参考范围.

Abstract：

Objective To verify the criteria proposed by National Academy of Clinical Biochemistry(NACB)guidelines in investigating the factors that affect serum TSH determination, and to determine the reference range of serum TSH in iodine-sufficient areas of China. Methods In 2007, 5 348 inhabitants were enrolled from 3 iodine-sufficient areas of Liaoning Province, and were asked to fulfill the questionnaire. Serum TSH, thyroid peroxidase antibody(TPOAb), and thyroglobulin antibody(TgAb)were determined, and thyroid ultrasonography was carried out. Results The distribution of TSH levels was skewed in healthy people and closely fit the curve of Gaussian distribution after logarithmic transformation. The levels of TSH in subjects of 12-19 years of age were significantly higher than those of other age groups(P＜0.01), and no significant difference was found among the latter groups. TSH level in females [(1.68±1.90)mIU/L] was higher than in males[(1.45±1.92)mIU/L, P＜0.01]. The reference range of TSH was 0.43-4.74 mIU/L in males, and 0.48-5.39 mIU/L in females. Family history of thyroid disease, abnormal thyroid ultrasonography, and positive thyroid antibodies were the factors that influenced TSH level. Conclusion The reference range of serum TSH in iodine-sufficient areas of China is established.     

Fasting and postprandial total ghrelin remain unchanged after short-term energy restriction

Adaptations that promote positive energy balance appear in response to dietary restriction. The aim of this study was to determine whether fasting and postprandial total ghrelin increase in response to short-term energy restriction. Fifteen adult male subjects were subjected to a 4-d energy restricted diet (-800 kcal/d). Body weight and composition, resting energy expenditure, respiratory quotient, fasting and postprandial appetite scores, and fasting and postprandial serum leptin and total ghrelin were determined before and after dietary intervention. Despite the fact that fat mass remained unchanged after the 4 d, fasting (-36%; P 相似文献   

An epidemiological study of the serum thyrotropin reference range and factors that influence serum thyrotropin levels in iodine sufficient areas of China

The aims of this study performed in 2007 were to verify the selection criteria proposed by the National Academy of Clinical Biochemistry (NACB) guidelines, to investigate factors that influence thyrotropin (TSH) levels, and to determine serum TSH reference range in iodine sufficient areas of China. After excluding 291 subjects, a total of 5,348 inhabitants from three iodine sufficient areas of Liaoning province were asked to fulfill the questionnaire, and take TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) measurements and a thyroid ultrasound examination. The distribution of TSH was right skewed in normal people. It has been customary to log transform the values to observe the Gaussian distribution. In the subjects 12-19 years of age, the TSH level was significantly higher than in the other age groups (p<0.001), while there were no significant difference in the TSH values of the other age groups. The TSH levels in females(1.68±1.90mIU/L) were significantly higher than in males (1.45±1.92mIU/L) (p<0.001). Therefore, the normal TSH range in males over age 20 was 0.43-4.74mIU/L, and in females the range was 0.48-5.39 mIU/L. A family history of thyroid disease, abnormal thyroid ultrasound, a thyroid antibody-positive status were the factors that influenced the TSH reference range. Non-thyroid disease did not impact the TSH reference range significantly. We recommend use of a TSH reference range 0.46-5.19mIU/L in iodine sufficient areas of China for males and females over 20 years old. We suggest using a normal thyroid ultrasound as a new criterion in addition to the NACB guidelines to determine the TSH reference range.     

年龄及种族特异性的血清促甲状腺激素参考范围

无下丘脑-垂体疾病时,血清促甲状腺素(TSH)是反映甲状腺功能的最敏感指标.过去的5年中,学者们着重于对TSH的参考范围(尤其是其上限)进行研究.首先,在美国人口的代表性样本人群中,对TSH、L4和甲状腺自身抗体进行了详细的分析[美国国家健康和营养调查Ⅲ(NHANESⅢ)],结果显示:随着年龄增长,TSH>4.5 mIU/L的发生率显著增加;在70岁以上没有甲状腺疾病和危险因素的人群中,TSH>4.5 mIU/L的发生率高达15%.     

年龄及种族特异性的血清促甲状腺激素参考范围

无下丘脑-垂体疾病时,血清促甲状腺素(TSH)是反映甲状腺功能的最敏感指标.过去的5年中,学者们着重于对TSH的参考范围(尤其是其上限)进行研究.首先,在美国人口的代表性样本人群中,对TSH、L4和甲状腺自身抗体进行了详细的分析[美国国家健康和营养调查Ⅲ(NHANESⅢ)],结果显示:随着年龄增长,TSH>4.5 mIU/L的发生率显著增加;在70岁以上没有甲状腺疾病和危险因素的人群中,TSH>4.5 mIU/L的发生率高达15%.     

