Thyroid dysfunction during pregnancy | Medicina Clínica (English Edition)

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Díez, Pedro Iglesias, Sergio Donnay" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Juan J." "apellidos" => "Díez" "email" => array:1 [ 0 => "juanjose.diez@salud.madrid.org" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Pedro" "apellidos" => "Iglesias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Sergio" "apellidos" => "Donnay" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Endocrinología y Nutrición, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Disfunción tiroidea y embarazo" ] ] "textoCompleto" => "IntroductionIn recent years, various scientific societies have issued their recommendations on the diagnosis and treatment of thyroid dysfunction during pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0230">1–8</a> The publication of the guides has had an impact on the actual treatment of pregnant women in both primary and specialized care. However, many of the recommendations are based on data from a small number of research ventures or scientific evidence of questionable quality. Furthermore, the guides differ in some key aspects, such as screening for thyroid dysfunction, in which the American Thyroid Association (ATA)<a class="elsevierStyleCrossRef" href="#bib0250">5</a> only recommends selective screening (SS) for the population at risk, while the Endocrine Society (ES)<a class="elsevierStyleCrossRef" href="#bib0255">6</a> offers private opinions, and the Spanish Society of Endocrinology and Nutrition (SEEN)<a class="elsevierStyleCrossRefs" href="#bib0240">3,7</a> advocates for universal screening (US).This review explains the most controversial aspects of the different forms of thyroid dysfunction that can complicate pregnancy. Their frequency of presentation (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)<a class="elsevierStyleCrossRefs" href="#bib0235">2,5,6,9,10</a> and healthcare importance are well known.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>HypothyroidismDiagnostic criteriaFor the diagnosis of hypothyroidism in the first trimester of pregnancy it is necessary to have clear criteria regarding the normal upper limit of the thyroid-stimulating hormone (TSH). The guidelines recommend this limit to be 2.5mU/l for the first trimester and 3.0mU/l for the second and third trimesters,<a class="elsevierStyleCrossRefs" href="#bib0235">2,5,6,8</a> but they stress that these limits should be applied only in cases where there are no characteristic reference intervals for each trimester.During the first trimester of the FaSTER study,<a class="elsevierStyleCrossRef" href="#bib0280">11</a> performed on 10,990 pregnant women, the normal upper limit of TSH was 4.28mU/l. Studies in Spain show similar results. In Catalonia, Vila et al.,<a class="elsevierStyleCrossRef" href="#bib0285">12</a> found that the upper limit for TSH was 5.76mU/l. In Aragon<a class="elsevierStyleCrossRef" href="#bib0290">13</a> this limit was somewhat lower (2.63mU/l), while in El Bierzo (3.59mU/l),<a class="elsevierStyleCrossRef" href="#bib0295">14</a> Cartagena (3.71mU/l),<a class="elsevierStyleCrossRef" href="#bib0300">15</a> Jaen (4.18mU/l)<a class="elsevierStyleCrossRef" href="#bib0305">16</a> and Valladolid (4.05mU/l)<a class="elsevierStyleCrossRef" href="#bib0310">17</a> the results are clearly above 2.5mU/l.Isolated hypothyroxinaemia is characterized by a decrease in the concentration of free thyroxine (T4) with normal TSH. Its diagnosis is difficult because the usual immunoassays in clinical laboratories do not determine the concentration of Free T4 in pregnancy reliably due to the physiological changes during pregnancy.<a class="elsevierStyleCrossRef" href="#bib0250">5</a> Therefore, in the absence of characteristic reference values, we can use the criteria listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.Impact of hypothyroidismOvert hypothyroidism is associated with maternal adverse effects (hypertension-preeclampsia, placental abruption, abortion, caesarean section, postpartum haemorrhage) and foetal adverse effects (preterm birth, low birth weight and increased perinatal morbidity and mortality),<a class="elsevierStyleCrossRefs" href="#bib0250">5,6</a> but these associations are not evident in the subclinical state. The FaSTER study found no association between subclinical hypothyroidism or hypothyroxinaemia and obstetric adverse effects.<a class="elsevierStyleCrossRef" href="#bib0280">11</a> Pregnant women with high TSH according to ATA and ES cut-offs, had no increased risk of preterm birth based on the Generation R study findings.<a class="elsevierStyleCrossRef" href="#bib0315">18</a>Impact of hypothyroidism on the offspring's neurocognitive development was established through the Haddow et al. study,<a class="elsevierStyleCrossRef" href="#bib0320">19</a> which showed that children born to hypothyroid mothers had a lower intelligence quotient (IQ) at 7–9 years of age compared to euthyroid women children. Isolated hypothyroxinaemia has also been associated with delayed motor and mental development in some studies,<a class="elsevierStyleCrossRefs" href="#bib0325">20,21</a> but not in others.<a class="elsevierStyleCrossRef" href="#bib0335">22</a> The recent Controlled Antenatal Thyroid Screening (CATS) study<a class="elsevierStyleCrossRef" href="#bib0340">23</a> evaluated 21,846 pregnant women randomized into a control group and a US group. Among the women who were diagnosed with hypothyroidism, 390 were treated with levothyroxine (L-T4) and 404 were untreated, with no IQ differences between the groups in children at 3 years of age.Following the above, both SEEN<a class="elsevierStyleCrossRef" href="#bib0240">3</a> and ES<a class="elsevierStyleCrossRef" href="#bib0255">6</a> recommend treatment in subclinical hypothyroidism regardless of antibody titre, while ATA<a class="elsevierStyleCrossRef" href="#bib0250">5</a> recommends treatment only in women with subclinical hypothyroidism with positive antithyroid antibodies. None of the guidelines recommends treatment for isolated hypothyroxinaemia.Thyroid autoimmunityPregnancies in euthyroid women with positive anti-thyroid peroxidase (aTPO, “thyroid peroxidase antibodies”) are associated with an increased risk of abortion and premature birth.<a class="elsevierStyleCrossRefs" href="#bib0275">10,24,25</a> Some authors have also found an association with delayed intellectual and motor development in the offspring.<a class="elsevierStyleCrossRef" href="#bib0325">20</a>Treatment with L-T4 has been used only in a small number of euthyroid pregnant women with positive autoimmunity. The study of Black et al.<a class="elsevierStyleCrossRef" href="#bib0350">25</a> included a group of 57 pregnant women with positive aTPO treated with L-T4, another group of 58 aTPO positive, untreated, and a control group of 869 with negative autoimmunity. The abortion and preterm delivery rates were significantly higher in women with positive aTPO, untreated, compared with those treated or those in the control group.<a class="elsevierStyleCrossRef" href="#bib0350">25</a>Since women with positive aTPO known before pregnancy have an increased risk of developing hypothyroidism during pregnancy, the guidelines recommend determining serum TSH during the first half of pregnancy every 4 weeks and at least once between weeks 26 and 32.<a class="elsevierStyleCrossRef" href="#bib0250">5</a> However, this protective approach applies only to women who know their antibody status. The guidelines consider that there is insufficient evidence to recommend screening antibodies during the first trimester.<a class="elsevierStyleCrossRefs" href="#bib0250">5,6</a> There is no strong evidence to justify recommending treatment with L-T4 to antibody positive euthyroid women.HyperthyroidismDiagnostic criteriaThe lower limit of normal TSH also varies with gestational age and the population studied.<a class="elsevierStyleCrossRef" href="#bib0355">26</a> In Spain, we found values of 0.1–0.5mU/l for the first trimester, from 0.21 to 0.36mU/l for the second, and from 0.29 to 0.36mU/l for the third.<a class="elsevierStyleCrossRefs" href="#bib0285">12–16</a> In case of not having the characteristic intervals, the guidelines recommend of 0.1, 0.2 and 0.3mU/l as the lower limits of normal TSH values for the first, second and third trimesters, respectively.<a class="elsevierStyleCrossRefs" href="#bib0235">2,5,6</a>From a practical standpoint, the diagnosis of clinical and subclinical hyperthyroidism in pregnant women can be established with the values shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. In total hormone determination, it should be noted that the normal upper limit during pregnancy is 50% higher than non-pregnant women.<a class="elsevierStyleCrossRefs" href="#bib0235">2,4–6</a>Differential diagnosisThe main causes of hyperthyroidism during pregnancy are gestational hyperthyroidism and Graves’ disease (GD) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0250">5,27</a> The former is carried out by increasing the placenta's human chorionic gonadotropin (hCG) (which can stimulate the TSH receptor) in the first 10–12 weeks of pregnancy. The degree of hyperthyroidism depends on the serum hCG<a class="elsevierStyleCrossRef" href="#bib0365">28</a> and often disappears after the first trimester.<a class="elsevierStyleCrossRef" href="#bib0365">28</a> The GD develops as a consequence of TSH receptor antibodies production (TRAb, “Thyrotropin Receptor Antibodies”), which are detectable in >95% of cases. It is characterized by typical manifestations of hyperthyroidism: goitre and ophthalmopathy.