妊娠与甲状腺功能减退症

妊娠期间甲状腺激素的合成、分泌、代谢、调节及甲状腺免疫环境均发生相应的改变,而甲状腺功能障碍亦可从月经、排卵、受孕、胚胎分化、分娩等各阶段影响妊娠结局.已发现,即使是亚临床甲状腺功能减退症,或甲状腺功能正常的自身免疫性甲状腺疾病,对妊娠亦产生不良影响.因此妊娠合并甲状腺功能减退症的早期诊断尤为重要.目前促甲状腺激素(TSH)仍作为诊断妊娠期甲状腺疾病首选的指标,推荐将2.5 mU/L作为妊娠早期母体血清TSH水平的保守上限值.有自身免疫性甲状腺疾病者在妊娠期发生甲状腺功能不足的几率较高,需密切监测.     

自身免疫性甲状腺疾病对妊娠结局和女性生育功能的影响

甲状腺自身免疫性疾病是育龄妇女的常见病,包括妊娠期甲状腺功能亢进症、甲状腺功能减退症及产后甲状腺炎。抗甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)及促甲状腺激素受体抗体(TRAb)是机体自身免疫功能紊乱的重要标志。甲状腺功能紊乱对妊娠妇女及胎儿可产生诸多不良影响。甲状腺功能正常但甲状腺自身抗体阳性的妊娠妇女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增高,应注意监测甲状腺功能。甲状腺自身免疫的存在可能与不孕不育以及自然流产等相关。对高危人群进行筛查、早期诊断并及时给予治疗,可有效降低妊娠不良结局的发生。     

妊娠期甲状腺功能保护

甲状腺疾病可以导致母儿不良妊娠结局,由于妊娠期甲状腺功能发生特异性变化,用非妊娠妇女的诊断标准评估妊娠期甲状腺功能可导致妊娠期甲状腺功能减退症漏诊、甲状腺功能亢进症误诊和药物治疗剂量不足。只有正确诊断妊娠期甲状腺疾病,合理保护妊娠期甲状腺功能,才能避免不良妊娠结局的发生和减少对新生儿远期生存质量的影响,对实现我国优生优育的国策具有非常重要的意义。     

妊娠期甲状腺功能减退症筛查的研究进展

由于妊娠期特殊的生理变化,使得碘需求量相应增加,即使轻至中度的碘摄入不足也可影响机体甲状腺激素的水平,导致甲状腺功能减退症。近年来妊娠期甲状腺功能减退症受到重视,大量研究证实妊娠期甲状腺功能减退症与不良妊娠结局(流产、早产等)有关,同时可影响子代智力发育。妊娠期甲状腺功能的筛查对妊娠结局及新生儿发育起到重要作用。妊娠期应对具有高危因素的妇女进行甲状腺功能筛查,特别是甲状腺功能减退的筛查。筛查时机各文献报道不一,我国指南推荐在妊娠8周前或妊娠前进行,临床使用的检测指标主要为促甲状腺激素及游离甲状腺素。     

妊娠期甲状腺功能亢进综合征的诊治

妊娠期甲状腺功能亢进综合征是妊娠早期常见的甲状腺功能异常。该病与妊娠早期血绒毛膜促性腺激素升高和促甲状腺激素（TSH）相应改变有关。伴随着怕热、多汗、情绪不稳、呕吐、心悸等临床症状。实验室检查TSH降低,游离甲状腺素（FT4）和总甲状腺素（TT4）增加,甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TgAb）和促甲状腺激素受体抗体（TRAb）阴性。治疗以对症支持治疗为主,不建议使用抗甲状腺药物。     

妊娠期母体甲状腺功能变化及其对胎儿的影响

妊娠期由于其特殊的生理过程甲状腺各项指标的变化很大,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。甲状腺激素是胎儿脑神经发育的必需激素,甲状腺激素缺乏严重影响胎儿的脑发育,近年来妊娠期甲状腺功能异常的发病率明显升高,可导致母儿不良妊娠结局。综述近年来关于妊娠期母体及胎儿甲状腺功能变化、相关母体甲状腺疾病发病情况及对胎儿的影响,旨在促进正确诊断妊娠期甲状腺疾病,合理保护妊娠期甲状腺功能,预防妊娠期甲状腺功能异常带来的一系列产科并发症及不良妊娠结局,避免新生儿远期生存质量的影响。     

