Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)

NHANES III measured serum TSH, total serum T(4), antithyroperoxidase (TPOAb), and antithyroglobulin (TgAb) antibodies from a sample of 17,353 people aged > or =12 yr representing the geographic and ethnic distribution of the U.S. population. These data provide a reference for other studies of these analytes in the U.S. For the 16,533 people who did not report thyroid disease, goiter, or taking thyroid medications (disease-free population), we determined mean concentrations of TSH, T(4), TgAb, and TPOAb. A reference population of 13,344 people was selected from the disease-free population by excluding, in addition, those who were pregnant, taking androgens or estrogens, who had thyroid antibodies, or biochemical hypothyroidism or hyperthyroidism. The influence of demographics on TSH, T(4), and antibodies was examined. Hypothyroidism was found in 4.6% of the U.S. population (0.3% clinical and 4.3% subclinical) and hyperthyroidism in 1.3% (0.5% clinical and 0.7% subclinical). (Subclinical hypothyroidism is used in this paper to mean mild hypothyroidism, the term now preferred by the American Thyroid Association for the laboratory findings described.) For the disease-free population, mean serum TSH was 1.50 (95% confidence interval, 1.46-1.54) mIU/liter, was higher in females than males, and higher in white non-Hispanics (whites) [1.57 (1.52-1.62) mIU/liter] than black non-Hispanics (blacks) [1.18 (1.14-1.21) mIU/liter] (P < 0.001) or Mexican Americans [1.43 (1.40-1.46) mIU/liter] (P < 0.001). TgAb were positive in 10.4 +/- 0.5% and TPOAb, in 11.3 +/- 0.4%; positive antibodies were more prevalent in women than men, increased with age, and TPOAb were less prevalent in blacks (4.5 +/- 0.3%) than in whites (12.3 +/- 0.5%) (P < 0.001). TPOAb were significantly associated with hypo or hyperthyroidism, but TgAb were not. Using the reference population, geometric mean TSH was 1.40 +/- 0.02 mIU/liter and increased with age, and was significantly lower in blacks (1.18 +/- 0.02 mIU/liter) than whites (1.45 +/- 0.02 mIU/liter) (P < 0.001) and Mexican Americans (1.37 +/- 0.02 mIU/liter) (P < 0.001). Arithmetic mean total T(4) was 112.3 +/- 0.7 nmol/liter in the disease-free population and was consistently higher among Mexican Americans in all populations. In the reference population, mean total T(4) in Mexican Americans was (116.3 +/- 0.7 nmol/liter), significantly higher than whites (110.0 +/- 0.8 nmol/liter) or blacks (109.4 +/- 0.8 nmol/liter) (P < 0.0001). The difference persisted in all age groups. In summary, TSH and the prevalence of antithyroid antibodies are greater in females, increase with age, and are greater in whites and Mexican Americans than in blacks. TgAb alone in the absence of TPOAb is not significantly associated with thyroid disease. The lower prevalence of thyroid antibodies and lower TSH concentrations in blacks need more research to relate these findings to clinical status. A large proportion of the U.S. population unknowingly have laboratory evidence of thyroid disease, which supports the usefulness of screening for early detection.     

Prevalence of goiter among schoolchildren from Gorgan, Iran, a decade after national iodine supplementation: association with age, gender, and thyroperoxidase antibodies