<a class="elsevierStyleCrossRef" href="#bib0360">27</a> Other causes of hyperthyroidism are rare.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The differentiation of these two main forms of hyperthyroidism (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>) is critical because the gestational type usually asymptomatic and transient, it is not associated with foetal obstetric complications, and therefore does not require specific treatment, while untreated GD can lead to severe maternal and foetal complications.<a class="elsevierStyleCrossRefs" href="#bib0245">4–6</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Treatment indications and risksThe maternal and foetal risks of clinical hyperthyroidism were documented in a recent study evaluating the prognosis of 208 hyperthyroid pregnant women compared to 403 healthy ones.<a class="elsevierStyleCrossRef" href="#bib0370">29</a> Maternal and foetal complications were more frequent in hyperthyroid women than in euthyroid women. In addition, the prognosis was worse in the poorly controlled hyperthyroid. There is, however, no evidence that subclinical hyperthyroidism is harmful to pregnancy, so treatment is not justified.Regular observation of thyroid function every 3–4 weeks is indicated in cases of gestational transient hyperthyroidism. A trial treatment with antithyroid agents would only be indicated in cases where the etiological diagnosis of hyperthyroidism is not clear.<a class="elsevierStyleCrossRefs" href="#bib0245">4–6</a>The guides agree that antithyroid agents are the treatment of choice for GD during pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0245">4–6</a> Although birth defects have been reported in 2–3% of infants exposed to antithyroid agents during organogenesis,<a class="elsevierStyleCrossRef" href="#bib0375">30</a> the drug currently recommended during the first trimester is propylthiouracil (PTU), and appears to be less teratogenic than methimazole (MMI).<a class="elsevierStyleCrossRefs" href="#bib0250">5,6,30</a> MMI could be used in this period if PTU is not available or in case of intolerance or inadequate response to it. Furthermore, given that PTU is sometimes associated to severe liver toxicity, it is recommended to monitor liver function and change every 3–4 weeks from PTU to MMI, starting the second trimester of pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0250">5,6</a>The aim of drug treatment is to use the lowest dose of antithyroid agents in order to keep the Free T4 concentration in the upper limit or just above the reference interval for nonpregnant women, or achieve a total T4 concentration of 1.5 times the normal upper limit.<a class="elsevierStyleCrossRefs" href="#bib0245">4,6</a>It is important to determine TRAb values from week 20 to 24 in pregnant women with present or past GD, because by crossing the placenta, they stimulate the foetal thyroid, leading to foetal hyperthyroidism.<a class="elsevierStyleCrossRef" href="#bib0375">30</a> This risk virtually disappears in pregnant women with undetectable TRAb values at the end of pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0250">5,6,29,30</a>Postpartum thyroiditisPostpartum thyroiditis (PPT) is an autoimmune destructive thyroid disease that develops within the first year after birth.<a class="elsevierStyleCrossRef" href="#bib0380">31</a> Its prevalence in the general population is ∼8%,<a class="elsevierStyleCrossRef" href="#bib0435">42</a> although there are different risk groups such as pregnant women with aTPO during pregnancy (40–60% prevalence), GD in remission (44%), history of previous PPT (42%), chronic viral hepatitis (25%), family history of thyroid disease (20%), diabetes mellitus type 1 (20%) and systemic lupus erythematosus (14%).<a class="elsevierStyleCrossRefs" href="#bib0250">5,6,32</a>A data analysis from 21 studies shows that most (∼48%) women with PPT experience an isolated episode of hypothyroidism while hyperthyroidism is present in ∼30%.<a class="elsevierStyleCrossRef" href="#bib0380">31</a> Only 22% of PPT cases manifest themselves in the classical form with a transient hyperthyroidism phase of 1–2 months, followed by another transient hypothyroidism phase of variable duration (∼2–3 months), with spontaneous recovery of the thyroid function, although some patients may be left with permanent hypothyroidism.<a class="elsevierStyleCrossRef" href="#bib0255">6</a>At present the guidelines do not recommend US for PPT. Screening only seems appropriate in women belonging to the previously mentioned risk groups. In this case the TSH should be monitored at 3 and 6 months postpartum.<a class="elsevierStyleCrossRef" href="#bib0255">6</a>Iodine requirementsThe iodine nutrition status of an individual or population can be determined by various indicators.<a class="elsevierStyleCrossRef" href="#bib0390">33</a> Those proposed by the European Commission,<a class="elsevierStyleCrossRef" href="#bib0390">33</a> as well as the recommended iodine intake are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. Iodine deficiency (ID) in pregnant women causes hypothyroxinaemia affecting foetal brain development. The beneficial effects of severe maternal ID correction on the psychoneurological development of the child,<a class="elsevierStyleCrossRef" href="#bib0395">34</a> as well as several meta-analyses demonstrating IQ reduction in 12–13.5 points in children with ID,<a class="elsevierStyleCrossRef" href="#bib0400">35</a> confirm the importance of severe ID. Similarly, mild and moderate ID can cause major foetal and maternal complications. It has been associated with an increased risk of maternal and foetal goitre,<a class="elsevierStyleCrossRef" href="#bib0405">36</a> and with intellectual impairment in the offspring.<a class="elsevierStyleCrossRef" href="#bib0410">37</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Since 2004, our country is listed by WHO among those with optimal iodine nutrition. However, a recent article<a class="elsevierStyleCrossRef" href="#bib0415">38</a> warns about the risk of ID reappearing if such nutritional deficiency was corrected by a silent or uncontrolled iodine prophylaxis. Recent studies<a class="elsevierStyleCrossRef" href="#bib0420">39</a> show ID persistence in pregnant population, therefore, SEEN maintains the specific recommendation of potassium iodide prescription before pregnancy, and, if possible, during the same and also during lactation.<a class="elsevierStyleCrossRef" href="#bib0425">40</a>Given the impossibility to identify by any means the individual ID risk of a pregnant woman, ATA<a class="elsevierStyleCrossRef" href="#bib0250">5</a> and ES<a class="elsevierStyleCrossRef" href="#bib0255">6</a> guidelines recommend daily supplementation with at least 150μg of iodine in all women planning pregnancy or who are pregnant or breastfeeding. The ES<a class="elsevierStyleCrossRef" href="#bib0255">6</a> also recommends, with a good degree of evidence that the risk assessment during pregnancy ID should be established basically depending on whether a country is in a situation of iodine sufficiency or iodine deficiency, and the availability or not of well-developed universal salt iodization (USI) programmes. According to these criteria, given the persistence of ID in part of the pregnant population and the absence of USI programmes in our country, the proposed recommendation<a class="elsevierStyleCrossRef" href="#bib0425">40</a> of universal iodine supplementation during pregnancy and lactation should be maintained.Screening for thyroid dysfunctionUS of pregnant women to detect hypothyroidism during the first trimester of pregnancy remain controversial. A single interventional study,<a class="elsevierStyleCrossRef" href="#bib0430">41</a> which proved the foetal and maternal benefits of treatment with L-T4 in pregnant women with subclinical hypothyroidism during the first trimester, pointed to the possible convenience of US. However, CATS<a class="elsevierStyleCrossRef" href="#bib0340">23</a> study, which demonstrated no benefit of L-T4 on neurocognitive development in children of mothers with hypothyroidism, has conditioned that almost all scientific societies,<a class="elsevierStyleCrossRefs" href="#bib0230">1,5,6</a> based on the lack of evidence regarding the potential benefits of such a measure, discourage the US and advocate SS in population at risk (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>There are arguments for and against US (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>). In addition, some events might question the exclusive performance of SS. With this procedure, a 33–81% of pregnant hypothyroid women would go undetected.<a class="elsevierStyleCrossRefs" href="#bib0270">9,42,43</a> Furthermore, the amplitude criteria applied to our pregnant population (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>) for SS proposed by ATA<a class="elsevierStyleCrossRef" href="#bib0250">5</a> and ES<a class="elsevierStyleCrossRef" href="#bib0255">6</a> would determine, in practice, an almost universal screening.<elsevierMultimedia ident="tbl0030"></elsevierMultimedia>The US cost-benefit studies are additional arguments for this strategy. The Dosiou et al.