Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75μg | Endocrinología y Nutrición (English Edition)

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The ATA and AACE recommend that only patients with peroxidase antibodies (anti-TPO) or thyroglobulin antibodies (anti-TG) are treated, based on a study which showed increased complications of pregnancy in these patients.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> By contrast, other guidelines advocate treatment of all pregnant women with subclinical hypothyroidism, regardless of plasma levels of thyroid antibodies.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The goal of treatment, if administered, is to achieve normal TSH levels for each trimester of pregnancy.There is no agreement either on how to calculate the starting thyroxine dose. Some authors suggest that dose is calculated based on patient weight (1μg/day),<a class="elsevierStyleCrossRef" href="#bib0025">5</a> while others recommend that dosage is based on TSH levels at diagnosis: 25μg/day if TSH level is 4–8mIU/mL; 50μg/day if TSH level is 8–12mIU/mL; 75μg/day if TSH level is greater than 12mIU/mL.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> A recent report by our group showed that a fixed dose of 50μg thyroxine in pregnant women with subclinical hypothyroidism allowed for maintaining TSH levels ranging from 3.0 to 4.5mIU/mL in approximately 80% of women, regardless of weight and baseline TSH level.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> This study subsequently analyzed the convenience of treating subclinical hypothyroidism in pregnant women with a daily dose of 75μg of thyroxine.Subjects and methodsA consecutive sample of women with plasma TSH levels higher than 4.5mIU/L was obtained from all women diagnosed with pregnancy in the Vigo health area between January and August 2012. Women with plasma FT4 levels less than 0.93ng/100mL (frank hypothyroidism), those who had ever been treated with thyroxine, and those previously diagnosed with any thyroid disease (including hypothyroidism, hyperthyroidism, goiter, and thyroid nodule) were excluded.The resulting cohort consisted of 116 pregnant women, all of whom received (as usual in our health area) 200μg/day of potassium iodide at least from the time pregnancy was diagnosed. One of the patients moved to another town in the second trimester of pregnancy, and pregnancy did not reach its term in another four patients.All pregnant women were informed of diagnosis of subclinical hypothyroidism and the need for treatment with thyroxine. The thyroxine dose of 75μg/day has become our standard since we found in a pregnant cohort that doses of 50μg/day is often inadequate and never excessive in this population.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> All pregnant women signed an informed consent.All women were prescribed since diagnosis of hypothyroidism a daily dose of 75μg of thyroxine (Eutirox® 75) administered 30min before breakfast, regardless of weight, height, presence of thyroid antibodies, or plasma TSH levels. TSH and FT4 levels were tested in all pregnant women 2, 4, and 6 months after diagnosis. When TSH levels in any test were higher than 4.5mIU/mL, thyroxine dose was increased by 25μg/day, and when levels were less than 0.3mIU/mL, thyroxine dose was reduced in the same amount.Plasma levels of thyroid peroxidase and thyroglobulin antibodies were tested in all pregnant women in the first trimester.Plasma TSH levels (normal range in our laboratory: 0.3–4.5mcU/mL) were tested using a chemiluminescent immunometric assay (Cobas 6000®, Roche, Mannheim, Germany), FT4 levels (0.9–2ng/100mL) and TPO antibodies (0–34IU/mL) using a competitive electrochemiluminescence immunoassay (Cobas 6000®, Roche, Mannheim, Germany), and TG antibodies (0–115IU/mL) with a chemiluminescent immunometric assay (Immulite 2000®, Siemens, Germany).Quantitative variables are given as mean±standard deviation. Differences between independent measurements of quantitative variables were analyzed using a Student's test for independent variables. Differences between repeated measurements of quantitative variables were analyzed using a Student's t test for related measurements. Differences with values of p<0.05 were considered significant.Results<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the age, gestational age, and changes over time in weight and TSH and FT4 levels of women during pregnancy. Mean TSH level was significantly higher at diagnosis of hypothyroidism as compared to the other three test times (performed 2, 4, or 6 months after diagnosis). No differences were found in TSH levels at 2, 4, and 6 months. No significant differences were also found when mean FT4 levels during pregnancy were compared.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Six women (5% of the sample) had TSH levels higher than 4.5mIU/mL in one test, and three of them had thyroid antibodies. This occurred in three women at the month 2 test, in two women at the month 4 test, and in one woman at the month 6 test. In all these women, titration of thyroxine dose to 100μg/day allowed for maintaining TSH levels within the desired range until delivery.A woman (0.9% of the sample) had a TSH level less than 0.3mIU/mL in the test performed at 4 months. Thyroxine dose reduction to 50μg/day allowed for maintaining her TSH levels within the desired range until delivery.At diagnosis of hypothyroidism, weights of pregnant women in the first and fourth quartiles of weight were 53.3±2.9kg and 79±11kg, respectively (p<0.001). Plasma TSH levels of pregnant women in the first quartile of weight were not significantly different from those of women in the fourth quartile neither at diagnosis nor at the tests performed at 2 or 6 months. In the month 4 tests, plasma TSH levels were significantly lower in pregnant women in the first quartile of weight as compared to the fourth quartile (1.82 vs 2.22mIU/mL; p=0.04). One