Thyroid disorders in infertile women.

Thyroid hormones have profound effects on reproduction and pregnancy. There is a known association of hyper- and hypothyroidism with menstrual disturbances and decreased fecundity. Women with reproductive failure also have an increased prevalence of organ specific autoimmunity compared to fertile women. The present study aims to answer the following questions: 1) is there an increased prevalence of thyroid antibodies in infertile women? 2) are thyroid antibodies associated with a particular cause of infertility? and 3) do these antibodies influence outcome of the in vitro fertilization procedure? The answers to the two first questions were evaluated with a case-control study looking at the occurrence of thyroid autoimmunity and thyroid function tests among women of infertile couples (n=438), presenting for the first time at the department of reproductive medicine. For comparison, a control population of parous women (n=100), matched for age, was included. In 45% of the infertile couples a female cause of infertility was identified: endometriosis (11%), tubal disease (30%) and ovarian dysfunction (59%). Male infertility was diagnosed in 38% and idiopathic infertility in 17% of the couples. Mean serum TSH levels were significantly higher in patients with infertility compared with control patients: 1.6 +/- 2.6 versus 1.2 +/- 0.7 mIU/L. The proportion of positive TPO-Abs was higher in all women of infertile couples, compared with controls (14% versus 8%), but the difference was not significant. Considering only the female causes of infertility a significant higher proportion of women had positive TPO-Abs compared with controls (18% versus 8%), and in particular a high prevalence of thyroid autoimmunity was found in women suffering from endometriosis (29%). Both hypo- and hyperthyroidism were more frequent when TPO-Abs were positive, compared to women without thyroid autoimmunity. The results of the present study indicate that endometriosis, increases the relative risk for associated thyroid autoimmunity to 2.3, and therefore screening for thyroid auto-antibodies could be systematically proposed in these women.     

Low concordance between positive antibodies to thyroperoxidase and thyroid ultrasound autoimmune pattern in pregnant women

The diagnostic and prognostic role of thyroid ultrasound (TUS) in pregnant women positive for antibodies to thyroperoxidase (TPOAb) is unclear. The aim of our study was to compare the relation of ultrasound thyroid texture to the thyroid laboratory tests in pregnant women and controls. Using a semi-quantitative assessment we compared TUS in two groups of women with positive TPOAb and/or with thyroid dysfunction (TSH out of 0.06-3.67 mIU/L): 186 women in 1(st) trimester of pregnancy recruited from universal screening and 67 asymptomatic age-comparable non-pregnant non-postpartum women recruited from screening of general population (controls). Women with previous history of thyroid diseases were excluded. Only 64/131 (48.9 %) of TPOAb-positive pregnant women were TUS-positive (TUS with autoimmune pattern) in comparison with 35/49 (71.4 %) TPOAb-positive controls (p <0.011). Pregnant women had more often TSH >10.0 mIU/L if they were TPOAb-positive/TUS-positive as compared to those TPOAb-positive/TUS-negative (8/64 (12.5 %) vs. 0/67 (0 %), p = 0.009). The prevalence of preterm deliveries among TPOAb-positive women was significantly lower if TPOAb-positivity was not accompanied by TUS-positivity (2/67 (3.0 %) vs. 10/64 (15.6 %) in TPOAb-positive/TUS-positive women, p = 0.028). In conclusion, nearly half of the TPOAb-positive pregnant women did not have an autoimmune pattern in TUS. Normal TUS image in TPOAb-positive pregnant women might be a protective factor for preterm delivery.     

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.     

Postpartum thyroid dysfunction in pregnant thyroid peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine supplementation safe?