<a class="elsevierStyleCrossRef" href="#bib0445">44</a> study concluded that US for the detection of hypothyroidism in pregnant women is cost-effective even when compared with the screening of high-risk women.Although the official position of the different scientific societies maintains the SS recommendation, routine clinical practice seems to distance itself from this position. At a meeting of the ATA, over 70% of physicians surveyed were in favour of US in pregnant women through TSH<a class="elsevierStyleCrossRef" href="#bib0450">45</a> determination. Finally, in 2009 and 2012, SEEN<a class="elsevierStyleCrossRefs" href="#bib0240">3,7</a> clearly favoured US regarding thyroid dysfunction detection in pregnant women.In conclusion, US implementation still requires more quality evidence which unequivocally justifies it. This can probably be achieved once some randomized studies currently under development are completed. Until then, US aimed at early diagnosis and treatment of overt hypothyroidism seems reasonable, as the potential maternal and foetal benefits are well above the disadvantages of this test. However, US would require the availability of reference values for TSH and L-T4 specific to each laboratory, as those proposed by some societies<a class="elsevierStyleCrossRefs" href="#bib0230">1,5,6</a> may overestimate the prevalence of thyroid dysfunction in pregnant women in Spain.<a class="elsevierStyleCrossRef" href="#bib0310">17</a>Conclusion and forward-looking visionThe currently valid guidelines and consensus fulfil their mission to facilitate the work of clinicians, but they must change according to the results of future research. As regard diagnosis, efforts need to be made so that the different healthcare areas have their own reference intervals, at least regarding TSH and Free T4, for each of the pregnancy trimesters. As to screening, risk criteria must be redefined with greater precision. The timing of screening should also be specified more precisely, as the critical neurodevelopmental period occurs early.As regard treatment, the iodine sufficiency must be guaranteed in all pregnant women, as its benefits are beyond doubt. Randomized and controlled trials conducted on a large number of patients to be published in the near future may clarify whether early treatment of different forms of thyroid dysfunction during pregnancy is associated with a reduction in obstetric complications or a positive impact on the offspring's neurodevelopment.Conflict of interestsThe authors declare no conflict of interests regarding this article." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres625687" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec638846" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres625686" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec638847" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Hypothyroidism" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Diagnostic criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Impact of hypothyroidism" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Thyroid autoimmunity" ] 7 => array:3 [ "identificador" => "sec0030" "titulo" => "Hyperthyroidism" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Diagnostic criteria" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Differential diagnosis" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Treatment indications and risks" ] ] ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Postpartum thyroiditis" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Iodine requirements" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Screening for thyroid dysfunction" ] 11 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusion and forward-looking vision" ] 12 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interests" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-07-24" "fechaAceptado" => "2014-08-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec638846" "palabras" => array:4 [ 0 => "Hypothyroidism" 1 => "Hyperthyroidism" 2 => "Pregnancy" 3 => "Clinical practice guidelines" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec638847" "palabras" => array:4 [ 0 => "Hipotiroidismo" 1 => "Hipertiroidismo" 2 => "Gestación" 3 => "Guías de práctica clínica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves’ disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Las recientes guías clínicas sobre disfunción tiroidea y embarazo han cambiado la atención sanitaria que se presta a la mujer gestante, pero sus recomendaciones están en constante revisión. Existe la necesidad de disponer de valores de referencia de la hormona estimulante del tiroides por trimestre y área geográfica para el correcto diagnóstico de disfunción tiroidea. No hay dudas sobre la necesidad de tratamiento del hipotiroidismo franco, pero hay opiniones variables sobre el tratamiento del subclínico. Los efectos adversos de la hipotiroxinemia aislada y de la autoinmunidad tiroidea requieren nuevas investigaciones. Es fundamental diferenciar el hipertiroidismo por enfermedad de Graves del llamado hipertiroidismo gestacional transitorio, habitualmente autolimitado. Es importante reconocer los factores de riesgo para la tiroiditis posparto. Para evitar graves consecuencias en la descendencia, se recomienda mantener una adecuada nutrición de yodo durante el embarazo mediante suplementos de este oligoelemento. Continúa la polémica sobre el cribado universal o selectivo de disfunción tiroidea durante la gestación, aunque las tendencias de algunas sociedades y de los últimos estudios de coste-beneficio son favorables al cribado universal. Los estudios aleatorizados y controlados en desarrollo actualmente deberán reducir las incertidumbres que aún persisten en el área de la disfunción tiroidea y el embarazo." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Díez JJ, Iglesias P, Donnay S. Disfunción tiroidea y embarazo. Med Clin (Barc). 2015;145:344–349." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "TgAb: thyroglobulin antibodies; aTPO: anti-thyroid peroxidase; LLN: lower limit of normal; ULN: upper limit of normal; TSH: thyroid-stimulating hormone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnosis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prevalence (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Hypothyroidism</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overt hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH≥10mU/l or TSH>2.5mU/l with Free T4<LLN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2–0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subclinical hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH>2.5mU/l with normal Free T4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2–4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Isolated hypothyroxinaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH≤2.5mU/l with Free T4<5–10 percentile \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1–2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Hypothyroidism</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overt hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH<0.01mU/l or TSH<0.1mU/l with Free T4 and Free T3>ULN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1–0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subclinical hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH<0.1mU/l with normal Free T4 and Free T3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6–1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Thyroid autoimmunity</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive antithyroid antibodies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">aTPO or TgAb>ULN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–20 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026511.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnostic criteria and prevalence of different forms of thyroid dysfunction during pregnancy." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "hCG: human chorionic gonadotropin; TRAb: thyroid-stimulating hormone receptor antibodies; TSH: thyroid-stimulating hormone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pathogenic mechanism \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">hCG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational transient thyrotoxicosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperemesis gravidarum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational trophoblastic disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hydatidiform mole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Choriocarcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TRAb \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Graves’ disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nodular hyperthyroidism disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nodular autonomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autonomous hyperfunctioning nodule \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Toxic multinodular goitre \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperthyroidism associated with thyroiditis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tissue destruction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Silent thyroiditis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Subacute thyroiditis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Miscellaneous</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exogenous thyrotoxicosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Levothyroxine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overdose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Factitious \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amiodarone, iodine, lithium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TSH-producing pituitary adenoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Familial gestational hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TSH Thyroid receptor hypersensitivity to hCG \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026514.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main causes and pathogenic mechanisms of hyperthyroidism during pregnancy." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "aTPO: anti-thyroid peroxidase; TRAb: thyroid-stimulating hormone receptor antibodies; T3: triiodothyronine; T4: thyroxine; −: absent or negative; +: present or positive." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gestational transient thyrotoxicosis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperthyroidism due to Graves’ disease \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family history of autoimmune thyroid disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other autoimmune diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">At diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">First trimester \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any trimester/pregestational \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Twin pregnancies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea and vomiting \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+/− \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperthyroidism pregestational symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptoms of hyperthyroidism during pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+/− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Goitre \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ophthalmopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3/T4 ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">aTPO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TRAb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstetric complications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk of foetal and neonatal hyperthyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Self-limited (∼first trimester) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unpredictable \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026515.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key differentiating characteristics of transient gestational thyrotoxicosis and hyperthyroidism due to Graves’ disease during pregnancy." ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "UIC: urinary iodine concentration; UIE: urinary iodine excretion; TSH: thyroid-stimulating hormone.Adapted from EFSA.<a class="elsevierStyleCrossRef" href="#bib0390">33</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Iodine intake markers</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Urinary iodine excretion</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Represents >90% of the daily intake of iodine</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Excellent recent iodine intake marker</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">While 24h UIE is preferable, spontaneous urine UIE mean values are used for assessing the demographic nutrition status of iodine</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">For an individual assessment with an accuracy of 20%, at least 10 consecutive 24h UIE determinations are required</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Iodine nutrition status markers</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Urinary iodine concentration</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Median UIC is used to define the iodine nutrition status of a specific population.</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Normal values have been defined depending on age and other conditions</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Thyroglobulin</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">It is a good marker of iodine nutrition status, especially in children and adolescents</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">TSH and thyroid hormones</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Primarily value thyroid function and secondarily iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Thyroid volume</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">It represents a marker of long-term iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">It can be determined by palpation or, more precisely, by ultrasound volumetric measurement</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">In epidemiological studies, the prevalence of goitre is another marker of iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Adequate iodine intake</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Adequate intake (μg/day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7–11 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1–10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11–14 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">120 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15–17 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥18 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Breastfeeding woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026513.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Intake and iodine nutrition status indicators." ] ] 4 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "aTPO: anti-thyroid peroxidase.Adapted from Abalovich et al.,<a class="elsevierStyleCrossRef" href="#bib0235">2</a> Stagnaro-Green et al.,<a class="elsevierStyleCrossRef" href="#bib0250">5</a> and De Groot et al.<a class="elsevierStyleCrossRef" href="#bib0255">6</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous history of thyroid disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family history of autoimmune thyroid disease, or hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Personal history of previous thyroid surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Personal history of craniocervical irradiation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptoms or signs in the current pregnancy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Goitre \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptoms or signs suggestive of thyroid disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current levothyroxine treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Presence of antithyroid antibodies, especially aTPO \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Type 1 diabetes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Another autoimmune disease (vitiligo, adrenal failure, hypoparathyroidism, atrophic gastritis, pernicious anaemia, etc.) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous obstetric history \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infertility \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous history of abortions or preterm deliveries \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other risk factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age>30 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morbid obesity (BMI≥40kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Women treated with amiodarone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Women treated with lithium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Living in regions with alleged iodine deficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recent exposure (6 weeks) to iodinated contrast agents \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026516.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factor groups for selective screening of thyroid dysfunction as recommended by the current clinical practice guidelines." ] ] 5 => array:7 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">In favour \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Against \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High prevalence of subclinical hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complications not clearly demonstrated in subclinical hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstetric complications demonstrated in clinical thyroid dysfunction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No effect on the IQ of the offspring during a trial \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Implications in the offspring's neurocognitive development \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doubts about the impact of isolated hypothyroxinaemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Detectable and treatable early stage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doubts about the impact of antithyroid antibodies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Easy analytical screening in first trimester \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Subclinical hyperthyroidism and transient gestational not associated with foetal morbidity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Effective, acceptable and inexpensive treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Possibility of inadequate dosing in pregnant women with subclinical hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potential treatment benefits for the mother and the offspring \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Possible misinterpretation of thyroid function tests by non-expert doctors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive cost-benefit balance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1026512.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Arguments for and against the implementation of a universal screening for thyroid dysfunction in pregnant women during the first trimester." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0230" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ACOG practice bulletin. 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Thyroid dysfunction during pregnancy

Disfunción tiroidea y embarazo

Juan J. Díeza,b,

Corresponding author

juanjose.diez@salud.madrid.org

Corresponding author.

