Clinical guidelines for management of thyroid nodule and cancer during pregnancy | Endocrinología y Nutrición (English Edition)

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Álvarez-Escolá" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Juan Carlos" "apellidos" => "Galofré" "email" => array:1 [ 0 => "jcgalofre@unav.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Garcilaso" "apellidos" => "Riesco-Eizaguirre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Álvarez-Escolá" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:1 [ "colaborador" => "on behalf of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition" ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Endocrinología, Clínica Universidad de Navarra, Pamplona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Endocrinología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Guía clínica para el manejo del nódulo tiroideo y cáncer de tiroides durante el embarazo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1721 "Ancho" => 2525 "Tamanyo" => 235794 ] ] "descripcion" => array:1 [ "en" => "Algorithm for the management of differentiated thyroid cancer diagnosed during pregnancy. Ca: carcinoma; US: thyroid ultrasound examination; mts: metastases; TG: thyroglobulin." ] ] ] "textoCompleto" => "IntroductionBoth the American Thyroid Association (ATA) and the Endocrine Society (ENDO) have recently published clinical guidelines reporting the main advances in recent years in the management of thyroid disease in pregnant women.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> These documents, especially the ATA guidelines, are comprehensive, and their recommendations largely overlap.We think that such a profusion of guidelines is unnecessary, because they may confound healthcare professionals.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Thus, we do not intend to provide an additional guideline, but to adapt and summarize for Spanish-speaking professionals the information included in the two American guidelines and, where appropriate, discuss any peculiarities specific to our situation. If a more in depth discussion of any concept is required, or the strength of or evidence for any particular recommendation needs to be known, the abovementioned guidelines may be consulted.The Clinical guidelines for the management of subclinical thyroid dysfunction during pregnancy were published a few years ago in Endocrinología y Nutrición.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> As a continuation of this document, the Clinical guidelines for the management of thyroid nodular disease in pregnancy have now been published. In order to allow for rapid consultation, the recommendations are presented in a clear, practical, and manageable question and answer format.Interpretation of thyroid function and goiter during pregnancyChanges occurring in the thyroid gland during pregnancy have been thoroughly studied in recent years and may be both morphological and functional.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> There are specific reference levels for both thyroid-releasing hormone (TSH) and other thyroid hormones during pregnancy, which should be taken into account and should be flagged by each laboratory to avoid erroneous interpretations.<a class="elsevierStyleCrossRefs" href="#bib0005">1,6,7</a> This is of paramount importance when monitoring patients with a history of differentiated thyroid cancer, as will be seen later.Thyroid cancer should be suspected in any patient consulting for goiter. It should therefore be taken into account that, depending on iodine intake, thyroid volume may increase during pregnancy by 10% (in areas with normal-high iodine intake) to 40% (in low intake areas). A study was conducted on 35 pregnant women in Valle de Arán, an area where iodine deficiency is traditionally endemic. The authors measured thyroid volume during the first and third trimesters of pregnancy. Median thyroid volume increased in these women from 7.5 to 9.5mL during pregnancy (p<0.001). The difference was also seen to be greater in women with multiple pregnancies. In agreement with studies in other geographical areas, this Spanish study concluded that both iodine deficiency and multiparity are goitrogen factors during pregnancy.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Pregnancy and thyroid nodulesThyroid nodule management during pregnancy is usually based on the standard diagnostic and treatment criteria for the condition. The special characteristics of pregnancy are associated with changes in nodule prevalence, size, and growth, and to indications for treatment, particularly surgery.As in non-pregnant women, ultrasound examination is essential in any thyroid nodule. Ultrasonography provides valuable information regarding the benign or malignant nature of nodules<a class="elsevierStyleCrossRef" href="#bib0045">9</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In accordance with general criteria, cytological evaluation using fine needle aspiration (FNA) is indispensable in assessing thyroid nodules. Obviously, pregnancy has no effect on the cytological diagnosis of thyroid nodules. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the most commonly used classification, the Bethesda system.<a class="elsevierStyleCrossRef" href="#bib0050">10</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>EpidemiologyBoth the appearance of new nodules and the volume of those already existing have been reported to increase during pregnancy.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> However, nodules usually return to their baseline size after delivery<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In a Spanish study, however, Jaén Díaz et al.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> found a 33.2% prevalence of thyroid nodules during the first trimester of pregnancy, which was slightly lower than the prevalence seen in controls (38.5%), although the difference was not statistically significant. This suggests that pregnancy does not promote the occurrence of thyroid nodules, in contrast to findings in studies in other countries.<a class="elsevierStyleCrossRefs" href="#bib0055">11,13,14</a> However, the high prevalence of thyroid nodules in pregnant women found in the Jaén Díaz et al. study<a class="elsevierStyleCrossRef" href="#bib0060">12</a> is also noteworthy because it was markedly higher than that reported in the majority of similar studies, where it ranged from 3% to 12%.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Does pregnancy cause any morphological disorder in the thyroid gland?</li></ul>Most research studies suggest that pregnancy increases the risk of developing new thyroid nodules and also promotes an increase in the size of previously existing nodules.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The size of pre-gestational nodules may increase by up to 50%, and a de novo nodule occurs during pregnancy in up to 20% of patients. This risk is also enhanced both by age and a higher number of pregnancies (multiparity is associated with a 10–15% increase).<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0010">2.What precautions may be taken to prevent the occurrence of thyroid nodules during pregnancy?</li></ul>Epidemiological data suggest that low iodine intake predisposes to the development of thyroid nodules. It is therefore highly recommended that potassium iodide supplements be taken throughout pregnancy. This supplementation also protects against the occurrence of hypothyroidism in the mother and fetus, in addition to providing the fetus with the iodine needed for thyroid hormone synthesis.The clinical management of thyroid nodules during pregnancy<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">3.How should thyroid nodules be managed in pregnant women?</li></ul>If a thyroid nodule is found during pregnancy, a thorough clinical history and physical examination should be performed. The history should include: (a) any family history of thyroid diseases (autoimmune and nodular) and carcinomas (medullary thyroid cancer, multiple endocrine neoplasia 2A, and colon cancer); (b) personal history, especially iodine intake, prior neck irradiation, and obstetric history; (c) signs and symptoms of thyroid dysfunction, especially changes over time in the thyroid nodule, must also be investigated; and (d) careful neck examination (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The general recommendation to perform thyroid function tests in any patient with thyroid nodules also applies to pregnant women.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Thus, a pregnant woman with a thyroid nodule should undergo a functional study including tests to measure TSH and free T4 levels.If morphological changes found at examination are confirmed, thyroid ultrasound examination should be performed and, if required, work-up should be completed with FNA. Pregnancy is not a contraindication for FNA, which may be performed at any time during pregnancy. The ultrasonographic findings suggesting the need for cytological analysis are summarized as follows: (a) any nodule greater than 1cm in size; (b) nodules with ultrasonographic characteristics suggesting malignancy; (c) the rapid growth or clinical suspicion of malignancy; (d) the discovery by ultrasonography of potentially metastatic neck adenopathies; and (e) the presence of risk factors such as a family history of thyroid cancer or a history of cervical radiotherapy. However, if ultrasonographic findings suggest a benign condition, FNA of nodules may be performed after delivery.Scintigraphy is contraindicated during pregnancy. However, according to the available information, an involuntary scintigraphy performed before week 12 of pregnancy does not appear to damage the fetal thyroid gland.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The presence of thyroid cancer does not usually cause impaired thyroid gland function. The measurement of circulating thyroglobulin levels is of no diagnostic or prognostic interest in this setting. There is no adequate information regarding the convenience of measuring calcitonin levels during pregnancy, unless there is a family history of medullary thyroid carcinoma. Pentagastrin stimulation is contraindicated in pregnancy.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">4.Should pregnant women be screened for thyroid changes?</li></ul>There is increasing evidence to support the advisability of thyroid function screening and physical examination of the neck as soon as the patient knows that she is pregnant.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> The benefit of correcting thyroid dysfunctions detected during the first trimester of pregnancy clearly outweighs the cost of screening.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>Few studies are available on the relationship between thyroid nodules and autoimmunity during pregnancy, and there are thus no recommendations regarding the advisability of measuring thyroid antibodies during pregnancy. Moreover, because of immune privilege during pregnancy, circulating levels of thyroid antibodies decrease during pregnancy, which may complicate the interpretation of the results.<a class="elsevierStyleCrossRef" href="#bib0090">18</a><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0025">5.What reference levels of thyroid hormones should be considered sufficient during pregnancy?</li></ul>For the abovementioned reasons, circulating TSH levels should range from 0.1 to 2.5mU/L during the first trimester of pregnancy. During the second and third trimesters, levels should be 0.2–3.0 and 0.3–3.0mU/L respectively.<a class="elsevierStyleCrossRef" href="#bib0005">1</a><ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0030">6.How should benign nodules be monitored during pregnancy?</li></ul>No special monitoring is required during pregnancy for thyroid nodules suspected of being benign based on ultrasound characteristics or found to be benign at cytological study and causing no compressive symptoms.Repeat ultrasound examination should be performed if a nodule grows rapidly. Both in these cases and when ultrasonographic changes suggesting malignancy occur, FNA should be repeated.The treatment of thyroid nodules during pregnancyOnce clinical, ultrasonographic, or cytological diagnosis has been made, benign thyroid nodules require no treatment.<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0035">7.Is levothyroxine suppression treatment useful during pregnancy?</li></ul>The treatment of nodular goiter with supraphysiological doses of levothyroxine is not recommended, because the suppression of TSH secretion may induce untoward adverse effects in both the mother and the fetus.<a class="elsevierStyleCrossRef" href="#bib0095">19</a><ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0040">8.When is surgery indicated for a thyroid nodule?</li></ul>If ultrasonographic or cytological changes occur in previously benign nodules or the course of the nodule casts doubt on its nature, surgery is recommended. Surgery is also indicated when compressive symptoms occur.Nodules with indeterminate (Bethesda categories 3, 4, and 5) or malignant (category 6) FNA results should undergo surgery (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Specific indications for surgery are addressed in question 12.