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ela ainda n&#227;o foi totalmente compreendida&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a> Al&#233;m disso&#44; constatou&#8208;se que v&#225;rias comorbidades&#44; como doen&#231;as cardiovasculares&#44; gastrintestinais&#44; neurol&#243;gicas e psiqui&#225;tricas&#44; aumentam em pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; a rela&#231;&#227;o entre a ros&#225;cea e doen&#231;as autoimunes envolvendo diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 1&#44; doen&#231;a cel&#237;aca&#44; artrite reumatoide e esclerose m&#250;ltipla tem sido enfatizada&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;7</span></a> Entretanto&#44; embora a frequ&#234;ncia de c&#226;ncer de tireoide tamb&#233;m tenha aumentado em pacientes com ros&#225;cea&#44; a autoimunidade da tireoide ainda n&#227;o foi estudada em detalhes na ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> A rela&#231;&#227;o da autoimunidade da tireoide com o c&#226;ncer da tireoide &#233; conhecida h&#225; muito tempo&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> Al&#233;m disso&#44; de modo semelhante &#224;s doen&#231;as da tireoide&#44; a associa&#231;&#227;o entre ros&#225;cea e doen&#231;as metab&#243;licas foi relatada em detalhes nos &#250;ltimos anos&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">10&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A hip&#243;tese do presente estudo &#233; que mecanismos patog&#234;nicos compartilhados podem fornecer uma liga&#231;&#227;o entre a ros&#225;cea e doen&#231;as da tireoide e&#44; portanto&#44; objetivamos investigar se h&#225; rela&#231;&#227;o entre doen&#231;as da tireoide &#40;hipo&#8208; e hipertireoidismo&#41; e ros&#225;cea&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Conduzimos um estudo caso&#8208;controle em 2&#46;091 pacientes com ros&#225;cea e 9&#46;572 controles pareados por idade e sexo&#44; atendidos no Ambulat&#243;rio de Dermatologia do Mugla Sitki Kocman University Training and Research Hospital entre 1&#176; de janeiro de 2015 e 31 de dezembro de 2019&#46; Obteve-se aprova&#231;&#227;o do Comit&#234; de &#201;tica da Mugla Sitki Kocman University&#46; Identificamos pacientes com ros&#225;cea com c&#243;digos CID &#40;Classifica&#231;&#227;o Internacional de Doen&#231;as&#41; de ros&#225;cea &#40;L71&#46;8 e L71&#46;9&#41; nos prontu&#225;rios do hospital&#46; Os controles foram selecionados consecutivamente aos pacientes apresentando v&#225;rias queixas dermatol&#243;gicas&#44; exceto ros&#225;cea&#46; Cada paciente com ros&#225;cea foi pareado por idade e sexo &#40;no tempo de calend&#225;rio&#41; com aproximadamente cinco controles&#46; Tamb&#233;m avaliamos todos os participantes quanto &#224; presen&#231;a de hipotireoidismo &#40;c&#243;digos CID&#58; E03&#46;8 e E03&#46;9&#41; e hipertireoidismo &#40;c&#243;digos CID&#58; E05&#46;9 e E05&#46;2&#41; utilizando c&#243;digos CID doen&#231;a&#8208;espec&#237;ficos&#46; O crit&#233;rio de inclus&#227;o do estudo foi idade &#8805; 18 anos para os pacientes e controles&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O programa estat&#237;stico SPSS para Windows v&#46; 22&#46;0 foi utilizado na an&#225;lise estat&#237;stica&#46; As vari&#225;veis descritivas foram demonstradas como m&#233;dia&#44; desvio&#8208;padr&#227;o e frequ&#234;ncia&#46; A distribui&#231;&#227;o das vari&#225;veis foi verificada com o teste de Kolmogorov&#8208;Smirnov&#46; Como nem todas as vari&#225;veis num&#233;ricas apresentavam distribui&#231;&#227;o normal&#44; o teste U de Mann&#8208;Whitney foi utilizado para os dados quantitativos&#46; O teste de Qui&#8208;Quadrado foi utilizado para a an&#225;lise dos dados qualitativos&#46; A an&#225;lise de regress&#227;o log&#237;stica condicional foi usada para calcular o <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; de caso&#8208;controle com intervalos de confian&#231;a &#40;IC&#41; de 95&#37;&#59; valores de p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 foram considerados significantes&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0030" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos 2&#46;091 pacientes com ros&#225;cea &#40;1&#46;546 mulheres&#44; 545 homens&#59; faixa et&#225;ria de 18 a 89 