of the six women who required a higher thyroxine dose was in the first quartile of weight, while the remaining five women were in the second and third quartiles (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>At diagnosis of hypothyroidism, plasma TSH levels of pregnant women in the first and fourth quartiles of TSH levels were 4.77±0.17 and 7.74±1.14mIU/mL, respectively (p<0.001). No significant differences were seen in plasma TSH levels between women in the first and fourth quartiles of TSH in the tests performed at 2 months (1.95 vs 2.66mIU/mL; p=0.08), 4 months (2.56 vs 2.48mIU/mL; p=0.78), or 6 months (2.31 vs 2.21mIU/mL; p=0.19) since diagnosis of hypothyroidism. Of the six patients in whom thyroxine dose was increased, one was in the first quartile of TSH levels at diagnosis, while three were in the third quartile and two in the fourth quartile.In the tests conducted at 2 months, 29 women (27% of the sample) has TSH levels higher than recommended by the ATA-AACE but lower than 4.5mIU/mL, which were maintained until delivery. Fifty-four pregnant women (48% of the sample) had at least one TSH value prior to pregnancy. The mean±standard deviation of TSH levels was 3.3±0.9mIU/mL.Forty-three patients (37% of the sample) had thyroid antibodies (thyroglobulin and/or peroxidase antibodies). Four of the six patients who required increased thyroxine doses during pregnancy belonged to this group.Of the four women in whom pregnancy did not reach its term, three had thyroid antibodies. The last TSH level before termination of their pregnancies was not significantly different from the mean value in the sample at that time.DiscussionThe range of TSH levels we have considered adequate in pregnant women in this study is not the same as recommended by the ATA-AACE. This is not an uncommon occurrence: a recent report showed that the upper limit for TSH levels in pregnant women used in different Spanish regions ranged from 2.63 and 4.75mIU/mL.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Fear of overtreatment is a factor that limits use of stricter ranges in actual clinical practice. Uncertainty about the clinical impact of subclinical hypothyroidism on pregnancy has also prompted use of wider TSH ranges by clinicians. Adoption of stricter TSH ranges would also increase prevalence of hypothyroidism to an extent difficult to assume by already overburdened clinical departments.We do not know whether or not intake of iron or multivitamin preparations by the group of women who required an increased thyroxine dose was similar to that of all other women. Three of the four women in whom pregnancy did not reach its term had thyroid antibodies (i.e. 75%, higher than the prevalence of these antibodies in the whole sample). Both circumstances may have led to bias limiting the conclusions of this study.Our data suggest that in pregnant women with subclinical hypothyroidism in whom the goal is to achieve TSH levels ranging from 0.3 to 4.5mIU/mL, there is no need to calculate the initial thyroxine dose based on patient weight or TSH level. A daily dose of 75μg of thyroxine is adequate in most these patients.In fact, the thyroxine dose calculated based on weight or TSH level appears to be low: administration of 1μg/kg/day to this cohort would result in a mean daily dose of 65μg; if TSH levels were used, only pregnant women with values higher than 12mIU/mL would receive 75μg/day of thyroxine.Our data suggest that if the goal was a TSH level within the ranges recommended by the ATA-AACE, 75μg/day of thyroxine would often be an inadequate dose. A dose of 100μg/day would probably be more adequate under these conditions.Despite the increase in weight over the course of pregnancy, the thyroxine dose needed by our cohort did not increase. This may be explained by the limited capacity of thyroxine to cross the placenta, so that its actual volume of distribution changes little over these months.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>We recommend clinicians use of 75μg/day as initial thyroxine dose in any pregnant woman with subclinical hypothyroidism–regardless of weight and TSH level–if the goal is to achieve a TSH level less than 4.5mIU/mL.Conflicts of interestThe authors state that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres355395" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background and objectives" 2 => "Patients and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec336659" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres355396" "titulo" => array:5 [ 0 => "Resumen" 1 => "Antecedentes y objetivos" 2 => "Pacientes y métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec336660" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Subjects and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-10-07" "fechaAceptado" => "2014-01-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec336659" "palabras" => array:5 [ 0 => "Hypothyroidism" 1 => "Pregnancy" 2 => "Dose" 3 => "Treatment" 4 => "Thyroxine" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec336660" "palabras" => array:5 [ 0 => "Hipotiroidismo" 1 => "Gestación" 2 => "Dosis" 3 => "Tratamiento" 4 => "Tiroxina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Background and objectivesTreatment of hypothyroid pregnant women is usually calculated based on weight (1μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75μg/day. Patients and methodsAll women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4.5mUI/mL were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5mUI/mL. ResultsA woman had a TSH level less than 0.3mUI/mL in a test; reduction of thyroxine dose to 50μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5mUI/mL in one test; in all of them, increase in thyroxine dose to 100μg/day allowed for maintaining the level within the desired range until delivery. ConclusionsFixed daily doses of thyroxine 75μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Antecedentes