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.     

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.     

甲状腺疾病与妊娠

妊娠期甲状腺激素的产生、循环、代谢、调节以及甲状腺免疫均会随妊娠的不同阶段而改变。相关的改变包括:(1)雌激素刺激的血清甲状腺素结合球蛋白水平升高。(2)由于人绒毛膜促性腺激素与促甲状腺激素(TSH)的同源性导致的甲状腺激素产生增加。(3)碘在胎盘的降解加快和在肾脏的排除增加。母体甲状腺这些生理性的变化为妊娠期甲状腺疾病的诊断和治疗带来困惑,因此,需要建立孕期特异的TSH、总T4和游离T4正常参考范围。遗憾的是,目前尚无这样的标准。如非妊娠状态一样,TSH也可以作为诊断妊娠期甲状腺疾病首选的指标,TSH检测不受方法学的限制,下限介于0.2~0.4 mIU/L之间,2.5 mIU/L可以作为TSH在妊娠早期正常范围保守的上限。TT4结果稳定,可以通过非妊娠状态的正常值乘以系数1.5来推断妊娠期的参考范围。妊娠期甲状腺功能减退的患者应该接受左旋T4(L-T4)替代治疗,并尽快使TSH低于2.5 mIU/L,L-T4的剂量在妊娠期要较妊娠前增加30%~50%。对于妊娠期甲状腺功能亢进的患者,丙硫氧嘧啶是首选的治疗药物。甲状腺功能正常的自身免疫性甲状腺炎的孕妇在妊娠期发生甲状腺功能减退、分娩后发生产后甲状腺炎的危险性提高,应该注意监测甲状腺功能。     

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.     

Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals

Objective The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester‐ and method‐specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer’s methodology, euthyroid definition and iodine status. Design Cross‐sectional dataset analysis. Subjects Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Measurements Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti‐TPOAb and anti‐TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. Results All participants had long‐term consumption of iodized salt and median urinary iodine of 150–200 μg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03–4·51, 0·05–4·50 and 0·47–4·54 mIU/l and FT4 11·8–21·0, 10·6–17·6 and 9·2–16·7 pmol/l. The manufacturer’s method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. Conclusions The trimester‐ and method‐based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.     

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。     

Maternal thyroid function during gestation is related to breech presentation at term

Objective To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. Design Prospective follow‐up study during three trimesters of gestation. Patients A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (≥37 weeks) delivery. Measurements Maternal thyroid parameters [TSH, free T4 (FT4) and auto‐antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. Results At term, 58 women (5·5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0·007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH ≥ 2·5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4·8% in the women with TSH < 2·50 mIU/l (P = 0·006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (≥2·5 mIU/l) at 36 weeks gestation (O.R.: 2·23, 95% CI: 1·14–4·39), but not at 12 and 24 weeks gestation. Conclusions Women with TSH levels above 2·5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.     

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.     

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.     

Thyroid autoimmunity and the risk of miscarriage

Approximately one-third of all pregnancies end in miscarriage. The etiology of recurrent abortion remains unknown in approximately 50% of all women. In the early 1990s it was discovered that unselected euthyroid women who present with thyroid antibodies (thyroid peroxidase and thyroglobulin) in the first trimester of pregnancy have a two-four-fold increase in their miscarriage rates. The majority of studies investigating women with recurrent abortion have also found a significant increase in thyroid antibody positivity compared with controls. Although the etiology of miscarriage in thyroid antibody women remains unknown, recent data have revealed a potential direct effect of thyroglobulin antibodies on pregnancy loss in a murine model. Uncontrolled studies assessing the effect of levothyroxine on decreasing the miscarriage rate in euthyroid antibody positive women, have demonstrated a decreased miscarriage rate.     

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.     

