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Autoinmune thyroid disease during pregnancy and postpartum
Autoinmune thyroid disease during pregnancy and postpartum
ML. FERNANDEZ-SOTOa, A. GONZALEZ-JIMÉNEZa, F. ESCOBAR-JIMÉNEZa
a Servicio de Endocrinología y Nutrición Clínica. Unidad de Gestación. Hospital Universitario San Cecilio. Granada
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Advances in our understanding of the mechanisms responsible for autoimmune thyroid disease &#40;AITD&#41; have been developed in a few years&#44; in large part by the application of novel molecular techniques&#46; There have been a major comprenhension about self-tolerance mechanisms and how these may fail&#44; antigen presentation&#44; funcional T cell subsets and specific T cell receptor &#40;TCRs&#41; in autoimmunity&#46; More gradually&#44; these findings are being translated to thyroid autoimmunity where undoubtedly&#44; the major advance in the last decade was the cloning and sequencing of the three major thyroid antigens&#58; thyroglobulin &#40;Tg&#41;&#44; thyroidperoxidase &#40;TPO&#41; and the TSH receptor &#40;TSH-R&#41;&#46; As a result&#44; detailed characterization of autoantibodies is now posible<span class="elsevierStyleSup">1</span> and its measurement useful in the clinical setting&#46;</p><p class="elsevierStylePara">Genetic predisposition&#44; together with ill-defined environmental and endogenous factors&#44; determines susceptibility to AITD&#46; Most attention has been focused on the role of HLA genes&#46; A meta-analysis found evidence only for HLA-DR3 and -DR4 association in Hashimoto&#39;s thyroiditis&#44; with a higher relative risk for the former<span class="elsevierStyleSup">2</span>&#46; However&#44; subsequent studies have failed to substantiate this&#46; Given this weak HLA association&#44; it seems likely that one or more non-HLA genes makes a major contribution to susceptibility and novel approaches will be required to identify these<span class="elsevierStyleSup">3</span>&#46; On the other hand&#44; we know more about the importance of environmental and endogenous &#40;most probably hormonal&#41; factors in thyroid autoimmunity<span class="elsevierStyleSup">4</span>&#46;</p><p class="elsevierStylePara">Another advance has been the recognition that the thyrocyte is not a helpless target of autoaggression&#44; being capable of expressing a wide array of immunologically active molecules&#44; which may exacerbate or diminish the autoimmune response<span class="elsevierStyleSup">5</span>&#46; Defining the contribution of thyrocytes to the intrathyroidal autoimmune response&#44; whether from released cytokines or surface-bound molecules will be crucial to our future understanding as well as holding the promise that these thyroid derived production might be therapeutical targets&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">AUTOIMMUNE THYROID DISEASE DURING PREGNANCY AND POSTPARTUM</span></p><p class="elsevierStylePara">Thyroid disorders are observed 4-to 5 -fold more frequently in women than in men&#44; in particular during the childbearing period&#46; It is therefore not unusual to encounter thyroid function abnormalities during a &#34;routine&#34; laboratory evaluation carried out for pregnant women&#46; Pregnancy is accompanied by profound alterations in thyroidal economy&#44; resulting from a complex combination of factors specific for the pregnant state&#58; the rise in T4-binding globulin concentrations&#44; the effect of hCG on the maternal thyroid&#44; alterations in the requirement for iodine and modifications in autoimmune regulation&#46;</p><p class="elsevierStylePara">Thyroid peroxidase &#40;TPO&#41; is now recognized as the specific antigen of thyroid microsoma&#46; A new sensitive method for detection of antibodies to TPO &#40;TPO-Ab&#41;&#44; has been developed a few years ago <span class="elsevierStyleSup">6</span>&#46; In our experience<span class="elsevierStyleSup">7</span>&#44; TPO-Ab determination using monoclonal antibody radioimmunoassay provides a clear improvement in the sensitivity of autoimmune thyroid disease diagnosis&#46; We propose that in terms of systematic screening of thyroid autoimmunity TPO-Ab is clearly to be preferred than classical antimicrosomal antibodies &#40;MIC-Ab&#41; and antithyroglobulin &#40;Tg-Ab&#41;<span class="elsevierStyleSup">8</span>&#46; </p><p class="elsevierStylePara"><img src="295.GIF" width="229" height="369"></img></p><p class="elsevierStylePara">In a cohort study of pregnant women with mild underlying abnormalities published in 