y objetivosLos métodos habituales de cálculo de la dosis inicial de tiroxina en el tratamiento de gestantes hipotiroideas usan el peso de las pacientes (1μg/kg/día) o la concentración plasmática de TSH. Este estudio analiza la idoneidad de tratar a estas mujeres con una dosis fija de 75μg/día de la hormona. Pacientes y métodosSe seleccionaron mediante un muestreo consecutivo a todas aquellas mujeres diagnosticadas de gestación en el área sanitaria de Vigo entre enero y agosto de 2012, sin antecedentes de tiroidopatía y con una concentración de TSH superior a 4,5mUI/ml y T4L normal. Las 116 gestantes de la muestra resultante recibieron tratamiento con 75μg/día de tiroxina, y se les hizo un análisis a los 2, 4 y 6 meses tras la instauración del tratamiento, modificándose la dosis de la hormona si la concentración de TSH era inferior a 0,3 o superior a 4,5mUI/ml. ResultadosUna de las pacientes tuvo, en un análisis, una concentración de TSH inferior a 0,3mUI/ml; el descenso de la dosis de tiroxina a 50μg/día permitió mantener dicha concentración en el rango deseado hasta el parto. Seis tuvieron en un análisis una concentración de TSH superior a 4,5mUI/ml; en todas ellas el aumento de la dosis de tiroxina a 100μg/día permitió mantener dicha concentración en el rango deseado hasta el parto. ConclusionesUna dosis de tiroxina 75μg/día permitió conseguir los objetivos de concentración de TSH de nuestro estudio en la mayoría de las gestantes con hipotiroidismo subclínico, independientemente de su peso y de su concentración inicial de TSH." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Penin M, Trigo C, López Y, Barragáns M. Tratamiento del hipotiroidismo subclínico en gestantes con una dosis fija diaria de 75μg de tiroxina. Endocrinol Nutr. 2014;61:347–350." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "The column “Diagnosis” shows the value of variables at diagnosis of hypothyroidism. All other columns give the value in the tests performed 2, 4, and 6 months after that time.TSH, thyroid-stimulating hormone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \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">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">2 months \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">4 months \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">6 months \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">Age (years) \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">28±5 \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">– \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">– \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">– \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">Gestational age (weeks) \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">10.1±3.9 \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">– \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">– \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">– \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">Weight (kg) \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">65.4±12.2 \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">69.1±13.3 \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">73.4±12.2 \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">79.3±11.4 \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">TSH (mIU/mL) \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">5.9±1.2 \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">2.3±1.2 \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">2.3±1.1 \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">2.2±1.1 \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">FT4 (ng/100mL) \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">1.1±0.1 \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">1.1±0.2 \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">1.0±0.2 \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">1.0±0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab530589.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Age, gestational age, and hormone levels (mean±standard deviation) during pregnancy." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Given as mean±standard deviation. The last column represents the number of patients in whom thyroxine dose during pregnancy.TSH, thyroid-stimulating hormone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \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">TSH at 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">TSH at 2 months \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">TSH at 4 months \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">TSH at 6 months \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">Dose increases \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">1st quartile \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">5.9±1.2 \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">2.4±1.8 \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">1.8±1.8<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">1.7±0.9 \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 \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">2nd quartile \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">7.9±2.3 \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">2.9±2.0 \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">2.4±1.9 \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">1.6±0.6 \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">2 \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">3rd quartile \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">5.8±1.2 \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">2.8±1.8 \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">2.6±1.2 \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">2.5±0.8 \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">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">4th quartile \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">5.8±1.5 \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">2.2±0.9 \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">2.2±1.1<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">1.8±0.8 \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab530590.