anos&#44; m&#233;dia de idade de 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;53&#41; e 9&#46;572 controles &#40;7&#46;009 mulheres&#44; 2&#46;563 homens&#59; faixa et&#225;ria de 18 a 89 anos&#44; m&#233;dia de 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;1&#41; pareados por idade&#44; sexo e tempo de calend&#225;rio do estudo &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Enquanto a taxa de preval&#234;ncia de hipotireoidismo foi significantemente maior em pacientes com ros&#225;cea &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;3&#59; IC 95&#37; de 1&#44;13&#8208;1&#44;49&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; n&#227;o houve diferen&#231;a significante na taxa de hipertireoidismo entre pacientes com ros&#225;cea e controles &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12&#59; IC 95&#37; de 0&#44;81&#8208;1&#44;53&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;497 &#8211; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A estratifica&#231;&#227;o por sexo tamb&#233;m revelou uma associa&#231;&#227;o significante entre hipotireoidismo e ros&#225;cea em mulheres &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;27&#59; IC 95&#37; de 1&#44;1&#8208;1&#44;47&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; e em homens &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;58&#59; IC 95&#37; de 1&#44;04&#8208;2&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;032&#41;&#44; respectivamente&#44; enquanto n&#227;o houve associa&#231;&#227;o significante entre hipertireoidismo e ros&#225;cea em ambos os sexos &#40;p &#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia de hipotireoidismo em pacientes com ros&#225;cea aumentou na faixa et&#225;ria de 40&#8208;49 anos e depois diminuiu na faixa de 80&#8208;89 anos&#44; compat&#237;vel com a frequ&#234;ncia geral de hipotireoidismo da popula&#231;&#227;o do estudo &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0050" class="elsevierStylePara elsevierViewall">A ros&#225;cea &#233; uma doen&#231;a cr&#244;nica e inflamat&#243;ria&#44; cuja patog&#234;nese ainda est&#225; sendo investigada&#46; Al&#233;m disso&#44; um n&#250;mero crescente de comorbidades est&#225; sendo relatado na ros&#225;cea&#44; sugerindo que os m&#233;dicos avaliem mais pormenorizadamente os pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;5</span></a> Dentre os fatores que nos incentivaram a conduzir o presente estudo&#44; em primeiro lugar est&#225; o fato de a ros&#225;cea ter sido associada a certas doen&#231;as autoimunes&#59; em segundo lugar&#44; o relatado aumento do c&#226;ncer de tireoide em pacientes com ros&#225;cea&#59; e&#44; por &#250;ltimo&#44; o fato de que doen&#231;as da tireoide tamb&#233;m est&#227;o associadas a processos inflamat&#243;rios&#44; bem como a doen&#231;as cardiovasculares&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;8&#44;10</span></a> No presente estudo&#44; relatou&#8208;se que a frequ&#234;ncia de hipotireoidismo aumentou significantemente em pacientes com ros&#225;cea&#44; e nenhuma associa&#231;&#227;o foi observada entre hipertireoidismo e ros&#225;cea&#46; Ap&#243;s estratifica&#231;&#227;o por sexo&#44; a associa&#231;&#227;o entre hipotireoidismo e ros&#225;cea se manteve em ambos os sexos&#46; A faixa et&#225;ria em que o hipotireoidismo foi mais comum&#44; entre 40 e 49 anos&#44; em pacientes com ros&#225;cea &#233; compat&#237;vel com toda a popula&#231;&#227;o do estudo em termos de frequ&#234;ncia de hipotireoidismo&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; v&#225;rios estudos sugeriram autoimunidade na ros&#225;cea&#46; Egeberg et al&#46; relataram que a ros&#225;cea est&#225; associada ao diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 1&#44; esclerose m&#250;ltipla&#44; doen&#231;a cel&#237;aca e artrite reumatoide&#44; principalmente em mulheres&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a> A infec&#231;&#227;o por <span class="elsevierStyleItalic">Helicobacter pylori</span>&#44; cujo envolvimento com a patog&#234;nese da ros&#225;cea j&#225; foi relatado&#44; pode ser enfatizada como outro achado sugestivo de autoimunidade na ros&#225;cea&#46; De fato&#44; diversas doen&#231;as autoimunes&#44; como artrite reumatoide&#44; tireoidite autoimune e p&#250;rpura