<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0045">9.How should hyperfunctioning thyroid nodules be treated?</li></ul>The treatment of hyperthyroidism in pregnant women is complex. Recommendations for the management of this condition are beyond the scope of these guidelines and have been reviewed in another publication.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> It should, however, be noted that treatment with radioactive iodine is contraindicated throughout pregnancy.The management of differentiated thyroid cancer diagnosed during pregnancyDifferentiated thyroid cancer is the second leading malignant tumor during pregnancy after breast cancer, with a prevalence of 14 per 100,000births.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In addition, 10% of all thyroid cancers occurring during childbearing age are diagnosed during pregnancy or within one year of delivery, and the most common histological type is papillar.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The management of differentiated thyroid cancer during pregnancy poses a number of diagnostic and therapeutic challenges for both the mother and fetus.<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0050">10.Is there an increased frequency of thyroid cancer in pregnant women with thyroid nodules?</li></ul>Three retrospective studies have reported an increased risk of malignancy in pregnant women with thyroid nodules. However, these studies had a patient selection bias, because they were conducted in tertiary reference hospitals where women with cancer may be overrepresented.<a class="elsevierStyleCrossRefs" href="#bib0110">22–24</a>Pregnancy may however be expected to promote the occurrence and growth of malignant nodules because of the relative iodine deficiency experienced by the mother, increased growth factors, the appearance of hormones with a stimulating activity similar to that of TSH, and high estrogen levels. The management of these patients therefore requires special consideration.<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0055">11.Does pregnancy affect the prognosis of thyroid cancer?</li></ul>Most studies suggest that pregnancy does not worsen the prognosis of women diagnosed with differentiated thyroid cancer.<a class="elsevierStyleCrossRefs" href="#bib0125">25–31</a> Only one of the seven studies published addressing this issue found an increased risk of disease persistence/recurrence in women diagnosed during pregnancy or within one year of delivery.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> This finding was related to the presence of high estrogen receptor expression levels in thyroid tumor cells. However, the patient sample in this study was small and poorly representative.In conclusion, no adequate evidence which could lead us to conclude that pregnancy worsens the prognosis of thyroid cancer is currently available. Consequently, thyroidectomy may be delayed in most pregnant patients until the postpartum period without this affecting the risk of recurrence or mortality.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The impact of pregnancy in women with anaplastic or medullary carcinoma has not been analyzed.<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0060">12.How should differentiated thyroid cancer diagnosed during pregnancy be managed?</li></ul>It should be taken into account that a conflict between the optimum treatment of the mother and fetal well-being very often exists. There is therefore an ethical dilemma. The decision as to which is the best therapeutic option should preferably be taken by a multidisciplinary team consisting of an endocrinologist, a surgeon, an obstetrician, a nuclear medicine specialist, and a neonatologist.There are two special considerations that should be taken into account in the management of women with differentiated thyroid cancer diagnosed during pregnancy: the absolute contraindication of the administration of radioactive iodine and the choice of the time of thyroidectomy. As noted above, it is usually advisable to delay surgery until the postpartum period, as there is no adequate evidence showing that pregnancy worsens cancer prognosis.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Thyroidectomy is recommended in the second trimester in the following cases: (a) aggressive or locally advanced histology (e.g. anaplastic or poorly differentiated carcinoma), (b) metastatic cervical lymph nodes (diagnosed by cytology), (c) severe compressive symptoms (e.g. tracheal obstruction), and (d) the significant growth of a malignant nodule (>50% in volume or >20% in diameter in two dimensions) before week 24 of pregnancy (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>If the malignant nodule does not meet the above conditions or is diagnosed toward the end of the second half of pregnancy, surgery may be delayed until the postpartum period. In such cases, it is recommended that levothyroxine suppression treatment aimed at maintaining TSH levels in the lower normal limit (0.1–1.5mU/L) be started.Circulating TSH and free T4 levels should be monitored every month, and ultrasound examination and thyroglobulin tests should be performed every three months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0065">13.What are the perioperative risks for the mother and fetus of thyroidectomy during pregnancy?</li></ul><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Surgery in the first trimester involves an unacceptable risk of miscarriage and impaired organogenesis. On the other hand, surgery during the third trimester is associated with an increased risk of preterm delivery. Thyroidectomy during the second trimester does therefore involve the lowest risk for the mother and fetus.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> However, if surgery is performed during pregnancy, the risk of postoperative maternal hypothyroidism (and potential hypoparathyroidism) should be taken into account.The management of pregnant women with a history of differentiated thyroid cancerSpecific considerations are required in the management of women with a history of differentiated thyroid cancer who want to become pregnant again. <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes these considerations.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Women with a history of differentiated thyroid cancer who desire pregnancy<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0070">14.What information should be given to women with a history of differentiated thyroid cancer who desire pregnancy?</li></ul>Women should be informed that pregnancy should be avoided in the 6–12months following the administration of the therapeutic dose of radioactive iodine in order to achieve the stabilization of the levothyroxine dose and to verify disease remission.<a class="elsevierStyleCrossRefs" href="#bib0010">2,33–35</a><ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0075">15.What are the potential risks in women previously receiving radioiodine therapy?</li></ul>Studies conducted on women previously given radioiodine for the treatment of differentiated thyroid cancer have not reported an increased risk of complications such as infertility, miscarriage, newborn mortality, congenital malformation, premature delivery, low birthweight, death in the first year of life, or cancer development.<a class="elsevierStyleCrossRefs" href="#bib0180">36,37</a><ul class="elsevierStyleList" id="lis0090"><li class="elsevierStyleListItem" id="lsti0080">16.Can a new pregnancy increase the risk of recurrence in women with a history of thyroid cancer?</li></ul>Often, the patient is mainly interested in knowing whether cancer recurrence may or may not occur as a consequence of a new pregnancy.From the pathophysiological viewpoint, it should be noted that both HCG and estrogens induce changes in serum TSH, FT4, and thyroglobulin levels during pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0035">7,38</a> Some studies have reported that estrogens may stimulate thyroglobulin gene expression, particularly during the third trimester, increasing potential thyroglobulin production in differentiated thyroid cancer. This occurs without stimulating proto-oncogene c-Myc and without promoting rapid cell proliferation.<a class="elsevierStyleCrossRefs" href="#bib0195">39,40</a> Moreover, some clinical studies suggest that circulating thyroglobulin levels may increase in the absence of a concomitant tumor, which may be a confounding factor.<a class="elsevierStyleCrossRef" href="#bib0200">40</a>.<a class="elsevierStyleCrossRef" href="#bib0205">41</a>Several studies, three of them published in the past five years, have assessed the impact of pregnancy in women with a history of differentiated thyroid cancer.<a class="elsevierStyleCrossRefs" href="#bib0200">40,42–44</a> Leboeuf et al.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> studied 36 women who had become pregnant a mean of 4.3 years after initial treatment for differentiated thyroid cancer. After delivery, eight of these women had thyroglobulin levels 20% greater than those found before pregnancy. Three of these women had active disease, and five had no evidence of disease. However, no recurrence was found in the early postpartum period in women with negative neck ultrasound whose serum thyroglobulin levels were less than 3.2ng/mL.Data from these studies suggest that pregnancy involves no risk of recurrence in women with no evidence of biochemical or structural disease before pregnancy. However, as previously noted (question 11), it has not been completely ruled out that pregnancy may represent a stimulus in patients with active disease.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Monitoring during pregnancy of women with a history of differentiated thyroid cancerIn any woman with hypothyroidism, it is crucial to maintain thyroid hormone levels within the specific reference intervals throughout pregnancy. Various studies have shown that even mild hypothyroidism is associated with adverse effects for the mother and fetus.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Thyroid hormone replacement requirements usually increase by 20–40%, which makes adjustment indispensable in the first eight weeks.<a class="elsevierStyleCrossRefs" href="#bib0230">46,47</a> In addition, other routinely used supplements, such as iron and calcium, may alter levothyroxine absorption.<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0085">17.How should the levothyroxine dose be adjusted?</li></ul>Thyroid hormone levels should always be measured when pregnancy is documented. Thyroid function tests should initially be repeated every four weeks until week 16–20, and then once between weeks 26 and 32. If an adjustment of the levothyroxine dose is required, thyroid hormones should be assessed again four weeks later.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>To provide guidance, it may be noted that mean increases in levothyroxine dose as compared to the pregestational dose over the three trimesters of pregnancy are 9%, 21%, and 26% respectively.<ul class="elsevierStyleList" id="lis0095"><li class="elsevierStyleListItem" id="lsti0090">18.Should TSH suppression be maintained during pregnancy?</li></ul>Goal TSH levels during pregnancy do not change as compared to before pregnancy. In low risk patients (T1-T2, N0, M0, with no aggressive histology), the goal is to achieve TSH levels ranging from 0.3 to 1.5mU/L. In patients with no evident biochemical or structural disease but with risk factors at diagnosis (T3-T4, N1, M1, or with an aggressive histology), the goal is to maintain circulating TSH levels ranging from 0.1 to 0.5mU/L. It should be noted, however, that if the risk of disease before pregnancy makes the maintenance of suppressed circulating TSH levels advisable, the same caution should be exercised during pregnancy, the levothyroxine dose being adjusted as appropriate.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> A study conducted on 25,765 women, 433 of whom had subclinical hyperthyroidism, was very illustrative of the adverse effects of this measure. Low TSH levels did not correlate to adverse effects in any of the women.<a class="elsevierStyleCrossRef" href="#bib0240">48</a><ul class="elsevierStyleList" id="lis0100"><li class="elsevierStyleListItem" id="lsti0095">19.Should iodine supplements be used?</li></ul>Despite prior thyroidectomy, patients with a history of thyroid cancer, like all other pregnant women, should take at least 250μg/day of iodine during pregnancy and breast-feeding.<a class="elsevierStyleCrossRef" href="#bib0245">49</a> In these cases, iodine supplements are administered to the mother to cover the requirements of the fetal thyroid.<a class="elsevierStyleCrossRef" href="#bib0005">1</a><ul class="elsevierStyleList" id="lis0105"><li class="elsevierStyleListItem" id="lsti0100">20.How should monitoring be performed?</li></ul>Most pregnant women with low-risk differentiated thyroid cancer only require monitoring of circulating TSH levels and adjustments of treatment, when needed, as well as an examination every three months.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Neither thyroglobulin measurement nor ultrasonography is required.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>However, women with high thyroglobulin levels before pregnancy or with morphological evidence of disease should be monitored with thyroglobulin tests and neck ultrasound in every trimester of pregnancy.