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p=0.04." ] ] ] "descripcion" => array:1 [ "en" => "TSH levels (mIU/mL) by quartiles of weight at diagnosis of hypothyroidism and after 2, 4, and 6 months." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "On the need for universal thyroid screening in pregnant women" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.L. Vila" 1 => "I. Velasco" 2 => "S. González" 3 => "F. Morales" 4 => "E. Sánchez" 5 => "S. Torrejón" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/EJE-13-0561" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2014" "volumen" => "170" "paginaInicial" => "R17" "paginaFinal" => "R30" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24128429" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Establishment of reference range for thyroid hormones in normal pregnant Indian women" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.K. Marwaha" 1 => "S. Chopra" 2 => "S. Gopalakrishnan" 3 => "B. Sharma" 4 => "R.S. Kanwar" 5 => "A. Sastry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1471-0528.2008.01673.x" "Revista" => array:6 [ "tituloSerie" => "BJOG" "fecha" => "2008" "volumen" => "115" "paginaInicial" => "602" "paginaFinal" => "606" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18333941" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Negro" 1 => "A. Schwartz" 2 => "R. Gismondi" 3 => "A. Tinelli" 4 => "T. Mangieri" 5 => "A. Stagnaro-Green" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2009-2009" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2010" "volumen" => "95" "paginaInicial" => "1699" "paginaFinal" => "1707" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20130074" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of thyiroid 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. Cobin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2011-2803" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2012" "volumen" => "97" "paginaInicial" => "2543" "paginaFinal" => "2565" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22869843" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypothyroidism during pregnancy: clinical manifestations, diagnosis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D. Ross" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2012" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical practice guidelines for hypothyroidism in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Garber" 1 => "R.H. Cobin" 2 => "H. Gharib" 3 => "J.V. Hennessey" 4 => "I. Klein" 5 => "J.I. Mechanick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4158/EP12280.GL" "Revista" => array:6 [ "tituloSerie" => "Endocr Pract" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "988" "paginaFinal" => "1028" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23246686" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment with fixed thyroxine doses in pregnant women with subclinical hypothyroidism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I. Seoane" 1 => "M. Penín" 2 => "R. Luna" 3 => "R. 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Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75μg

Tratamiento del hipotiroidismo subclínico en gestantes con una dosis fija diaria de 75μg de tiroxina

Manuel Penin

Corresponding author

manuelpenin@wanadoo.es

Corresponding author.

, Cristina Trigo, Yolanda López, María Barragáns

Servicio de Endocrinología y Nutrición, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diagnosis and treatment of hypothyroidism in pregnant women are frequently controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Most&#44; but not all&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> studies show decreased plasma levels of thyroid-stimulating hormone &#40;TSH&#41; during pregnancy&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;7</span></a> and both the American thyroid Association &#40;ATA&#41; and the American Association of Clinical Endocrinologists &#40;AACE&#41; recommend use of the following specific normal ranges for pregnant women&#58; first trimester&#44; 0&#46;1&#8211;2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; second trimester&#44; 0&#46;2&#8211;3&#46;0<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; and third trimester&#44; 0&#46;3&#8211;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; instead of the standard range used in non-pregnant women &#40;0&#46;3&#8211;4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Unlike in frank hypothyroidism&#44; there is no agreement on the indications for treatment in pregnant women with subclinical hypothyroidism &#40;increased TSH levels with normal FT4&#41;&#46; The ATA and AACE recommend that only patients with peroxidase antibodies &#40;anti-TPO&#41; or thyroglobulin antibodies &#40;anti-TG&#41; are treated&#44; based on a study which showed increased complications of pregnancy in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> By contrast&#44; other guidelines advocate treatment of all pregnant women with subclinical hypothyroidism&#44; regardless of plasma levels of thyroid antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The goal of treatment&#44; if administered&#44; is to achieve normal TSH levels for each trimester of pregnancy&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">There is no agreement either on how to calculate the starting thyroxine dose&#46; Some authors suggest that dose is calculated based on patient weight &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> while others recommend that dosage is based on TSH levels at diagnosis&#58; 