de Henoch&#8208;Sch&#246;nlein&#44; j&#225; foram associadas &#224; infec&#231;&#227;o por <span class="elsevierStyleItalic">H&#46; pylori</span> al&#233;m da ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">14&#44;15</span></a> Al&#233;m disso&#44; Wozniacka et al&#46; relataram que 53&#44;3&#37; de 101 pacientes com ros&#225;cea tinham um t&#237;tulo de ANA &#8805; 1&#58;160&#44; e nenhum dos pacientes com t&#237;tulos elevados de ANA desenvolveu doen&#231;a autoimune conhecida durante o per&#237;odo de seguimento de dois anos&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> Entretanto&#44; embora a maioria das doen&#231;as da tireoide seja autoimune&#44; as mesmas n&#227;o foram muito estudadas na ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">A rela&#231;&#227;o da ros&#225;cea com doen&#231;as da tireoide foi investigada em alguns estudos&#44; com resultados conflitantes&#46; James et al&#46; avaliaram o hipotireoidismo em pacientes com psor&#237;ase e ros&#225;cea e encontraram taxas de preval&#234;ncia de 17&#44;5&#37; e 19&#44;7&#37;&#44; respectivamente&#46; Embora tenha sido observado que a taxa de hipotireoidismo era relativamente baixa &#40;13&#44;8&#37;&#41; em pacientes com outras doen&#231;as dermatol&#243;gicas&#44; eles n&#227;o mencionaram essa diferen&#231;a como significante&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> Em outro estudo&#44; Berksoy Hayta et al&#46; investigaram os n&#237;veis s&#233;ricos de horm&#244;nios tireoidianos livres&#44; autoanticorpos tireoidianos&#44; prolactina&#44; sulfato de de&#8208;hidroepiandrosterona &#40;DHEA&#8208;S&#41;&#44; cortisol basal&#44; prote&#237;na C&#8208;reativa e taxas de hemossedimenta&#231;&#227;o em 72 pacientes com ros&#225;cea e 62 controles&#44; e n&#227;o relataram associa&#231;&#227;o significante entre os grupos em rela&#231;&#227;o &#224; presen&#231;a de doen&#231;a da tireoide&#46; No entanto&#44; eles relataram que os n&#237;veis de PCR&#44; anticorpo anti&#8208;microssomal &#40;anti&#8208;M&#41; e prolactina aumentaram em pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> Artanta&#351; et al&#46; examinaram achados cut&#226;neos de 220 pacientes com doen&#231;a da tireoide e relataram a frequ&#234;ncia de acne ros&#225;cea de 3&#44;6&#37; em geral&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a> No presente estudo&#44; uma taxa significantemente maior de hipotireoidismo foi observada no grupo ros&#225;cea &#40;14&#44;3&#37;&#41; em compara&#231;&#227;o ao grupo controle &#40;11&#44;3&#37;&#41;&#44; tanto no sexo masculino&#44; quanto no feminino&#46; Entretanto&#44; como os autoanticorpos s&#233;ricos da tireoide n&#227;o foram avaliados nos participantes&#44; n&#227;o foi poss&#237;vel demonstrar os dados sobre quantos dos participantes tinham doen&#231;as autoimunes da tireoide&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Embora as comorbidades tenham sido investigadas na ros&#225;cea&#44; a frequ&#234;ncia do c&#226;ncer de tireoide foi avaliada apenas em alguns estudos&#46; Considerando que Li et al&#46; relataram um risco aumentado de c&#226;ncer de tireoide em pacientes com ros&#225;cea nos Estados Unidos&#44; Egeberg et al&#46; n&#227;o observaram risco aumentado de c&#226;ncer de tireoide em pacientes com ros&#225;cea em seu estudo de coorte na popula&#231;&#227;o dinamarquesa&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">8&#44;21</span></a> A resposta inflamat&#243;ria e a fun&#231;&#227;o imune desempenham um papel fundamental na patog&#234;nese do c&#226;ncer de tireoide&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> De fato&#44; a autoimunidade da tireoide e o c&#226;ncer de tireoide&#44; particularmente o carcinoma papil&#237;fero de tireoide&#44; foram estudados e associados h&#225; v&#225;rias d&#233;cadas&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> A inflama&#231;&#227;o pode ser um elo potencial entre a ros&#225;cea e o c&#226;ncer de tireoide&#46; A associa&#231;&#227;o relatada entre ros&#225;cea e c&#226;ncer de tireoide pode dar suporte aos nossos resultados&#44; considerando que o hipotireoidismo autoimune &#233; a causa mais comum de hipotireoidismo&#44; assim como a autoimunidade da tireoide e o c&#226;ncer de tireoide est&#227;o altamente