Article

Thyroid insufficiency during pregnancy: Complications and implications for screening

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  • "V.Fazzi" Hospital
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Abstract

In 2007, clinical practice guidelines concerning the management of thyroid dysfunction during pregnancy and postpartum were published in the Journal of Clinical Endocrinology and Metabolism. They were elaborated on by a panel of experts, representative of the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, the American Association of Clinical Endocrinologists and the Endocrine Society. In women not known to have thyroid dysfunction, universal screening during pregnancy is not recommended, but thyroid function tests are advised in those with prior therapeutic head or neck irradiation, a history of preterm delivery, in cases of infertility and in the presence of risk factors for thyroid disease. Risks factors for thyroid dysfunction are considered as a personal or family history of thyroid diseases, presence of thyroid antibodies (when known), personal history of autoimmune diseases and the presence of signs or symptoms suggesting hypo- or hyperthyroidism. In this review, we summarize the modifications of the pituitarythyroid axis during pregnancy, with particular attention on thyroid insufficiency. We consider the most important risk factors for thyroid dysfunction and focus our attention on the complications for the progeny, deriving from a condition of maternal thyroid impairment. We will discuss the matters in favor of or against a thyroid-screening program at the beginning of pregnancy.

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... Hypothyroidism is a pathological condition characterized by a reduction of T 3 and T 4 and an increase in TSH levels in the serum [34] [25]. Hypothyroidism has 4% of incidence worldwide among women at fertile age and this frequency increases during the pregnancy due to the physiological stress that this condition imposes to the thyroid gland [35]. The main causes of maternal hypothyroidism is a low I − diet [31] and autoimmune disease against the thyroid gland [36]. ...
... Although maternal hypothyroidism is highly frequent condition in pregnant women, maternal hypothyroxinemia could be even more frequent, given that maternal hypothyroxinemia could be a condition that antecedes maternal hypothyroidism [33]. Maternal hypothyroxinemia is a TH deficiency characterized by low T 4 and normal T 3 and TSH levels [35][36][37][38]. The hypothyroxinemic pregnant women will not have detectable symptoms given that levels of T 3 are normal [38]. ...
... However, the lack of T 4 will impair irreversible the fetus development [39]. It has been reported that one of 20 women suffer hypothyroxinemia being this condition 200 times more frequent than congenital hypothyroidism [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Maternal hypothyroxinemia could be induced by several factors among them are the low I − diet [40], some drugs like amiodarone [41], viral infection [42,43] and autoimmune diseases against thyroid gland [36]. ...
Article
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Thyroid hormones (THs) during pregnancy contribute significantly to cellular differentiation and development in several tissues of the offspring, principally the central nervous system (CNS). TH deficiencies, such as hypothyroidism or hypothyroxinemia, are highly frequent during pregnancy worldwide and known to be detrimental for the development of the fetus. The function of CNS in the offspring gestated under TH deficiency will be irreversible impaired, causing low intellectual quotient, attention deficit, and mental retardation. On the other hand, little is known about the effects of TH deficiency in the offspring immune system, being the prevalent notion that the effects are reversible and only for a while will affect the number of B and T cells. Recent studies have shown that maternal hypothyroidism can altered the function of immune system in the offspring, rendering the female offspring more susceptible to suffer autoimmune-inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE) and to be more resistant to a bacterial infection. In this article we discuss these recent findings, as well as the possible mechanisms underlying these effects and the potential implications for human health.
... Maternal and fetal thyroid insufficiency has been found to cause neurologic impairment and mental retardation in the infant [11,12]. Apart from its effect on the neurological development of the child, hypothyroidism has been found to increase the risk of miscarriage, pregnancy induced hypertension, preeclampsia, anemia, placental abruption, preterm delivery, low birth weight of baby, fetal death and post-partum hemorrhage [13,14]. However when adequately treated these maternal and fetal complications were seen to be averted [15]. ...
... The blood samples for TSH estimation from the obstetrics ward, observation room and labour room are sent to the Central Clinical laboratory. There are many studies which have shown that thyroid dysfunction during pregnancy results in adverse pregnancy outcome like preeclampsia, preterm delivery, delivery of low birth weight baby, and intrauterine foetal death [13,14,16]. This prospective study was designed to verify the findings of previous studies regarding adverse pregnancy outcome in pregnant ladies with thyroid dysfunction . ...
... Hypothyroidism is a common subclinical incidence in about 3-7% of pregnant women and production of thyroid hormones as well as iodine requirements increases by about 50% [1][2][3]. In iodine-sufficient countries, the thyroid gland increases in size by about 10% and to a greater extent in countries known with iodine deficiency during pregnancy [4]. ...
Objectives: Pregnancy is a critical period keenly regulated by both maternal and foetal factors and a shift in these factors could result in severe complications manifesting in foetal and adult life. However, maternal hypothyroidism before and/or during pregnancy is a critical factor. This study investigated the effect of maternal hypothyroidism on glucose tolerance and thyroid function in male and female offspring. Methods: Fifteen adult female Wistar rats were divided into three groups: Group 1 (sham-control), Group 2 (thyrodectomized) and Group 3 (thyroidectomised + L-thyroxine treated). Blood thyroxine (T4) level was measured on the day 10 after thyroidectomy in Groups 1 and 2, and day 35 in Group 3. Males were introduced to the female rats after T4 measurement. At PND-112, T4 levels of their offspring were measured. Oral Glucose Tolerance Test (OGTT) was measured in offspring at PND-133. Results: Thyroxine reduced significantly in Group 2 and their offspring (male and female) compared to Group 3 while gestation period was prolonged significantly in Group 2 compared to Group 1. Hypothyroid male offspring showed depressed glucose tolerance, however, no effect was observed in female offspring. Conclusions: This study suggests that maternal hypothyroidism prolonged gestation period, induced foetal hypothyroidism in both genders and depressed glucose tolerance in male offspring.
... 6 Maternal hypothyroidism may also be associated with adverse fetal and obstetric outcomes as observed in hyperthyroidism, while premature birth, low birth-weight, increased neonatal respiratory distress, & more admissions to the neonatal intensive care unit have been described in babies born to mothers with hypothyroidism. 3,7 The detrimental effect of hypothyroidism during pregnancy is on fetal brain development. Proper maternal thyroid function is important to the developing fetal neurons, 8 particularly in the 1 st trimester of pregnancy when the fetus is completely dependent on the mother for thyroid hormone. ...