1991&#44; it was noted that women who are euthyroid but carry positive thyroid antibodies at the onset of pregnancy&#44; have an increased risk of developing hypothyroidism during gestation<span class="elsevierStyleSup">9</span>&#46; We therefore investigated more systematically the role of autoimmune thyroid disease &#40;AITD&#41; on thyroid function during pregnancy&#46; The systematic screening at the time of the initial visit &#40;before 16 weeks&#41; of thyroid autoantibodies among 437 healthy pregnant women&#44; with no previous history of thyroid disorder&#44; has showed a 9&#37; prevalence of positive TPO-Ab titers&#44; a 2&#46;6&#37; for positive Tg-Ab titers and a 6&#46;5&#37; for positive MIC-Ab&#46; These percentages were not different from the nonpregnant female which is in the range of 5-10&#37; reported by other authors<span class="elsevierStyleSup">10</span>&#46; We have found a highly significant positive correlation between TPO-Ab and MIC-Ab during early pregnancy in a subset of the sample&#46; The same significant positive correlation&#44; was found between TPO-Ab and Tg-Ab&#44; in the complete cohort of pregnant women before 16 weeks &#40;fig&#46; 1&#41;&#46; </p><p class="elsevierStylePara"><img src="295A.GIF" width="476" height="211"></img></p><p class="elsevierStylePara">Thyroid antibody titers were monitored sequentially during gestation and postpartum&#46; A significant decline&#44; both in TPO-Ab and Tg-Ab was observed during late gestation &#40;fig&#46; 2&#41;&#46; These results provide evidence the immunosuppressive effect of pregnancy as a general phenomenon&#46; We propose that if systematic screening of thyroid autoimmunity is to be organized during pregnancy&#44; antibody determination should be carried out as early as possible during gestation&#46;</p><p class="elsevierStylePara">Women with a positive test for TPO-Ab early in gestation showed a highly significant decrease in FT4 and increased TSH levels in the late trimester of gestation&#44; despite a significant decline in TPO-Ab titers&#46; These results are in agreement with Glinoer et al<span class="elsevierStyleSup">11</span>&#44; who recently showed that women with asymptomatic autoimmune thyroid disease who are euthyroid in early pregnancy carry a significant and progressive risk of becoming hypothyroid during gestation&#44; despite a marked reduction in antibody titers&#46; Progression to subclinical hypothyroidism was associated with and predicted by serum TSH levels and TPO-Ab titers in the first trimester&#46; Hence&#44; these parameters can be used to provide useful markers to identify those women who carry a higher risk and&#44; therefore&#44; initiate hormone substitution therapy&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Iodine and AITD during pregnancy</span></p><p class="elsevierStylePara">Some experimental studies<span class="elsevierStyleSup">12</span> have showed that iodine supplementation might be associated with an increase of thyroid autoantibodies&#46; These results have been recently refuted<span class="elsevierStyleSup">13</span> in a group of women who received iodine supplementation &#40;300 Fg KI&#47;day&#41; during pregnancy&#46; In this study no mother developed autoantibodies during pregnancy and those mothers having already positive TPO-Ab at the beginning of the gestation showed no increase of the antibody titers&#46; </p><p class="elsevierStylePara"><img src="295B.GIF" width="476" height="273"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Fetal loss and AITD</span></p><p class="elsevierStylePara">Another important question concerns the rate of spontaneous abortions in women with positive TPO-Ab&#46; Our studies<span class="elsevierStyleSup">9</span> were the first to report a strong correlation between positive thyroid antibodies and the risk of spontaneous miscarriage in women who were clinically and biochemically euthyroid&#46; Similar findings were reported by Stagnaro et al<span class="elsevierStyleSup">14</span> and Bussen et al<span class="elsevierStyleSup">15</span>&#44; emphasizing the notion that the risk of miscarriage occurs primarily in the first trimester and that women with a history of consecutive abortions carry an even greater risk&#46; The most plausible hypothesis is that such women present an underlying more generalized defect in autoimmunity&#44; leading to increased fetal loss<span class="elsevierStyleSup">16</span>&#46; Therefore&#44; the early determination of thyroid auto-Ab&#44; and in particular TPO-Ab&#44; could serve as a sensitive marker to identify women at