, Pedro Iglesiasa, Sergio Donnayc

a Servicio de Endocrinología, Hospital Universitario Ramón y Cajal, Madrid, Spain

b Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, Spain

c Unidad de Endocrinología y Nutrición, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; various scientific societies have issued their recommendations on the diagnosis and treatment of thyroid dysfunction during pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#8211;8</span></a> The publication of the guides has had an impact on the actual treatment of pregnant women in both primary and specialized care&#46; However&#44; many of the recommendations are based on data from a small number of research ventures or scientific evidence of questionable quality&#46; Furthermore&#44; the guides differ in some key aspects&#44; such as screening for thyroid dysfunction&#44; in which the <span class="elsevierStyleItalic">American Thyroid Association</span> &#40;ATA&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> only recommends selective screening &#40;SS&#41; for the population at risk&#44; while the <span class="elsevierStyleItalic">Endocrine Society</span> &#40;ES&#41;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> offers private opinions&#44; and the Spanish Society of Endocrinology and Nutrition &#40;SEEN&#41;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;7</span></a> advocates for universal screening &#40;US&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This review explains the most controversial aspects of the different forms of thyroid dysfunction that can complicate pregnancy&#46; Their frequency of presentation &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;5&#44;6&#44;9&#44;10</span></a> and healthcare importance are well known&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Hypothyroidism</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnostic criteria</span><p id="par0015" class="elsevierStylePara elsevierViewall">For the diagnosis of hypothyroidism in the first trimester of pregnancy it is necessary to have clear criteria regarding the normal upper limit of the <span class="elsevierStyleItalic">thyroid-stimulating hormone</span> &#40;TSH&#41;&#46; The guidelines recommend this limit to be 2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l for the first trimester and 3&#46;0<span class="elsevierStyleHsp" style=""></span>mU&#47;l for the second and third trimesters&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;5&#44;6&#44;8</span></a> but they stress that these limits should be applied only in cases where there are no characteristic reference intervals for each trimester&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">During the first trimester of the FaSTER study&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">11</span></a> performed on 10&#44;990 pregnant women&#44; the normal upper limit of TSH was 4&#46;28<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#46; Studies in Spain show similar results&#46; In Catalonia&#44; Vila et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">12</span></a> found that the upper limit for TSH was 5&#46;76<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#46; In Aragon<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">13</span></a> this limit was somewhat lower &#40;2&#46;63<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;&#44; while in El Bierzo &#40;3&#46;59<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a> Cartagena &#40;3&#46;71<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a> Jaen &#40;4&#46;18<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">16</span></a> and Valladolid &#40;4&#46;05<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a> the results are clearly above 2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Isolated hypothyroxinaemia is characterized by a decrease in the concentration of free thyroxine &#40;T4&#41; with normal TSH&#46; Its diagnosis is difficult because the usual immunoassays in clinical laboratories do not determine the concentration of Free T4 in pregnancy reliably due to the physiological changes during pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> Therefore&#44; in the absence of characteristic reference values&#44; we can use the criteria listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Impact of hypothyroidism</span><p id="par0030" class="elsevierStylePara elsevierViewall">Overt hypothyroidism is associated with maternal adverse effects &#40;hypertension-preeclampsia&#44; <span class="elsevierStyleItalic">placental abruption</span>&#44; abortion&#44; caesarean section&#44; postpartum haemorrhage&#41; and foetal adverse effects &#40;preterm birth&#44; low birth weight and increased perinatal morbidity and mortality&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6</span></a> but these associations are not evident in the subclinical state&#46; The FaSTER study found no association between subclinical hypothyroidism or hypothyroxinaemia and obstetric adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">11</span></a> Pregnant women with high TSH according to ATA and ES cut-offs&#44; had no increased risk of preterm birth based on the Generation R study findings&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">18</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Impact of hypothyroidism on the offspring&#39;s neurocognitive development was established through the Haddow et al&#46; study&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">19</span></a> which showed that children born to hypothyroid mothers had a lower intelligence quotient &#40;IQ&#41; at 7&#8211;9 years of age compared to euthyroid women children&#46; Isolated hypothyroxinaemia has also been associated with delayed motor and mental development in some studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">20&#44;21</span></a> but not in others&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">22</span></a> The recent <span class="elsevierStyleItalic">Controlled Antenatal Thyroid Screening</span> &#40;CATS&#41; study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">23</span></a> evaluated 21&#44;846 pregnant women randomized into a control group and a US group&#46; Among the women who were diagnosed with hypothyroidism&#44; 390 were treated with levothyroxine &#40;L-T4&#41; and 404 were untreated&#44; with no IQ differences between the groups in children at 3 years of age&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Following the above&#44; both SEEN<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> and ES<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> recommend treatment in subclinical hypothyroidism regardless of antibody titre&#44; while ATA<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> recommends treatment only in women with subclinical hypothyroidism with positive antithyroid antibodies&#46; None of the guidelines recommends treatment for isolated hypothyroxinaemia&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Thyroid autoimmunity</span><p id="par0045" class="elsevierStylePara elsevierViewall">Pregnancies in euthyroid women with positive <span class="elsevierStyleItalic">anti-thyroid peroxidase</span> &#40;aTPO&#44; &#8220;thyroid peroxidase antibodies&#8221;&#41; are associated with an increased risk of abortion and premature birth&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">10&#44;24&#44;25</span></a> Some authors have also found an association with delayed intellectual and motor development in the offspring&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">20</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment with L-T4 has been used only in a small number of euthyroid pregnant women with positive autoimmunity&#46; The study of Black et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">25</span></a> included a group of 57 pregnant women with positive aTPO treated with L-T4&#44; another group of 58 aTPO positive&#44; untreated&#44; and a control group of 869 with negative autoimmunity&#46; The abortion and preterm delivery rates were significantly higher in women with positive aTPO&#44; untreated&#44; compared with those treated or those in the control group&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">25</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Since women with positive aTPO known before pregnancy have an increased risk of developing hypothyroidism during pregnancy&#44; the guidelines recommend determining serum TSH during the first half of pregnancy every 4 weeks and at least once between weeks 26 and 32&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> However&#44; this protective approach applies only to women who know their antibody status&#46; The guidelines consider that there is insufficient evidence to recommend screening antibodies during the first trimester&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6</span></a> There is no strong evidence to justify recommending treatment with L-T4 to antibody positive euthyroid women&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Hyperthyroidism</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Diagnostic criteria</span><p id="par0060" class="elsevierStylePara elsevierViewall">The lower limit of normal TSH also varies with gestational age and the population studied&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">26</span></a> In Spain&#44; we found values of 0&#46;1&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l for the first trimester&#44; from 0&#46;21 to 0&#46;36<span class="elsevierStyleHsp" style=""></span>mU&#47;l for the second&#44; and from 0&#46;29 to 0&#46;36<span class="elsevierStyleHsp" style=""></span>mU&#47;l for the third&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">12&#8211;16</span></a> In case of not having the characteristic intervals&#44; the guidelines recommend of 0&#46;1&#44; 0&#46;2 and 0&#46;3<span class="elsevierStyleHsp" style=""></span>mU&#47;l as the lower limits of normal TSH values for the first&#44; second and third trimesters&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;5&#44;6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">From a practical standpoint&#44; the diagnosis of clinical and subclinical hyperthyroidism in pregnant women can be established with the values shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; In total hormone determination&#44; it should be noted that the normal upper limit during pregnancy is 50&#37; higher than non-pregnant women&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2&#44;4&#8211;6</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Differential diagnosis</span><p id="par0070" class="elsevierStylePara elsevierViewall">The main causes of hyperthyroidism