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The management of women with differentiated thyroid cancer during lactation<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0105">21.What considerations should be taken into account during breast-feeding?</li></ul>Breast-feeding may be safe in women with a history of differentiated thyroid cancer.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> It should, however, be noted that radioiodine should not be administered during lactation and until at least four weeks after its discontinuation,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> because the lactating breast concentrates a significant amount of iodine.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> However, it is advisable to delay radioiodine administration until three months after breast-feeding has been stopped to ensure the normalization of the increased activity of the sodium-iodine symporter caused by lactation.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> If urgent treatment is needed, 123I scintigraphy may be performed to assess breast residual uptake. Treatment should be delayed if a higher than normal radioactivity level is found.Involution of the lactating breast is variable, and there is evidence that bromocriptine is able to accelerate it.<a class="elsevierStyleCrossRef" href="#bib0255">51</a> This drug may be prescribed in special cases “outside of its specified indications for use”.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Breast-feeding cannot, of course, be resumed after radioiodine administration.Conflicts of interestThe authors state that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xres328469" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec310348" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres328470" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec310347" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Interpretation of thyroid function and goiter during pregnancy" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Pregnancy and thyroid nodules" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Epidemiology" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "The clinical management of thyroid nodules during pregnancy" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "The treatment of thyroid nodules during pregnancy" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "The management of differentiated thyroid cancer diagnosed during pregnancy" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "The management of pregnant women with a history of differentiated thyroid cancer" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Women with a history of differentiated thyroid cancer who desire pregnancy" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Monitoring during pregnancy of women with a history of differentiated thyroid cancer" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "The management of women with differentiated thyroid cancer during lactation" ] ] ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 6 => array:2 [ "identificador" => "xack78108" "titulo" => "Acknowledgements" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-05-30" "fechaAceptado" => "2013-08-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec310348" "palabras" => array:4 [ 0 => "Guideline" 1 => "Thyroid nodule" 2 => "Thyroid cancer" 3 => "Pregnancy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec310347" "palabras" => array:4 [ 0 => "Guía" 1 => "Nódulo tiroideo" 2 => "Cáncer de tiroides" 3 => "Embarazo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare-ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La conducta a seguir con el nódulo tiroideo y el cáncer de tiroides en la paciente embarazada requiere especiales consideraciones. El abordaje diagnóstico y terapéutico del nódulo tiroideo se rige por los criterios habituales en las pacientes no embarazadas. Por su parte, el manejo del cáncer diferenciado de tiroides durante la gestación implica una serie de retos para la madre y el feto. Los datos disponibles muestran que el embarazo no supone un aumento de riesgo de aparición o recurrencia de cáncer de tiroides, pero no está completamente descartado que la gestación pueda representar un estímulo en pacientes con enfermedad activa. Es importante tener en cuenta que en caso de ser necesario el tratamiento quirúrgico se recomienda llevarlo a cabo durante el segundo trimestre o, preferentemente, tras el parto. La mayoría de las gestantes con enfermedad de bajo riesgo solo requieren el ajuste del tratamiento con levotiroxina. Sin embargo, en mujeres que tienen valores elevados de tiroglobulina antes de la gestación o con datos morfológicos de persistencia de enfermedad deberá realizarse un seguimiento periódico mediante la determinación de tiroglobulina y realización de ecografías cervicales. La gestación supone una contraindicación absoluta para la administración de 131I." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Galofré JC, Riesco-Eizaguirre G, Álvarez-Escolá C, en representación del Grupo de Trabajo de Cáncer de Tiroides de la Sociedad Española de Endocrinología y Nutrición. Guía clínica para el manejo del nódulo tiroideo y cáncer de tiroides durante el embarazo. Endocrinol Nutr. 2014;61:130–138." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1721 "Ancho" => 2525 "Tamanyo" => 235794 ] ] "descripcion" => array:1 [ "en" => "Algorithm for the management of differentiated thyroid cancer diagnosed during pregnancy. Ca: carcinoma; US: thyroid ultrasound examination; mts: metastases; TG: thyroglobulin." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Ultrasound feature \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Suspicious feature \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Echogenicity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypoechogenic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodule margins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Irregular \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral halo of nodule \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intranodular vascularization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Calcifications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of microcalcifications \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dimensions of nodule axes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodules higher than wider \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laterocervical adenopathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Present \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab480792.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Ultrasound features of thyroid nodules suggesting malignancy." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Category \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Cytological diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Risk of malignancy (%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not diagnostic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Benign \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ayipia/follicular lesion of uncertain significance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Follicular neoplasm/suspected follicular neoplasm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15–30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Suspicious for malignancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60–75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Malignant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97–99 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab480794.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Cytological diagnostic criteria “Bethesda Classification”." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical history</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodule characteristics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assess growth and presence of local symptomsThyroid dysfunction symptoms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Personal history \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neck radiotherapyUsual iodine intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family history \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid carcinoma: papillary or medullary, and multiple endocrine neoplasia type 2Colon carcinoma: familial polyposis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physical examination</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neck palpation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodule characteristics, presence of local adenopathiesSystemic signs of thyroid dysfunction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laboratory</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid profile \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Goal: TSH, <2.5mU/L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid ultrasound examination</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytological study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any solid nodule>1cm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fine needle aspiration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Any nodule with suspicious ultrasonographic features \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Iodine supplements \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200μg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab480790.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Action protocol in the first visit of a pregnant patient with thyroid nodules." ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Appearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Characteristic \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Microscopic pathology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aggressive histology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gross pathology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Locally advanced disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of metastatic structural disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cervical lymph node metastases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical course \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Significant nodule growth (>50% in volume or >20% in diameter in two dimensions) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe compressive symptoms \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab480793.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications for surgery of a thyroid nodule in the second trimester of pregnancy." ] ] 5 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Before pregnancy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Pregnancy should be avoided in the 6–12 months following the administration of therapeutic radioiodine doses- A history of radioiodine treatment involves no increased risk of infertility, miscarriage, neonatal mortality, congenital malfomations, premature delivery, low birthweight, death during the first year of life, or cancer development- Pregnancy involves no risk of recurrence in women with no evidence of biochemical or structural disease before pregnancy. However, it may represent a stimulus in patients with active disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monitoring during pregnancy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- In any woman with hypothyroidism, it is essential to maintain thyroid hormone levels adequate for the time of pregnancy- Low-risk patients: these only require TSH monitoring and treatment adjustment when needed, and examination every 3 months- High-risk patients: if TSH suppression was recommended before pregnancy due to the risk of disease, it should be maintained during pregnancy, with the levothyroxine dose being adjusted. In women with high thyroglobulin levels before pregnancy or with morphological evidence of persistent disease, neck ultrasound should be performed every trimester \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monitoring during breast-feeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Breast-feeding is safe in women with a history of differentiated thyroid cancer- Radioiodine should not be administered during lactation and for at least four weeks after breast-feeding has stopped \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab480791.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Considerations regarding pregnancy and lactation in women with a history of differentiated thyroid cancer." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:51 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Stagnaro-Green" 1 => "M. Abalovich" 2 => "E. Alexander" 3 => "F. Azizi" 4 => "J. Mestman" 5 => "R. Negro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Thyroid" "fecha" => "2011" "volumen" => "2110" "paginaInicial" => "1081" "paginaFinal" => "1125" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. De Groot" 1 => "M. Abalovich" 2 => "E.K. Alexander" 3 => "N. Amino" 4 => "L. Barbour" 5 => "R.H. 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Clinical guidelines for management of thyroid nodule and cancer during pregnancy