年龄及种族特异性的血清促甲状腺激素参考范围

无下丘脑-垂体疾病时,血清促甲状腺素(TSH)是反映甲状腺功能的最敏感指标.过去的5年中,学者们着重于对TSH的参考范围(尤其是其上限)进行研究.首先,在美国人口的代表性样本人群中,对TSH、L4和甲状腺自身抗体进行了详细的分析[美国国家健康和营养调查Ⅲ(NHANESⅢ)],结果显示:随着年龄增长,TSH>4.5 mIU/L的发生率显著增加;在70岁以上没有甲状腺疾病和危险因素的人群中,TSH>4.5 mIU/L的发生率高达15%.     

Admissions for hepatitis B reactivation in patients receiving immunosuppressive therapy remain unchanged from 1999 to 2014

Background

Reactivation of hepatitis B virus (HBV) replication in patients with chronic or past HBV infection receiving immunosuppressive therapy (IST) can be prevented through HBV screening and prophylactic antiviral therapy. We aimed to determine the occurrence of severe HBV reactivation secondary to IST in the era of HBV nucleos/tide analogs, the implicated IST, and outcomes.

Methods

We conducted a retrospective chart review of adult patients who were HBsAg+ and HBV DNA+ and had received IST within 90 days of admission to our hospital.

Results

Of 1446 patients with HBV diagnosis code admitted from 1999 to 2014, 17 had HBV reactivation, 8 of whom were admitted after 2009. Nine patients had hematologic conditions, three solid organ transplants, one hepatocellular carcinoma, and four other nonmalignant diseases. Implicated IST included chemotherapy, prednisone, antirejection therapies, budesonide, and a JAK-2 inhibitor. Three patients were screened for HBV prior to IST, but none was given antiviral prophylaxis. Six patients were initially admitted to other facilities, only two were tested for HBV, and one was started on antiviral therapy prior to transfer. At admission to our hospital, all 17 were HBsAg+ and HBV DNA+. Despite antiviral therapy, five patients decompensated, three died, and two had a liver transplant.

Conclusion

Severe HBV reactivation requiring hospital admission continues to occur because HBV screening was not performed and a prophylactic antiviral not given to those who tested positive. HBV reactivation can occur in a variety of clinical settings and in association with drugs not considered to be highly immunosuppressive.

     

Patients with stable, therapeutic INR values should remain on warfarin

The second decade of the 21st century will be remembered as a significant milestone in the treatment and prevention of thromboembolic diseases. The approval of target-specific oral anticoagulants (TSOACs) means that patients with atrial fibrillation (AF) have, for the first time ever, multiple treatment options for the prevention of embolic stroke. Evidence from the landmark registration trials convincingly shows that the TSOACs are at least as safe and effective as warfarin in this setting. Because the new agents do not require routine coagulation monitoring and have very few drug or dietary interactions, they offer both convenience and, possibly, a public health benefit if they are used by patients who otherwise would have declined to take warfarin. However, patients on a highly stable, therapeutic dose of warfarin should not expect better health outcomes if switching to a TSOAC.     

The significance of clinical euthyroidism on reference range for thyroid hormones

BACKGROUND: The reference range for thyroid hormones and thyroid stimulating hormone (TSH) is usually established either by using the manufacturer's recommendations or by analyzing blood tests from a serum bank or from the local laboratory staff, assuming that they are healthy and euthyroid. The aim of this study was to examine the significance of clinical euthyroidism and a normal basal oxygen consumption on the reference range for thyroid hormones and TSH. METHODS: A clinical examination, including information on medication, was performed on 31 apparently healthy persons. The following determinations were made for all of the subjects: basal oxygen consumption, serum TSH, serum total T(3), and serum total T(4). T(4) uptake for calculation of FT(4)I was also measured. RESULTS: The clinical examination and determination of VO(2) reduced what initially appeared to be a euthyroid and healthy population by 32%. This also resulted in a narrower reference interval than that suggested by the manufacturer (range) (TSH: 0.35-5.50 mU/l, T(4): 58-140 nmol/l, T(3): 0.9-2.8 nmol/l) or than that established in the initially selected population (TSH=0.76-3.90 mU/l, T(4)=54-168 nmol/l, T(3)=1.27-2.74 nmol/l, FT(4)I=64-123 a.u.). In the finally selected population, this was TSH=0.76-3.90 mU/l, T(4)=59-127 nmol/l, T(3)=1.45-2.74 nmol/l, and FT(4)I=64-120 a.u. CONCLUSION: The method of selecting the population for establishing the reference interval for thyroid hormones and TSH influences the reference ranges. Neglecting to deal with this problem may invalidate screening procedures, especially for subclinical diseases.     