25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day if TSH level is 4&#8211;8<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day if TSH level is 8&#8211;12<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day if TSH level is greater than 12<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> A recent report by our group showed that a fixed dose of 50<span class="elsevierStyleHsp" style=""></span>&#956;g thyroxine in pregnant women with subclinical hypothyroidism allowed for maintaining TSH levels ranging from 3&#46;0 to 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL in approximately 80&#37; of women&#44; regardless of weight and baseline TSH level&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This study subsequently analyzed the convenience of treating subclinical hypothyroidism in pregnant women with a daily dose of 75<span class="elsevierStyleHsp" style=""></span>&#956;g of thyroxine&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A consecutive sample of women with plasma TSH levels higher than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;L was obtained from all women diagnosed with pregnancy in the Vigo health area between January and August 2012&#46; Women with plasma FT4 levels less than 0&#46;93<span class="elsevierStyleHsp" style=""></span>ng&#47;100<span class="elsevierStyleHsp" style=""></span>mL &#40;frank hypothyroidism&#41;&#44; those who had ever been treated with thyroxine&#44; and those previously diagnosed with any thyroid disease &#40;including hypothyroidism&#44; hyperthyroidism&#44; goiter&#44; and thyroid nodule&#41; were excluded&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The resulting cohort consisted of 116 pregnant women&#44; all of whom received &#40;as usual in our health area&#41; 200<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day of potassium iodide at least from the time pregnancy was diagnosed&#46; One of the patients moved to another town in the second trimester of pregnancy&#44; and pregnancy did not reach its term in another four patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">All pregnant women were informed of diagnosis of subclinical hypothyroidism and the need for treatment with thyroxine&#46; The thyroxine dose of 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day has become our standard since we found in a pregnant cohort that doses of 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day is often inadequate and never excessive in this population&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> All pregnant women signed an informed consent&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">All women were prescribed since diagnosis of hypothyroidism a daily dose of 75<span class="elsevierStyleHsp" style=""></span>&#956;g of thyroxine &#40;Eutirox<span class="elsevierStyleSup">&#174;</span> 75&#41; administered 30<span class="elsevierStyleHsp" style=""></span>min before breakfast&#44; regardless of weight&#44; height&#44; presence of thyroid antibodies&#44; or plasma TSH levels&#46; TSH and FT4 levels were tested in all pregnant women 2&#44; 4&#44; and 6 months after diagnosis&#46; When TSH levels in any test were higher than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; thyroxine dose was increased by 25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day&#44; and when levels were less than 0&#46;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; thyroxine dose was reduced in the same amount&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Plasma levels of thyroid peroxidase and thyroglobulin antibodies were tested in all pregnant women in the first trimester&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Plasma TSH levels &#40;normal range in our laboratory&#58; 0&#46;3&#8211;4&#46;5<span class="elsevierStyleHsp" style=""></span>mcU&#47;mL&#41; were tested using a chemiluminescent immunometric assay &#40;Cobas 6000<span class="elsevierStyleSup">&#174;</span>&#44; Roche&#44; Mannheim&#44; Germany&#41;&#44; FT4 levels &#40;0&#46;9&#8211;2<span class="elsevierStyleHsp" style=""></span>ng&#47;100<span class="elsevierStyleHsp" style=""></span>mL&#41; and TPO antibodies &#40;0&#8211;34<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&#41; using a competitive electrochemiluminescence immunoassay &#40;Cobas 6000<span class="elsevierStyleSup">&#174;</span>&#44; Roche&#44; Mannheim&#44; Germany&#41;&#44; and TG antibodies &#40;0&#8211;115<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&#41; with a chemiluminescent immunometric assay &#40;Immulite 2000<span class="elsevierStyleSup">&#174;</span>&#44; Siemens&#44; Germany&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Quantitative variables are given as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; Differences between independent measurements of quantitative variables were analyzed using a Student&#39;s test for independent variables&#46; Differences between repeated measurements of quantitative variables were analyzed using a Student&#39;s <span class="elsevierStyleItalic">t</span> test for related measurements&#46; Differences with values of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 were considered significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the age&#44; gestational age&#44; and changes over time in weight and TSH and FT4 levels of women during pregnancy&#46; Mean TSH level was significantly higher at diagnosis of hypothyroidism as compared to the other three test times &#40;performed 2&#44; 4&#44; or 6 months after diagnosis&#41;&#46; No differences were found in TSH levels at 2&#44; 4&#44; and 6 months&#46; No significant differences were also found when mean FT4 levels during pregnancy were compared&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Six women &#40;5&#37; of the sample&#41; had TSH levels higher than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL in one test&#44; and three of them had thyroid