In moderately iodine-deficient, pregnant, thyroid peroxidase antibody (TPO-Ab)-positive women the role of iodine supplementation in the development of postpartum thyroid dysfunction (PPTD) was studied in a placebo-controlled, randomized, double blind trial. Screening for TPO-Ab was performed in early pregnancy in a population of healthy pregnant Danish women with no previous diagnosed thyroid disease (prevalence, 117 of 1,284; 9.1%). The participants were randomized, stratified according to TPO-Ab level, to three groups. All participants received a daily vitamin and mineral tablet with 150 microg iodine or no iodine. The +/+ group received iodine during pregnancy and the postpartum period, the +/- group received iodine during pregnancy only, and the -/- group received no iodine supplementation. A total of 66 TPO-Ab positive women were followed, and in the postpartum period sera were collected at 8-week interval for biochemical evaluation of thyroid function and antibody level. Compliance was evaluated by 24-h urinary iodine measurements. PPTD developed in 55% of the participants. In 67% of the cases abnormal TSH was accompanied by abnormalities in thyroid hormones, whereas 33% had abnormal serum TSH only. There was no statistically significant difference in the frequency of PPTD in the three groups: +/+ group, 59% (95% confidence interval, 36-79%); +/- group, 60% (36-81%); and -/- group, 46% (26-67%). There were also no differences in the severity of the PPTD, as evaluated by duration and grade of deviation of TSH and thyroid hormones from normality. The occurrence, severity, and type of PPTD predominantly depended on the TPO-Ab level: TPO-Ab below 200 U/L at screening, 35% developed PPTD; TPO-Ab of 200-900 U/L, 54%; and TPO-Ab above 900 U/L, 75% developed PPTD. Women with low levels of antibodies predominantly remained euthyroid or had hyperthyroidism only, whereas women with high antibody levels had hyperthyroidism followed by hypothyroidism or hypothyroidism only. We conclude that iodine supplementation (150 microg) during pregnancy and the postpartum period to TPO-Ab-positive women living in an area with mild to moderate iodine deficiency did not induce or worsen PPTD. The study confirmed that screening for TPO-Ab in early pregnancy can predict women at high risk for development of PPTD.     

子痫前期患者甲状腺功能变化观察

目的观察子痫前期(PE)孕妇甲状腺功能的变化。方法 174例子痫前期患者,其中轻度PE 83例,重度PE 91例,另选择301例正常妊娠晚期妇女为正常对照组。采用电化学发光技术(ECL)检测血清TSH、FT4、TPO-Ab水平。结果 PE组TSH为2.69(0.58～12.88)mIU/L、FT4为12.13(8.65～17.06)pmol/L、TPOAb为12.55(5.0～98.36)IU/mL,正常对照组分别为2.14(0.56～6.89)mIU/L、12.52(9.30～17.14)pmol/L、8.03(5～21.96)IU/mL,两组患者TSH、FT4、TPOAb相比P均<0.05。PE组轻度PE患者TSH为2.41(0.66～7.77)mIU/L、FT4为12.80(9.27～17.95)pmol/L、TPOAb为13.30(5.0～102.79)IU/mL,重度PE患者分别为3.17(0.14～15.95)mIU/L、11.47(8.53～16.37)pmol/L、11.20(5.0～150.02)IU/mL,轻重度PE患者TSH、FT4、TPOAb相比P均<0.05。子痫前期孕妇血清TSH、TPOAb明显升高、FT4水平明显降低(P均<0.05);与轻度PE相比,重度PE孕妇血清TSH明显升高、FT4水平明显降低(P均<0.05);PE孕妇TPOAb阳性率达12.1%(21/174),与同期筛查组相比P>0.05;子痫前期患者合并各种甲状腺疾病,低T4血症发生率显著高于同期筛查组(P均<0.05)。结论子痫前期患者血清TSH、TPOAb升高、FT4降低。     

The effect of infertility medication on thyroid function in hypothyroid women who conceive.