risk&#46; TPO-Ab have been shown to cross the placenta<span class="elsevierStyleSup">9</span>&#59; however&#44; the effect of these antibodies on fetal growth and subsequent development is not well known&#46; It&#39;s noteworthy the study of Pop et al<span class="elsevierStyleSup">17</span>&#44; who concluded that children of pregnant women who have elevated TPO-Ab but normal thyroid function are at increased risk for decreased cognitive development&#46; However&#44; larger samples of women with TPO-Ab are needed to determine whether impaired childhood development is related to the titer of TPO-Ab or envirommental factors&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Smoking and AITD during pregnancy</span></p><p class="elsevierStylePara">There is an increasing suggestion of an effect of smoking on autoimmune thyroid disease&#46; In particular&#44; smoking has been shown to worsen Graves disease and Graves&#39; ophthalmopathy<span class="elsevierStyleSup">18</span>&#46; The exact role of smoking on the autoimmune mechanism is unclear&#46; However&#44; it is known that smoking has an antithyroid effect<span class="elsevierStyleSup">19</span>&#46; We have shown a significant elevation in levels of TPO-Ab in pregnant women who smoked more than 10 cigarettes&#47;day before gestation&#44; compared with those who smoked less than 10 cigarettes&#47;day or who were not smokers&#46; A test for Tg-Ab showed similar results &#40;fig&#46; 3&#41;&#46; We recommend systematic screening for TPO-Ab in women who smoke prior to or during early gestation in view of the effects of pregnancy on autoimmune thyroid disease<span class="elsevierStyleSup">20</span>&#46; Those with a positive TPO-Ab should be followed serially with testing for FT4 and TSH during gestation and the postpartum period as the risk of clinical thyroid disease in women with elevated TPO-Ab levels is big&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">GRAVES DISEASE DURING PREGNANCY AND POSTPARTUM</span></p><p class="elsevierStylePara">Even though the immunological consequences of pregnancy are not yet fully elucidated&#44; major influences on the course of autoimmune disease have been recognized for decades&#46; In particular&#44; pregnancy associated improvement in the hyperthyroidism of Graves&#44; disease &#40;GD&#41; and exacerbation of hyperthyroidism during the postpartum period have been described<span class="elsevierStyleSup">21</span>&#46;</p><p class="elsevierStylePara">The prevalence of hyperthyroidism in pregnant women has been reported to be in the range 0&#46;05-0&#46;2&#37;&#46; Between 1974 and 1990 in the Los Angeles County &#40;University of Southern of California&#41; the prevalence of hyperthyroidism was 0&#46;1&#37;<span class="elsevierStyleSup">22</span>&#46; A screening of thyroid function in 9&#46;453 early pregnant women residing in Japan revealed that 0&#46;4&#37; had hyperthyroidism &#40;mainly untreated GD&#41; and another 0&#46;4&#37; had a transient subclinical hyperthyroidism<span class="elsevierStyleSup">23</span>&#46; When the diagnosis of GD has not yet been established before the beginning of pregnancy&#44; the disorder is not always readily suspected clinically&#44; mainly because the symptoms and signs of mild to moderate hyperthyroidism may mimick the hypermetabolic state of normal pregnancy&#46; Some findings such as a heart rate above 100 per minute&#44; diffuse goiter and weight loss may be relevant and help in the diagnosis&#46; Thyroid stimulating antibodies &#40;TSAb&#41; are considered to be the cause of hyperthyroidism in GD&#46; Accurate diagnosis of GD is important&#44; because untreated hyperthyroidism is associated with increased fetal loss&#44; premature labor&#44; and low birth weight<span class="elsevierStyleSup">24</span>&#46; The severity of hyperthyroidism frequently decreases during gestation in patients with Graves&#44; disease&#44; which often tends to recur after term&#46; Due to the immune suppression associated with the pregnancy state&#44; there is a progressive decrease in the titers of TSAb&#44; as gestation progresses<span class="elsevierStyleSup">24</span>&#46; The reduced availability of iodine for the maternal thyroid may also play a role to improve the course of the disorder&#44; at least when pregnancy occurs in women who reside in areas with a restricted iodine supply&#46; It should&#44; however&#44; be noted that transient exacerbations of hyperthyroidism near the end of the first trimester &#40;associated with peak hCG&#41; are not exceptional<span class="elsevierStyleSup">25</span>&#46;</p><p