Letter to the Editor
Universal screening of thyroid dysfunction in the pregnant population
Cribado universal de la disfunción tiroidea en la población gestante
Lluís Vilaa,
, Inés Velascob, Stella Gonzálezc, Francisco Moralesd, Emilia Sáncheze, José Maria Laillaf, Txanton Martinez-Astorquizag, Manel Puig-Domingoh
Corresponding author
a Servicio de Endocrinología y Nutrición, Hospital de Sant Joan Despí Moisés Broggi, Barcelona, Spain
b Servicio de Ginecología y Obstetricia, Hospital de Río Tinto, Huelva, Spain
c Servicio de Endocrinología y Nutrición, Hospital Carlos Haya, Málaga, Spain
d Endocrinología y Nutrición, UGEN, Hospital Universitario Virgen del Rocío, Sevilla, Spain
e Facultad de Ciencias de la Salud Blanquerna, Universitat Ramon Llull, Barcelona, Spain
f Servicio de Ginecología y Obstetricia, Hospital de Sant Joan de Déu, Barcelona, Spain
g Servicio de Ginecología y Obstetricia, Hospital de Cruces, Bilbao, Spain
h Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
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Huelva, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Carlos Haya, Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Endocrinología y Nutrición, UGEN, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Facultad de Ciencias de la Salud Blanquerna, Universitat Ramon Llull, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Ginecología y Obstetricia, Hospital de Sant Joan de Déu, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Ginecología y Obstetricia, Hospital de Cruces, Bilbao, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cribado universal de la disfunción tiroidea en la población gestante" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Universal screening for thyroid dysfunction in pregnant women is an extremely complex subject which has stirred up broad debate and opposing positions regarding the convenience or inconvenience of performing universal versus selective screening. The recently published consensus document advocates universal screening because adequate evidence to justify it is considered to be available.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Some of our arguments are debated in the letter of G. Giménez-Pérez published in this issue. As regards the prevalence of hypothyroidism, the values given under the Stagnaro et al. reference (0.3–0.5%)<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> are based on studies by Casey et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and Allan et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In both these studies, prevalence was estimated based on previously calculated or established reference values (RVs) for TSH. In the Casey study, clinical hypothyroidism was defined as a TSH level above the 97.5th percentile and a free thyroxine value below the 2nd percentile. These criteria were met by 0.2% of the total sample. In the Allan et al. study, pregnant women with TSH levels higher than 10<span class="elsevierStyleHsp" style=""></span>mU/mL (0.4% of all study patients) were considered to have clinical hypothyroidism. Thus, the prevalence estimated in both studies corresponded to women who were hypothyroid at the time of the control. The document discusses the possibility that prevalence may be higher and, actually, Blatt et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> (the first edition, in an electronic version, was published in 2011) found a 2.4% prevalence of clinical hypothyroidism using a TSH cut-off point of 2.5<span class="elsevierStyleHsp" style=""></span>μIU/mL, based on specific RVs for each trimester of pregnancy. Very few studies are available in Spain on the prevalence of thyroid dysfunction in pregnant women. This is why mention is made of the results of the study conducted in Asturias of more than 2,000 women.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> While it is true that the study has not been published and the reference is to the abstract of a conference, its relevance lies in the fact that, in addition to recruiting a large population, the prevalence of hypothyroidism was calculated based on their own RFs and was found to be 1.96%. G. Giménez-Pérez states that the most adequate estimate of the prevalence of clinical hypothyroidism in this population is 0.23%, as reported by Lazarus.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In accordance to the American Thyroid Association (ATA) recommendations for thyroid dysfunction screening in pregnancy and using this latter prevalence figure, in 2010 there may have been in Spain approximately 290 women with clinical hypothyroidism younger than 30 years who did not meet other criteria for screening.</p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Regarding the screening test.</span> The document discusses in depth the limitations of immunoassays for measuring free thyroxine (FT<span class="elsevierStyleInf">4</span>) during pregnancy, caused by changes in transporter proteins. The sentence “there could be no absolute FT<span class="elsevierStyleInf">4</span> value that may define hypothyroxinemia with these techniques” is taken literally from the opinion of Soldin et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However, it is also stated that some authors have found that some immunoassay techniques may provide a good approximation to the standard provided by tandem mass spectrometry,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> which has in turn be shown to have a good correlation to the gold standard in the different trimesters of pregnancy. Our document also widely discusses the significance of detecting isolated hypothyroxinemia, because of its relationship to moderate neurodevelopmental delay according to various studies.