OBJECTIVE: To determine whether infertility medications alter thyroid status in patients with treated hypothyroidism, and whether resulting pregnancies require additional thyroid supplementation compared with those conceived spontaneously. DESIGN: Prospective observational study of 18 infertility patients with treated hypothyroidism who conceived between July 2005 and July 2006 with or without infertility medications. Thyroid studies were performed prior to conception, at the time of pregnancy diagnosis, and approximately 6 weeks after an increase in thyroid replacement dose. MAIN OUTCOME: Orally medicated conceptions were similar to spontaneous conceptions on all thyroid related variables, and therefore the two groups were combined for analysis. Although there was a nonsignificant difference in thyrotropin (TSH) levels postconception (3.8 mIU/L vs. 2.2 mIU/L, p = 0.30), there was no difference in TSH levels after increase in thyroid replacement dose (1.7 mIU/L vs. 1.1 mIU/L, p = 0.30) between patients who conceived after gonadotropin stimulation compared with those who conceived spontaneously or with oral medications. The mean percent dose increases for the nongonadotropin and gonadotropin pregnancy groups were 30.6% and 32.4%, respectively. CONCLUSIONS: Hypothyroid patients who conceive after gonadotropin stimulation or with oral medications for ovulation induction do not need additional thyroid supplementation compared with those who conceive spontaneously.     

The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests

OBJECTIVE Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence of thyroid function abnormalities in a psychiatric population on admission (as compared to the prevalence in a normal population), and (2) whether such thyroid function abnormalities are associated with the occurrence or development of cognitive and affective disorders. DESIGN Serum was collected 2–3 weeks after hospitalization in 3 major clinics from 3756 psychiatric patients in 1987–1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same area (n = 1877). The prevalence study was followed by a case-control study involving patients from one clinic that had routinely assigned a DSM-IIIR classification to its patients. Cases were those admissions with thyroid abnormalities and three subgroups of cases were randomly formed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to random controls from the same psychiatric population, viz patients without thyroid abnormalities (n = 83). Comparison was with respect to their psychiatric follow-up diagnosis (the investigator was blinded to the thyroid test results). RESULTS Prevalence study. The percentage of patients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4–4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) >4.0 mU/l and 4.1% (134/3316) <0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects with abnormal TSH, indicating the predominantly subclinical character of the thyroid alteration. In comparison, the healthy area controls over 55 years of age showed the same prevalence of positive TPO-antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l. Case-control study. In the case control analysis differences could not be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective disorders which were more prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this association, analyses were also carried out excluding patients with such prior drug use. In these analyses affective disorders were still more prevalent in patients with a low serum TSH (particularly in males, 40% in cases vs 9% in controls, P < 0.05). The most significant association was however between TPO-antibody positivity (and in particular with high titre and/or with TSH > 4.0 mU/l) and a subgroup of the affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases vs 0% in controls, P < 0.001). CONCLUSION Thoug h causal relations cannot be determined from this cross-sectional study, this admission survey found early forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs, highly significantly associated with rapid cycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.     

甲状腺自身抗体阳性妇女孕期干预对婴儿甲状腺功能的影响

目的 探讨甲状腺自身抗体阳性妇女孕期甲状腺功能干预对婴儿甲状腺功能的影响.方法选择产前检查发现的甲状腺过氧化物酶抗体(TPOAb)和(或)甲状腺球蛋白抗体(TgAb)阳性妊娠妇女55例.随机分为干预组(子代为A)36例和非干预组(子代为B)19例,设同期自身抗体阴性对照组(子代为N)30例.选择左旋甲状腺素片作为干预制剂.采用化学发光酶免疫分析法测定3组入选后和分娩前空腹血清TPOAb、TgAb、TSH、TT3、TT4、FT3、FT4水平,同时测定母体尿碘含量.新生儿出生后测定脐血、出生后3～4周及8～10周静脉血TSH、TT3、TT4、FT3、FT4水平.结果干预组、非干预组母体基线血清TSH水平显著高于对照组(P＜0.05).分娩前非干预组与另两组比较,血清TSH增高和TT3、TT4、FT4降低具有统计学差异(P＜0.05或P＜0.01).胎儿出生后脐血TSH水平在B组(7.06±1.31)mIU/L和A组(6.23±1.26)mIU/L均显著高于N组(5.48±1.17)mIU/L(P＜0.01或P＜0.05).出生3～4周新生儿B组血清TSH(3.21±0.70)mIU/L高于N组[(2.72±0.51)mIU/L]和A组[(2.78±0.42)mIU/L,均P＜0.05].出生8～10周婴儿B组血清TSH[(2.99±0.57)mIU/L]高于N组[(2.48±0.68)mIU/L,P＜0.05].多元逐步回归分析,母体TSH、TPOAb及尿碘含量与婴儿TSH独立相关.结论不同甲状腺功能状态的妊娠妇女,其子代出生后的甲状腺功能存在差异.胎儿出生后甲状腺功能与母亲甲状腺自身抗体及孕期甲状腺功能状态有关.     