Article
Background & objective:Thyroid disorders are among the common endocrine problems during pregnancy with well-known adverse effects on both mother and fetus. Many of these adverse effects could be prevented or ameliorated by early detection and appropriate treatment of conditions, provided routine antenatal thyroid screening is done. Considering this view, the present study was aimed to find the prevalence of thyroid disorders and their spectrum in pregnancy in order to justify the necessity of routine antenatal thyroid screening. Methods: This cross-sectional study was conducted in the Department of Obstetrics & Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period 1 year from July 2012 to June 2013 on pregnant women to screen for the thyroid disorders in pregnancy. Based on predefined eligibility criteria, a total of 246 pregnant women up to 36 weeks of gestation were consecutively included in the study. A short history with brief physical examination was done followed by collection of blood samples. Thyroid function was assessed by measuring serum levels of thyroid stimulating hormone (TSH). Serum free thyroxin (FT4) level was estimated in 71 cases, where TSH value was deranged. Trimester specific reference range of serum TSH was used to define hypothyroid, euthyroid and hyperthyroid cases. The suspected risk factors were then compared between abnormal and euthyroid groups to find their association with thyroid disorders. Result: The results of the study showed that the overall prevalence of abnormal thyroid function status was 30.9% (hypothyroidism 29.7% and hyperthyroidism 1.2%) based on normal range of serum TSH in different trimesters of pregnancy. Pregnant women with thyroid disorders were generally older than their euthyroid counterparts (p = 0.039). Hypothyroid state was fairly common with advancing gestation (21.3%, 30.3% and 34% in the 1st, 2nd, and 3rd, trimesters respectively). Pregnant women with personal or family history of thyroid disease in the past exhibited a higher prevalence of abnormal thyroid function than those who did not have such history (p = 0.041 and p = 0.044 respectively). Past menstrual irregularity, past history of subfertility or abortion were significantly associated with thyroid disorders (p = 0.042, p = 0.004 and p < 0.001 respectively). Presence of goitre (21.1%) in current pregnancy also showed significant association with thyroid dysfunction (p = 0.001). The risk of developing abnormal thyroid function was observed to be 3.6(95% CI = 1.9 – 6.4) times higher in those who had at least one risk factor than those who did not have any risk factors (p < 0.001). However, a sizable portion (27.6%) of pregnant women without any risk factors developed abnormal thyroid function. Conclusion: The study concluded that one in every three women may have thyroid disorder during pregnancy, primarily hypothyroidism. Adopting risk factor-based screening for thyroid disorders in pregnancy, there is every chance that a substantial number of cases with thyroid dysfunction may be missed. Therefore, routine antenatal thyroid screening is recommended. Ibrahim Card Med J 2020; 10 (1&2): 74-83
... Pregnancy can complicated with either hyperthyroidism: occur in 2/1000 pregnancies (9) caused by thyroiditis which either (10) : acute, sub acute thyroiditis and chronic thyroiditis. Or hypothyroidism which is mainly occur due to either autoimmune thyroiditis or iodine deficiency (1) , can be presented as either overt hypothyroidism which is presented with clinical feature of hypothyroidism, low T4, raised TSH (11) , it occurs in only 1-3 per 1000 pregnant women (12) , or subclinical hypothyroidism which occurs in 2.5% of pregnant women (raised TSH and normal or low normal T4) and these women are often asymptomatic, but around 50-60% will have some evidence of autoimmune thyroid disease (positive TPOAbs and or thyroglobulin antibodies (TGAbs)) in iodine-sufficient areas (13,14) . ...
Article
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Background: Diabetes mellitus and thyroid disorder have been shown to mutually influence each other and association between both conditions has long been reported. On one hand, diabetes mellitus affects thyroid function tests to variable extents, and on the other hand, thyroid hormone contributes to the regulation of carbohydrate metabolism and pancreatic function. Objective: To determine the thyroid dysfunction and the presence of anti-thyroid peroxidase antibodies during (24-28) weeks of gestation in pregnant women with gestational diabetes mellitus and type1 diabetes. Methods: A case control study, at Al-Yarmouk Teaching Hospital, Department of Obstetrics and Gynecology for one year from April 2013 till the end of April 2014. Ninety five pregnant women were enrolled in this study in their 24-28 weeks of gestation, of them forty pregnant women with negative oral glucose tolerance test, fifteen pregnant women with type 1 diabetes mellitus and forty pregnant women with gestational diabetes mellitus (impaired oral glucose tolerance test). For all pregnant women, blood samples were taken for measurement of free thyroxin, thyroid stimulatory hormone and anti-thyroid peroxidase antibodies. Results: The mean ±SD level of free thyroxin were significantly lower in pregnant women with gestational diabetes (15.0 pmol/l ±5.5) and in pregnant women with type 1 diabetes (17.7 pmol/l ±8.3) compared with control group (22.4±5.9) with P < 0.001. TSH level showed no statistically difference among the participated group with P = 218. As well the percentage of those with positive anti-thyroid peroxidase antibody have shown that (26.7%) of patient with type 1 diabetes were positive to antibodies, and this percentage was higher than that of control group (10.0%) and gestational diabetes group (15.0%), but the difference fail to reach the level of significance. Conclusion: Thyroid dysfunctions are common during pregnancy, especially pregnancies with type 1 diabetes and those complicated with gestational diabetes. There is significantly higher incidence of hypothyroxinaemia and increase anti-thyroid peroxidase antibodies in these pregnancies than the control pregnant women.
... Pregnancy can complicated with either hyperthyroidism: occur in 2/1000 pregnancies (9) caused by thyroiditis which either (10) : acute, sub acute thyroiditis and chronic thyroiditis. Or hypothyroidism which is mainly occur due to either autoimmune thyroiditis or iodine deficiency (1) , can be presented as either overt hypothyroidism which is presented with clinical feature of hypothyroidism, low T4, raised TSH (11) , it occurs in only 1-3 per 1000 pregnant women (12) , or subclinical hypothyroidism which occurs in 2.5% of pregnant women (raised TSH and normal or low normal T4) and these women are often asymptomatic, but around 50-60% will have some evidence of autoimmune thyroid disease (positive TPOAbs and or thyroglobulin antibodies (TGAbs)) in iodine-sufficient areas (13,14) . ...
Article
Full-text available
Background: Diabetes mellitus and thyroid disorder have been shown to mutually influence each other and association between both conditions has long been reported. On one hand, diabetes mellitus affects thyroid function tests to variable extents, and on the other hand, thyroid hormone contributes to the regulation of carbohydrate metabolism and pancreatic function. Objective: To determine the thyroid dysfunction and the presence of anti-thyroid peroxidase antibodies during (24-28) weeks of gestation in pregnant women with gestational diabetes mellitus and type1 diabetes. Methods: A case control study, at Al-Yarmouk Teaching Hospital, Department of Obstetrics and Gynecology for one year from April 2013 till the end of April 2014. Ninety five pregnant women were enrolled in this study in their 24-28 weeks of gestation, of them forty pregnant women with negative oral glucose tolerance test, fifteen pregnant women with type 1 diabetes mellitus and forty pregnant women with gestational diabetes mellitus (impaired oral glucose tolerance test). For all pregnant women, blood samples were taken for measurement of free thyroxin, thyroid stimulatory hormone and anti-thyroid peroxidase antibodies. Results: The mean ±SD level of free thyroxin were significantly lower in pregnant women with gestational diabetes (15.0 pmol/l ±5.5) and in pregnant women with type 1 diabetes (17.7 pmol/l ±8.3) compared with control group (22.4±5.9) with P < 0.001. TSH level showed no statistically difference among the participated group with P = 218. As well the percentage of those with positive anti-thyroid peroxidase antibody have shown that (26.7%) of patient with type 1 diabetes were positive to antibodies, and this percentage was higher than that of control group (10.0%) and gestational diabetes group (15.0%), but the difference fail to reach the level of significance. Conclusion: Thyroid dysfunctions are common during pregnancy, especially pregnancies with type 1 diabetes and those complicated with gestational diabetes. There is significantly higher incidence of hypothyroxinaemia and increase anti-thyroid peroxidase antibodies in these pregnancies than the control pregnant women.