class="elsevierStylePara">From 1988-1990 we analyzed in a prospective sequential study the changes in thyroid function and in the TSAb in patients with GD during pregnancy and postpartum&#46; The patients constituted two different groups&#46; One group was untreated before becoming pregnant and was named &#34;remission group&#34;&#46; The other group was taking antithyroid treatment&#44; and was named &#34;active group&#34;&#46; Striking differences during pregnancy and postpartum period were shown when active and remission groups were compared&#46; During early gestation some women with active GD&#44; associated with a high rate of miscarriage &#40;20&#37;&#41;&#46; However&#44; throughout gestation these women improve&#44; with a significant reduction of dosage of ATD&#46; They started with mean dosage of 22 mg&#47;day of methimazole and the mean dosage at delivery was 10 mg&#47;day&#46; The improvement observed during the la&#46; te gestation&#44; is likely to be related to the reduction in TSAb titers&#46;</p><p class="elsevierStylePara">In the whole group&#44; the levels of antibodies to TSH receptor decreased during pregnancy and increased after delivery&#44; indicating that antibody production is regulated by events specific to pregnancy&#46; As has been reported&#44; immunosuppressive factors originating from the fetus&#44; the placenta&#44; or the mother &#40;decreased circulating T-helper cells&#41;&#44; could play a role in the level of antibodies to the TSH receptor<span class="elsevierStyleSup">26</span>&#46; The production of antibodies to the TSH receptor may be activated after delivery resulting in postpartum thyroid dysfunction&#46; Fifty-five percent of the women in the active and 24&#37; in the remission groups had a relapse of their hyperthyroidism&#44; associated with an increase in the level of antibodies to TSH receptor&#46; These findings suggest that the level of antibodies to TSH receptor is related to the frequency of relapse of hyperthyroidism&#46; Hashizume et al<span class="elsevierStyleSup">27</span>&#44; provided evidence that the administration of L-thyroxine during the last trimester of pregnancy and the first year after delivery was effective in maintaining a lower level of TSAb and in decreasing the rate of postpartum hyperthyroidism in patients with GD&#46; However&#44; not everybody is in agreement with these results and the controversy still persists<span class="elsevierStyleSup">28</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Treatment of Graves&#39; disease during pregnancy</span></p><p class="elsevierStylePara">Antithyroid drugs &#40;ATD&#41; are the therapy of choice in pregnant women&#44; unless the severity of the condition justifies a more radical approach by surgery &#40;which is then preferably carried out in the second trimester&#41;&#46; Preference is usually given to propylthiouracil &#40;PTU&#41; over methimazole &#40;or carbimazole&#41;&#44; although this choice is not mandatory&#44; as long as the minimal dose of ATD is implemented<span class="elsevierStyleSup">29</span>&#46; A controversial issue is whether the combined therapy &#40;ATD associated to L-thyroxine&#41; may be effective in controlling maternal hyperthyroidism and avoid fetal hypothyroidism and goiter&#46; We do not recommend this combined therapy for the following reasons&#58; first&#44; transplacental passage of thyroid hormones is negligible and doesn&#39;t prevent the increase of fetal TSH&#59; second&#44; it may lead to the administration of larger doses of ATD which may cause fetal hypothyroidism and goiter&#46;</p><p class="elsevierStylePara">In our personal experience&#44; the combined therapy does not provide any help in the management of hyperthyroidism during pregnancy&#46; We propose the use of the lowest dose ATD dose to maintain free thyroid hormones in the normal range or even in the upper limit of normality&#46; It has been shown that such levels in maternal blood are associated with free hormone concentrations in the fetus that remain in the mid-range of normal values<span class="elsevierStyleSup">30</span>&#46;</p><p class="elsevierStylePara">Pregnancy complicated by hyperthyroidism is widely recognized as a cause of impaired fetal outcome&#46; Momotani et al<span class="elsevierStyleSup">29</span>&#44; in a large number of hyperthyroid pregnant women observed that hyperthyroidism at the time of conception was associated to abortion in 25&#37; and premature delivery in 15&#37; of the women compared with 13 and 10&#37; in euthyroid patients&#46;</p><p class="elsevierStylePara">It is