antibodies&#46; This occurred in three women at the month 2 test&#44; in two women at the month 4 test&#44; and in one woman at the month 6 test&#46; In all these women&#44; titration of thyroxine dose to 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day allowed for maintaining TSH levels within the desired range until delivery&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A woman &#40;0&#46;9&#37; of the sample&#41; had a TSH level less than 0&#46;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL in the test performed at 4 months&#46; Thyroxine dose reduction to 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day allowed for maintaining her TSH levels within the desired range until delivery&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">At diagnosis of hypothyroidism&#44; weights of pregnant women in the first and fourth quartiles of weight were 53&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9<span class="elsevierStyleHsp" style=""></span>kg and 79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>kg&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Plasma TSH levels of pregnant women in the first quartile of weight were not significantly different from those of women in the fourth quartile neither at diagnosis nor at the tests performed at 2 or 6 months&#46; In the month 4 tests&#44; plasma TSH levels were significantly lower in pregnant women in the first quartile of weight as compared to the fourth quartile &#40;1&#46;82 vs 2&#46;22<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46; One of the six women who required a higher thyroxine dose was in the first quartile of weight&#44; while the remaining five women were in the second and third quartiles &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">At diagnosis of hypothyroidism&#44; plasma TSH levels of pregnant women in the first and fourth quartiles of TSH levels were 4&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17 and 7&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;14<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; No significant differences were seen in plasma TSH levels between women in the first and fourth quartiles of TSH in the tests performed at 2 months &#40;1&#46;95 vs 2&#46;66<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#44; 4 months &#40;2&#46;56 vs 2&#46;48<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;78&#41;&#44; or 6 months &#40;2&#46;31 vs 2&#46;21<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;19&#41; since diagnosis of hypothyroidism&#46; Of the six patients in whom thyroxine dose was increased&#44; one was in the first quartile of TSH levels at diagnosis&#44; while three were in the third quartile and two in the fourth quartile&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the tests conducted at 2 months&#44; 29 women &#40;27&#37; of the sample&#41; has TSH levels higher than recommended by the ATA-AACE but lower than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; which were maintained until delivery&#46; Fifty-four pregnant women &#40;48&#37; of the sample&#41; had at least one TSH value prior to pregnancy&#46; The mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation of TSH levels was 3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Forty-three patients &#40;37&#37; of the sample&#41; had thyroid antibodies &#40;thyroglobulin and&#47;or peroxidase antibodies&#41;&#46; Four of the six patients who required increased thyroxine doses during pregnancy belonged to this group&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Of the four women in whom pregnancy did not reach its term&#44; three had thyroid antibodies&#46; The last TSH level before termination of their pregnancies was not significantly different from the mean value in the sample at that time&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The range of TSH levels we have considered adequate in pregnant women in this study is not the same as recommended by the ATA-AACE&#46; This is not an uncommon occurrence&#58; a recent report showed that the upper limit for TSH levels in pregnant women used in different Spanish regions ranged from 2&#46;63 and 4&#46;75<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Fear of overtreatment is a factor that limits use of stricter ranges in actual clinical practice&#46; Uncertainty about the clinical impact of subclinical hypothyroidism on pregnancy has also prompted use of wider TSH ranges by clinicians&#46; Adoption of stricter TSH ranges would also increase prevalence of hypothyroidism to an extent difficult to assume by already overburdened clinical departments&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We do not know whether or not intake of iron or multivitamin preparations by the group of women who required an increased thyroxine dose was similar to that of all other women&#46; Three of the four women in whom pregnancy did not reach its term had thyroid antibodies &#40;i&#46;e&#46; 75&#37;&#44; higher than the prevalence of these antibodies in the whole sample&#41;&#46; Both circumstances may have led to bias limiting the conclusions of this study&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Our data suggest that in pregnant women with subclinical hypothyroidism in whom the goal is to achieve TSH levels ranging from 0&#46;3 to 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#44; there is no need to calculate the initial thyroxine dose based on patient weight or TSH level&#46; A daily dose of 75<span class="elsevierStyleHsp" style=""></span>&#956;g of thyroxine is adequate in most these patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In fact&#44; the thyroxine dose calculated based on weight or TSH level appears to be low&#58; administration of 1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;day to this cohort would result in a mean daily dose of 65<span class="elsevierStyleHsp" style=""></span>&#956;g&#59; if TSH levels