... Overt hypothyroidism occurs in only about 5% of all women who have a high TSH. During the last decade, it has become apparent that untreated maternal hypothyroidism and subclinical hypothyroidism in pregnancy is associated with adverse fetal and obstetric outcomes [11, 12]. These events include miscarriages, anaemia in pregnancy, preeclampsia, abruptio placenta, and postpartum haemorrhage while premature birth, low birth weight, increased neonatal respiratory distress, and more admissions to the neonatal intensive care unit have been described in babies born to mothers with hypothyroidism [13] . ...
Article
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There is a high incidence of thyroid dysfunction during pregnancy resulting in adverse maternal (miscarriages, anaemia in pregnancy, preeclampsia, abruptio placenta and post-partum haemorrhage) and fetal effects (premature birth, low birth weight, increased neonatal respiratory distress) which may justify screening for thyroid function during early pregnancy with interventional levothyroxine therapy for thyroid hypofunction. There is a greater prevalence of subclinical hypothyroidism in women with delivery before 32 weeks and there is even an association between thyroid autoimmunity and adverse obstetric outcome, which is independent of thyroid function. Higher maternal TSH levels even within the normal reference range are associated with an increased risk of miscarriages, fetal and neonatal distress and preterm delivery. There are few prospective randomised trials to substantiate the benefit of screening and the recently reported CATS study did not show a benefit in child IQ at age 3 years. Nevertheless there seems to be a case for screening to prevent adverse obstetric outcomes. The clinical epidemiological evidence base does not justify universal screening at the present time. However, it is probable that more evidence will be produced which may alter this view in the future.
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Purpose: The Danish TeleCare North trial has developed a telehealth system, Telekit, which is used for self-management by patients diagnosed with chronic obstructive pulmonary disease (COPD). Self-management is the engagement in one's own illness and health by monitoring and managing one's symptoms and signs of illness. The study examines the association between COPD patients' use of Telekit and their functional health literacy and the association between their use of Telekit and their specific technological communication skills. Methods: A consecutive sample of participants (n=60) from the TeleCare North trial were recruited. Face-to-face interviews were conducted with each participant to collect demographic data. Functional health literacy was measured with the Danish TOFHLA test. Participants completed a non-standardised questionnaire about their health status, their use of the Telekit system, and their specific technological communication skills. Binary logistic regressions were performed to examine how functional health literacy and specific technological communication skills influenced the use of Telekit by giving users an enhanced sense of freedom, security, control, and a greater awareness of COPD symptoms. Results: Participants (27 women, 33 men) had a mean age of 70 (SD: 8.37) years. Functional health literacy levels were classified as inadequate in 14 (23%) participants, as marginal in 12 (20%), and as adequate in 34 (57%). Participants self-reported a feeling of increased security (72%), greater freedom (27%), more control (62%), and greater awareness of symptoms (50%) when using Telekit. The use of Telekit was not significantly associated with levels of functional health literacy or with the number of specific technological communication skills (p>0.05) based on the binary logistic regressions. Conclusion: The enhanced sense of security, freedom, control, and the greater awareness of COPD symptoms achieved by using Telekit were unassociated both with the patients' score of functional health literacy and with their specific technological communication skills. On the basis of our results it seems that the specific technological communication skills and functional health literacy are not a prerequisite for the use of the Telekit system.
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Thyroid dysfunction is the second most common endocrine disorder, only after diabetes mellitus, affecting females in reproductive age group. Pregnancy is associated with profound repercussions on the thyroid status of a lady. Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, pre-eclampsia, preterm delivery and reduced intellectual function in the offspring. Thus, maintenance of euthyroid state is of utmost important for maternal and fetal well being during pregnancy as well as after. The Endocrine Society has issued latest guidelines regarding the diagnosis and management of thyroid dysfunction related to pregnancy. All the clinicians should be well aware of the latest recommendations regarding management of thyroid dysfunction in pregnancy and in postpartum phase and practice them accordingly.
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Screening for thyroid disease in pregnancy remains a contentious issue. This review presents these diverging views and discusses their reasons as well as the relevant facts. The final aim is to establish the information gaps and limitations - technological or otherwise - which still need to be eliminated in order to settle the debate conclusively. The prevalence of the more common thyroid dysfunctions that occur in and after pregnancy is discussed. The subsequent impact of these disorders on mother and offspring is also described. Special focus is placed on the benefits and setbacks of currently available and newly proposed investigations, which assay serum hormone levels, serum autoantibody levels, and/or use clinical data. It is pointed out that the relevance of screening varies from one region of the world to the other, based on the content of iodine and selenium in food and water. The review then discusses the current major arguments for and against screening, as well as recommendations and proposed alternatives.
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Advances in understanding the physiology of thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal function on obstetric outcome and foetal well-being. Pubmed search was done using the terms thyroid and pregnancy. Areas of agreement are the following: gestational normative reference ranges for thyroid function tests are required for proper interpretation of any abnormalities. Measurement of thyroid-stimulating antibodies and antithyroid peroxidase antibodies is useful for diagnosis of thyroid disease in pregnancy. Treatment of Graves’ hyperthyroidism should be done with propylthiouracil for first trimester only, then carbimazole or methimazole. Patients on levothyroxine require an increase in dosage during gestation. Areas of controversy are the following: total thyroxine (TT4) versus Free T4 (FT4) assays in pregnancy. Screening for thyroid function in early gestation: should it be routinely performed on everyone? What tests are appropriate? Growing points are the following: physiology of thyroxine delivery to the foetus. Establishment of gestational thyroid hormone reference ranges. Evaluation of strategies to screen thyroid function in early pregnancy. Areas timely for developing research are the following: placental thyroid hormone physiology, thyroid hormone therapy and screening thyroid function.