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> When hypothyroxinemia is not isolated, but associated with elevated TSH, we think that treatment should be considered. It is undoubtedly very important that each center has its own RVs, but if these are not available, the ATA recommends a cut-off point of 2.5<span class="elsevierStyleHsp" style=""></span>μU/mL in the first trimester. It is true that this figure may overestimate the prevalence of hypothyroidism in certain populations, as stated by Allan et al. Our document mentions this possibility, and explicitly states in the recommendations that “the availability of RVs for these hormones for each population, measured using the laboratories own procedures, is indispensable”. It should be noted, however, that different studies, such as the one conducted by Negro et al. in Italy, showed a greater obstetric morbidity in women with TSH levels above 2.5<span class="elsevierStyleHsp" style=""></span>μU/mL,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and that the situation worsened in the presence of positive anti-peroxidase antibodies (TPO Ab). On the other hand, the use of RVs for the general population may underestimate the number of cases with hypothyroidism. Laboratories should make an effort to establish their own RVs.</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">About effective treatment.</span> It is true that further controlled studies are required to confirm the level of evidence concerning the effectiveness of the treatment of clinical hypothyroidism in pregnant women. However, we think that total agreement exists on the need to treat clinical hypothyroidism in any patient and even more in pregnant women. In any case, the question is how to define hypothyroidism in pregnant women, and with which hormone values. A level of maximum evidence is not needed to treat a pregnant woman with high TSH levels and low thyroxine levels. The risks of clinical hypothyroidism during pregnancy are well known. The evidence concerning treatment benefits is sufficient for treating women in this situation, as recommended by the extensive review by Vissenberg<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and by the ATA.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> On the other hand, the risk of thyroxine treatment is virtually nil. Placental type 3 deiodinase neutralizes a hypothetical excess while, conversely, the fetus is put at risk if it does not receive sufficient thyroxine, especially in the first trimester of pregnancy. The Männistö et al. study<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> is one of the few reporting greater obstetric morbidity in cases of clinical hypothyroidism, but the study also predicted an odds ratio of 3.2 for fetal mortality in women with positive TPO Ab.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In studies by Negro et al. and Lazarus et al.,<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,14</span></a> blood samples of the respective control groups were frozen and tested after delivery. Thus, all women diagnosed with hypothyroidism in screening groups from both studies and those diagnosed among women considered to be at risk, in the Negro study, were treated with thyroxine. In the Lazarus study, no benefit was seen in the cognitive function of children born to treated hypothyroid mothers, probably because treatment was started in the second trimester of pregnancy. This would support the importance of early diagnosis and treatment, preferably even before conception. The Lazarus study did not assess potential changes in obstetric morbidity. The Negro study, conducted in women at low risk of thyroid dysfunction, found a very significant decrease in obstetric complications in treated as compared to untreated women (women in whom diagnosis was known after delivery). As regards subclinical hypothyroidism, no guidelines directly recommend treatment. The systematic review by Vissenberg concluded that inadequate evidence is available to recommend whether to treat or not.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> When faced with this dilemma, only the clinical criterion remains, but it is very clear if, in addition to subclinical hypothyroidism, associated positive thyroid autoimmunity exists, or if an obstetric history that may be related to thyroid dysfunction, such as delayed fetal growth, pre-eclampsia, or recurrent abortion is found. The criteria for the clinical diagnosis of hypothyroidism are very clear, and the purpose of the recommendation to screen is the early detection and treatment of the pregnant population affected by this disease. On the other hand, it is also indispensable to assess the results of any screening. The evidence for a favorable benefit/risk ratio that some studies may provide should be confirmed in practice. Screening programs should therefore be assessed.