妊娠期TPO-Ab阳性亚临床甲状腺功能减退症对妊娠结局的影响

甲状腺激素是胚胎期胎儿大脑发育所必需。妊娠期亚临床甲状腺功能减退症(简称:亚甲减)可能导致流产、早产、胎盘早剥、低出生体重儿、妊娠期糖尿病等不良妊娠结局,重度亚甲减患者发展为甲状腺功能减退症的风险较高。甲状腺过氧化酶抗体(TPO-Ab)是反映自身免疫性甲状腺疾病的特异指标,通过激活补体、抗体依赖细胞介导的细胞毒性作用和致敏T细胞杀伤作用引起甲状腺滤泡损伤,是亚甲减病因分析和预后评估的重要指标。TPO-Ab阳性是妊娠期亚甲减的一种常见类型,现就妊娠期TPO-Ab阳性亚甲减对妊娠结局的影响进行综述。     

妊娠期亚临床甲状腺功能减退与血清铁蛋白关系的研究进展

亚临床甲状腺功能减退(SCH)是妊娠期妇女最常见的甲状腺疾病，与早产、流产、胎儿宫内生长受限、婴儿认知发育受损等不良妊娠结局密切相关，血清促甲状腺激素(TSH)升高是其主要诊断依据。铁缺乏(ID)是妊娠期最常见的营养缺乏症，血清铁蛋白(SF)水平反映机体的铁储备情况，是诊断ID的敏感指标。研究表明，SCH时TSH与SF水平呈负相关，SF水平与甲状腺功能密切相关，其水平降低是SCH发生的危险因素。本文旨在分析TSH与SF的作用机制以及孕妇SCH与铁代谢的相关性，以期为妊娠期SCH的尽早诊断及治疗提供新思路。     

甲状腺自身抗体与复发性流产

摘要：甲状腺自身抗体是一种以自身甲状腺组织作为靶抗原的自身抗体,主要包括抗甲状腺过氧化物酶抗体、甲状腺球蛋白抗体及促甲状腺激素受体抗体,三者均是反映自身免疫性甲状腺疾病的特异指标。甲状腺自身抗体的存在可能与复发性流产有相关性,应对高危人群进行甲状腺自身抗体的筛查、早期诊断并及时给予治疗,可有效降低妊娠不良结局的发生。     

孕妇亚临床型甲状腺功能减退症的预防与治疗

甲状腺激素是胎儿神经发育的必需激素。胎儿甲状腺激素缺乏可以导致神经系统发育障碍，严重者可发生呆小症。对孕妇进行碘营养监测和恰当的补碘治疗以保证妊娠期间甲状腺激素的足量供应．产后及时筛查和治疗新生儿先天性甲状腺功能减退症，均是保障儿童智力健康的有效手段。值得注意的是，孕妇自身甲状腺功能异常也可能对胎儿神经发育有不利的影响，但相关的研究一直没有受到足够的重视。近年来，随着对亚临床甲状腺疾病认识不断深入和激素检测技术水平的提高，防治孕妇的甲状腺功能减退症、特别是亚临床型甲状腺功能减退症，保护胎儿正常的神经发育和提高后代智力水平正在成为产科学、优生学和内分泌学界的一个研究热点。     

妊娠合并甲状腺功能异常:子痫前期风险与防范

妊娠期甲状腺功能异常性疾病通常表现为妊娠期甲状腺功能亢进(甲亢)或妊娠期甲状腺功能减退症(甲减),未经治疗的妊娠期甲状腺功能异常可导致多种母儿并发症并引起不良妊娠结局,无论是甲亢还是甲减均可增加子痫前期的发病风险,且子痫前期合并甲状腺功能异常使病情变得更为复杂,增加母儿不良预后的风险。故在孕前和孕早期对妊娠期甲状腺功能进行筛查,通过以药物为主的治疗手段使孕期甲状腺激素水平保持在正常范围,以及严密的监护等有助于降低妊娠期子痫前期的发病风险,改善子痫前期合并甲状腺功能异常患者的妊娠结局。     