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Free thyroxin (FT4) concentrations, total thyroxin/thyroxin-binding globulin (T4/TBG) ratios, and thyrotropin (TSH) and albumin concentrations were measured in serum in a longitudinal study in each of the three trimesters of 25 normal pregnancies. In late pregnancy, FT4 estimates by assays reputedly either affected or unaffected by albumin were in the lower half of the reference range for nonpregnant subjects. T4/TBG ratios and albumin concentrations were similarly lower. FT4 overall was significantly (P less than 0.001) correlated with these latter two values. Serum TSH concentrations increased as FT4 declined in late pregnancy. Nonesterified fatty acid (NEFA) concentrations were too low to displace T4 from its binding proteins and were not correlated with other measurements. Within any one of the trimesters, FT4 and T4/TBG were independent of variations in TBG or albumin concentrations. This implies that lower FT4 concentrations in late pregnancy are real, merely coinciding with parallel decreases in albumin. They are not artefacts of albumin-affected assays.
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Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.
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We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.
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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.
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Epidemiological studies and case reports show that even a relatively minor degree of maternal hypothyroxinemia during the first half of gestation is potentially dangerous for optimal fetal neurodevelopment. Our experimental approach was designed to result in a mild and transient period of maternal hypothyroxinemia at the beginning of corticogenesis. Normal rat dams received the goitrogen 2-mercapto-1-methyl-imidazole for only 3 d, from embryonic d 12 (E12) to E15. Maternal thyroid hormones decreased transiently to 70% of normal serum values, without clinical signs of hypothyroidism. Dams were injected daily with 5-bromo-2'-deoxyuridine (BrdU) during 3 d, from E14-E16 or E17-E19. Their pups were tested for audiogenic seizure susceptibility 39 d after birth (P39) and killed at P40. Cells that had incorporated BrdU were identified by immunocytochemistry, and quantified: numerous heterotopic cells were found, whether labeled at E14-E16 or E17-E19, that were identified as neurons. The cytoarchitecture and the radial distribution of BrdU-labeled neurons was significantly affected in the somatosensory cortex and hippocampus of 83% of the pups. The radial distribution of gamma-aminobutyric acidergic neurons was, however, normal. The infusion of dams with T4 between E13 and E15 avoided these alterations, which were not prevented when the T4 infusion was delayed to E15-E18. In total, 52% of the pups born to the goitrogen-treated dams responded to an acoustic stimulus with wild runs, followed in some by seizures. When extrapolated to man, these results stress the need for prevention of hypothyroxinemia before midpregnancy, however moderate, and whichever the underlying cause.
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Hypothyroidism, hyperthyroidism, and positive thyroid autoantibody status all affect successful reproductive function. All infertile patients should undergo a TSH and prolactin evaluation. In the future, the role of subclinical hypothyroidism may be further evaluated by dynamic TRH testing. The subtle subclinical hypothyroid abnormalities now being investigated may offer an explanation for the 15% of patients with unexplained infertility. Hyperthyroidism, although not primarily considered a cause of infertility, shows diverse effects that impact successful pregnancy outcome. By understanding the basis of hyperthyroxinemic hyperemetic pregnancies in women, we may further characterize the interactions of hCG, the TSH receptor, and other thyroid-stimulating factors. The recently reported association of thyroid autoantibodies with reproductive failure suggests a possible role of T-cell dysregulation and further implicates an immune component in the etiology of reproductive failure. The reader is advised to review the intricacies of thyroid testing and physiology during pregnancy in a basic review.
Article
Hypothyroidism rarely complicates pregnancy because most affected women are anovulatory. In this report, we describe 28 complicated pregnancies cared for over a ten-year period at Parkland Memorial Hospital. In the group of 16 pregnancies in 14 overtly hypothyroid women, maternal complications were common and included anemia (31%), preeclampsia (44%), placental abruption (19%), postpartum hemorrhage (19%), and cardiac dysfunction. Perinatal morbidity and mortality were also high mainly because of placental abruption, and reflected frequent low birth weight (31%) and fetal death (12%). In a group of 12 women with subclinical hypothyroidism, these complications were less impressive. We speculate that overt thyroid deficiency is associated with adverse pregnancy outcome related to preeclampsia and placental abruption. Thyroxine replacement probably improves these outcomes even if subclinical hypothyroidism persists.
Article
During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.
Article
To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P<0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P < 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.
Article
In this report we describe 26 pregnancies complicated by hypothyroidism cared for over 6.5 years at AIIMS, New Delhi. In 2 women hypothyroidism was diagnosed during pregnancy; others were diagnosed before pregnancy and continued to receive thyroxine replacement therapy throughout pregnancy. The thyroxine treatment needed readjustment in 7 (26.9%) pregnancies to maintain euthyroidism. Maternal complications included anaemia (23.0%), pregnancy induced hypertension (26.9%), postpartum haemorrhage (7.7%), intrauterine growth retardation (15.4%), postdatism (30.8%), and deficient lactation (19.2%). Perinatal mortality was 3.9%. No case of stillbirth occurred probably because of intensive fetal monitoring and timely termination of pregnancies on evidence of intrauterine fetal compromise. One neonatal death occurred due to fetal thyrotoxicosis. In these cases close surveillance during pregnancy is needed to maintain optimum thyroid hormone concentration, and intensive fetal monitoring is required to achieve a good perinatal outcome.
Article
Data were analyzed from 77 pregnancies in 65 hypothyroid women treated with levothyroxine (T4) to determine (a) how often, how severely, and when serum thyrotropin (TSH) and free T4 concentrations become abnormal during pregnancy in women taking constant T4 doses and (b) how much to increase T4 doses to normalize elevated serum TSH levels. Group I consisted of 36 women with previous thyroid ablation. Group II consisted of 29 women with Hashimoto's thyroiditis. Serum TSH levels rose above normal (greater than 4 microU/mL) during pregnancy more often in Group I (76%) than in Group II (47%) during treatment with constant T4 doses, and mean serum free T4 levels decreased significantly in both groups, by 47% in Group I and by 35% in Group II, compared to preconception values. Serum TSH concentrations rose above 20 microU/mL in 22% of the women, and serum free T4 concentrations fell below normal in 13%. Elevated serum TSH levels usually were detected by the first TSH test during pregnancy, as early as 4 weeks gestation. Of those women tested after an initial normal serum TSH value during pregnancy, 30% had an elevated serum TSH concentration later in the pregnancy. Of 12 women followed through two pregnancies, 10 had elevated serum TSH values in both pregnancies, 1 had normal serum TSH values in both, and 1 had discordant serum TSH values.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
colon; Marked changes in renal function occur with pregnancy. We present a summary of these changes in this review and give insight into possible mechanisms if they are known. Controversies exist regarding the therapy of pregnancy- induced hypertension and asymptomatic and recurrent bacteriuria. The current views on these topics are given. Specific renal diseases are summarized, including transplantation, and optimum management strategies and maternal and fetal prognosis during pregnancy are given.
Article
The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.
Article
A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high.