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In this regard, protocols are being designed to assess the results of screening in some of the areas where it is implemented, in order to provide additional evidence to our current understanding of the subject. Clinical hypothyroidism is easy to diagnose, even in pregnant women, may affect a significant number of pregnant women, is easily treated, and its treatment poses little risk and, when adequate, may provide benefits. Our document also supports the need for implementing training programs for non-endocrinologists (family physicians, gynecologists, and midwives). In this regard, quite a number of hospitals teaching basic courses on thyroid disease for general practitioners include sessions on the importance of the thyroid gland in pregnancy. On the other hand, it should not be forgotten that active screening for gestational diabetes, more complex from the organizational viewpoint and involving a greater therapeutic difficulty, started more than 30 years ago, and nobody questions today that this type of program, coordinated with other professionals and targeting the pregnant population, may achieve reliable results in clinical practice. The culture for this type of action already exists in medical practice. In the setting of thyroid function screening in pregnant women, this represents an intense work plan which our group (iodine deficiency disorders and thyroid dysfunction) is already implementing. We therefore think that the screening of pregnant women to detect clinical hypothyroidism is justified and feasible.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vila L, Velasco I, González S, Morales F, Sánchez E, Lailla JM, et al. Cribado universal de la disfunción tiroidea en la población gestante. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 8 | 5 | 13 |
| 2024 September | 13 | 6 | 19 |
| 2024 August | 19 | 6 | 25 |
| 2024 July | 8 | 4 | 12 |
| 2024 June | 10 | 14 | 24 |
| 2024 May | 12 | 4 | 16 |
| 2024 April | 15 | 10 | 25 |
| 2024 March | 41 | 9 | 50 |
| 2024 February | 17 | 8 | 25 |
| 2024 January | 17 | 9 | 26 |
| 2023 December | 14 | 7 | 21 |
| 2023 November | 17 | 9 | 26 |
| 2023 October | 19 | 9 | 28 |
| 2023 September | 14 | 2 | 16 |
| 2023 August | 14 | 7 | 21 |
| 2023 July | 11 | 8 | 19 |
| 2023 June | 6 | 2 | 8 |
| 2023 May | 14 | 13 | 27 |
| 2023 April | 9 | 7 | 16 |
| 2023 March | 19 | 15 | 34 |
| 2023 February | 15 | 6 | 21 |
| 2023 January | 13 | 14 | 27 |
| 2022 December | 23 | 4 | 27 |
| 2022 November | 17 | 13 | 30 |
| 2022 October | 17 | 18 | 35 |
| 2022 September | 19 | 8 | 27 |
| 2022 August | 22 | 9 | 31 |
| 2022 July | 17 | 11 | 28 |
| 2022 June | 10 | 8 | 18 |
| 2022 May | 16 | 6 | 22 |
| 2022 April | 20 | 8 | 28 |
| 2022 March | 20 | 9 | 29 |
| 2022 February | 18 | 3 | 21 |
| 2022 January | 26 | 6 | 32 |
| 2021 December | 37 | 10 | 47 |
| 2021 November | 16 | 14 | 30 |
| 2021 October | 16 | 11 | 27 |
| 2021 September | 14 | 11 | 25 |
| 2021 August | 11 | 10 | 21 |
| 2021 July | 16 | 8 | 24 |
| 2021 June | 13 | 15 | 28 |
| 2021 May | 24 | 9 | 33 |
| 2021 April | 41 | 7 | 48 |
| 2021 March | 53 | 11 | 64 |
| 2021 February | 13 | 9 | 22 |
| 2021 January | 19 | 9 | 28 |
| 2020 December | 10 | 10 | 20 |
| 2020 November | 18 | 4 | 22 |
| 2020 October | 9 | 5 | 14 |
| 2020 September | 12 | 7 | 19 |
| 2020 August | 11 | 6 | 17 |
| 2020 July | 19 | 14 | 33 |
| 2020 June | 13 | 4 | 17 |
| 2020 May | 14 | 13 | 27 |
| 2020 April | 19 | 0 | 19 |
| 2020 March | 17 | 5 | 22 |
| 2020 February | 13 | 3 | 16 |
| 2020 January | 10 | 6 | 16 |
| 2019 December | 17 | 13 | 30 |
| 2019 November | 5 | 7 | 12 |
| 2019 October | 9 | 11 | 20 |
| 2019 September | 16 | 17 | 33 |
| 2019 August | 19 | 3 | 22 |
| 2019 July | 11 | 20 | 31 |
| 2019 June | 13 | 33 | 46 |
| 2019 May | 61 | 13 | 74 |
| 2019 April | 3 | 4 | 7 |
| 2019 March | 4 | 1 | 5 |
| 2019 February | 9 | 6 | 15 |
| 2019 January | 6 | 4 | 10 |
| 2018 December | 5 | 7 | 12 |
| 2018 November | 9 | 3 | 12 |
| 2018 October | 7 | 2 | 9 |
| 2018 September | 11 | 5 | 16 |
| 2018 August | 7 | 3 | 10 |
| 2018 July | 7 | 2 | 9 |
| 2018 June | 5 | 2 | 7 |
| 2018 May | 8 | 2 | 10 |
| 2018 April | 9 | 3 | 12 |
| 2018 March | 8 | 0 | 8 |
| 2018 February | 8 | 3 | 11 |
| 2018 January | 12 | 1 | 13 |
| 2017 December | 15 | 1 | 16 |
| 2017 November | 12 | 2 | 14 |
| 2017 October | 11 | 2 | 13 |
| 2017 September | 15 | 3 | 18 |
| 2017 August | 14 | 3 | 17 |
| 2017 July | 21 | 2 | 23 |
| 2017 June | 12 | 4 | 16 |
| 2017 May | 11 | 4 | 15 |
| 2017 April | 18 | 0 | 18 |
| 2017 March | 20 | 27 | 47 |
| 2017 February | 27 | 6 | 33 |
| 2017 January | 14 | 0 | 14 |
| 2016 December | 24 | 3 | 27 |
| 2016 November | 5 | 4 | 9 |
| 2016 October | 23 | 3 | 26 |
| 2016 September | 26 | 1 | 27 |
| 2016 August | 22 | 2 | 24 |
| 2016 July | 22 | 5 | 27 |
| 2016 June | 20 | 6 | 26 |
| 2016 May | 22 | 9 | 31 |
| 2016 April | 19 | 5 | 24 |
| 2016 March | 25 | 12 | 37 |
| 2016 February | 27 | 9 | 36 |
| 2016 January | 23 | 10 | 33 |
| 2015 December | 22 | 7 | 29 |
| 2015 November | 18 | 7 | 25 |
| 2015 October | 26 | 8 | 34 |
| 2015 September | 23 | 3 | 26 |
| 2015 August | 22 | 8 | 30 |
| 2015 February | 1 | 0 | 1 |
| 2015 January | 1 | 0 | 1 |
| 2014 September | 1 | 0 | 1 |
| 2014 May | 1 | 0 | 1 |
| 2014 February | 0 | 1 | 1 |
| 2014 January | 1 | 0 | 1 |
| 2013 November | 0 | 1 | 1 |
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