BACKGROUND: One decade after universal salt iodization in Iran, goiter prevalence, urinary iodine concentration (UIC) and thyroperoxidase antibody (TPOAb) values were assessed among schoolchildren in Gorgan, Iran. METHODS: From 2003-2004, 500 girls and 900 boys aged 7-11 yr were evaluated for goiter by palpation. UIC was measured in 183 randomly-selected goitrous children. Serum TSH, T4, and TPOAb were measured in 53 goitrous and 30 non-goitrous children with adequate UIC. RESULTS: Goiter was detected in 370 (26.4%) children. Goiter was present in 31% of girls and 17% of boys age 9 (p<0.012); 37% of girls and 20% of boys age 10 (p<0.003); and 52% of girls and 19% of boys age 11 (p<0.0001). Median (range) UIC for all goitrous children sampled was 190 (20-600) microg/l; 220 (30590) in boys and 170 (20-600) in girls (p=0.001). Eight point seven percent of goitrous children and 22% of goitrous girls aged 10-11 had UIC<100 microg/l, while 47% of the goitrous children had UIC> or =200 microg/ l. TPOAb was present in 52.8% of goitrous children and 10% of non-goitrous children (p=0.0001). TPOAb was present in 53.9% of 10-11 and 22.7% of 7-9 yr old goitrous and non-goitrous children (p=0.003) with adequate UIC. Median (range) TSH was 2.9 (0.3-10.9) mlU/I in TPO-positive and 1.8 (0.5-4.1) in TPO-negative children (p=0.001). CONCLUSIONS: Gorgan, Iran, is an iodine-sufficient area and almost half of schoolchildren have more than adequate UIC. TPOAb is associated with endemic goiter. Despite sufficient UIC overall, some school-aged girls remain at risk of iodine deficiency.     

Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study

OBJECTIVE: Overt or subclinical thyroid dysfunction is common within the community, yet the significance of subtle anomalies in thyroid function tests remains contentious. The aims of this study were to: (a) establish reference intervals for serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in the Busselton community of south-western Western Australia; and (b) determine the prevalence of thyroid hormone anomalies in this community. SUBJECTS AND DESIGN: In 1981, 2115 adults residing in Busselton participated in a cross-sectional health survey that involved blood collection and a questionnaire on lifestyle and general health history. MEASUREMENTS: Serum samples were analysed for FT4, TSH, TPOAb and TgAb by immunochemiluminescent assays. RESULTS: Based on standard statistical approaches and using guidelines recommended by the National Academy of Clinical Biochemistry (NACB), reference intervals were derived for each analyte: 9-23 pmol/l for FT4, 0.4-4.0 mIU/l (TSH), < 35 KIU/l (TPOAb) and < 55 KIU/l (TgAb). The prevalence of elevated thyroid antibodies was 12.4% among subjects without a history of thyroid disease and is more common in women than in men. Elevated thyroid antibody levels were observed at both extremes of TSH abnormality, but were more commonly increased when TSH levels were above 4.0 mIU/l (63% subjects) than for those with TSH levels 0.4-4.0 mIU/l (7.8% subjects). CONCLUSIONS: This study establishes the prevalence of antibodies to thyroperoxidase and thyroglobulin in a community-based sample and reference intervals for free T4 and TSH. When the NACB decision limits are applied to older men or women, there is a markedly increased number with 'elevated' autoantibody levels compared to sex- and age-specific reference intervals.     

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.     

Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women

Excessive iodine exposure was reported to be associated with thyroid dysfunctions. The aim of this study is to evaluate the link between excess urinary iodine as the prime indicator of excessive iodine intake and autoimmune subclinical hypothyroidism (SCH) among Egyptian women. Seventy three women with autoimmune SCH and 60 age- matched healthy women as controls were enrolled in this study. TSH, FT4, urinary iodine concentrations (UIC) and thyroid peroxidase antibody (TPOAb) were estimated. The levels of urinary iodine were significantly higher in patients with SCH as compared with control subjects, (326.97 112.98 vs. 274.45 98.75 microg/l, p<0.01). In patients with SCH, there was a significant correlation between UIC and TSH levels. Also, a significant correlation between UIC and TPOAb was found. We conclude that excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction among Egyptian women.     

National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction

CONTEXT: The setting of the TSH upper reference limit impacts the diagnosis of mild hypothyroidism and is currently controversial. OBJECTIVE: Our objective was to evaluate factors influencing the TSH reference range. DESIGN: Nonpregnant subjects aged 12 yr and older from National Health and Nutrition Examination Survey III were used to study the relationships between TSH, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies in different ethnic groups. RESULTS: TPOAb prevalence was lowest (<3%) when TSH was between 0.1 and 1.5 mIU/liter in women and between 0.1 and 2.0 mIU/liter in men and progressively increased to above 50% when TSH exceeded 20 mIU/liter. TSH reference range parameters (2.5th, 50th, and 97.5th percentiles) were analyzed according to thyroid antibody status, race/ethnicity, and age for the 14,202 subjects made up of non-Hispanic Blacks (B), non-Hispanic whites (W), and Mexican-Americans (M) who did not report thyroid disease or taking thyroid-altering medications and whose total T(4) was within the reference range. For each age group of each ethnicity, the inclusion of antibody-positive subjects increased TSH medians and upper limits (97.5th percentiles). The TSH upper limit was lower for the entire B cohort vs. W or M. However, this difference was lost when age cohorts with a similar prevalence of TPOAb (B age 40-49 yr vs. W and M age 20-29 yr) were compared. CONCLUSIONS: Ethnic differences in TSH were not present when populations with the same relative frequency of thyroid antibodies were compared. TSH upper reference limits may be skewed by TPOAb-negative individuals with occult autoimmune thyroid dysfunction.     