Article
Thyroid gland size was ultrasonographically determined in 35 pregnant women who live in an area with moderate iodine deficiency. Iodide salt was administered to group A (n = 17), whereas group B (n = 18) was used as a control. Each group was tested for thyroid-stimulating hormone serum levels, iodine excretion, and thyroid volume. In both groups thyroid-stimulating hormone levels were similar and did not change throughout pregnancy. The iodine excretion at the third trimester in the treated group was significantly (p less than 0.01) higher than that of group B (100.0 +/- 39.0 versus 50.0 +/- 37.0 micrograms iodine per 24 hours, respectively). Initially, thyroid volume did not differ between the two groups. At the end of pregnancy, no difference was found in thyroid size in group A, whereas in the untreated women it increased significantly (p less than 0.0001) with a mean increase of 1.6 +/- 0.6 ml (16.2% +/- 6.0%). These results show that the increased thyroid size in the control group was mainly a result of relative iodine deficiency and that iodoprophylaxis should be warranted even in areas with moderate iodine deficiency to prevent the increase in thyroid size and, probably, to avoid the risk of maternal and fetal hypothyroidism.
Article
Evaluation of thyroid status by measurement of free thyroid hormone concentrations seems particularly helpful in conditions with altered serum binding proteins. In pregnancy, a condition of increased thyroxine binding globulin, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations have been reported to be normal, increased or decreased. In the present study we have measured serum total and free thyroid hormone concentrations in pregnant women, their newborns and nonpregnant women. Serum FT4 and FT3 concentrations have been measured with 10 different commercially available kits and the results obtained have been compared. Serum total thyroid hormone concentrations in pregnant women were significantly higher than in their newborns and in nonpregnant women. Maternal serum FT4 concentrations measured with the different kits were always significantly lower than values in nonpregnant women. Furthermore, with one kit, the mean maternal serum FT4 concentration was below the normal range and with many kits, a large number of maternal serum samples had serum FT4 concentrations below the normal range. With all kits, except two, neonatal serum FT4 concentrations were higher than values in their respective mothers and, in general, lower than values in nonpregnant women. Serum FT3 concentrations in nonpregnant women were in the normal range, except with one kit, in which the mean serum FT3 concentration was below the normal range. Serum FT3 concentrations in newborns resulted markedly lower than in parturient and in non pregnant women. With almost all kits, serum FT3 values were below the normal range in many maternal samples. With one kit, maternal serum FT3 concentrations resulted higher than in nonpregnant women, whereas with the other kits serum FT3 concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid.
Article
Background and Methods. Women with hypothyroidism have been thought not to require an increase in thyroxine replacement during pregnancy. To evaluate the effects of pregnancy on thyroxine requirements, we retrospectively reviewed the thyroid function of 12 women receiving treatment for primary hypothyroidism before, during, and after pregnancy. Results. In all patients, the serum thyrotropin level increased during pregnancy. The mean (±SE) serum freethyroxine index decreased from 111.0±5.8 before pregnancy to 86.5±5.2 during pregnancy (normal, 64 to 142; P<0.05), and the mean serum thyrotropin level increased from 2.0±0.5 mU per liter before pregnancy to 13.5±3.3 mU per liter during pregnancy (normal, 0.5 to 5.0 mU per liter; P<0.01). Because of high thyrotropin levels, the thyroxine dose was increased in 9 of the 12 patients. Among the three patients who did not require an increased thyroxine dose were two with low serum thyrotropin levels before pregnancy, suggesting excessive replacement at that time. The mean thyroxine dose before pregnancy was 0.102±0.009 mg per day; it was increased to 0.148±0.015 mg per day during pregnancy (P<0.01). Conclusions. Our results indicate that the need for thyroxine increases in many women with primary hypothyroidism when they are pregnant, as reflected by an increase in serum thyrotropin concentrations. Although the effects of this modest level of hypothyroidism are not known, we think it prudent to monitor thyroid function throughout gestation and after delivery and to adjust the thyroxine dose to maintain a normal serum thyrotropin level. (N Engl J Med 1990; 323:91–6.)
Article
To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.
Article
Thyroid disorders are often ubiquitous and insidious in their presentation. They have been implicated in a broad spectrum of reproductive disorders ranging from abnormal sexual development to menstrual irregularities and infertility. If pregnancy occurs in a patient with thyroid disease, the physician must ensure that therapeutic measures instituted to restore the health of the mother do not adversely affect the developing fetus. This review examines the role of thyroid disease in disorders confronting the obstetrician/gynecologist and provides a theoretical framework upon which to base practical management decisions.
Article
Thyroxine-binding globulin (TBG(, thyroxine-binding pre-albumin (TBPA), thyroxine (T4), free-T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were studied throughout apparently normal pregnancy in 290 cases grouped in 2 week intervals. TBG increased to a plateau level reached in the 24th week and was hereafter unchanged until term. T4 showed an increase until the 16th week of pregnancy and levelled off to a constant level for the rest of the pregnancy. Free-T4 declined to almost subnormal values for the non-pregnancy state which was reached around the 20th week of pregnancy. T3 showed a slight and definite increase in the beginning of pregnancy and levelled off to a constant value after the 14th week. TSH increased towards the end of pregnancy also showing its maximum during the last 4 weeks. TBPA showed constant values throughout pregnancy. The results are discussed in view of the use of modern techniques and previously missing data in literature (TBPA).
Article
A prospective study was undertaken in 87 healthy pregnant women with thyroid antibodies and normal thyroid function at initial presentation [asymptomatic autoimmune thyroid disorders (AITD)]. The aims of the study were to assess whether women with AITD constitute a group at risk of developing subclinical hypothyroidism during pregnancy, and whether a mild thyroid function impairment may be associated with obstetrical repercussions. The women investigated were selected among a cohort of 1660 consecutive pregnancies on the basis of 1) no previous history of thyroid disease, 2) euthyroidism at initial presentation, and 3) positive thyroglobulin antibodies and/or thyroid peroxidase antibodies (TPO-Ab). Women with AITD had a basal TSH value significantly higher, albeit still normal, in the first trimester (1.6 vs. 0.9 mU/L; P < 0.001) than that in women with healthy pregnancies used as controls. Despite a 60% average reduction in TPO-Ab titers during gestation, serum TSH remained higher in women with AITD than in controls throughout gestation: at delivery, 40% of the cases had serum TSH levels above 3 mU/L, and 16% had serum TSH levels above 4 mU/L. A TRH test carried out in the days after parturition showed an exaggerated response in 50% of the cases. Furthermore, free T4 concentrations were in the range of hypothyroid values in 42% of the women. Obstetrical repercussions were observed, namely increased rates of spontaneous miscarriage and premature deliveries. In conclusion, women with asymptomatic AITD who are euthyroid in early pregnancy carry a significant risk of developing hypothyroidism progressively during gestation, despite a marked reduction in antibody titers. Hypothyroidism results from the reduced ability of the gland to adjust to the changes in thyroidal economy associated with pregnancy. At the individual level, progression to subclinical hypothyroidism was broadly predictable on the basis of serum TSH levels and TPO-Ab titers in the first trimester. Hence, these parameters provide useful markers to identify women who carry a higher risk, allowing for a close monitoring of thyroid function during pregnancy and the administration of L-T4 in specific cases. Taken together with the known incidences of postpartum thyroiditis and hypothyroidism in women with AITD, the present observations in our opinion justify systematic screening of thyroid autoimmunity during pregnancy.