were used&#44; only pregnant women with values higher than 12<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL would receive 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day of thyroxine&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our data suggest that if the goal was a TSH level within the ranges recommended by the ATA-AACE&#44; 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day of thyroxine would often be an inadequate dose&#46; A dose of 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day would probably be more adequate under these conditions&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Despite the increase in weight over the course of pregnancy&#44; the thyroxine dose needed by our cohort did not increase&#46; This may be explained by the limited capacity of thyroxine to cross the placenta&#44; so that its actual volume of distribution changes little over these months&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">We recommend clinicians use of 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day as initial thyroxine dose in any pregnant woman with subclinical hypothyroidism&#8211;regardless of weight and TSH level&#8211;if the goal is to achieve a TSH level less than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres355395"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Background and objectives"
            2 => "Patients and methods"
            3 => "Results"
            4 => "Conclusions"
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          "identificador" => "xpalclavsec336659"
          "titulo" => "Keywords"
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        2 => array:2 [
          "identificador" => "xres355396"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Antecedentes y objetivos"
            2 => "Pacientes y m&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
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        ]
        3 => array:2 [
          "identificador" => "xpalclavsec336660"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Subjects and methods"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Results"
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        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Discussion"
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        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Conflicts of interest"
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        9 => array:1 [
          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-10-07"
    "fechaAceptado" => "2014-01-26"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec336659"
          "palabras" => array:5 [
            0 => "Hypothyroidism"
            1 => "Pregnancy"
            2 => "Dose"
            3 => "Treatment"
            4 => "Thyroxine"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec336660"
          "palabras" => array:5 [
            0 => "Hipotiroidismo"
            1 => "Gestaci&#243;n"
            2 => "Dosis"
            3 => "Tratamiento"
            4 => "Tiroxina"
          ]
        ]
      ]
    ]
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment of hypothyroid pregnant women is usually calculated based on weight &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;day&#41; and TSH levels&#46; This study assessed the usefulness of treating these women with a fixed dose of 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area &#40;Spain&#41; without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4&#46;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;mL were enrolled by consecutive sampling&#46; All 116 women in the sample were treated with a fixed daily dose of thyroxine 75<span class="elsevierStyleHsp" style=""></span>&#956;g-thyroxine levels were measured at two&#44; four&#44; and six months&#44; and thyroxine dose was modified if TSH level was lower than 0&#46;3 or higher than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;mL&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A woman had a TSH level less than 0&#46;3<span class="elsevierStyleHsp" style=""></span>mUI&#47;mL in a test&#59; reduction of thyroxine dose to 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day allowed for maintaining TSH level within the desired range until delivery&#46; Six women had TSH levels over 4&#46;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;mL in one test&#59; in all of them&#44; increase in thyroxine dose to 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day allowed for maintaining the level within the desired range until delivery&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Fixed daily doses of thyroxine 75<span class="elsevierStyleHsp" style=""></span>&#956;g allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism&#44; irrespective of their weight and baseline TSH level&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los m&#233;todos habituales de c&#225;lculo de la dosis inicial de tiroxina en el tratamiento de gestantes hipotiroideas usan el peso de las pacientes &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;d&#237;a&#41; o la concentraci&#243;n plasm&#225;tica de TSH&#46; Este estudio analiza la idoneidad de tratar a estas mujeres con una dosis fija de 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;d&#237;a de la hormona&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se seleccionaron mediante un muestreo consecutivo a todas aquellas mujeres diagnosticadas de gestaci&#243;n en el &#225;rea sanitaria de Vigo entre enero y agosto de 2012&#44; sin antecedentes de tiroidopat&#237;a y con una concentraci&#243;n de TSH superior a 4&#44;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml y T4L normal&#46; Las 116 gestantes de la muestra resultante recibieron tratamiento con 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;d&#237;a de tiroxina&#44; y se les hizo un an&#225;lisis a los 2&#44; 4 y 