Hypothyroidism and isolated hypothyroxinemia in pregnancy,from physiology to the clinic

Many changes occur in the physiology of the maternal thyroid gland to maintain an adequate level of thyroid hormones (THs) at each stage of gestation during normal pregnancy, however, some factors can produce low levels of these hormones, which can alter the onset and progression of pregnancy. Deficiency of THs can be moderate or severe, and classified as overt or clinical hypothyroidism, subclinical hypothyroidism, and isolated hypothyroxinemia. Overt hypothyroidism has been reported in 0.3–1.9% and subclinical hypothyroidism in approximately 1.5–5% of pregnancies. With respect to isolated hypothyroxinemia, the frequency has been reported in approximately 1.3% of pregnant women, however it can be as high as 25.4%. Worldwide, iodine deficiency is the most common cause of hypothyroidism, however, in iodine-sufficient countries like the United States, the most common cause is autoimmune thyroiditis or Hashimoto's thyroiditis. The diagnosis and timely treatment of deficiency of THs (before or during the first weeks of gestation) can significantly reduce some of the related adverse effects, such as recurrent pregnancy loss, preterm delivery, gestational hypertension, and alterations in the offspring. However, so far there is no consensus on the reference levels of thyroid hormones during pregnancy to establish the diagnosis and there is no consensus on universal screening of women during first trimester of pregnancy to identify thyroid dysfunction, to give treatment and to reduce adverse perinatal events, so it is necessary to carry out specific studies for each population that provide information about it.     

Thyroid disorders in pregnancy

PURPOSE OF REVIEW: There is now increasing understanding of the association between not only overt, but also subclinical, thyroid disorders and dysfunction with adverse reproductive outcome. In particular, hypothyroidism and thyroid autoimmunity disorders have been shown to have both short- and long-term consequences on mother and child. An updated review is merited to revise many of the traditional views on thyroid disorders in pregnancy. RECENT FINDINGS: Thyroid disorders constitute the commonest group of pre-gestational endocrine disorders found in pregnant women. In mothers taking antithyroid medications, breastfeeding is considered safe. The relatively high prevalence of hypothyroidism, especially subclinical hypothyroidism, the significance of screening and treatment, and the roles of iodine insufficiency and thyroid antibodies on the outcome of pregnancy and long-term neurological development of the offspring have been documented. In hypothyroid women, the dose of thyroxine replacement often needs to be adjusted from as early as the first trimester to maintain an adequate circulating thyroxine concentration. SUMMARY: Apart from overt hyperthyroidism and hypothyroidism diagnosed before and during pregnancy, biochemical abnormalities or evidence of thyroid autoimmunity in clinically euthyroid women can affect both obstetric outcome and long-term neurological development of the offspring. Screening for thyroid function and autoimmunity, and timely and appropriate treatment, will improve pregnancy outcome. The thyroid function of infants born to mothers with thyroid disorders should also be assessed as serial monitoring and treatment may be necessary.     

Schilddrüse bei unerfülltem Kinderwunsch, in Schwangerschaft und Stillzeit

The thyroid gland is an important organ with regard to fertility, pregnancy and lactation. The diagnosis of thyroid disorders is done clinically and by laboratory analysis. In cases of subfertility especially subclinical hypothyroidism can lead to irregular cycles and luteal phase insufficiency. Circulating thyroid antibodies can be associated with an increased rate of spontaneous abortions. Thyroid function has to be well controlled during pregnancy to avoid severe problems for the mother (e.g. pre-eclampsia) as well as for the fetus. Adequate diagnostic assessment before pregnancy should be the goal. Different thyroid disorders can be observed in the postpartum patient. In unclear clinical situations during the postpartum period, consideration should be given to monitoring thyroid function. The systematic diagnostic work-up and therapy are described in this review.     