Article
To relate hypothyroidism to perinatal outcome. A cohort of 68 hypothyroid patients with no other medical illnesses was divided into two groups according to the initial thyroid function tests. The first group had 23 women with overt hypothyroidism, and the second had 45 subjects with subclinical hypothyroidism. We sought to identify the pregnancy outcomes of gestational hypertension, low birth weight, fetal death, congenital anomalies, maternal anemia, and postpartum hemorrhage. Gestational hypertension--namely, eclampsia, preeclampsia, and pregnancy-induced hypertension--was significantly more common in the overt and subclinical hypothyroid patients than in the general population, with rates of 22, 15, and 7.6%, respectively. In addition, 36% of the overt and 25% of the subclinical hypothyroid subjects who remained hypothyroid at delivery developed gestational hypertension. Low birth weight in both overt and subclinical hypothyroid patients was secondary to premature delivery for gestational hypertension. Except for one stillbirth and one case of clubfeet, hypothyroidism was not associated with adverse fetal and neonatal outcomes. Normalization of thyroid function tests may prevent gestational hypertension and its attendant complications in hypothyroid patients.
Article
Roberts J. Jenkins C, Wilson R, Pearson C, Franklin IA, MacLean MA, McKillop JH, Walker JJ. Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies. Eur J Endocrinol 1996;134:84–6. ISSN 0804–4643 The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5 ⁺ /CD20 ⁺ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5 ⁺ /20 ⁺ positive cells (0.8 ± 0.3 vs 0.5 ± 0.1 vs 1.1 ± 0.3 × 10 ⁸ /l: p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage. R Wilson, Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK
Article
Liesenkötter KP, Göpel W, Bogner U, Stach B, Grüters A. Earliest prevention of endemic goiter by iodine supplementation during pregnancy. Eur J Endocrinol 1996;134:443–8. ISSN 0804–4643 During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency. To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies, we have investigated the thyroid volume, thyroid function, urinary iodine excretion and antibodies to thyroid peroxidase at 10–12 weeks of gestation and postpartum in 38 mothers receiving 300 μg potassium iodide/day and in 70 mothers without iodine supplementation. In all of their newborns thyroid volume was determined by ultrasound. The thyrotropin (TSH) levels and antibodies to thyroid peroxidase (TPO-ab) in the neonates were measured in dried blood spots on filter paper from their newborn screening. Urinary iodine excretion was increased significantly after iodine supplementation in mothers (p < 0.001) and their newborns (<0.05). No hypo- or hyperthyroidism was observed in the mothers or newborns. Interestingly, no difference of maternal thyroid volumes was observed between the two groups after pregnancy, but the volumes of the thyroid glands in newborns of mothers who received iodine were significantly (p < 0.004) lower (0.7 ± 0.4 ml) than in the control group (1.5 ± 1.1 ml). There was no change in the frequency of TPO-ab in either group after pregnancy. In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn. This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab. Klaus Peter Liesenkötter, Kinderklinik Kaiserin Auguste Victoria Haus (KAVH), Virchow-Klinikum der Medizinische Fakultät der Humboldt-Universität zu Berlin, Heubnerweg 6, 14059 Berlin, Germany
Article
Thyroid status is frequently assessed during pregnancy, both to evaluate suspected thyroid abnormalities, and to monitor the status, of pre-existing thyroid disease. However, the production, circulation, and disposal of thyroid hormone are all altered in pregnancy. Interpretation of thyroid function studies in the pregnant patient must be performed based on an understanding of the normal physiologic changes at each stage of pregnancy. Examples of pregnancy-associated changes include, estrogen-stimulated increase in serum thyroxine binding globulin, chorionic gonadotropin stimulated T4 and T3 production from the thyroid gland, and accelerated degradation of thyroid hormone by the placenta. The serum-TSH alone is usually not adequate to assess thyroid status in pregnancy, and the various conditions that can effect this measurement are described. The pattern of thyroid studies in pregnancy is important in diagnosing thyroid disease, and it may indicate physiologic adaptations to optimize maternal thyroid status for fetal development.
Article
A prospective study was undertaken to evaluate urinary iodine excretion and changes of maternal thyroid function during pregnancy in healthy women living in the southwest of France. The cohort included a total of 347 pregnant women (mean age 28.0+/-0.5 years). Iodine concentration in a random urine sample and thyroid tests (free thyroxine [FT4], free triiodothyronine [FT3], thyrotropin (TSH), thyroxine-binding globulin [TBG], and thyroglobulin [Tg]) were measured at initial presentation (before 12 weeks of gestation), and during the ninth month of pregnancy. A thyroid ultrasound was performed 1 to 5 days after delivery in 246 mothers. Mean urinary iodine levels were low during the first trimester (6.9+/-0.4 microg/dL), as well as during the ninth month of pregnancy (8.6+/-0.6 microg/dL). During pregnancy, FT4 and T3 concentrations decreased (p < .001), and TSH and Tg concentrations increased (p < .001). Thyroid hypertrophy (thyroid volume greater than 18 mL) was present in 15.4% of women whose first trimester urinary iodine concentration was less than 5 microg/dL, but was present in only 3.5% of women whose urinary iodine concentration was greater than 10 microg/dL. A goiter (thyroid volume greater than 22 mL) was present in 11% of the mothers. In conclusion, this prospective study shows that urinary iodine excretion is low in pregnant women living in the southwest of France. This low iodine intake is associated with reduced circulating thyroid hormone levels and growth of the thyroid gland. These data point to the need of an increased iodine supply in these pregnant women to reduce the potential consequences of low iodine intake on maternal thyroid economy.
Article
Iodine deficiency in a population causes increased prevalence of goiter and, more importantly, may increase the risk for intellectual deficiency in that population. The National Health and Nutrition Examination Surveys [NHANES I (1971-1974) and (NHANES III (1988-1994)] measured urinary iodine (UI) concentrations. UI concentrations are an indicator of the adequacy of iodine intake for a population. The median UI concentrations in iodine-sufficient populations should be greater than 10 microg/dL, and no more than 20% of the population should have UI concentrations less than 5 microg/dL. Median UI concentrations from both NHANES I and NHANES III indicate adequate iodine intake for the overall U.S. population, but the median concentration decreased more than 50% between 1971-1974 (32.0+/-0.6 microg/dL) and 1988-1994 (14.5+/-0.3 microg/dL). Low UI concentrations (<5 microg/dL) were found in 11.7% of the 1988-1994 population, a 4.5-fold increase over the proportion in the 1971-1974 population. The percentage of people excreting low concentrations of iodine (UI, <5 microg/dL) increased in all age groups. In pregnant women, 6.7%, and in women of child-bearing age, 14.9% had UI concentrations below 5 microg/dL. The findings in 1988-1994, although not indicative of iodine deficiency in the overall U.S. population, define a trend that must be monitored.