Autoimmune thyroid disease in pregnancy and the postpartum period: relationship to spontaneous abortion.

The aim of this study was to determine the prevalence of autoimmune thyroid disease and the risk of miscarriage in autoimmune thyroid antibody (ATA)-positive women. Eight hundred seventy-six subjects completed the study, and 12.3% were thyroid antibody-positive (4.5% tested positive for both thyroid peroxidase antibody [TPO-Ab] and thyroglobulin autoantibody [Tg-Ab], 4.79% were TPO-Ab-positive only, and 3.1% were Tg-Ab-positive only). Fifty percent of the ATA-positive women and 14.1% of the ATA-negative group had a history of spontaneous abortion. Forty-eight of the ATA-positive women developed postpartum autoimmune thyroid dysfunction (PATD). Of these, 50% had hypothyroidism alone, 31.3% had transient hyperthyroidism followed by hypothyroidism, and 18.8% had transient thyrotoxicosis alone. Of the 48 PATD subjects, 12.5% developed persistent hypothyroidism. None of the ATA-negative women developed any form of thyroid dysfunction. The thyroid-stimulating hormone (TSH) levels in the ATA-positive group were significantly higher than those in the ATA-negative group, and only the ATA-positive women with a history of abortion had significantly higher TSH and lower free thyroxine (FT4) concentrations than the other subgroups. The results revealed a 5.5% prevalence rate for PATD in the study population. In addition to TPO-Ab, Tg-Ab is a useful marker for autoimmune thyroiditis.     

High Incidence of Positive Autoantibodies against Thyroid Peroxidase and Thyroglobulin in Patients with Sarcoidosis

OBJECTIVE  Although abnormalities of the humoral immune system, such as increased immunoglobulin production, are known in sarcoidosis, the relationship between sarcoidosis and autoimmune disorders is uncertain. We studied the incidence of thyroid autoantibodies and the prevalence of Hashimoto's thyroiditis in patients with sarcoidosis.
PATIENTS AND MEASUREMENTS  Sixty-two patients with pulmonary sarcoidosis, diagnosed by a combination of clinical, radiographic and histological findings, were studied. As controls, three groups of subjects aged 40 and over without a known history of thyroid disease (60 patients with pulmonary diseases other than sarcoidosis, 88 hospital employees and 82 company workers), were also analysed. Antibodies against thyroid peroxidase (TPO-Ab) and purified thyroglobulin (Tg-Ab) were measured by radioimmunoassay and antibodies against microsomal antigen (MCHA) and thyroglobulin (TGHA), by haemagglutination.
RESULTS  Seventeen of 62 patients (27.4%) had either positive TPO-Ab or Tg-Ab or both. All the patients with positive thyroid autoantibodies were of middle or advanced age, and the incidence of positive TPO-Ab/Tg-Ab in patients with sarcoidosis aged 40 and over was 54.5% in males, 32.4% in females and 37.8% overall. The prevalence was significantly higher in males compared to age-matched control males (0–7.7% in the controls), and in female patients was twice that found in controls (11.8–16.3%). Seven patients had Hashimoto's thyroiditis, indicating that the prevalence was 11.3%, and much higher than that previously reported.
CONCLUSIONS  The data show a remarkably high incidence of thyroid autoantibodies in patients of middle or advanced age with sarcoidosis, especially in males, and a higher prevalence of Hashimoto's thyroiditis than in previous reports.     