strongly recommended that thyroid stimulating antibodies &#40;TSAb&#41; titers are assayed in early pregnancy and the last trimester&#44; because high TSAb levels predict the risk of neonatal hyperthyroidism and of recurrences of thyrotoxicosis during the postpartum period<span class="elsevierStyleSup">31</span>&#46;</p><p class="elsevierStylePara">Another controversial issue is breast feeding in mothers treated with ATD&#46; For many years&#44; breast-feeding was forbidden if ATD drugs were being used&#46; Some studies have documented that&#44; after a single dose of 400 mg of PTU the concentration of the drug in the milk was only 10&#37; of that of serum and that only 90 &#181;g of PTU were present in the milk collected over four hours<span class="elsevierStyleSup">32</span>&#46; Therefore mothers with GD who are receiving PTU have been advised that breast-feeding their infants is safe<span class="elsevierStyleSup">33&#44;34</span>&#46;</p><p class="elsevierStylePara">In a recent study&#44; serum thyroid hormones in newborns whose mothers were treated with maintenance doses of me thimazole were within the normal range limits<span class="elsevierStyleSup">35</span>&#46; Further studies should be conducted to evaluate the safety of long-term treatment before recommending breast feeding in the mother treated with antithyroid drugs&#46;</p><p class="elsevierStylePara">Not autoimmune gestational hyperthyroidism or gestational transient thyrotoxicosis &#40;GTT&#41; has been also characterized<span class="elsevierStyleSup">36</span>&#46; This form of hyperthyroidism is different from GD&#44; in that it occurs in women without a past history of GD and without detectable thyroid stimulating antibodies&#46; GTT is not always clinically apparent&#44; because it is most often transient&#46; Its etiology is directly related to the thyrotropic stimulation of the thyroid gland associated with hCG&#46;</p><p class="elsevierStylePara">Glinoer et al<span class="elsevierStyleSup">37</span> found an overall prevalence of 2&#46;4&#37; in a prospective cohort study undertaken between the 8th and 14th week of gestation&#46; Symptoms compatible with hyperthyroidism were present&#44; namely weight loss&#44; absence of weight increase&#44; tachycardia and fatigue&#46; Patients with GTT manifested free T4 concentrations in the thyrotoxic range and circulating hCG abnormally elevated&#46; Most women required no treatment with antithyroid drugs and were given beta-blocking agents for a short period&#44; with a noticeable improvement of symptoms&#46; In all cases&#44; GTT was transient and the normalization of free T<span class="elsevierStyleInf">4</span> concentrations paralleled the decrease in hCG&#46; GTT was not associated with a less favourable outcome of pregnancy&#46; The presence of a variant hCG molecule with a potent thyrotropic activity is possible and has been advocated by several authors<span class="elsevierStyleSup">38</span>&#44; although this hypothesis is not absolutely required to explain the disorder&#46; The cause of the anomaly in hCG regulation is presently unknown&#46; Clinicians should be aware of the disorder and closely monitor thyroid function tests and hCG levels in women with symptoms suggesting hyperthyroidism and with early gestational emesis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">POSTPARTUM THYROIDITIS</span></p><p class="elsevierStylePara">Postpartum thyroiditis &#40;PPT&#41; is usually characterized by the development of transient hyperthyroidism and transient hypothyroidism three to six months after delivery&#46; The condition is associated with the presence of circulating anti-TPO in the great majority of cases&#44; and a pathogenetic similarity to Hashimoto&#39;s autoimmune thyroiditis has been suggested&#46; Only half of the women identified as anti-TPO positive at around 12 to 16 weeks gestation will develop PPT&#46; The other 50&#37; will be euthyroid anti-TPO positive in the postpartum period<span class="elsevierStyleSup">39</span>&#46; The incidence of PPT varies from 5-9&#37;<span class="elsevierStyleSup">40</span>&#46; In our area with mild iodine deficiency we found a 5&#46;7&#37; prevalence of PPT at 3 months postpartum &#40;1&#46;9&#37; of patients had hypothyroidism and 3&#46;8&#37; had hyperthyroidism&#41;<span class="elsevierStyleSup">41</span>&#46; In Catalunya&#44; where the iodine intake is sufficient&#44; the reported prevalence was 9&#46;3&#37;<span class="elsevierStyleSup">42</span>&#46; This variation may be due to the frequency of postpartum assessment&#44; especially with regard