6 meses tras la instauraci&#243;n del tratamiento&#44; modific&#225;ndose la dosis de la hormona si la concentraci&#243;n de TSH era inferior a 0&#44;3 o superior a 4&#44;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Una de las pacientes tuvo&#44; en un an&#225;lisis&#44; una concentraci&#243;n de TSH inferior a 0&#44;3<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#59; el descenso de la dosis de tiroxina a 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;d&#237;a permiti&#243; mantener dicha concentraci&#243;n en el rango deseado hasta el parto&#46; Seis tuvieron en un an&#225;lisis una concentraci&#243;n de TSH superior a 4&#44;5<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#59; en todas ellas el aumento de la dosis de tiroxina a 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;d&#237;a permiti&#243; mantener dicha concentraci&#243;n en el rango deseado hasta el parto&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Una dosis de tiroxina 75<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;d&#237;a permiti&#243; conseguir los objetivos de concentraci&#243;n de TSH de nuestro estudio en la mayor&#237;a de las gestantes con hipotiroidismo subcl&#237;nico&#44; independientemente de su peso y de su concentraci&#243;n inicial de TSH&#46;</p>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Penin M&#44; Trigo C&#44; L&#243;pez Y&#44; Barrag&#225;ns M&#46; Tratamiento del hipotiroidismo subcl&#237;nico en gestantes con una dosis fija diaria de 75<span class="elsevierStyleHsp" style=""></span>&#956;g de tiroxina&#46; Endocrinol Nutr&#46; 2014&#59;61&#58;347&#8211;350&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The column &#8220;Diagnosis&#8221; shows the value of variables at diagnosis of hypothyroidism&#46; All other columns give the value in the tests performed 2&#44; 4&#44; and 6 months after that time&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">TSH&#44; thyroid-stimulating hormone&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">10&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">TSH levels &#40;mIU&#47;mL&#41; by quartiles of weight at diagnosis of hypothyroidism and after 2&#44; 4&#44; and 6 months&#46;</p>"
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                      "titulo" => "On the need for universal thyroid screening in pregnant women"
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                            0 => "L&#46;L&#46; Vila"
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                            3 => "F&#46; Morales"
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                        "tituloSerie" => "Eur J Endocrinol"
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                        "volumen" => "170"
                        "paginaInicial" => "R17"
                        "paginaFinal" => "R30"
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                            0 => "R&#46;K&#46; Marwaha"
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                            2 => "S&#46; Gopalakrishnan"
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                            4 => "R&#46;S&#46; Kanwar"
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                      "doi" => "10.1111/j.1471-0528.2008.01673.x"
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Article information

ISSN: 21735093
Original language: English

DOI:10.1016/j.endoen.2014.06.013

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	64	2	66
2024 September	119	3	122
2024 August	101	4	105
2024 July	95	7	102
2024 June	78	5	83
2024 May	82	4	86
2024 April	91	6	97
2024 March	112	2	114
2024 February	159	11	170
2024 January	185	12	197
2023 December	155	22	177
2023 November	125	15	140
2023 October	138	14	152
2023 September	84	9	93
2023 August	103	7	110
2023 July	80	11	91
2023 June	98	14	112
2023 May	107	9	116
2023 April	86	11	97
2023 March	72	13	85
2023 February	79	9	88
2023 January	98	9	107
2022 December	63	5	68
2022 November	42	13	55
2022 October	48	19	67
2022 September	45	19	64
2022 August	54	14	68
2022 July	44	13	57
2022 June	34	7	41
2022 May	45	23	68
2022 April	70	16	86
2022 March	109	16	125
2022 February	90	8	98
2022 January	65	10	75
2021 December	56	11	67
2021 November	42	11	53
2021 October	37	18	55
2021 September	56	38	94
2021 August	58	28	86
2021 July	43	20	63
2021 June	35	16	51
2021 May	52	11	63
2021 April	138	18	156
2021 March	107	14	121
2021 February	95	11	106
2021 January	115	9	124
2020 December	93	10	103
2020 November	79	18	97
2020 October	55	7	62
2020 September	58	11	69
2020 August	78	7	85
2020 July	53	13	66
2020 June	65	3	68
2020 May	73	9	82
2020 April	74	5	79
2020 March	64	4	68
2020 February	52	4	56
2020 January	49	9	58
2019 December	53	4	57
2019 November	55	13	68
2019 October	43	6	49
2019 September	26	9	35
2019 August	26	2	28
2019 July	23	17	40
2019 June	35	10	45
2019 May	96	20	116
2019 April	27	9	36
2019 March	11	3	14
2019 February	11	8	19
2019 January	5	10	15
2018 December	8	4	12
2018 November	6	1	7
2018 October	8	2	10
2018 September	11	2	13
2018 August	6	3	9
2018 July	15	4	19
2018 June	6	1	7
2018 May	15	3	18
2018 April	8	1	9
2018 March	11	0	11
2018 February	7	0	7
2018 January	11	0	11
2017 December	11	1	12
2017 November	9	1	10
2017 October	19	1	20
2017 September	19	2	21
2017 August	19	5	24
2017 July	15	3	18
2017 June	29	7	36
2017 May	24	3	27
2017 April	35	3	38
2017 March	27	4	31
2017 February	28	3	31
2017 January	10	1	11
2016 December	15	4	19
2016 November	17	5	22
2016 October	32	2	34
2016 September	29	5	34
2016 August	16	1	17
2016 July	26	5	31
2016 June	21	7	28
2016 May	32	9	41
2016 April	23	8	31
2016 March	36	5	41
2016 February	15	10	25
2016 January	35	9	44
2015 December	21	9	30
2015 November	23	5	28
2014 October	0	1	1
2014 September	2	1	3
2014 August	1	2	3

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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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