Ethnic differences in TSH but not in free T4 concentrations or TPO antibodies during pregnancy

OBJECTIVE: To describe the TSH, free T4 and thyroid peroxidase antibody (TPO-Ab) concentrations during pregnancy among four ethnic groups and to determine reference values for these parameters during normal pregnancy. METHODS: Cross-sectional study of a cohort of 3270 pregnant women living in the city of Amsterdam. Blood samples were drawn at first booking in the first or second trimester. TSH, free T4 and TPO-Ab concentrations were determined. Four ethnic groups were studied: Dutch, Surinam, Turkish and Moroccan. RESULTS: Plasma TSH increased and free T4 decreased from the first to the second trimester of pregnancy for all the ethnic groups. Ethnic differences were observed in TSH concentrations, with Dutch females having the highest TSH levels compared to the other three ethnic groups. The median TSH difference was 0.16 mU/l between the Dutch and Moroccan women, 0.15 mU/l between the Dutch and Surinam women and 0.10 mU/l between the Dutch and Turkish women. These could not be explained by differences in age, parity and current smoking status. No differences were seen in free T4 concentrations between the four ethnic groups. The prevalence of TPO-Ab was comparable across the ethnic groups (about 6% in each); the concentration of TPO-Ab was also comparable among the ethnic groups. The Dutch women had a higher lower-limit (2.5 percentile) of the TSH reference range than the Surinam, Turkish and Moroccan women, ranging from 0.14 mU/l for the Surinam and Moroccan to 0.27 mU/l for the Dutch women. CONCLUSION: The increase in TSH and decrease in free T4 values during pregnancy correspond to previous reported studies. Pregnant Dutch women had consistently higher TSH values than the ethnic group, but corresponding free T4 levels and TPO-Ab did not differ between these ethnic groups.     

Assisted reproduction and thyroid autoimmunity: an unfortunate combination?

The association between positive thyroid antibodies and an increased miscarriage rate in pregnancies after assisted reproduction technology (ART) remains controversial. We wanted to clarify this issue by performing a prospective cohort study in 234 women by systematically screening for thyroid peroxidase antibodies (TPO-Ab), serum TSH, and free T(4)(FT(4)) before the first ART cycle. Women with overt thyroid dysfunction were excluded. Fourteen percent of the cohort had positive TPO-Ab. Baseline characteristics [age, 33 +/- 5 yr; TSH, 1.6 (0.02-4.1) mU/liter; and FT(4), 12.2 (9.1-18) ng/liter] were comparable to those of the 86% of women without antibodies [age, 32 +/- 5 yr; TSH, 1.3 (0.05-3.6) mU/liter; and FT(4), 11.7 (9.5-16.5) ng/liter]. In the antibody-positive group, the pregnancy rate was 53% vs. 43% in the antibody-negative group, with an odds ratio of 0.67 [95% confidence interval (CI) (0.32-1.41); P = not significant]; however within the group that was pregnant, the miscarriage rate was 53% and 23%, respectively, with an odds ratio of 3.77 [95% CI (1.29-11.05); P = 0.016]. The age of the women was an independent risk factor for miscarriage, odds ratio 1.08 [95% CI (1.03-1.15); P = 0.005]. We conclude that women with positive TPO-Ab before the first ART cycle have a significantly increased risk for miscarriage.     

A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. DESIGN: A population study including 4649 randomly selected subjects. MEASUREMENTS: Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. RESULTS: Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23). CONCLUSION: We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.     

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.     