The thyroid during pregnancy: a physiological and pathological stress test

Pregnancy and the postpartum are times of marked and rapid change in the thyroid gland. Normal physiological changes include enhanced thyroid hormone production, modulation of thyroid hormone metabolism by placental deiodinases, and decreasing titers of thyroid antibodies in thyroid antibody positive women. Hyperemesis gravidarum is associated with suppressed thyroid stimulating hormone levels and free T4 elevations. Graves' disease typically becomes quiescent during pregnancy, followed by a postpartum flare. Women with pre-existing hypothyroidism frequently require an increase in their levothryoxine requirement in the 1(st) trimester, and subclinical hypothyroidism early in pregnancy is linked to both miscarriage and impaired neurological development in the unborn child. Postpartum thyroiditis occurs in 7.2% of women, and euthyroid women who are thyroid antibody positive in the 1(st) trimester of pregnancy have a doubling of the miscarriage rate.     

Thyroid disease and female reproduction

The menstrual pattern is influenced by thyroid hormones directly through impact on the ovaries and indirectly through impact on SHBG, PRL and GnRH secretion and coagulation factors. Treating thyroid dysfunction can reverse menstrual abnormalities and thus improve fertility. In infertile women, the prevalence of autoimmune thyroid disease (AITD) is significantly higher compared to parous age-matched women. This is especially the case in women with endometriosis and polycystic ovarian syndrome (PCOS). AITD does not interfere with normal foetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without AITD. During the first trimester, however, pregnant women with AITD carry a significantly increased risk for miscarriage compared to women without AITD, even when euthyroidism was present before pregnancy. It has also been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with AITD. It is therefore advisable to measure thyroid function and detect AITD in infertile women before ART, and to follow-up these parameters after COH and during pregnancy when AITD was initially present. Women with thyroid dysfunction at early gestation stages should be treated with l-thyroxine to avoid pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with AITD remains controversial. To date, there is a lack of well-designed randomized clinical trials to elucidate this controversy.     

Graves病患者甲状腺激素水平正常后sTSH长期抑制机制的探讨

目的 探讨临床上部分Graves病(GD)患者经抗甲状腺药物(ATD)治疗后甲状腺激素水平达到正常,但促甲状腺素(TSH)仍长期处于被抑制状态的机制.方法 入选初发122例GD甲亢患者,予以初始等效剂量的ATD治疗,每月随访时根据甲状腺功能测定的结果酌情减量,并适时添加左旋甲状腺素(L-T4).当甲状腺激素(FT3、FT4)水平持续正常3个月即达随访标准,复查FT3、FT4、sTSH、TSH受体抗体(TRAb),并根据TRAb是否阳性分组比较.结果 122例GD甲亢患者经(7.1±1.1)个月的ATD治疗后,甲状腺激素水平均已经达到正常3个月.随访时,58例TRAb转为阴性,64例TRAb持续阳性.两组甲状腺激素水平无差异, TRAb阳性组的sTSH水平明显低于阴性组[0.044 mIU/L(0.001～4.163 mIU/L) vs 1.749 mIU/L(0.079～4.646 mIU/L),P＜0.01];血清sTSH水平与TRAb呈明显负相关(r=-0.539,P＜0.01),与FT3、FT4、年龄、病程、治疗时间、L-T4剂量、L-T4添加时间等均无相关性.结论 药物治疗过程中,甲状腺激素水平正常的GD患者,其TSH水平长期受抑制的原因与高水平TRAb相关,可能由于TRAb直接与垂体内TSH受体结合,通过超短环反馈抑制TSH的分泌所致.     