during pregnancy are gestational hyperthyroidism and Graves&#8217; disease &#40;GD&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;27</span></a> The former is carried out by increasing the placenta&#39;s <span class="elsevierStyleItalic">human chorionic gonadotropin</span> &#40;hCG&#41; &#40;which can stimulate the TSH receptor&#41; in the first 10&#8211;12 weeks of pregnancy&#46; The degree of hyperthyroidism depends on the serum hCG<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">28</span></a> and often disappears after the first trimester&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">28</span></a> The GD develops as a consequence of <span class="elsevierStyleItalic">TSH receptor antibodies</span> production &#40;TRAb&#44; &#8220;Thyrotropin Receptor Antibodies&#8221;&#41;&#44; which are detectable in &#62;95&#37; of cases&#46; It is characterized by typical manifestations of hyperthyroidism&#58; goitre and ophthalmopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a> Other causes of hyperthyroidism are rare&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The differentiation of these two main forms of hyperthyroidism &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; is critical because the gestational type usually asymptomatic and transient&#44; it is not associated with foetal obstetric complications&#44; and therefore does not require specific treatment&#44; while untreated GD can lead to severe maternal and foetal complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">4&#8211;6</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment indications and risks</span><p id="par0080" class="elsevierStylePara elsevierViewall">The maternal and foetal risks of clinical hyperthyroidism were documented in a recent study evaluating the prognosis of 208 hyperthyroid pregnant women compared to 403 healthy ones&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a> Maternal and foetal complications were more frequent in hyperthyroid women than in euthyroid women&#46; In addition&#44; the prognosis was worse in the poorly controlled hyperthyroid&#46; There is&#44; however&#44; no evidence that subclinical hyperthyroidism is harmful to pregnancy&#44; so treatment is not justified&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regular observation of thyroid function every 3&#8211;4 weeks is indicated in cases of gestational transient hyperthyroidism&#46; A trial treatment with antithyroid agents would only be indicated in cases where the etiological diagnosis of hyperthyroidism is not clear&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The guides agree that antithyroid agents are the treatment of choice for GD during pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">4&#8211;6</span></a> Although birth defects have been reported in 2&#8211;3&#37; of infants exposed to antithyroid agents during organogenesis&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a> the drug currently recommended during the first trimester is propylthiouracil &#40;PTU&#41;&#44; and appears to be less teratogenic than methimazole &#40;MMI&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6&#44;30</span></a> MMI could be used in this period if PTU is not available or in case of intolerance or inadequate response to it&#46; Furthermore&#44; given that PTU is sometimes associated to severe liver toxicity&#44; it is recommended to monitor liver function and change every 3&#8211;4 weeks from PTU to MMI&#44; starting the second trimester of pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The aim of drug treatment is to use the lowest dose of antithyroid agents in order to keep the Free T4 concentration in the upper limit or just above the reference interval for nonpregnant women&#44; or achieve a total T4 concentration of 1&#46;5 times the normal upper limit&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">4&#44;6</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">It is important to determine TRAb values from week 20 to 24 in pregnant women with present or past GD&#44; because by crossing the placenta&#44; they stimulate the foetal thyroid&#44; leading to foetal hyperthyroidism&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a> This risk virtually disappears in pregnant women with undetectable TRAb values at the end of pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6&#44;29&#44;30</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Postpartum thyroiditis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Postpartum thyroiditis &#40;PPT&#41; is an autoimmune destructive thyroid disease that develops within the first year after birth&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a> Its prevalence in the general population is &#8764;8&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">42</span></a> although there are different risk groups such as pregnant women with aTPO during pregnancy &#40;40&#8211;60&#37; prevalence&#41;&#44; GD in remission &#40;44&#37;&#41;&#44; history of previous PPT &#40;42&#37;&#41;&#44; chronic viral hepatitis &#40;25&#37;&#41;&#44; family history of thyroid disease &#40;20&#37;&#41;&#44; diabetes mellitus type 1 &#40;20&#37;&#41; and systemic lupus erythematosus &#40;14&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">5&#44;6&#44;32</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">A data analysis from 21 studies shows that most &#40;&#8764;48&#37;&#41; women with PPT experience an isolated episode of hypothyroidism while hyperthyroidism is present in &#8764;30&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a> Only 22&#37; of PPT cases manifest themselves in the classical form with a transient hyperthyroidism phase of 1&#8211;2 months&#44; followed by another transient hypothyroidism phase of variable duration &#40;&#8764;2&#8211;3 months&#41;&#44; with spontaneous recovery of the thyroid function&#44; although some patients may be left with permanent hypothyroidism&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">At present the guidelines do not recommend US for PPT&#46; Screening only seems appropriate in women belonging to the previously mentioned risk groups&#46; In this case the TSH should be monitored at 3 and 6 months postpartum&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Iodine requirements</span><p id="par0120" class="elsevierStylePara elsevierViewall">The iodine nutrition status of an individual or population can be determined by various indicators&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Those proposed by the European Commission&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> as well as the recommended iodine intake are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; Iodine deficiency &#40;ID&#41; in pregnant women causes hypothyroxinaemia affecting foetal brain development&#46; The beneficial effects of severe maternal ID correction on the psychoneurological development of the child&#44;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a> as well as several meta-analyses demonstrating IQ reduction in 12&#8211;13&#46;5 points in children with ID&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> confirm the importance of severe ID&#46; Similarly&#44; mild and moderate ID can cause major foetal and maternal complications&#46; It has been associated with an increased risk of maternal and foetal goitre&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a> and with intellectual impairment in the offspring&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">37</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Since 2004&#44; our country is listed by WHO among those with optimal iodine nutrition&#46; However&#44; a recent article<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">38</span></a> warns about the risk of ID reappearing if such nutritional deficiency was corrected by a silent or uncontrolled iodine prophylaxis&#46; Recent studies<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">39</span></a> show ID persistence in pregnant population&#44; therefore&#44; SEEN maintains the specific recommendation of potassium iodide prescription before pregnancy&#44; and&#44; if possible&#44; during the same and also during lactation&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">40</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Given the impossibility to identify by any means the individual ID risk of a pregnant woman&#44; ATA<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> and ES<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> guidelines recommend daily supplementation with at least 150<span class="elsevierStyleHsp" style=""></span>&#956;g of iodine in all women planning pregnancy or who are pregnant or breastfeeding&#46; The ES<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> also recommends&#44; with a good degree of evidence that the risk assessment during pregnancy ID should be established basically depending on whether a country is in a situation of iodine sufficiency or iodine deficiency&#44; and the availability or not of well-developed universal salt iodization &#40;USI&#41; programmes&#46; According to these criteria&#44; given the persistence of ID in part of the pregnant population and the absence of USI programmes in our country&#44; the proposed recommendation<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">40</span></a> of universal iodine supplementation during pregnancy and lactation should be maintained&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Screening for thyroid dysfunction</span><p id="par0135" class="elsevierStylePara elsevierViewall">US of pregnant women to detect hypothyroidism during the first trimester of pregnancy remain controversial&#46; A single interventional study&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">41</span></a> which proved the foetal and maternal benefits of treatment with L-T4 in pregnant women with subclinical hypothyroidism during the first trimester&#44; pointed to the possible convenience of US&#46; However&#44; CATS<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">23</span></a> study&#44; which demonstrated no benefit of L-T4 on neurocognitive development in children of mothers with hypothyroidism&#44; has conditioned that almost all scientific societies&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> based on the lack of evidence regarding the potential benefits of such a measure&#44; discourage the US and advocate SS in population at risk &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">There are arguments for and against US &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#46; In addition&#44; some events might question the exclusive performance of SS&#46; With this procedure&#44; a 33&#8211;81&#37; of