Guía clínica para el manejo del nódulo tiroideo y cáncer de tiroides durante el embarazo

Juan Carlos Galofréa,

Corresponding author

jcgalofre@unav.es

Corresponding author.

, Garcilaso Riesco-Eizaguirreb, Cristina Álvarez-Escoláb, on behalf of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition

a Departamento de Endocrinología, Clínica Universidad de Navarra, Pamplona, Spain

b Servicio de Endocrinología, Hospital Universitario La Paz, Madrid, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algorithm for the management of differentiated thyroid cancer diagnosed during pregnancy&#46; Ca&#58; carcinoma&#59; US&#58; thyroid ultrasound examination&#59; mts&#58; metastases&#59; TG&#58; thyroglobulin&#46;</p>"
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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">Both the American Thyroid Association &#40;ATA&#41; and the Endocrine Society &#40;ENDO&#41; have recently published clinical guidelines reporting the main advances in recent years in the management of thyroid disease in pregnant women&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> These documents&#44; especially the ATA guidelines&#44; are comprehensive&#44; and their recommendations largely overlap&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We think that such a profusion of guidelines is unnecessary&#44; because they may confound healthcare professionals&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Thus&#44; we do not intend to provide an additional guideline&#44; but to adapt and summarize for Spanish-speaking professionals the information included in the two American guidelines and&#44; where appropriate&#44; discuss any peculiarities specific to our situation&#46; If a more in depth discussion of any concept is required&#44; or the strength of or evidence for any particular recommendation needs to be known&#44; the abovementioned guidelines may be consulted&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The Clinical guidelines for the management of subclinical thyroid dysfunction during pregnancy were published a few years ago in <span class="elsevierStyleItalic">Endocrinolog&#237;a y Nutrici&#243;n</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> As a continuation of this document&#44; the Clinical guidelines for the management of thyroid nodular disease in pregnancy have now been published&#46; In order to allow for rapid consultation&#44; the recommendations are presented in a clear&#44; practical&#44; and manageable question and answer format&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interpretation of thyroid function and goiter during pregnancy</span><p id="par0020" class="elsevierStylePara elsevierViewall">Changes occurring in the thyroid gland during pregnancy have been thoroughly studied in recent years and may be both morphological and functional&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> There are specific reference levels for both thyroid-releasing hormone &#40;TSH&#41; and other thyroid hormones during pregnancy&#44; which should be taken into account and should be flagged by each laboratory to avoid erroneous interpretations&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#44;7</span></a> This is of paramount importance when monitoring patients with a history of differentiated thyroid cancer&#44; as will be seen later&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Thyroid cancer should be suspected in any patient consulting for goiter&#46; It should therefore be taken into account that&#44; depending on iodine intake&#44; thyroid volume may increase during pregnancy by 10&#37; &#40;in areas with normal-high iodine intake&#41; to 40&#37; &#40;in low intake areas&#41;&#46; A study was conducted on 35 pregnant women in Valle de Ar&#225;n&#44; an area where iodine deficiency is traditionally endemic&#46; The authors measured thyroid volume during the first and third trimesters of pregnancy&#46; Median thyroid volume increased in these women from 7&#46;5 to 9&#46;5<span class="elsevierStyleHsp" style=""></span>mL during pregnancy &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The difference was also seen to be greater in women with multiple pregnancies&#46; In agreement with studies in other geographical areas&#44; this Spanish study concluded that both iodine deficiency and multiparity are goitrogen factors during pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pregnancy and thyroid nodules</span><p id="par0030" class="elsevierStylePara elsevierViewall">Thyroid nodule management during pregnancy is usually based on the standard diagnostic and treatment criteria for the condition&#46; The special characteristics of pregnancy are associated with changes in nodule prevalence&#44; size&#44; and growth&#44; and to indications for treatment&#44; particularly surgery&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As in non-pregnant women&#44; ultrasound examination is essential in any thyroid nodule&#46; Ultrasonography provides valuable information regarding the benign or malignant nature of nodules<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In accordance with general criteria&#44; cytological evaluation using fine needle aspiration &#40;FNA&#41; is indispensable in assessing thyroid nodules&#46; Obviously&#44; pregnancy has no effect on the cytological diagnosis of thyroid nodules&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the most commonly used classification&#44; the Bethesda system&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Epidemiology</span><p id="par0040" class="elsevierStylePara elsevierViewall">Both the appearance of new nodules and the volume of those already existing have been reported to increase during pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; nodules usually return to their baseline size after delivery<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In a Spanish study&#44; however&#44; Ja&#233;n D&#237;az et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> found a 33&#46;2&#37; prevalence of thyroid nodules during the first trimester of pregnancy&#44; which was slightly lower than the prevalence seen in controls &#40;38&#46;5&#37;&#41;&#44; although the difference was not statistically significant&#46; This suggests that pregnancy does not promote the occurrence of thyroid nodules&#44; in contrast to findings in studies in other countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;13&#44;14</span></a> However&#44; the high prevalence of thyroid nodules in pregnant women found in the Ja&#233;n D&#237;az et al&#46; study<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> is also noteworthy because it was markedly higher than that reported in the majority of similar studies&#44; where it ranged from 3&#37; to 12&#37;&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Does pregnancy cause any morphological disorder in the thyroid gland&#63;</span></p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">Most research studies suggest that pregnancy increases the risk of developing new thyroid nodules and also promotes an increase in the size of previously existing nodules&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The size of pre-gestational nodules may increase by up to 50&#37;&#44; and a de novo nodule occurs during pregnancy in up to 20&#37; of patients&#46; This risk is also enhanced both by age and a higher number of pregnancies &#40;multiparity is associated with a 10&#8211;15&#37; increase&#41;&#46;<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What precautions may be taken to prevent the occurrence of thyroid nodules during pregnancy&#63;</span></p></li></ul></p><p id="par0060" class="elsevierStylePara elsevierViewall">Epidemiological data suggest that low iodine intake predisposes to the development of thyroid nodules&#46; It is therefore highly recommended that potassium iodide supplements be taken throughout pregnancy&#46; This supplementation also protects against the occurrence of hypothyroidism in the mother and fetus&#44; in addition to providing the fetus with the iodine needed for thyroid hormone synthesis&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">The clinical management of thyroid nodules during pregnancy</span><p id="par0065" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should thyroid nodules be managed in pregnant women&#63;</span></p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">If a thyroid nodule is found during pregnancy&#44; a thorough clinical history and physical examination should be performed&#46; The history should include&#58; &#40;a&#41; any family history of thyroid diseases &#40;autoimmune and nodular&#41; and carcinomas &#40;medullary thyroid cancer&#44; multiple endocrine neoplasia 2A&#44; and colon cancer&#41;&#59; &#40;b&#41; personal history&#44; especially iodine intake&#44; prior neck irradiation&#44; and obstetric history&#59; &#40;c&#41; signs and symptoms of thyroid dysfunction&#44; especially changes over time in the thyroid nodule&#44; must also be investigated&#59; and &#40;d&#41; careful neck examination &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The general recommendation to perform thyroid function tests in any patient with thyroid nodules also applies to pregnant women&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Thus&#44; a pregnant woman with a thyroid nodule should undergo a functional study including tests to measure TSH and free T4 levels&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">If morphological changes found at examination are confirmed&#44; thyroid ultrasound examination should be performed and&#44; if required&#44; work-up should be completed with FNA&#46; Pregnancy is not a contraindication for FNA&#44; which may be performed at any time during pregnancy&#46; The ultrasonographic findings suggesting the need for cytological analysis are summarized as follows&#58; &#40;a&#41; any nodule greater than 1<span class="elsevierStyleHsp" style=""></span>cm in size&#59; &#40;b&#41; nodules with ultrasonographic characteristics suggesting malignancy&#59; &#40;c&#41; the rapid growth or clinical suspicion of malignancy&#59; &#40;d&#41; the discovery by ultrasonography of potentially metastatic neck adenopathies&#59; and &#40;e&#41; the presence of risk factors such as a family history of thyroid cancer or a history of cervical radiotherapy&#46; However&#44; if ultrasonographic findings suggest a benign condition&#44; FNA of nodules may be performed after delivery&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Scintigraphy is contraindicated during pregnancy&#46; However&#44; according to the available information&#44; an involuntary scintigraphy performed before week 12 of pregnancy does not appear to damage the fetal thyroid gland&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The presence of thyroid cancer does not usually cause impaired thyroid gland function&#46; The measurement of circulating thyroglobulin levels is of no diagnostic or prognostic interest in this setting&#46; There is no adequate information regarding the convenience of measuring calcitonin levels during pregnancy&#44; unless there is a family history of medullary thyroid carcinoma&#46; Pentagastrin stimulation is contraindicated in pregnancy&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Should pregnant women be screened for thyroid changes&#63;</span></p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">There is increasing evidence to support the advisability of thyroid function screening and physical examination of the neck as soon as the patient knows that she is pregnant&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The benefit of correcting thyroid dysfunctions detected during the first trimester of pregnancy clearly outweighs the cost of screening&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Few studies are available on the relationship between thyroid nodules and autoimmunity during pregnancy&#44; and there are thus no recommendations regarding the advisability of measuring thyroid antibodies during pregnancy&#46; Moreover&#44; because of immune privilege during pregnancy&#44; circulating levels of thyroid antibodies decrease during pregnancy&#44; which may complicate the interpretation of the results&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What reference levels of thyroid hormones should be considered sufficient during pregnancy&#63;</span></p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">For the abovementioned reasons&#44; circulating TSH levels should range from 0&#46;1 to 2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;L during the first trimester of pregnancy&#46; During the second and third trimesters&#44; levels should be 0&#46;2&#8211;3&#46;0 and 0&#46;3&#8211;3&#46;0<span