Article
Maternal thyroid function during early pregnancy is an important determinant of early fetal brain development because the fetal thyroid is unable to produce any T4 before 12-14 weeks' gestation. Overt maternal hypothyroidism as seen in severe iodine-deficient areas is associated with severely impaired neurological development of the offspring. At present, it is not known whether low free T4 (fT4) levels during pregnancy in healthy women from iodine sufficient areas may affect fetal neurodevelopment. Neurodevelopment was assessed at 10 months of age in a cohort of 220 healthy children, born after uncomplicated pregnancies and deliveries, using the Bayley Scales of Infant Development. Maternal TSH, fT4 and TPO antibody status were assessed at 12 and 32 weeks' gestation. Maternal gestational fT4 concentration was defined as an independent parameter for child development. Children of women with fT4 levels below the 5th (< 9.8 pmol/l, n = 11) and 10th (< 10.4 pmol/l, n = 22) percentiles at 12 weeks' gestation had significantly lower scores on the Bayley Psychomotor Developmental Index (PDI) scale at 10 months of age, compared to children of mothers with higher fT4 values (t test, mean difference: 14.1, 95% confidence interval (CI): 5.9-22 and 7.4, 95% CI: 1.1-13.9, respectively). At 32 weeks' gestation, no significant differences were found. In the group of women with the lowest 10th percentile fT4 concentrations at 12 weeks' gestation, a positive correlation was found between the mothers' fT4 concentration and children's PDI scores (linear regression, R: 0.46, P = 0.03). After correction for confounding variables, a fT4 concentration below the 10th percentile at 12 weeks' gestation was a significant risk factor for impaired psychomotor development (RR): 5.8, 95% CI: 1.3-12.6). Low maternal plasma fT4 concentrations during early pregnancy may be an important risk factor for impaired infant development.
Article
When thyroid deficiency occurs simultaneously in a pregnant woman and her fetus, the child's neuropsychological development is adversely affected. Whether developmental problems occur when only the mother has hypothyroidism during pregnancy is not known. In 1996 and 1997, we measured thyrotropin in stored serum samples collected from 25,216 pregnant women between January 1987 and March 1990. We then located 47 women with serum thyrotropin concentrations at or above the 99.7th percentile of the values for all the pregnant women, 15 women with values between the 98th and 99.6th percentiles, inclusive, in combination with low thyroxine levels, and 124 matched women with normal values. Their seven-to-nine-year-old children, none of whom had hypothyroidism as newborns, underwent 15 tests relating to intelligence, attention, language, reading ability, school performance, and visual-motor performance. The children of the 62 women with high serum thyrotropin concentrations performed slightly less well on all 15 tests. Their full-scale IQ scores on the Wechsler Intelligence Scale for Children, third edition, averaged 4 points lower than those of the children of the 124 matched control women (P= 0.06); 15 percent had scores of 85 or less, as compared with 5 percent of the matched control children. Of the 62 women with thyroid deficiency, 48 were not treated for the condition during the pregnancy under study. The full-scale IQ scores of their children averaged 7 points lower than those of the 124 matched control children (P=0.005); 19 percent had scores of 85 or less. Eleven years after the pregnancy under study, 64 percent of the untreated women and 4 percent of the matched control women had confirmed hypothyroidism. Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.
Article
Pregnancies complicated by abruption result in increased frequency of perinatal death and decreased fetal size and gestational duration, yet the extent of placental separation and its effect on these adverse outcomes is unknown. To assess the contribution of placental abruption and extent of placental separation to stillbirth, preterm delivery, and fetal growth restriction. Hospital-based, retrospective cohort study. Mount Sinai Hospital, New York City, NY. A total of 53,371 pregnancies occurring in 40,789 women who were delivered of singleton births between 1986 and 1996. Risks and relative risks for stillbirth (>20 weeks), preterm delivery (<37 weeks), and fetal growth restriction (birth weight below 10th percentile for gestational age) in relation to abruption. The incidence of abruption was 1 % (n = 530). Abruption was associated with an 8.9-fold (95% confidence interval [CI], 6.0-13.0) adjusted relative risk (aRR) of stillbirth. Preterm birth proportions among women with and without abruption were 39.6% and 9.1 %, respectively, yielding an aRR of 3.9 (95% CI, 3.5-4.4). In the abruption group, 14.3% of neonates were growth restricted, compared with 8.1 % among all other births (aRR, 2.0; 95% CI, 1.5-2.4). Extent of placental separation had a profound effect on stillbirth (aRR for 75% separation, 31.5; 95% CI, 17.0-58.4), although evident only among those with at least 50% separation. However, the risk of preterm delivery was substantially increased even for mild abruptions (aRR for 25% separation, 5.5; 95% CI, 4.2-7.3). In this cohort, placental abruption had a profound impact on stillbirth, preterm delivery, and fetal growth restriction. The risk of stillbirth was dramatically increased for severe placental separation, but preterm delivery was common even among women with lesser degrees of placental separation.
Article
To examine the relation between certain pregnancy complications and thyroid stimulating hormone (TSH) measurements in a cohort of pregnant women. TSH was measured in sera obtained from women during the second trimester as part of routine prenatal care. Information was then collected about vaginal bleeding, premature delivery, low birthweight, abruptio placentae, pregnancy induced hypertension, need for cesarean section, low Apgar scores, and fetal and neonatal death. Among 9403 women with singleton pregnancies, TSH measurements were 6 mU/l or greater in 209 (2.2%). The rate of fetal death was significantly higher in those pregnancies (3.8%) than in the women with TSH less than 6 mU/l (0.9%, odds ratio 4.4, 95% confidence interval 1.9-9.5). Other pregnancy complications did not occur more frequently. From the second trimester onward, the major adverse obstetrical outcome associated with raised TSH in the general population is an increased rate of fetal death. If thyroid replacement treatment avoided this problem this would be another reason to consider population screening.
Article
To establish gestation-related reference intervals for thyroid hormones in a Chinese population. A prospective study with 343 healthy pregnant women (5-41 weeks) and 63 non-pregnant controls. Thyroid stimulating hormone (TSH), free thyroxine (T4) and tri-iodothyronine (T3) (and human chorionic gonadotrophin) were measured by immunoassays. The median, 2.5th and 97.5th percentiles at 4-week intervals were calculated. Data were also analysed for significant trends using ANOVA. Free T3 decreased during pregnancy, whereas free T4 initially increased, peaking between 9-13 weeks and then decreased, the decline becoming significant by week 21. TSH mirrored changes in free T4. The gestation-related reference intervals for thyroid hormones should alleviate the misinterpretation of thyroid function in pregnancy.