pregnant hypothyroid women would go undetected&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">9&#44;42&#44;43</span></a> Furthermore&#44; the amplitude criteria applied to our pregnant population &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41; for SS proposed by ATA<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> and ES<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> would determine&#44; in practice&#44; an almost universal screening&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">The US cost-benefit studies are additional arguments for this strategy&#46; The Dosiou et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">44</span></a> study concluded that US for the detection of hypothyroidism in pregnant women is cost-effective even when compared with the screening of high-risk women&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Although the official position of the different scientific societies maintains the SS recommendation&#44; routine clinical practice seems to distance itself from this position&#46; At a meeting of the ATA&#44; over 70&#37; of physicians surveyed were in favour of US in pregnant women through TSH<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">45</span></a> determination&#46; Finally&#44; in 2009 and 2012&#44; SEEN<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;7</span></a> clearly favoured US regarding thyroid dysfunction detection in pregnant women&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In conclusion&#44; US implementation still requires more quality evidence which unequivocally justifies it&#46; This can probably be achieved once some randomized studies currently under development are completed&#46; Until then&#44; US aimed at early diagnosis and treatment of overt hypothyroidism seems reasonable&#44; as the potential maternal and foetal benefits are well above the disadvantages of this test&#46; However&#44; US would require the availability of reference values for TSH and L-T4 specific to each laboratory&#44; as those proposed by some societies<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> may overestimate the prevalence of thyroid dysfunction in pregnant women in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion and forward-looking vision</span><p id="par0160" class="elsevierStylePara elsevierViewall">The currently valid guidelines and consensus fulfil their mission to facilitate the work of clinicians&#44; but they must change according to the results of future research&#46; As regard <span class="elsevierStyleItalic">diagnosis</span>&#44; efforts need to be made so that the different healthcare areas have their own reference intervals&#44; at least regarding TSH and Free T4&#44; for each of the pregnancy trimesters&#46; As to <span class="elsevierStyleItalic">screening</span>&#44; risk criteria must be redefined with greater precision&#46; The timing of screening should also be specified more precisely&#44; as the critical neurodevelopmental period occurs early&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">As regard <span class="elsevierStyleItalic">treatment</span>&#44; the iodine sufficiency must be guaranteed in all pregnant women&#44; as its benefits are beyond doubt&#46; Randomized and controlled trials conducted on a large number of patients to be published in the near future may clarify whether early treatment of different forms of thyroid dysfunction during pregnancy is associated with a reduction in obstetric complications or a positive impact on the offspring&#39;s neurodevelopment&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests regarding this article&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Hypothyroidism"
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              "identificador" => "sec0015"
              "titulo" => "Diagnostic criteria"
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              "titulo" => "Impact of hypothyroidism"
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          "titulo" => "Thyroid autoimmunity"
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          "titulo" => "Hyperthyroidism"
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              "titulo" => "Treatment indications and risks"
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          "titulo" => "Postpartum thyroiditis"
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        ]
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-07-24"
    "fechaAceptado" => "2014-08-19"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec638846"
          "palabras" => array:4 [
            0 => "Hypothyroidism"
            1 => "Hyperthyroidism"
            2 => "Pregnancy"
            3 => "Clinical practice guidelines"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec638847"
          "palabras" => array:4 [
            0 => "Hipotiroidismo"
            1 => "Hipertiroidismo"
            2 => "Gestaci&#243;n"
            3 => "Gu&#237;as de pr&#225;ctica cl&#237;nica"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women&#44; although their recommendations are under constant revision&#46; Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism&#46; There is no doubt on the need of therapy for overt hypothyroidism&#44; while therapy for subclinical hypothyroidism is controversial&#46; Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity&#46; Differentiation between hyperthyroidism due to Graves&#8217; disease and the usually self-limited gestational transient thyrotoxicosis is critical&#46; It is also important to recognize risk factors for postpartum thyroiditis&#46; Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring&#46; Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women&#46; Opinions of some scientific societies and recent cost-benefit studies favour universal screening&#46; Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las recientes gu&#237;as cl&#237;nicas sobre disfunci&#243;n tiroidea y embarazo han cambiado la atenci&#243;n sanitaria que se presta a la mujer gestante&#44; pero sus recomendaciones est&#225;n en constante revisi&#243;n&#46; Existe la necesidad de disponer de valores de referencia de la hormona estimulante del tiroides por trimestre y &#225;rea geogr&#225;fica para el correcto diagn&#243;stico de disfunci&#243;n tiroidea&#46; No hay dudas sobre la necesidad de tratamiento del hipotiroidismo franco&#44; pero hay opiniones variables sobre el tratamiento del subcl&#237;nico&#46; Los efectos adversos de la hipotiroxinemia aislada y de la autoinmunidad tiroidea requieren nuevas investigaciones&#46; Es fundamental diferenciar el hipertiroidismo por enfermedad de Graves del llamado hipertiroidismo gestacional transitorio&#44; habitualmente autolimitado&#46; Es importante reconocer los factores de riesgo para la tiroiditis posparto&#46; Para evitar graves consecuencias en la descendencia&#44; se recomienda mantener una adecuada nutrici&#243;n de yodo durante el embarazo mediante suplementos de este oligoelemento&#46; Contin&#250;a la pol&#233;mica sobre el cribado universal o selectivo de disfunci&#243;n tiroidea durante la gestaci&#243;n&#44; aunque las tendencias de algunas sociedades y de los &#250;ltimos estudios de coste-beneficio son favorables al cribado universal&#46; Los estudios aleatorizados y controlados en desarrollo actualmente deber&#225;n reducir las incertidumbres que a&#250;n persisten en el &#225;rea de la disfunci&#243;n tiroidea y el embarazo&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; D&#237;ez JJ&#44; Iglesias P&#44; Donnay S&#46; Disfunci&#243;n tiroidea y embarazo&#46; Med Clin &#40;Barc&#41;&#46; 2015&#59;145&#58;344&#8211;349&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">TgAb&#58; thyroglobulin antibodies&#59; aTPO&#58; anti-thyroid peroxidase&#59; LLN&#58; lower limit of normal&#59; ULN&#58; upper limit of normal&#59; TSH&#58; thyroid-stimulating hormone&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prevalence &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Hypothyroidism</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Overt hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mU&#47;l or TSH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l with Free T4<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>LLN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&#8211;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Subclinical hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l with normal Free T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Isolated hypothyroxinaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l with Free T4<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5&#8211;10 percentile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Hypothyroidism</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Overt hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01<span class="elsevierStyleHsp" style=""></span>mU&#47;l or TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleHsp" style=""></span>mU&#47;l with Free T4 and Free T3<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;1&#8211;0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Subclinical hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleHsp" style=""></span>mU&#47;l with normal Free T4 and Free T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&#8211;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Thyroid autoimmunity</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Positive antithyroid antibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">aTPO or TgAb<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#8211;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1026511.png"