to the recognition of postpartum hyperthyroidism&#44; which may last only a few weeks&#46; PPT is usually transient&#44; although permanent hypothyroidism may ocur in up to 30&#37; of patients<span class="elsevierStyleSup">43</span>&#46; Lazarus et al<span class="elsevierStyleSup">44</span>&#44; observed that there is about a 70&#37; risk of developing PPT after a subsequent pregnancy if the condition has ocurred previously&#46; Some authors have suggested that the titer of anti-TPO antibodies is a valid predictor of the severity of PPT and possibly of recurrent disease<span class="elsevierStyleSup">45</span>&#46; Although women with PPT after the first pregnancy had a greater incidence of thyroid enlargement than PPT negative TPO-Ab positive women&#44; the presence or absence of goitre is not an accurate predictor of subsequent disease&#46; These data reinforce the suggestion that women who are found to have thyroid dysfunction or circulating thyroid antibodies after pregnancy should be carefully assessed after a second birth&#46; </p><p class="elsevierStylePara"><img src="295C.GIF" width="229" height="126"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">TYPE 1 DIABETES MELLITUS AND AUTOIMMUNE THYROID DISEASE DURING PREGNANCY AND POSTPARTUM</span></p><p class="elsevierStylePara">Type 1 diabetes mellitus is commonly associated with other autoimmune endocrine disorders&#46; Thyroid autoantibodies occur more frequently in these patients than in the normal population<span class="elsevierStyleSup">46</span>&#46; Furthermore&#44; an increased prevalence of subclinical hypothyroidism has been reported in pregnant women with diabetes<span class="elsevierStyleSup">47</span>&#46; Several studies have found a wide range of prevalence of postpartum thyroid dysfunction &#40;10 to 25&#37;&#41; in patients with type 1 diabetes mellitus<span class="elsevierStyleSup">48</span>&#46; This is a 3- fold increase compared to a similar study by the same group in a non-diabetic population&#46;</p><p class="elsevierStylePara">We have shown that the prevalence of a positive test for TPO-Ab is increased in patients with type 1 diabetes mellitus and we reported a prevalence of 38&#37; in our study population&#44; with a higher frequency in women than in men&#46; Our study in patients with type 1 diabetes mellitus showed a fourfold increase in thyroid antibody positivity in comparison with the autoantibody prevalence of 8&#46;7&#37; previously found by our group in healthy subjects<span class="elsevierStyleSup">7</span>&#46;</p><p class="elsevierStylePara">Thus&#44; we studied the immunologic aspects and function of the thyroid gland in women with pregestational diabetes before conception&#44; during pregnancy&#44; and during the immediate postpartum period&#46; Our goal was to evaluate the degree to which thyroid function was affected during these various periods and to determine whether glycemic control and neonatal complications correlated with thyroid status&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Pregestational diabetes and antithyroid antibodies</span></p><p class="elsevierStylePara">Seven our of 20 women &#40;35&#37;&#41; had positive anti-TPO-Ab levels before pregnancy&#46; The level of antibodies progressively declined during pregnancy&#44; but they were never entirely negative&#46; With the anticipated reactivation of the immune system during the postpartum period&#44; 40&#37; &#40;8&#47;20&#41; of the women had positive antibody levels&#46; The prevalence of positive anti-TPO of 38&#37; in these women is equal to that previously described in subjects with type 1 diabetes mellitus<span class="elsevierStyleSup">7</span>&#59; and 3 to 4 times greater that found in the general population before&#44; during&#44; and after pregnancy<span class="elsevierStyleSup">10</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Antithyroid antibodies and thyroid function</span></p><p class="elsevierStylePara">During pregnancy&#44; none of the women with negative antithyroid antibodies had a change in thyroid function&#59; however&#44; in three of the seven patients &#40;43&#37;&#41;&#44; with positive anti TPO-Ab&#44; hypothyroidism &#40;TSH&#62;10 mU&#47;l&#41; developed during pregnancy or the postpartum period and necessitated replacement therapy with thyroid hormone&#46; Of the pregnant women with pregestational diabetes&#44; 15&#37; developed alterations in thyroid function during pregnancy - similar to the rate previously described by Jovanovic and Peterson<span class="elsevierStyleSup">47</span> and 2 to 3 times higher than that