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin,thyroid reserve,and thyroid antibodies

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.     

正常甲状腺功能人群血清促甲状腺激素变化的五年随访研究

目的 探讨正常甲状腺功能者5年随访时促甲状腺激素(TSH)的异常率和影响这一人群TSH发生异常的因素.方法 3个不同碘营养背景的农村社区的3403例甲状腺功能正常者中,80.1%(2727例)接受了筛查后的5年随访,测定其血清TSH和甲状腺自身抗体水平.结果 随访对象中,68例(2.5%)TSH异常降低(<0.3 mU/L),64例(2.4%)TSH异常增高(>4.8 mU/L).logistic回归分析显示,初访时甲状腺过氧化物酶抗体(TPOAb)阴性而随访时阳性(OR=5.5)、初访和随访TPOAb均阳件(OR=4.0)、随访时甲状腺球蛋白抗体(TgAb)阳性(OR=3.7)和初访时TSH<1.0 mU/L(OR=2.6)是TSH异常降低的危险因素;而缺碘基础上补碘至碘足量(OR=4.8)、长期碘过量(OR=3.9)、随访时TgAb阳性(OR=3.7)、初访和随访TPOAb均阳性(OR=3.6)、初访时TPOAb阴性而随访时阳性(OR=2.7)和TSH>1.9 mU/L(OR=2.6)是TSH异常增高的危险因素.结论 与轻度碘缺乏相比,碘足量和碘过量足TSH由正常转为异常升高的危险因素,缺碘基础上补碘至碘足量导致TSH转为异常升高的危险性更高于长期碘过量.初访TSH处于1.0～1.9 mU/L时,5年随访时发生TSH异常的几率最小.     

桥本甲状腺炎患者血管内皮功能受损与低度炎症反应的关系

目的 探讨低水平的炎症反应在血脂正常的桥本甲状腺炎(HT)患者血管内皮功能受损中的作用.方法 将58例HT患者,分为甲状腺功能正常组(甲功正常组)28例,亚临床甲状腺功能减退组(甲减组)30例,并有28例正常人(对照组)纳入本实验.空腹静脉取血检测甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、促甲状腺素(TSH)、游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)、一氧化氮(NO)和超敏C-.反应蛋白(hs-CRP).结果 HT患者的甲功正常组、甲减组,分别与对照组比较,NO显著下降(P均＜0.01),而TgAb、TPOAb、hs-CRP则显著升高(P均＜0.01).HT患者中,甲功正常组与甲减组两两比较,NO、TgAb、TPOAb、hs-CRP均没有统计学差异(P均＞0.05).结论 血脂正常的HT患者存在血管内皮功能受损,可能是由于自身免疫异常的长期低水平的炎症反应,参与了HT患者的血管内皮功能损伤.     

Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes

OBJECTIVE: In a follow-up study, we determined the prevalence, incidence, and natural course of positive antithyroperoxidase antibodies (TPOAbs) and antithyroglobulin antibodies (TgAbs) in the general population and examined the influences of iodine intake. DESIGN: The study was conducted in Panshan, Zhangwu, and Huanghua, regions with mildly deficient, more than adequate, and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 3018 participated in the 5-yr follow-up study. Serum TSH, TPOAb, and TgAb levels were measured. RESULTS: Among subjects in Panshan, Zhangwu, and Huanghua, the prevalence of positive TPOAbs was 11.23, 11.83 and 12.02%, respectively, whereas 11.23, 11.17, and 11.26% of subjects were TgAb positive, respectively. In the older population (> or =45 yr), TgAb-positive individuals were more frequent in Huanghua than Panshan and Zhangwu (P < 0.05). The 5-yr cumulative incidence of positive TPOAb was 2.08, 3.84, and 2.84% in Panshan, Zhangwu, and Huanghua, respectively, whereas 2.91, 3.64, and 5.07% of subjects were TgAb positive, respectively (P < 0.05), corresponding to the increase in iodine intake. Subjects who were TPOAb and/or TgAb positive at baseline developed thyroid dysfunctions more frequently than those without antibodies (14.44 vs. 3.31%, P < 0.01); their incidence of elevated TSH levels was 1.32, 8.46, and 15.38% in Panshan, Zhangwu, and Huanghua, respectively (P < 0.05). CONCLUSIONS: Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody-positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb.     

Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment

Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6-12 months off therapy. Our study is the first that has aimed to evaluate the natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the IFN-alpha withdrawal as well as to investigate the potential role of the autoantibody pattern at the end of treatment to predict the long-term outcome. Our study group included 114 patients (79 males, 35 females), mean age 48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month treatment with recombinant IFN-alpha for C virus-related chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4), FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-) and all but one of them remained so for the following evaluations. The remaining 36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the whole length of the study (persistent thyroiditis); 10 patients became Abs- 6 months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing thyroiditis); 10 patients reverted to autoantibody negativity at different observation times (transient thyroiditis). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN treatment was significantly related to the highest risk of having chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree percentile). None of the patients showed overt thyroid dysfunction throughout the study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12 cases, the functional abnormality was accompanied by the presence of thyroid autoantibodies. Eight of these 12 patients belonged to the group with persistent thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroid dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the positivity for both TgAb and TPOAb at the end of IFN therapy was significantly correlated with the highest risk of having subclinical hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no evidence of preexisting thyroid disease: 1) the negativity for thyroid autoantibodies after IFN treatment is a protective factor for the developing thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha-related thyroid autoimmunity is not a complete reversible phenomenon because some patients can develop chronic thyroiditis; 3) high autoantibody levels at the end of IFN therapy are related to the risk of having chronic thyroid autoimmunity; and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive factor for the presence of thyroid dysfunction, even if subclinical, many years after IFN withdrawal.     

The relationship between serum thyrotropin and components of metabolic syndrome

To explore the relationship between serum thyrotropin and components of metabolic syndrome in a Chinese cohort. A total of 1534 adult inhabitants in DaDong district of Shenyang were asked to fulfill the questionnaire, complete physical examination and OGTT. Blood samples were collected to test thyrotropin (TSH), fasting plasma glucose (FPG), OGTT 2h PG, fasting insulin (FINS), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C). Serum TSH in metabolic syndrome group was higher than that in the non-metabolic syndrome group (2.54 mIU/L vs. 2.22 mIU/L, p<0.05). TG level increased significantly in subclinical hypothyroid group compared with euthyroid subjects (1.73±0.12 mmol/L vs. 1.47±0.03 mmol/L, p<0.05), and HDL-C decreased significantly in patients with subclinical hypothyroidism compared with euthyroid subjects (1.26±0.27 mmol/L vs. 1.33±0.27 mmol/L, p<0.05). The prevalence of hypertension was higher in the subclinical hypothyroid group than that in euthyroid group (42.86% vs. 33.2%, p<0.05). The serum TSH within the reference range was positively related with the prevalence of overweight/obesity. Slight increase in serum TSH maybe a risk factor for metabolic syndrome.     

开展亚临床甲状腺功能减退症的临床研究

亚临床甲状腺功能减退症 (甲减 )是一种常见的内分泌专业亚临床疾病 ,主要诊断依据是血清TSH水平增高 ,而血清FT4正常。亚临床甲减的主要不良后果是发展为临床甲减和促进缺血性心脏病的发生。影响亚临床甲减发展为临床甲减的主要因素有两个 :血清TSH水平和甲状腺自身抗体 ,两个因素有叠加作用。甲状腺激素替代治疗对于阻止亚临床甲减发展为临床甲减的效果尚不确切 ;亚临床甲减与高胆固醇血症、高血压、吸烟和糖尿病一样 ,构成动脉粥样硬化和心肌梗塞的独立危险因素 ,其对此两病的危险度分别为 1.9和 3 .1。甲状腺素纠正亚临床甲减对降低血清胆固醇有一定效果 ;妊娠妇女的亚临床甲减对后代的智力影响已经引起高度关注。我国一组根据对流行病学调查的结果 ,提出了血清TSH、甲状腺自身抗体 (TPOAb、TgAb)的正常值范围 ,以及与疾病相关的甲状腺自身抗体的切割点值 ,可供参考。     