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria and prevalence of different forms of thyroid dysfunction during pregnancy&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">hCG&#58; human chorionic gonadotropin&#59; TRAb&#58; thyroid-stimulating hormone receptor antibodies&#59; TSH&#58; thyroid-stimulating hormone&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pathogenic mechanism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Gestational hyperthyroidism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">hCG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gestational transient thyrotoxicosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hyperemesis gravidarum</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gestational trophoblastic disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hydatidiform mole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Choriocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Autoimmune hyperthyroidism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TRAb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Graves&#8217; disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Nodular hyperthyroidism disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nodular autonomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Autonomous hyperfunctioning nodule</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Toxic multinodular goitre</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Hyperthyroidism associated with thyroiditis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tissue destruction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Silent thyroiditis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Subacute thyroiditis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Miscellaneous</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Exogenous thyrotoxicosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Levothyroxine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Overdose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Factitious&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Drugs</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Amiodarone&#44; iodine&#44; lithium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">TSH-producing pituitary adenoma</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Familial gestational hyperthyroidism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TSH Thyroid receptor hypersensitivity to hCG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1026514.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Main causes and pathogenic mechanisms of hyperthyroidism during pregnancy&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">aTPO&#58; anti-thyroid peroxidase&#59; TRAb&#58; thyroid-stimulating hormone receptor antibodies&#59; T3&#58; triiodothyronine&#59; T4&#58; thyroxine&#59; &#8722;&#58; absent or negative&#59; &#43;&#58; present or positive&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gestational transient thyrotoxicosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperthyroidism due to Graves&#8217; disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family history of autoimmune thyroid disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other autoimmune diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">At diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">First trimester&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any trimester&#47;pregestational&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Twin pregnancies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea and vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperthyroidism pregestational symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptoms of hyperthyroidism during pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Goitre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ophthalmopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3&#47;T4 ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">aTPO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TRAb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstetric complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk of foetal and neonatal hyperthyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Self-limited &#40;&#8764;first trimester&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Unpredictable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Key differentiating characteristics of transient gestational thyrotoxicosis and hyperthyroidism due to Graves&#8217; disease during pregnancy&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">UIC&#58; urinary iodine concentration&#59; UIE&#58; urinary iodine excretion&#59; TSH&#58; thyroid-stimulating hormone&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Adapted from EFSA&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Iodine intake markers</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Urinary iodine excretion</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Represents &#62;90&#37; of the daily intake of iodine</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Excellent recent iodine intake marker</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>While 24<span class="elsevierStyleHsp" style=""></span>h UIE is preferable&#44; spontaneous urine UIE mean values are used for assessing the <span class="elsevierStyleItalic">demographic</span> nutrition status of iodine</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>For an <span class="elsevierStyleItalic">individual</span> assessment with an accuracy of 20&#37;&#44; at least 10 consecutive 24<span class="elsevierStyleHsp" style=""></span>h UIE determinations are required</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Iodine nutrition status markers</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Urinary iodine concentration</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Median UIC is used to define the iodine nutrition status of a specific population&#46;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Normal values have been defined depending on age and other conditions</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Thyroglobulin</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>It is a good marker of iodine nutrition status&#44; especially in children and adolescents</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">TSH and thyroid hormones</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Primarily value thyroid function and secondarily iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Thyroid volume</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>It represents a marker of long-term iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>It can be determined by palpation or&#44; more precisely&#44; by ultrasound volumetric measurement</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>In epidemiological studies&#44; the prevalence of goitre is another marker of iodine nutrition status</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Adequate iodine intake</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Adequate intake &#40;&#956;g&#47;day&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>7&#8211;11 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#8211;10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>11&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>15&#8211;17 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#8805;18 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Gestation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Breastfeeding woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Intake and iodine nutrition status indicators&#46;</p>"
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      4 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">aTPO&#58; anti-thyroid peroxidase&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Adapted from Abalovich et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a> Stagnaro-Green et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a> and De Groot et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Previous history of thyroid disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Family history of autoimmune thyroid disease&#44; or hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Personal history of previous thyroid surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Personal history of craniocervical irradiation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Symptoms or signs in the current pregnancy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Goitre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Symptoms or signs suggestive of thyroid disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Current levothyroxine treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Autoimmune diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Presence of antithyroid antibodies&#44; especially aTPO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Type 1 diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Another autoimmune disease &#40;vitiligo&#44; adrenal failure&#44; hypoparathyroidism&#44; atrophic gastritis&#44; pernicious anaemia&#44; etc&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Previous obstetric history</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Infertility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Previous history of abortions or preterm deliveries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Other risk factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Morbid obesity &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Women treated with amiodarone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Women treated with lithium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Living in regions with alleged iodine deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Recent exposure &#40;6 weeks&#41; to iodinated contrast agents&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">In favour&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Against&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High prevalence of subclinical hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Complications not clearly demonstrated in subclinical hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstetric complications demonstrated in clinical thyroid dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No effect on the IQ of the offspring during a trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Implications in the offspring&#39;s neurocognitive development&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Doubts about the impact of isolated hypothyroxinaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Detectable and treatable early stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Doubts about the impact of antithyroid antibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Easy analytical screening in first trimester&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Subclinical hyperthyroidism and transient gestational not associated with foetal morbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Effective&#44; acceptable and inexpensive treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possibility of inadequate dosing in pregnant women with subclinical hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potential treatment benefits for the mother and the offspring&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible misinterpretation of thyroid function tests by non-expert doctors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive cost-benefit balance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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