妊娠早期合并亚临床型甲状腺功能异常的超声表现

目的 探讨妊娠早期甲状腺血清学异常患者甲状腺超声表现特点.方法 选择2018年1月-2019年1月在深圳市龙岗区人民医院就诊的53例孕妇进行甲状腺超声检查.入组孕妇在孕早期检测血清促甲状腺激素(TSH)、血清游离甲状腺素(FT4)、甲状腺过氧化物酶抗体(TPoAb)水平并首次发现甲状腺功能或血清TPoAb 抗体水平异常.比较血清TPoAb≥45 IU/mL和血清TPoAb<45 IU/mL孕妇甲状腺回声异常发生率及腺体血流增多发生率差异.结果 53例孕妇当中其中有41例为亚临床型甲状腺功能亢进,5例为亚临床型甲状腺功能减低,7例为单纯TPoAb水平的增高.41例亚临床型甲状腺功能亢进孕妇中,35例不伴有TPoAb 水平升高的孕妇甲状腺超声表现未见明确异常,而其余有TPoAb水平升高的6例孕妇当中有2例孕妇(33.3%)甲状腺实质回声有弥漫性的改变;5例亚临床型甲状腺功能减低的孕妇当中,其中3例不伴有TPoAb水平升高的孕妇甲状腺实质回声出现弥漫性的改变,而2例伴有TPoAb水平升高的孕妇中1例(50.0%)出现甲状腺实质回声弥漫性改变;7例单纯TPoAb 水平升高的孕妇中,其中4例孕妇(57.1%)甲状腺实质回声出现弥漫性改变.在所有血清TPoAb水平升高的15例孕妇中,10例孕妇血清TPoAb≥45 IU/mL,5例孕妇血清TPoAb<45 IU/mL.血清TPoAb≥45 IU/mL的孕妇甲状腺回声异常发生率高于血清TPoAb<45 IU/mL的孕妇(7/10 vs 0/5);血清TPoAb≥45 IU/mL的孕妇甲状腺血流增多发生率高于血清TPoAb<45 I U/m L的孕妇(4/1 0 vs 1/5).结论 妊娠期具有甲状腺血清学检测指标异常的患者当中,可以出现不同的超声影像学表现,但超声影像学表现与血清学检测结果 并不完全一致.     

Thyroid autoimmunity and miscarriage: a meta-analysis

Objective To investigate whether thyroid autoimmunity (TAI) is associated with increased risk of miscarriage in euthyroid women. Methods An electronic search was conducted using the databases Medline, PubMed, EMBASE and the Cochrane library, from inception to October 2010. A systematic review of the studies on the association between TAI and miscarriage was performed. The odd ratios of case–control studies and relative risks of cohort studies were pooled respectively. The software Review Manager (version 4.3.1) was applied for meta‐analysis. Results The search strategy identified 53 potentially relevant publications, 22 of which were included in the meta‐analysis. A clear association between thyroid autoimmunity and miscarriage was observed with a pooled odds ratio of 2·55 (95% CI 1·42–4·57, P = 0·002) in eight case–control studies and a pooled relative risk of 2·31 (95% CI 1·90–2·82, P < 0·000 01) in 14 cohort studies. Women with TAI were found to have slightly higher age [age difference, 1·29 years] (95% CI 0·43–2·16, P = 0·003) and thyroid‐stimulating hormone (TSH) levels [TSH difference, 0·61 mIU/l] (95% CI 0·51–0·71, P < 0·000 01) compared with those without TAI. Conclusion Based on the currently available evidence, it appears that the presence of thyroid autoimmunity is associated with an increased risk of spontaneous miscarriage in euthyroid women.     

甲状腺自身免疫与流产关联性的meta分析

目的 综合评价甲状腺自身免疫(TAI)与流产的关联性.方法 通过文献检索收集2009年3月以前发表的有关甲状腺自身免疫与流产相关性的病例对照研究以及队列研究,剔除不符合要求的文献,以漏斗图检验入选文献的发表偏倚,并根据各入选文献的同质性检验结果进行数据合并,分别计算合并OR值与RR值,应用meta分析软件包RevMan 4.3.1进行计算.结果 经检索得到23篇文献,剔除综述4篇,余19项临床研究均符合本次meta分析的纳入标准.纳入的19项研究中,7项为病例对照研究,12项为队列研究.7项病例对照研究得到的合并OR值为2.72(95% CI 1.27～5.80,P=0.01);12项队列研究得到的合并RR值为2.41(95% CI 1.96～2.96,P＜0.01).甲状腺自身抗体(TA)阳性妇女较TA阴性者平均年长1.29岁(95% CI 0.43～2.16,P=0.003),TA阳性妇女的TSH较TA阴性者平均高0.61 mIU/L(95% CI 0.51～0.71,P＜0.01).结论 TAI与流产显著关联.除了TA的直接效应以外,TA阳性孕妇轻度的增龄与甲状腺功能不足亦可能是导致流产风险增加的潜在原因.     