found by Gray et al<span class="elsevierStyleSup">49</span> in non-pregnant women with diabetes&#46; In the immediate postpartum period&#44; the prevalence of thyroid dysfunction was also 15&#37; &#40;3 of &#47;20 patients&#41;&#46; In the group with negative antithyroid antibody levels&#44; the prevalence was 8&#37;&#44; significantly less than that seen in the women with positive antibody levels &#173;29&#37; &#40;2 of 7&#41;&#46; The global prevalence of thyroid dysfunction during pregnancy is reported to be between 10&#46;5&#37; found by Bech et al<span class="elsevierStyleSup">48</span> and 25&#37; by &#193;lvarez-Marfany et al<span class="elsevierStyleSup">50</span>&#46; These last two studies conducted postpartum follow-up of patients for 1 year&#44; whereas our study had a 3-month postpartum follow-up<span class="elsevierStyleSup">50</span>&#46;</p><p class="elsevierStylePara">Our prevalence rate may indeed have been greater than 15&#37; had follow-up of patients been continued for up to one year as well&#46; In all studies&#44; the development of thyroid dysfunction was greater in those women with increased anti-TPO-Ab&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Thyroid autoimmunity and glycemic control</span></p><p class="elsevierStylePara">Metabolic control was acceptable for both groups under study with glycosylated hemoglobin &#40;HbA1c &#41; levels below 7&#37; before and during pregnancy&#46; Nevertheless&#44; in the second and third trimesters&#44; HbA1c levels in the group with positive anti-TPO-Ab were significantly higher than in the negative group &#40;table 1&#41;&#46; Another notable point is that&#44; despite both groups having similar characteristics &#40;table 2&#41;&#44; the insulin dose per kilogram of body weight was also significantly higher<span class="elsevierStyleSup">51</span>&#46; These results are in agreement with those reported by Bech et al<span class="elsevierStyleSup">48</span> who also found higher HbA1c levels in pregnant patients with diabetes and positive anti-TPO-Ab than those with negative anti-TPO-Ab&#46; In light of these results and considering the work of Vjvodic et al<span class="elsevierStyleSup">52</span> who suggest that hypothyroidism is a risk factor for gestational diabetes&#44; we must ask whether a relationship exists between insulin resistance in pregnant patients with dia betes and elevated anti-TPO-Ab levels&#46; If there is a relationship with insulin resistance&#44; is it attributable to the hypothyroidism or are the actual anti-thyroid antibodies responsible&#63; The answer continues to be evasive&#46; </p><p class="elsevierStylePara"><img src="295D.GIF" width="229" height="122"></img></p><p class="elsevierStylePara">Thyroid status and fetal outcome</p><p class="elsevierStylePara">In contrast with previous investigations that have found a negative correlation between neonatal outcome and anti-TPO-Ab levels&#44; our study failed to show a correlation between neonatal complications and the presence or absence of antithyroid antibodies<span class="elsevierStyleSup">53</span>&#46; This result is somewhat surprising&#44; and we believe it may&#44; in part&#44; be due to small sample size&#46; We have previously demonstrated increased fetal losses in patients with elevated antithyroid antibodies that have crossed the placenta<span class="elsevierStyleSup">9</span>&#46;</p><p class="elsevierStylePara">The increased prevalence of positive antithyroid antibodies in patients with type 1 diabetes mellitus as well as the relationship with thyroid dysfunction during pregnancy and the postpartum period&#44; in addition to the possible repercussions on maternal glycemic control and ultimately the well-being of the neonate&#44; makes it strongly advisable to screen for antithyroid antibodies routinely in all women with diabetes who are planning pregnancy&#46; Additionally&#44; those testing positively should be monitored with serial free T4 and TSH each trimester and in the postpartum period<span class="elsevierStyleSup">54&#44;55</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">GRATEFULNESS</span></p><p class="elsevierStylePara">This work was supported by grants from National Health Service &#40;1986-1988&#41;&#44; from Andalusian Health Service &#40;1992-1995&#41; and from Fondo de Investigaci&#243;n Sanitaria &#40;1996&#41;&#46;</p>"
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Article information
ISSN: 15750922
Original language: English
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es en pt

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