class="elsevierStyleHsp" style=""></span>mU&#47;L respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should benign nodules be monitored during pregnancy&#63;</span></p></li></ul></p><p id="par0130" class="elsevierStylePara elsevierViewall">No special monitoring is required during pregnancy for thyroid nodules suspected of being benign based on ultrasound characteristics or found to be benign at cytological study and causing no compressive symptoms&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Repeat ultrasound examination should be performed if a nodule grows rapidly&#46; Both in these cases and when ultrasonographic changes suggesting malignancy occur&#44; FNA should be repeated&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">The treatment of thyroid nodules during pregnancy</span><p id="par0140" class="elsevierStylePara elsevierViewall">Once clinical&#44; ultrasonographic&#44; or cytological diagnosis has been made&#44; benign thyroid nodules require no treatment&#46;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Is levothyroxine suppression treatment useful during pregnancy&#63;</span></p></li></ul></p><p id="par0150" class="elsevierStylePara elsevierViewall">The treatment of nodular goiter with supraphysiological doses of levothyroxine is not recommended&#44; because the suppression of TSH secretion may induce untoward adverse effects in both the mother and the fetus&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a><ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">When is surgery indicated for a thyroid nodule&#63;</span></p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">If ultrasonographic or cytological changes occur in previously benign nodules or the course of the nodule casts doubt on its nature&#44; surgery is recommended&#46; Surgery is also indicated when compressive symptoms occur&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Nodules with indeterminate &#40;Bethesda categories 3&#44; 4&#44; and 5&#41; or malignant &#40;category 6&#41; FNA results should undergo surgery &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Specific indications for surgery are addressed in question 12&#46;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9&#46;</span><p id="par0170" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should hyperfunctioning thyroid nodules be treated&#63;</span></p></li></ul></p><p id="par0175" class="elsevierStylePara elsevierViewall">The treatment of hyperthyroidism in pregnant women is complex&#46; Recommendations for the management of this condition are beyond the scope of these guidelines and have been reviewed in another publication&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It should&#44; however&#44; be noted that treatment with radioactive iodine is contraindicated throughout pregnancy&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">The management of differentiated thyroid cancer diagnosed during pregnancy</span><p id="par0180" class="elsevierStylePara elsevierViewall">Differentiated thyroid cancer is the second leading malignant tumor during pregnancy after breast cancer&#44; with a prevalence of 14 per 100&#44;000<span class="elsevierStyleHsp" style=""></span>births&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In addition&#44; 10&#37; of all thyroid cancers occurring during childbearing age are diagnosed during pregnancy or within one year of delivery&#44; and the most common histological type is papillar&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The management of differentiated thyroid cancer during pregnancy poses a number of diagnostic and therapeutic challenges for both the mother and fetus&#46;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">10&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Is there an increased frequency of thyroid cancer in pregnant women with thyroid nodules&#63;</span></p></li></ul></p><p id="par0190" class="elsevierStylePara elsevierViewall">Three retrospective studies have reported an increased risk of malignancy in pregnant women with thyroid nodules&#46; However&#44; these studies had a patient selection bias&#44; because they were conducted in tertiary reference hospitals where women with cancer may be overrepresented&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;24</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Pregnancy may however be expected to promote the occurrence and growth of malignant nodules because of the relative iodine deficiency experienced by the mother&#44; increased growth factors&#44; the appearance of hormones with a stimulating activity similar to that of TSH&#44; and high estrogen levels&#46; The management of these patients therefore requires special consideration&#46;<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">11&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Does pregnancy affect the prognosis of thyroid cancer&#63;</span></p></li></ul></p><p id="par0205" class="elsevierStylePara elsevierViewall">Most studies suggest that pregnancy does not worsen the prognosis of women diagnosed with differentiated thyroid cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#8211;31</span></a> Only one of the seven studies published addressing this issue found an increased risk of disease persistence&#47;recurrence in women diagnosed during pregnancy or within one year of delivery&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> This finding was related to the presence of high estrogen receptor expression levels in thyroid tumor cells&#46; However&#44; the patient sample in this study was small and poorly representative&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In conclusion&#44; no adequate evidence which could lead us to conclude that pregnancy worsens the prognosis of thyroid cancer is currently available&#46; Consequently&#44; thyroidectomy may be delayed in most pregnant patients until the postpartum period without this affecting the risk of recurrence or mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The impact of pregnancy in women with anaplastic or medullary carcinoma has not been analyzed&#46;<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">12&#46;</span><p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should differentiated thyroid cancer diagnosed during pregnancy be managed&#63;</span></p></li></ul></p><p id="par0225" class="elsevierStylePara elsevierViewall">It should be taken into account that a conflict between the optimum treatment of the mother and fetal well-being very often exists&#46; There is therefore an ethical dilemma&#46; The decision as to which is the best therapeutic option should preferably be taken by a multidisciplinary team consisting of an endocrinologist&#44; a surgeon&#44; an obstetrician&#44; a nuclear medicine specialist&#44; and a neonatologist&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">There are two special considerations that should be taken into account in the management of women with differentiated thyroid cancer diagnosed during pregnancy&#58; the absolute contraindication of the administration of radioactive iodine and the choice of the time of thyroidectomy&#46; As noted above&#44; it is usually advisable to delay surgery until the postpartum period&#44; as there is no adequate evidence showing that pregnancy worsens cancer prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Thyroidectomy is recommended in the second trimester in the following cases&#58; &#40;a&#41; aggressive or locally advanced histology &#40;e&#46;g&#46; anaplastic or poorly differentiated carcinoma&#41;&#44; &#40;b&#41; metastatic cervical lymph nodes &#40;diagnosed by cytology&#41;&#44; &#40;c&#41; severe compressive symptoms &#40;e&#46;g&#46; tracheal obstruction&#41;&#44; and &#40;d&#41; the significant growth of a malignant nodule &#40;&#62;50&#37; in volume or &#62;20&#37; in diameter in two dimensions&#41; before week 24 of pregnancy &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0240" class="elsevierStylePara elsevierViewall">If the malignant nodule does not meet the above conditions or is diagnosed toward the end of the second half of pregnancy&#44; surgery may be delayed until the postpartum period&#46; In such cases&#44; it is recommended that levothyroxine suppression treatment aimed at maintaining TSH levels in the lower normal limit &#40;0&#46;1&#8211;1&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;L&#41; be started&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Circulating TSH and free T4 levels should be monitored every month&#44; and ultrasound examination and thyroglobulin tests should be performed every three months &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">13&#46;</span><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What are the perioperative risks for the mother and fetus of thyroidectomy during pregnancy&#63;</span></p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0255" class="elsevierStylePara elsevierViewall">Surgery in the first trimester involves an unacceptable risk of miscarriage and impaired organogenesis&#46; On the other hand&#44; surgery during the third trimester is associated with an increased risk of preterm delivery&#46; Thyroidectomy during the second trimester does therefore involve the lowest risk for the mother and fetus&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> However&#44; if surgery is performed during pregnancy&#44; the risk of postoperative maternal hypothyroidism &#40;and potential hypoparathyroidism&#41; should be taken into account&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">The management of pregnant women with a history of differentiated thyroid cancer</span><p id="par0260" class="elsevierStylePara elsevierViewall">Specific considerations are required in the management of women with a history of differentiated thyroid cancer who want to become pregnant again&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes these considerations&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Women with a history of differentiated thyroid cancer who desire pregnancy</span><p id="par0265" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">14&#46;</span><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What information should be given to women with a history of differentiated thyroid cancer who desire pregnancy&#63;</span></p></li></ul></p><p id="par0275" class="elsevierStylePara elsevierViewall">Women should be informed that pregnancy should be avoided in the 6&#8211;12<span class="elsevierStyleHsp" style=""></span>months following the administration of the therapeutic dose of radioactive iodine in order to achieve the stabilization of the levothyroxine dose and to verify disease remission&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;33&#8211;35</span></a><ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">15&#46;</span><p id="par0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What are the potential risks in women previously receiving radioiodine therapy&#63;</span></p></li></ul></p><p id="par0285" class="elsevierStylePara elsevierViewall">Studies conducted on women previously given radioiodine for the treatment of differentiated thyroid cancer have not reported an increased risk of complications such as infertility&#44; miscarriage&#44; newborn mortality&#44; congenital malformation&#44; premature delivery&#44; low birthweight&#44; death in the first year of life&#44; or cancer development&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a><ul class="elsevierStyleList" id="lis0090"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">16&#46;</span><p id="par0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Can a new pregnancy increase the risk of recurrence in women with a history of thyroid cancer&#63;</span></p></li></ul></p><p id="par890" class="elsevierStylePara elsevierViewall">Often&#44; the patient is mainly interested in knowing whether cancer recurrence may or may not occur as a consequence of a new pregnancy&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">From the pathophysiological viewpoint&#44; it should be noted that both HCG and estrogens induce changes in serum TSH&#44; FT4&#44; and thyroglobulin levels during pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;38</span></a> Some studies have reported that estrogens may stimulate thyroglobulin gene expression&#44; particularly during the third trimester&#44; increasing potential thyroglobulin production in differentiated thyroid cancer&#46; This occurs without stimulating proto-oncogene c-Myc and without promoting rapid cell proliferation&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;40</span></a> Moreover&#44; some clinical studies suggest that circulating thyroglobulin levels may increase in the absence of a concomitant tumor&#44; which may