Thyroid autoimmunity and miscarriage

To ascertain the strength of the association between thyroid autoimmunity and miscarriage, we performed a meta-analysis of both case-control and longitudinal studies performed since 1990 when this association was first described. A clear association between the presence of thyroid antibodies and miscarriage was found with an odds ratio (OR) of 2.73 (95 % confidence interval (CI), 2.20-3.40) in eight case-control and ten longitudinal (OR, 2.30; 95 % CI, 1.80-2.95) studies. This association may be explained by a heightened autoimmune state affecting the fetal allograft, of which thyroid antibodies are just a marker. Alternatively, the association can be partly explained by the slightly higher age of women with antibodies compared with those without (mean+/-S.D. age difference, 0.7+/-1.0 years; P<0.001). A third possibility is mild thyroid failure, as thyroid-stimulating hormone (TSH) levels in antibody-positive but euthyroid women are higher than in antibody-negative women: difference 0.81+/-0.58 mU/l (P=0.005). Randomized clinical trials with l-thyroxine (aiming at TSH values between 0.4 and 2.0 mU/l) and with selenium (to decrease antibodies against thyroid peroxidase) are clearly needed to elucidate further the nature of this association.     

Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery

Thyroid disease is common in pregnancy and is associated with miscarriage, preterm delivery and postpartum thyroiditis (PPT). Systemic lupus erythematosus (SLE) is associated with miscarriage and preterm delivery. The hypotheses of the study are (1) pregnant women with SLE will have a high prevalence of undiagnosed hypothyroidism and a high prevalence of PPT, and (2) women with SLE and thyroid disease will have an increased incidence of adverse pregnancy outcomes as compared with pregnant women with SLE who do not have thyroid disease. This was a retrospective study of the Hopkins Lupus Cohort. All women had thyroid-stimulating hormone and thyroid antibodies assayed on frozen sera. In total, 63 pregnant women who met the ACR classification for SLE were evaluated. Outcome measures were the prevalence of thyroid disease during pregnancy and postpartum, and pregnancy outcomes. Some 13% of the women were on thyroid hormone prior to becoming pregnant, 11% were diagnosed with hypothyroidism during pregnancy, and 14% developed PPT. The prevalence of preterm delivery was 67% in women with thyroid disease and 18% in women who were thyroid disease free (p?=?0.002). The presence of thyroid antibodies was not correlated with preterm delivery. Pregnant women with SLE have an increased prevalence of thyroid disease. Women with SLE and thyroid disease have an increased prevalence of preterm delivery.     

Effects of L-thyroxine and iodide on the development of autoimmune postpartum thyroiditis

In the present study we examined the influence of L-T4 and iodide on autoimmune postpartum thyroiditis. Women at risk of developing the disease were identified in early pregnancy by the presence of moderate or high titers of antibodies against thyroid peroxidase (TPOAb). They were given no treatment (n = 20), 0.1 mg L-T4 daily (n = 18), or 0.15 mg iodide daily (n = 20) for 40 weeks postpartum. Changes in thyroid function were seen in all women, although in nine hormone values remained within the reference ranges of erthymoid individuals. In each group of women, thyrotoxicosis occurred around 2-3 months postpartum, followed by a gradual rise of TPOAb. Subsequently, around 5-7 months postpartum, a hypothyroid phase was observed. TSH elevations (greater than 5 mU/L) occurred in 9 of 18 women in spite of treatment with 0.1 mg L-T4 although elevations were lower than in the other two groups. Among those women who developed abnormal thyroid function, the hormone changes appeared greater in the iodide-treated group than in the control group, suggesting that in certain patients iodide may aggravate rather than ameliorate the disease. All 58 women showed a reduction of TPOAb during pregnancy and a transient rise during the postpartum year. The extent of TPOAb elevations did not differ between the groups. Thus, the administration of L-T4 prevented hypothyroid symptoms, but did not alter the course of the postpartum thyroiditis, which appears not to be accelerated by events of target cell origin.