Schilddrüse und Schwangerschaft

Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function. Both overt and subclinical hypothyroidism have adverse effects on the course of pregnancy and development of the fetus. Hypothyroidism should be diagnosed and corrected before initiation of pregnancy. If hypothyroidism is diagnosed during pregnancy, thyroid function should be normalized as rapidly as possible. Adequate iodine intake is important. By hyperthyroidism differentiation of Graves’ disease from gestational thyrotoxicosis is possible by evidence of autoimmunity (morphologic change of goiter and TSH-receptor antibodies). For overt hyperthyroidism due to Graves’ disease or hyperfunctioning thyroid nodules antithyroid drug therapy should be either initiated or adjusted to maintain the maternal thyroid hormone levels for free T4 in the upper reference range for nonpregnant women. TSH screening should be obtained of patients who are at increased risk (such as miscarriage, preterm deliver miscarriage or history of thyroid disease, Age >?30 years, goiter, autoimmune disease such as diabetes mellitus type 1).     

Schilddrüsenentzündungen in Schwangerschaft und Stillzeit

Thyroiditis during pregnancy can adversely effect development of the fetus, making early recognition and adequate treatment of paramount importance. In women with both clinical and subclinical hypothyroidism the miscarriage rate was found to be higher than in euthyroid women. In addition, hypothyroidism during early pregnancy may impair the subsequent mental development of the offspring. The major reason for hypothyroidism during pregnancy is Hashimoto’s thyroiditis, an autoimmune disease with high levels of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG). Even in euthyroid patients, the risk of miscarriage may be higher if anti-thyroid antibodies are present. Postpartum thyroiditis is similar to Hashimoto’s thyroiditis and is associated with the development of antibodies against TPO and TG. Subacute granulomatous thyroiditis (de Quervain) is a painful inflammation of the thyroid gland presumably associated with a viral infection. Non-steroidal anti-inflammatory drugs (NSAIDs) are the treatment of choice in non-pregnant women and in men but are contraindicated during pregnancy so that glucocorticoids are used instead. Extremely rare forms of thyroiditis are acute suppurative thyroiditis and Riedel’s thyroiditis, a chronic fibrotic disorder of the thyroid gland.     

The influence of iodine deficiency during pregnancy of fetal and neonatal development

The iodine is fundamental substrate for thyroid hormones synthesis. Thyroxine and triiodothyronine play a crucial role in human brain development and maturation. It is well known, that not only fetal, but also maternal thyroid hormones are essential for normal prenatal central nervous system development. During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. With decreasing iodine intake, maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. The severity of iodine deficiency and hypothyroidism in the mother during early and midgestation is related to the severity of the neural damage in the fetus. In severe iodine deficiency, central nervous system damage is already irreversible at birth and can only be prevented by correction of the maternal iodine deficiency early in pregnancy. Therefore iodine supplementation during pregnancy is now strongly recommended.     

Thyroid (dys-)function in normal and disturbed pregnancy

Introduction

During pregnancy, physiologic changes in maternal thyroid function take place especially due to hormonal as well as metabolic processes. Human chorionic gonadotropin activates the maternal thyroid gland leading to increased thyroid hormone production. A sufficient availability of maternal thyroid hormones is essential for fetal development, especially during the first trimester of pregnancy, when the fetal thyroid gland is not yet functional.

Materials and Methods

Current knowledge of thyroid dysfunction including thyroid autoimmunity, hypothyroidism or hyperthyroidism is summarized with special focus on miscarriage and pregnancy disorders. Therefore, a Medline research as well as an analysis of current guidelines on thyroid function and pregnancy was performed.

Results

A study focusing on TSH levels in normal and disturbed pregnancies, the risk of miscarriage in association with thyroid autoantibodies, and (subclinical) hypothyroidism in infertile and fertile women were included.

Conclusion

Maternal thyroid dysfunction negatively affects pregnancy outcome. Besides a routine iodine supplementation in pregnant women and treatment of hypo as well as hyperthyroidism, TSH levels should routinely be measured in women during childbearing years and adjusted to concentrations <2.5 mIU/l in order to optimize maternal health and fetal development.     

Thyroid disease in pregnancy: A review of diagnosis,complications and management

Malfunction of the thyroid gland is the second most common endocrine disorder encountered during pregnancy. It is well known that overt disease of the thyroid gland, either hyper or hypo can adversely affect pregnancy outcome. There is also an ongoing debate surrounding the issue of subclinical hypothyroidism and its effect on the cognitive development of the unborn child. The goal of this paper is to present a systematic review of the literature and the current recommendations for diagnosis and treatment of thyroid disease in pregnancy and postpartum.