河北某水源性高碘地区成人甲状腺疾病的流行病学调查

目的：调查水源性高碘地区－河北省黄骅市歧口村、高头村≥14岁人群甲状腺疾病的流行状况,方法：入户问卷调查4230人的基础上,采样调查1074人,所有采样调查对象均详细填与甲状腺疾病调查表,接受体检查和B超检查,测定血清促甲状腺激素（TSH）、甲状腺自身抗体（TAA）和甲状腺球蛋白（TG）,留取空腹尿样测量尿碘、TSH异常者测定甲状腺激素和TSH受体抗体（TRAb）。结果：采样人群的尿碘中位数为614．61μg/L。临床甲状腺功能亢进症（甲亢）和亚临床甲亢的患病率分别为1．21％和1．12％;临床甲亢中92．3％为Graves病所致,亚临床甲亢中75％TRAb阳性;回顾性分析普遍食盐碘化前后临床甲亢平均年发病率差异无显著性,临床甲状腺功能减低症（甲减）和亚临床甲减的患病率分别为1．96％和6．05％,患者TAA阳性率分别为85．71％和29．23％。采样人群甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TGAb）阳性率分别为11．6％和9．3％。弥漫性甲状腺肿,结节性甲状腺肿、单发结节和多发结节的患病率分别为3．26％、2．61％、1．77％和6．4％。甲状腺癌病率为91．58／10万,结论：在尿磺中位数为614．61μg/L的碘营养状态下,甲状腺功能减退症和甲状腺癌患病率显著增高,提示这一碘摄入量并不安全。     

左旋甲状腺素治疗妊娠期亚临床甲减妇女对后代神经智力发育影响的前瞻性研究

目的 通过前瞻性观察妊娠期亚临床甲状腺功能减退(甲减)妇女左旋甲状腺素(L-T4)治疗后甲状腺功能指标的动态变化和后代神经智力的发育情况,探讨L-T4对妊娠期亚临床甲减妇女后代神经智力发育的影响.方法17例亚临床甲减孕妇未接受治疗(SCH组),23例亚临床甲减孕妇接受L-T4治疗(SCH+LT4组),24例正常孕妇(C组)作为对照组.3组孕妇分别在妊娠12周(G12)、16周(G16)、20周(G20)、24周(G24)、28周(G28)、32周(G32)和(或)36周(G36)接受随访检查,检测血清TSH、TT4、FT4、TT3、FT3、甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb).应用Bayley量表对所有孕妇的后代在14～30月龄检测智力和运动评分.结果SCH组、SCH+LT4组和C组孕妇后代的智力发育指数(MDI)分别为115.12分、118.56分和117.63分;运动发育指数(PDI)分别为115.47分、120.65分和117.50分.与其他两组比较,SCH+LT4组MDI和PDI评分均较高,SCH组MDI和PDI评分均较低,但3组间比较没有统计学差异.SCH组孕妇的血清TSH在妊娠过程中始终保持在2.0 mIU/L以上,各时点都明显高于C组(均P＜0.05);血清TT4和FT4水平除G28和G32外其他时点均略低于同时点C组水平.SCH+LT4组孕妇基础血清TSH水平明显高于其他两组(均P＜0.01),血清TT4和FT4水平则低于其他两组;在接受L-T4治疗后血清TSH水平明显下降,自G12至孕末期始终与C组水平相当,且低于同时点SCH组孕妇的水平;血清TT4和FT4水平则明显升高至与对照组相当的水平.结论L-T4的及时治疗能够维持妊娠早期亚临床甲减患者妊娠全程血清TSH在正常水平,这很可能会避免后代智力和运动能力发育水平的下降.     