Article
A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.
Article
In the present review, an attempt was made to describe current knowledge and concepts concerning the complex relationships that link thyroid autoimmunity (TAI) and hypothyroidism with female and male infertility, as well as abnormalities occurring during pregnancy, such as pregnancy loss and maternal and fetal repercussions associated with hypothyroidism. In the case of infertility, although the clinical relevance of TAI is somewhat controversial, when all available information is considered the results strongly suggest that when infertility is due to well-defined female causes, autoimmunity is involved and TAI constitutes a useful marker of the underlying immune abnormality, independently of thyroid function disorders. In the case of pregnancy loss, the vast majority of available studies clearly establish that TAI (even with no overt thyroid dysfunction) is associated with a significant increase in miscarriage risk. To find an association, however, does not imply a causal relationship, and the aetiology of increased pregnancy loss associated with TAI remains presently not completely understood. With regard to maternal repercussions during gestation, the main risk associated with TAI is the occurrence of hypothyroidism and obstetric complications (premature birth, pre-eclampsia, etc.). Thus, systematic screening of TAI and hypothyroidism during early pregnancy, monitoring of thyroid function with/without L-thyroxine treatment and follow-up during post-partum have proved helpful and important in order to manage these patients adequately. Finally, with regard to potential repercussions affecting the offspring, recent evidence suggests that thyroid maternal underfunction, even when considered mild (or subclinical), may be associated with an impairment of fetal brain development. When present only during the first half of gestation, maternal hypothyroxinaemia is a risk factor for impaired fetal brain development, due to insufficient transfer of maternal thyroid hormones to the feto-placental unit. When hypothyroidism is not restricted to the first trimester and worsens as gestation progresses (as in untreated hypothyroidism), the fetus may also be deprived of adequate amounts of thyroid hormones during later neurological maturation and development, leading to poorer school performance and lower IQ.
Article
To investigate the pituitary-thyroid axis function in the early neonatal period of newborns to hypothyroid mothers who have been apparently adequately treated. Among the 27,386 full-term newborns delivered over a 6-year period, 259 were born to 250 treated hypothyroid mothers (0.9%); 246 of these newborns constituted the study group. Controls were 139 term healthy neonates from healthy group-matched mothers. The study infants and controls underwent thyroid function tests in a prospective design. A single blood sample was collected from each infant at 25-120 hours of life. Compared with the controls, serum thyroid-stimulating hormone (TSH) levels were higher in the study neonates (P <.005), as were those of serum free thyroxine (T4) (P <.03), particularly at 49 hours of life or older (P <.001). At 49-120 hours, 44.7% of the study group newborns had serum free T4 levels greater than the 95th percentile of the controls (P <.001), and 16.8% had significantly higher TSH levels (P <.001). Serum free T4 correlated positively with TSH in the controls (r =.316) but not in the study newborns (r =.062, P =.36). Neonatal TSH at 49 hours or older correlated positively with maternal TSH during pregnancy in the 18 cases where maternal TSH values during pregnancy were available (r =.751, P <.001). Birth weight and head circumference were significantly lesser in the study group (P <.001). The impaired intrauterine growth and the unduly elevated serum values of TSH and serum free T4 found in a substantial fraction of the study newborns might reflect an insufficient level of hormone replacement therapy of their hypothyroid mothers during pregnancy, despite an assumed adequate management. Gestational hypothyroidism requires close monitoring.
Article
To evaluate the impact of maternal hypothyroxinaemia during early gestation (fT4 below the lowest tenth percentile and TSH within the reference range: 0.15-2.0 mIU/l) on infant development, together with any subsequent changes in fT4 during gestation. A prospective 3-year follow-up study of pregnant women and their children up to the age of 2 years. Child development was assessed by means of the Bayley Scales of Infant Development in children of women with hypothyroxinaemia (fT4 below the tenth percentile at 12 weeks' gestation) at 12 weeks' gestation (cases), and in children of women with fT4 between the 50th and 90th percentiles at 12 weeks' gestation, matched for parity and gravidity (controls). Maternal thyroid function (fT4 and TSH) was assessed at 12, 24 and 32 weeks' gestation. The mental and motor function of 63 cases and 62 controls was compared at the age of 1 year, and of 57 cases and 58 controls at the age of 2 years. Children of women with hypothyroxinaemia at 12 weeks' gestation had delayed mental and motor function compared to controls: 10 index points on the mental scale (95% CI: 4.5-15 points, P = 0.003) and eight on the motor scale at the age of 1 year (95% CI: 2.3-12.8 points, P = 0.02), as well as eight index points on the mental (95% CI: 4-12 points, P = 0.02), and 10 on the motor scale (95%CI: 6-16 points, P = 0.005) at the age of 2 years. Children of hypothyroxinaemic women in whom the fT4 concentration was increased at 24 and 32 weeks' gestation had similar scores to controls, while in the controls, the developmental scores were not influenced by further declines in maternal fT4 at 24 and 32 weeks' gestation. Maternal hypothyroxinaemia during early gestation is an independent determinant of a delay in infant neurodevelopment. However, when fT4 concentrations increase during pregnancy in women who are hypothyroxinaemic during early gestation, infant development appears not to be adversely affected.
Article
Mild maternal hypothyroidism during pregnancy can adversely affect infant development. We studied thyrotropin (TSH) levels in mothers of premature and low-birth-weight infants in Colombia, where iodized salt supplements the diet to correct iodine deficiency. The additional impact of salt restriction in mothers with hypertensive disorders was examined. Blood was spotted on filter paper from 404 mothers and their infants. Using radioimmunoassay (RIA), TSH was measured in the mothers, and TSH and thyroxine in their infants at three postpartum times. Initially, mothers had high TSH levels (i.e., TSH > 10 mU/L in half the mothers at the first assessment). Fourteen days later, only 9.3%, and at calculated term 7.5% were greater than 10 mU/L. Maternal TSH levels correlated with infant birth weight and gestational age (r = 0.47, and r = 0.49, p < 0.01). Initial TSH values were higher in salt restricted (20.1 +/- 2 mU/L, n = 76) versus control mothers (14.6 +/- 0.85, n = 328, p < 0.01), dropping dramatically in both groups 14 days later (to 3.4 +/- 0.7 mU/L vs. 2.8 +/- 0.4 mU/L) and at calculated term (2.8 +/- 0.4 mU/L vs. 2.3 +/- 0.6 mU/L). Increased maternal TSH levels during pregnancy in an iodine-deficient area may be aggravated by salt restriction. Monitoring TSH and supplementing iodine or thyroxine are recommended in pregnancy, especially if dietary salt restriction is prescribed.
Article
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.