be a confounding factor&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a><span class="elsevierStyleSup">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Several studies&#44; three of them published in the past five years&#44; have assessed the impact of pregnancy in women with a history of differentiated thyroid cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;42&#8211;44</span></a> Leboeuf et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> studied 36 women who had become pregnant a mean of 4&#46;3 years after initial treatment for differentiated thyroid cancer&#46; After delivery&#44; eight of these women had thyroglobulin levels 20&#37; greater than those found before pregnancy&#46; Three of these women had active disease&#44; and five had no evidence of disease&#46; However&#44; no recurrence was found in the early postpartum period in women with negative neck ultrasound whose serum thyroglobulin levels were less than 3&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Data from these studies suggest that pregnancy involves no risk of recurrence in women with no evidence of biochemical or structural disease before pregnancy&#46; However&#44; as previously noted &#40;question 11&#41;&#44; it has not been completely ruled out that pregnancy may represent a stimulus in patients with active disease&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Monitoring during pregnancy of women with a history of differentiated thyroid cancer</span><p id="par0315" class="elsevierStylePara elsevierViewall">In any woman with hypothyroidism&#44; it is crucial to maintain thyroid hormone levels within the specific reference intervals throughout pregnancy&#46; Various studies have shown that even mild hypothyroidism is associated with adverse effects for the mother and fetus&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Thyroid hormone replacement requirements usually increase by 20&#8211;40&#37;&#44; which makes adjustment indispensable in the first eight weeks&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#44;47</span></a> In addition&#44; other routinely used supplements&#44; such as iron and calcium&#44; may alter levothyroxine absorption&#46;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">17&#46;</span><p id="par0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should the levothyroxine dose be adjusted&#63;</span></p></li></ul></p><p id="par0325" class="elsevierStylePara elsevierViewall">Thyroid hormone levels should always be measured when pregnancy is documented&#46; Thyroid function tests should initially be repeated every four weeks until week 16&#8211;20&#44; and then once between weeks 26 and 32&#46; If an adjustment of the levothyroxine dose is required&#44; thyroid hormones should be assessed again four weeks later&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">To provide guidance&#44; it may be noted that mean increases in levothyroxine dose as compared to the pregestational dose over the three trimesters of pregnancy are 9&#37;&#44; 21&#37;&#44; and 26&#37; respectively&#46;<ul class="elsevierStyleList" id="lis0095"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">18&#46;</span><p id="par0335" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Should TSH suppression be maintained during pregnancy&#63;</span></p></li></ul></p><p id="par0340" class="elsevierStylePara elsevierViewall">Goal TSH levels during pregnancy do not change as compared to before pregnancy&#46; In low risk patients &#40;T1-T2&#44; N0&#44; M0&#44; with no aggressive histology&#41;&#44; the goal is to achieve TSH levels ranging from 0&#46;3 to 1&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;L&#46; In patients with no evident biochemical or structural disease but with risk factors at diagnosis &#40;T3-T4&#44; N1&#44; M1&#44; or with an aggressive histology&#41;&#44; the goal is to maintain circulating TSH levels ranging from 0&#46;1 to 0&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;L&#46; It should be noted&#44; however&#44; that if the risk of disease before pregnancy makes the maintenance of suppressed circulating TSH levels advisable&#44; the same caution should be exercised during pregnancy&#44; the levothyroxine dose being adjusted as appropriate&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> A study conducted on 25&#44;765 women&#44; 433 of whom had subclinical hyperthyroidism&#44; was very illustrative of the adverse effects of this measure&#46; Low TSH levels did not correlate to adverse effects in any of the women&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a><ul class="elsevierStyleList" id="lis0100"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">19&#46;</span><p id="par0345" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Should iodine supplements be used&#63;</span></p></li></ul></p><p id="par0350" class="elsevierStylePara elsevierViewall">Despite prior thyroidectomy&#44; patients with a history of thyroid cancer&#44; like all other pregnant women&#44; should take at least 250<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day of iodine during pregnancy and breast-feeding&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> In these cases&#44; iodine supplements are administered to the mother to cover the requirements of the fetal thyroid&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><ul class="elsevierStyleList" id="lis0105"><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">20&#46;</span><p id="par0355" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">How should monitoring be performed&#63;</span></p></li></ul></p><p id="par0360" class="elsevierStylePara elsevierViewall">Most pregnant women with low-risk differentiated thyroid cancer only require monitoring of circulating TSH levels and adjustments of treatment&#44; when needed&#44; as well as an examination every three months&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Neither thyroglobulin measurement nor ultrasonography is required&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">However&#44; women with high thyroglobulin levels before pregnancy or with morphological evidence of disease should be monitored with thyroglobulin tests and neck ultrasound in every trimester of pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">The management of women with differentiated thyroid cancer during lactation</span><p id="par0370" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">21&#46;</span><p id="par0375" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">What considerations should be taken into account during breast-feeding&#63;</span></p></li></ul></p><p id="par0380" class="elsevierStylePara elsevierViewall">Breast-feeding may be safe in women with a history of differentiated thyroid cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> It should&#44; however&#44; be noted that radioiodine should not be administered during lactation and until at least four weeks after its discontinuation&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> because the lactating breast concentrates a significant amount of iodine&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> However&#44; it is advisable to delay radioiodine administration until three months after breast-feeding has been stopped to ensure the normalization of the increased activity of the sodium-iodine symporter caused by lactation&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> If urgent treatment is needed&#44; <span class="elsevierStyleSup">123</span>I scintigraphy may be performed to assess breast residual uptake&#46; Treatment should be delayed if a higher than normal radioactivity level is found&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall">Involution of the lactating breast is variable&#44; and there is evidence that bromocriptine is able to accelerate it&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> This drug may be prescribed in special cases &#8220;outside of its specified indications for use&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Breast-feeding cannot&#44; of course&#44; be resumed after radioiodine administration&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0390" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy&#46; The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women&#46; On the other hand&#44; differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus&#46; The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence&#44; although flare-ups cannot be completely ruled out in women with active disease&#46; If surgery is needed&#44; it should be performed during the second term or&#44; preferably&#44; after delivery&#46; A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy&#46; However&#44; women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy&#46; Pregnancy is an absolute contraindication for radioactive iodine administration&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La conducta a seguir con el n&#243;dulo tiroideo y el c&#225;ncer de tiroides en la paciente embarazada requiere especiales consideraciones&#46; El abordaje diagn&#243;stico y terap&#233;utico del n&#243;dulo tiroideo se rige por los criterios habituales en las pacientes no embarazadas&#46; Por su parte&#44; el manejo del c&#225;ncer diferenciado de tiroides durante la gestaci&#243;n implica una serie de retos para la madre y el feto&#46; Los datos disponibles muestran que el embarazo no supone un aumento de riesgo de aparici&#243;n o recurrencia de c&#225;ncer de tiroides&#44; pero no est&#225; completamente descartado que la gestaci&#243;n pueda representar un est&#237;mulo en pacientes con enfermedad activa&#46; Es importante tener en cuenta que en caso de ser necesario el tratamiento quir&#250;rgico se recomienda llevarlo a cabo durante el segundo trimestre o&#44; preferentemente&#44; tras el parto&#46; La mayor&#237;a de las gestantes con enfermedad de bajo riesgo solo requieren el ajuste del tratamiento con levotiroxina&#46; Sin embargo&#44; en mujeres que tienen valores elevados de tiroglobulina antes de la gestaci&#243;n o con datos morfol&#243;gicos de persistencia de enfermedad deber&#225; realizarse un seguimiento peri&#243;dico mediante la determinaci&#243;n de tiroglobulina y realizaci&#243;n de ecograf&#237;as cervicales&#46; La gestaci&#243;n supone una contraindicaci&#243;n absoluta para la administraci&#243;n de <span class="elsevierStyleSup">131</span>I&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Galofr&#233; JC&#44; Riesco-Eizaguirre G&#44; &#193;lvarez-Escol&#225; C&#44; en representaci&#243;n del Grupo de Trabajo de C&#225;ncer de Tiroides de la Sociedad Espa&#241;ola de Endocrinolog&#237;a y Nutrici&#243;n&#46; Gu&#237;a cl&#237;nica para el manejo del n&#243;dulo tiroideo y c&#225;ncer de tiroides durante el embarazo&#46; Endocrinol Nutr&#46; 2014&#59;61&#58;130&#8211;138&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1721
            "Ancho" => 2525
            "Tamanyo" => 235794