Tobacco smoking and thyroid function: a population-based study

BACKGROUND: The association between tobacco smoking and thyroid function is incompletely understood. METHODS: In a cross-sectional, population-based study conducted between August 15, 1995, and June 18, 1997, of 20 479 women and 10 355 men without previously known thyroid disease, we calculated the geometric mean serum concentration of thyrotropin and the prevalence of hypothyroidism and hyperthyroidism among current, former, and never smokers. RESULTS: Among women, the mean thyrotropin level was lower in current (1.33 mIU/L; 95% confidence interval [CI], 1.29-1.36 mIU/L) and former smokers (1.61 mIU/L; 95% CI, 1.56-1.65 mIU/L) compared with never smokers (1.66 mIU/L; 95% CI, 1.63-1.70 mIU/L). Similarly, among men, the mean thyrotropin level was lower in current (1.40 mIU/L; 95% CI, 1.36-1.44 mIU/L) and former smokers (1.61 mIU/L; 95% CI, 1.57-1.66 mIU/L) compared with never smokers (1.70 mIU/L; 95% CI, 1.66-1.75 mIU/L). In former smokers, thyrotropin levels increased gradually with time since smoking cessation (P for trend < .001). Among current smokers, moderate daily smoking was associated with higher thyrotropin levels than heavier smoking. In women, the prevalence of overt hypothyroidism was lower in current smokers compared with never smokers (odds ratio, 0.60; 95% CI, 0.38-0.95), whereas the prevalence of overt hyperthyroidism was higher among current smokers (odds ratio, 2.37; 95% CI, 1.34-4.20). The associations related to subclinical thyroid dysfunction were similar to those for overt thyroid disease. CONCLUSIONS: These findings indicate that smoking is negatively associated with hypothyroidism but positively associated with hyperthyroidism. The associations with smoking cessation suggest that smoking may have reversible effects on thyroid function. Notably, we report for the first time, to our knowledge, a lower prevalence of overt hypothyroidism among current smokers.     

Euthyroid women with autoimmune disease undergoing assisted reproduction technologies: the role of autoimmunity and thyroid function

Thyroid dysfunction and the presence of thyroid antibodies increase the risk of infertility and miscarriage. The aim of the present study was to assess if patients with autoimmune thyroid disease undergoing assisted reproduction technologies (ART) are afflicted by poor pregnancy and/or delivery rate and if the outcome is conditioned by pre-ART thyroid status. The study was retrospective (from January 2000 to January 2005) and was carried out at the Division of Physiopathology of Human Reproduction. Women who underwent ART were tested for TSH, free T4 (FT4), thyroid peroxidase antibodies (TPOAb) before and during pregnancy. A total of 416 euthyroid women were selected; 42 (10.1%) were TPOAb (+). Women >35 yr were excluded. The endpoints were pregnancy and delivery rates. RESULTS: no differences in pregnancy and delivery rates were observed between women with and without antibodies. In TPOAb (+), women who failed to become pregnant or miscarried displayed higher TSH values before ART (2.8 mIU/l) compared to the ones who delivered (1.6 mIU/l; p=0.032) and compared to TPOAb (-) (1.1 mIU/l; p=0.018). CONCLUSIONS: in euthyroid women undergoing ART the pregnancy and delivery rates are not affected by the presence of TPOAb. In TPOAb (+) high-normal TSH values are associated with increased risk of unsuccessful pregnancy or subsequent miscarriage. Further studies are required to ascertain possible benefits of levo-T4 (L-T4) in such patients.     