The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.

OBJECTIVE: The aim of the present study was to analyze the current status of morphologic and functional thyroid abnormalities in a previously iodine-deficient area. METHODS: The population based Study of Health in Pomerania (SHIP) comprised 4310 participants, aged 20-79 years. Thyroid function (thyrotropin [TSH] free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. Data from 3941 participants with no known thyroid disorders were analyzed. RESULTS: The median iodine urine excretion was 12.4 microg/dL. The rate of decreased serum TSH levels (<0.3 mIU/L) was 11.3%; 2.2% of participants had suppressed serum TSH levels (<0.1 mIU/L). The prevalence of subclinical hyperthyroidism was 1.8%, the prevalence of overt hyperthyroidism 0.4%. Elevated TSH levels were found in 1.2% of individuals. Subclinical hypothyroidism was observed in 0.5%, overt hypothyroidism in 0.7% of the sample. Elevated TPOAb were detected in 7% of subjects, 4.1% of participants had TPOAb greater than 200 IU/mL. The prevalence of goiter was 35.9%. An inhomogeneous echo pattern was detected in 35.2% and nodules in 20.2% of participants. Diffuse autoimmune thyroiditis was diagnosed in 47 subjects (1.2%). CONCLUSION: There are a number of thyroid disorders in this previously iodine-deficient region. Further studies are required to investigate the change of thyroid disorders during iodine supplementation programs.     

High iodine intake is a risk factor of post-partum thyroiditis: result of a survey from Shenyang, China

The aim of the present study is to obtain the epidemiological data on post-partum thyroiditis (PPT) firstly in Chinese women, and to tryto evaluate whether excessive intake of iodine in post-partum women imposes any danger of occurring PPT. Sixty hundred and ten pregnant women were involved in the cohort just before delivery. Four hundred and eighty-eight (80%) of them accepted taking part in follow-ups more than 6 months post-partum. A blood sample was taken from participants before delivery and every 3 months post-partum for testing of serum TSH, thyroid autoantibodies. Free T3 (FT3), free T4 (FT4) and TSH receptor antibody (TRAb) were detected if TSH was abnormal. The iodine nutrition was evaluated according to the mean level of the fasting urinary iodine excretions at different times during the studying period, and participants were subgrouped into 3 categories with low, adequate and high iodine intake. For those participants who had thyroid dysfunction within 6 months post-partum, the follow-up persisted for 1 yr. Of 488 pregnant women, PPT developed in 11.9% (58/488). Given overt and subclinical PPT, the prevalence was 7.17% (no.=35) and 4.71% (no.=23), respectively. There was a strong association between the presence of thyroid peroxidase antibody (TPOAb) at delivery and the risk of developing PPT [RR=6.76, 95% (CI) 4.42-10.34]. Overt cases had much higher titers of TPOAb than subclinical patients (all p<0.05). The median urinary iodine (MUI) of patients with PPT was significantly higher than that of healthy women (231.93 vs 199.88 microg/l p=0.00153). Both the prevalence of PPT and positive TPOAb rise with the increment of iodine intakes. Pregnant women with high iodine intake had more risk of developing PPT when compared with those with low iodine intake (RR=2.92, 95%CI 1.31-6.50). We concluded that positive TPOAb was of value for predicting the occurrence and severity of PPT, and a high iodine intake was a risk factor triggering PPT.     

Subclinical Thyroid Dysfunction and the Risk of Heart Failure Events: An Individual Participant Data Analysis From 6 Prospective Cohorts

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.     

Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure

We aimed to analyze the natural course of subclinical hypothyroidism, quantify the incidence rate of overt hypothyroidism, and evaluate the risk factors for the development of definitive thyroid failure in elderly patients. One hundred seven patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and no previous history of thyroid disease were prospectively studied. Subjects were followed up for 6-72 months (mean, 31.7 months) with repeated determinations of TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism, and 40 (37.4%) showed normalization of their TSH values. The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter, respectively. Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline. A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration (P < 0.0001). In conclusion, TSH concentration is the most powerful predictor for the outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr. Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism. We recommend follow-up with clinical and biochemical monitoring in these patients.     

TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study)

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.