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algorithm for the management of differentiated thyroid cancer diagnosed during pregnancy&#46; Ca&#58; carcinoma&#59; US&#58; thyroid ultrasound examination&#59; mts&#58; metastases&#59; TG&#58; thyroglobulin&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Ultrasound feature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Suspicious feature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Echogenicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypoechogenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodule margins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Irregular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Peripheral halo of nodule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intranodular vascularization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Calcifications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of microcalcifications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dimensions of nodule axes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodules higher than wider&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laterocervical adenopathies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab480792.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ultrasound features of thyroid nodules suggesting malignancy&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Category&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Cytological diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Risk of malignancy &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not diagnostic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benign&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ayipia&#47;follicular lesion of uncertain significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follicular neoplasm&#47;suspected follicular neoplasm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#8211;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspicious for malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#8211;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#8211;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab480794.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cytological diagnostic criteria &#8220;Bethesda Classification&#8221;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clinical history</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nodule characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess growth and presence of local symptomsThyroid dysfunction symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Personal history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neck radiotherapyUsual iodine intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thyroid carcinoma&#58; papillary or medullary&#44; and multiple endocrine neoplasia type 2Colon carcinoma&#58; familial polyposis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Physical examination</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neck palpation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodule characteristics&#44; presence of local adenopathiesSystemic signs of thyroid dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Laboratory</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thyroid profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Goal&#58; TSH&#44; &#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Thyroid ultrasound examination</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cytological study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Any solid nodule<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fine needle aspiration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Any nodule with suspicious ultrasonographic features&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Iodine supplements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Action protocol in the first visit of a pregnant patient with thyroid nodules&#46;</p>"
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      4 => array:7 [
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        "etiqueta" => "Table 4"
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        "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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Appearance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Characteristic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microscopic pathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aggressive histology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gross pathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Locally advanced disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of metastatic structural disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cervical lymph node metastases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical course&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Significant nodule growth &#40;&#62;50&#37; in volume or &#62;20&#37; in diameter in two dimensions&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe compressive symptoms&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Indications for surgery of a thyroid nodule in the second trimester of pregnancy&#46;</p>"
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        "etiqueta" => "Table 5"
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        "tabla" => array:1 [
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                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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Before pregnancy</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- Pregnancy should be avoided in the 6&#8211;12 months following the administration of therapeutic radioiodine doses<span class="elsevierStyleHsp" style=""></span>- A history of radioiodine treatment involves no increased risk of infertility&#44; miscarriage&#44; neonatal mortality&#44; congenital malfomations&#44; premature delivery&#44; low birthweight&#44; death during the first year of life&#44; or cancer development<span class="elsevierStyleHsp" style=""></span>- Pregnancy involves no risk of recurrence in women with no evidence of biochemical or structural disease before pregnancy&#46; However&#44; it may represent a stimulus in patients with active disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><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" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Monitoring during pregnancy</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- In any woman with hypothyroidism&#44; it is essential to maintain thyroid hormone levels adequate for the time of pregnancy<span class="elsevierStyleHsp" style=""></span>- Low-risk patients&#58; these only require TSH monitoring and treatment adjustment when needed&#44; and examination every 3 months<span class="elsevierStyleHsp" style=""></span>- High-risk patients&#58; if TSH suppression was recommended before pregnancy due to the risk of disease&#44; it should be maintained during pregnancy&#44; with the levothyroxine dose being adjusted&#46; In women with high thyroglobulin levels before pregnancy or with morphological evidence of persistent disease&#44; neck ultrasound should be performed every trimester&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><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" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Monitoring during breast-feeding</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- Breast-feeding is safe in women with a history of differentiated thyroid cancer<span class="elsevierStyleHsp" style=""></span>- Radioiodine should not be administered during lactation and for at least four weeks after breast-feeding has stopped&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:51 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Stagnaro-Green"
                            1 => "M&#46; Abalovich"
                            2 => "E&#46; Alexander"
                            3 => "F&#46; Azizi"
                            4 => "J&#46; Mestman"
                            5 => "R&#46; Negro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thyroid"
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                        "volumen" => "2110"
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                    ]
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                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of thyroid dysfunction during pregnancy and postpartum&#58; an endocrine society clinical practice guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; De Groot"
                            1 => "M&#46; Abalovich"
                            2 => "E&#46;K&#46; Alexander"
                            3 => "N&#46; Amino"
                            4 => "L&#46; Barbour"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optimal care of the pregnant woman with thyroid disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Stagnaro-Green"
                          ]
                        ]
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
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              ]
            ]
            3 => array:3 [
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              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical guideline for the diagnosis and treatment of subclinical thyroid dysfunction in pregnancy"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Working Group on Subclinical Thyroid Dysfunction of the Spanish Endocrinology Society"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;C&#46; Galofre Ferrater"
                            1 => "J&#46;J&#46; Corrales Hernandez"
                            2 => "B&#46; Perez Corral"
                            3 => "A&#46; Canton Blanco"
                            4 => "N&#46; Alonso Pedrol"
                            5 => "A&#46; Perez Perez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
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            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thyroid function inside and outside of pregnancy&#58; what do we know and what don&#8217;t we know&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "R&#46;C&#46; Smallridge"
                            1 => "D&#46; Glinoer"
                            2 => "J&#46;G&#46; Hollowell"
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                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thyroid"
                        "fecha" => "2005"
                        "volumen" => "151"
                        "paginaInicial" => "54"
                        "paginaFinal" => "59"
                      ]
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                ]
              ]
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            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thyroid hormones according to gestational age in pregnant Spanish women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46;P&#46; Bocos-Terraz"
                            1 => "S&#46; Izquierdo-Alvarez"
                            2 => "J&#46;L&#46; Bancalero-Flores"
                            3 => "R&#46; Alvarez-Lahuerta"
                            4 => "A&#46; Aznar-Sauca"
                            5 => "E&#46; Real-Lopez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1756-0500-2-237"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Res Notes"
                        "fecha" => "2009"
                        "volumen" => "2"
                        "paginaInicial" => "237"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19939287"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
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              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trimester-specific changes in maternal thyroid hormone&#44; thyrotropin&#44; and thyroglobulin concentrations during gestation&#58; trends and associations across trimesters in iodine sufficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "O&#46;P&#46; Soldin"
                            1 => "R&#46;E&#46; Tractenberg"
                            2 => "J&#46;G&#46; Hollowell"
                            3 => "J&#46; Jonklaas"
                            4 => "N&#46; Janicic"
                            5 => "S&#46;J&#46; Soldin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thyroid"
                        "fecha" => "2004"
                        "volumen" => "1412"
                        "paginaInicial" => "1084"
                        "paginaFinal" => "1090"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Iodine status and thyroid volume changes during pregnancy&#58; results of a survey in Aran Valley &#40;Catalan Pyrenees&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Vila"
                            1 => "G&#46; Legaz"
                            2 => "C&#46; Barrionuevo"
                            3 => "M&#46;L&#46; Espinel"
                            4 => "R&#46; Casamitjana"
                            5 => "J&#46; Munoz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Endocrinol Invest"
                        "fecha" => "2008"
                        "volumen" => "3110"
                        "paginaInicial" => "851"
                        "paginaFinal" => "855"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of thyroid nodules detected at us&#58; Society of Radiologists in Ultrasound Consensus Conference Statement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;C&#46; Frates"
                            1 => "C&#46;B&#46; Benson"
                            2 => "J&#46;W&#46; Charboneau"
                            3 => "E&#46;S&#46; Cibas"
                            4 => "O&#46;H&#46; Clark"
                            5 => "B&#46;G&#46; Coleman"
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        "texto" => "<p id="par0395" class="elsevierStylePara elsevierViewall">The other members of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition are&#58; El&#237;as &#193;lvarez Garc&#237;a&#44; Emma Anda Api&#241;aniz&#44; Amparo Calleja&#44; Sergio Donnay&#44; Jos&#233; Manuel G&#243;mez-S&#225;ez&#44; Edelmiro Men&#233;ndez Torre&#44; Pablo Moreno Llorente&#44; Mar&#237;a Angustias Muros&#44; Elena Navarro Gonz&#225;lez&#44; Vicente Pereg&#44; Bego&#241;a P&#233;rez Corral&#44; Javier Santamar&#237;a Sandi&#44; Pilar Santisteban&#44; and Carles Zaf&#243;n Llopis&#46;</p>"
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Article information