妊娠早期母亲亚临床甲状腺功能减退症对其后代脑发育影响的前瞻性研究

目的 研究妊娠早期母亲亚临床甲状腺功能减退症(甲减)对其20～30月龄后代智力和运动发育的影响.方法对来自沈阳市10家医院的妊娠8周左右的妇女1 761名,测定血清TSH、FT4、甲状腺过氧化物酶抗体(TPOAb)及尿碘水平.以TSH≥2.5 mIU/L为切点筛查到亚临床甲减孕妇38例,采用妊娠特异性甲状腺功能参考范围将其进一步分为两个亚组:A组(2.5 mIU/L≤TSH＜3.93 mIU/L),18例;B组(TSH≥3.93 mIU/L),20例.同时选择同一队列中30名甲状腺功能正常、TPOAb阴性的妊娠妇女作为对照组.对研究对象的后代在20～30月龄时进行智力和运动发育指数测评.结果妊娠早期母亲亚临床甲减组及A、B亚组后代平均智力评分分别比对照组低6.55、3.39和9.40分(P=0.001、P=0.125及P＜0.001),平均运动评分分别比对照组低6.31、4.35和8.07分(P=0.003、P=0.070及P=0.001).智力评分和运动评分与母亲血清TSH水平呈明显负相关(r=-0.425,P＜0.001;r=-0.394,P=0.001).多组间比较显示不同水平TSH影响后代智力和运动评分(F=9.277,P＜0.001;F=5.909,P=0.004).有序logistic回归分析显示母亲血清TSH≥3.93 mIU/L导致后代智力和运动评分降低的风险分别是对照组的8.66、6.27倍(OR=8.66,95%CI 2.72～27.57;OR=6.27,95%CI 2.03～19.34).结论采用妊娠特异性的诊断标准诊断的妊娠早期母亲亚临床甲减是其20～30月龄后代智力和运动发育评分减低的独立危险因素.     

Results of infertility investigations and follow-up among 312 infertile women and their partners in Kigali, Rwanda

The objectives of this study were to assess the outcome of infertility investigations and an 18-month follow-up of 312 infertile women and their partners in Rwanda. Between November 2007 and May 2009, an infertility research clinic was opened. Infertile couples received basic infertility investigations, the available treatment was provided and couples were followed up over an 18-month period. The infertility remained unexplained in 3%, was due to a female factor in 31%, due to a male factor in 16% or due to a combination of male and female causes in 50% of fully investigated couples (n = 224). A tubal factor was found in 69% of women, a male factor in 64% of men. Predictors for tubal infertility in women included a history of high-risk sexual behaviour, HIV infection and a history of sexually transmitted infection (STI) symptoms in the male partner. After 12-18 months of follow-up, 40 pregnancies (16%) had occurred in 244 women. Our study shows high rates of tubal and male factor infertility in Rwanda. Pregnancy rates were low after conventional therapy. In order to provide effective and affordable treatment for infertility in resource-poor countries the development of low-cost assisted reproductive technologies are needed.     

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.     

Reference limits for serum thyrotropin in a Japanese population

The aim of the present study was to establish new reference intervals for serum thyrotropin (TSH) levels in Japanese subjects without antithyroid antibodies. We reviewed the serum TSH level of all patients 20 years of age and over who attended the outpatient clinic of our hospital between January 1, 2003, and September 20, 2010. The thyroid gland of every patient was examined by ultrasonography, and subjects found to have a normal thyroid were chosen. The following subjects were excluded: subjects with past history of thyroid diseases; subjects whose serum was positive for antithyroid antibodies; pregnant women; patients taking medication that might affect their free thyroxine (fT(4)) level or TSH levels. Ultimately, 1388 subjects were included in the reference population. The serum TSH levels shifted to higher ranges as the age of the groups increased. The calculated reference range was 0.39-4.29 mIU/L in the 20-29-year-old group, 0.34-3.90 mIU/L in the 30-39-year-old group, 0.56-5.02 mIU/L in the 40-49-year-old group, 0.51-5.30 mIU/L in the 50-59-year-old group, 0.60-4.85 mIU/L in the 60-69-year-old group, 0.62-6.15 mIU/L in the over 70-year-old group. The results of this study showed that the upper limit of the normal range of serum TSH levels increased with age in a Japanese population. Since the number of elderly reference subjects was relatively small, further study is needed. Setting the age- and race-specific reference limits for serum TSH levels is important in order to prevent significant misclassifications of patients with abnormal TSH levels.