Resistin levels are normal in hypothyroidism and remain unchanged after attainment of euthyroidism: relationship with insulin levels and anthropometric parameters

The aim of this controlled prospective study was to investigate resistin levels in hypothyroidism before and after restoration of euthyroidism and correlate the results with body weight (BW), body fat (BF), waist circumference (WC), body mass index (BMI) and serum insulin levels. Fifty-three hypothyroid patients with Hashimoto's disease (6 males, 47 females) and 30 controls matched for age, BMI and BF were investigated. Anthropometric parameters, resistin and insulin levels were measured. All patients were started on levothyroxine treatment and 4 to 5 months after initiation of treatment the investigations were repeated. Hypothyroid patients exhibited normal resistin values, which were no different from controls (mean+/-SD 7.4+/-4.0 vs 5.1+/-3.5 ng/ml, p=0.063). Normalization of circulating thyroid hormone levels produced no significant change in resistin levels (7.4+/-4.0 vs 6.8+/-4.2 ng/ml, p=ns) and post-treatment resistin levels did not differ from euthyroid controls. Furthermore, no gender difference was demonstrated in resistin levels either before (6.4+/-3.7 for males vs 7.6+/-4.1 ng/ml for females, p=ns) or after therapy (7.9+/-4.3 vs 6.7+/-4.3 ng/ml, for males and females respectively, p=ns), nor was there a difference in resistin levels in either sex induced by treatment of hypothyroidism (6.4+/-3.7 vs 7.9+/-4.3 ng/ml for males, p=ns, and 7.6+/-4.1 vs 6.7+/-4.3 ng/ml for females, p=ns). However, a small but significant difference in resistin levels was found between female patients and female controls (7.6+/-4.1 vs 5.0+/-4.0 ng/ml, p=0.047). Insulin levels and homeostasis model assessment insulin resistance (HOMA-IR) index did not differ before and after treatment in hypothyroid patients (13.0+/-10.2 vs 12.6+/-11.8 microU/ml, 22.7+/-1.4 vs 21.8+/-1.3, respectively, p=ns for both) or between patients and controls. In conclusion, our results demonstrate that resistin levels are normal in hypothyroidism and remain within normal range after attainment of euthyroidism. Resistin is not associated with serum insulin and HOMA-IR index, as well as BMI, BF, WC and BW.     

Binding of thyrotropin to lentil lectin is unchanged by thyrotropin-releasing hormone administration in three patients with thyrotropin-producing pituitary adenomas.

Glycoproteins have increased affinity for lentil lectin when fucose residues are bound to N-acetylglucosamine in the "core region" of their asparagine-linked oligosaccharides. In three patients with thyrotropin (TSH)-producing pituitary tumors, the proportion of serum TSH isoforms that bound to lentil (70.8% +/- 15%) was higher than that seen for TSH from normal persons (32.5 +/- 8%). Unlike normal subjects, the concentration of TSH circulating in the tumor patients after acute administration of TSH-releasing hormone (TRH) did not rise, and the TSH did not exhibit increased binding to lentil compared to basal TSH. The TSH binding to lentil in one tumor patient decreased after metoclopramide, but TSH binding to lentil generally remained unchanged after metoclopramide or L-dopa administration. We conclude that human thyrotropic tumor tissue, unlike normal thyrotrophs, generally fails to release more highly fucosylated isoforms of TSH after pharmacologic stimulation, perhaps because the tumor tissue is less readily modulated by endocrine stimuli, or because the TSH is already relatively highly fucosylated.     

关于丙氨酸氨基转移酶的参考范围

丙氨酸氨基转移酶(ALT)是肝脏疾病实验室检测的一项重要项目,检测方法有多种,不同方法所测得的参考范围各不相同.上海市曾于1975年组织临床肝病学专家、临床检验专家和流行病学专家共同进行了上海市居民的Reitman法(赖氏法)检测ALT参考范围的调查.     

Patients with severe nonthyroidal illness and serum thyrotropin concentrations in the hypothyroid range

This report compares three patients with severe nonthyroidal illness and serum thyrotropin concentrations in the range normally associated with hypothyroidism (greater than 20 microU/ml) and a severely ill patient with primary hypothyroidism. No evidence for primary thyroid disease was found among the severely ill patients. Serial studies showed that, in general, the elevated thyrotropin level was associated with an increase in serum thyroxine concentration. Serum free thyroxine concentration, triiodothyronine-to-thyroxine ratio, and thyrotropin response to thyrotropin-releasing hormone were in the range reported in severe nonthyroidal illness and clearly different from that in the severely ill patient with primary hypothyroidism. Serum thyrotropin concentration in severe nonthyroidal illness may be elevated in the range previously thought to be diagnostic of primary hypothyroidism.