ISSN: 21735093
Original language: English

DOI:10.1016/j.endoen.2014.02.014

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2022 July	147	17	164
2022 June	174	27	201
2022 May	172	32	204
2022 April	131	25	156
2022 March	208	31	239
2022 February	208	24	232
2022 January	161	20	181
2021 December	149	18	167
2021 November	151	22	173
2021 October	202	50	252
2021 September	164	17	181
2021 August	132	18	150
2021 July	142	24	166
2021 June	379	29	408
2021 May	320	30	350
2021 April	424	33	457
2021 March	319	46	365
2021 February	244	33	277
2021 January	199	50	249
2020 December	151	29	180
2020 November	203	28	231
2020 October	102	24	126
2020 September	137	69	206
2020 August	162	26	188
2020 July	157	26	183
2020 June	109	31	140
2020 May	125	32	157
2020 April	125	27	152
2020 March	155	20	175
2020 February	154	28	182
2020 January	149	36	185
2019 December	137	27	164
2019 November	141	15	156
2019 October	134	13	147
2019 September	146	31	177
2019 August	92	18	110
2019 July	89	36	125
2019 June	129	32	161
2019 May	273	54	327
2019 April	130	29	159
2019 March	45	5	50
2019 February	42	9	51
2019 January	41	9	50
2018 December	32	3	35
2018 November	64	3	67
2018 October	49	6	55
2018 September	191	8	199
2018 August	96	2	98
2018 July	61	4	65
2018 June	22	4	26
2018 May	32	7	39
2018 April	40	2	42
2018 March	29	2	31
2018 February	21	2	23
2018 January	27	2	29
2017 December	17	1	18
2017 November	31	4	35
2017 October	19	1	20
2017 September	31	5	36
2017 August	34	3	37
2017 July	32	2	34
2017 June	36	8	44
2017 May	155	8	163
2017 April	69	2	71
2017 March	106	25	131
2017 February	156	4	160
2017 January	28	6	34
2016 December	33	13	46
2016 November	44	6	50
2016 October	55	4	59
2016 September	90	12	102
2016 August	47	15	62
2016 July	30	1	31
2016 June	21	8	29
2016 May	36	12	48
2016 April	31	26	57
2016 March	27	15	42
2016 February	19	8	27
2016 January	23	8	31
2015 December	23	9	32
2015 November	30	5	35
2015 March	0	1	1
2014 August	0	2	2
2014 June	1	0	1
2014 May	1	1	2
2014 April	0	2	2

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Now is Endocrinología, Diabetes y Nutrición (English ed.). More information

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Now is Endocrinología, Diabetes y Nutrición (English ed.). More information

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