correlacionados&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;22</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Ros&#225;cea e doen&#231;as da tireoide tamb&#233;m s&#227;o semelhantes em termos de condi&#231;&#245;es metab&#243;licas e vias inflamat&#243;rias que as acompanham&#46; Os horm&#244;nios tireoidianos t&#234;m um papel fundamental no metabolismo de lip&#237;dios e glicose&#44; na homeostase energ&#233;tica e tamb&#233;m na press&#227;o arterial&#46; Portanto&#44; um dist&#250;rbio do metabolismo glicose&#8208;lip&#237;deo&#44; hipercolesterolemia e a forma&#231;&#227;o de aterosclerose s&#227;o mais frequentes em pacientes com hipotireoidismo&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> A ros&#225;cea tamb&#233;m foi associada a doen&#231;as cardiovasculares em v&#225;rios estudos com altera&#231;&#245;es metab&#243;licas semelhantes ao hipotireoidismo&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#8211;13</span></a> Al&#233;m disso&#44; o aumento da express&#227;o de marcadores inflamat&#243;rios&#44; incluindo metaloproteinases da matriz&#44; particularmente MMP&#8208;9&#44; foi demonstrado na ros&#225;cea&#44; bem como no hipotireoidismo&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">23&#8211;26</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">O presente estudo tem algumas limita&#231;&#245;es&#46; Em primeiro lugar&#44; ele foi baseado em banco de dados e&#44; portanto&#44; est&#225; sujeito a erros de codifica&#231;&#227;o&#46; N&#227;o foi poss&#237;vel distinguir os diferentes subtipos e gravidades da ros&#225;cea&#44; e tamb&#233;m as doen&#231;as da tireoide como autoimunes ou n&#227;o autoimunes&#46; Outra limita&#231;&#227;o do estudo foi o fato de incluir apenas indiv&#237;duos turcos&#44; bem como sua realiza&#231;&#227;o em um centro &#250;nico e&#44; portanto&#44; a incapacidade de generaliza&#231;&#227;o do estudo&#46; Al&#233;m disso&#44; como o presente estudo &#233; do tipo observacional&#44; n&#227;o &#233; poss&#237;vel determinar a causalidade&#44; se a ros&#225;cea leva ao hipotireoidismo ou vice&#8208;versa&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">Doen&#231;as da tireoide foram investigadas em pacientes com ros&#225;cea&#44; considerando que ambas as doen&#231;as t&#234;m origens inflamat&#243;rias e autoimunes&#46; Foi observado que a taxa de hipotireoidismo estava significantemente aumentada em pacientes com ros&#225;cea&#44; em ambos os sexos&#46; A frequ&#234;ncia de hipotireoidismo foi maior na faixa et&#225;ria de 40 a 49 anos em pacientes com ros&#225;cea&#44; compat&#237;vel com a popula&#231;&#227;o estudada&#46; O hipotireoidismo pode ser uma comorbidade da ros&#225;cea e a investiga&#231;&#227;o de um poss&#237;vel hipotireoidismo pode ser uma abordagem apropriada na avalia&#231;&#227;o de pacientes com ros&#225;cea&#46; Estudos futuros s&#227;o necess&#225;rios para confirmar a associa&#231;&#227;o entre ros&#225;cea e hipotireoidismo em outras popula&#231;&#245;es&#44; para explicar as vias comuns dessas doen&#231;as em detalhes e recomendar exames de rotina no seguimento de doen&#231;as da tireoide em pacientes com ros&#225;cea&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">Asli Akin Belli&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; an&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Emine Tugba Alatas&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; an&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Asude Kara Polat&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Gulhan Akbaba&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0110" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A frequ&#234;ncia de doen&#231;as autoimunes e c&#226;ncer da tireoide tem aumentado em pacientes com ros&#225;cea&#46; Entretanto&#44; os estudos que investigam doen&#231;as da tireoide na ros&#225;cea s&#227;o escassos&#44; com resultados conflitantes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Investigar a rela&#231;&#227;o entre doen&#231;as da tireoide e ros&#225;cea&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Um estudo caso&#8208;controle foi conduzido com 2&#46;091 pacientes com ros&#225;cea&#44; pareados por idade e sexo com 9&#46;572 controles&#46; Os pacientes com ros&#225;cea foram identificados pelos c&#243;digos CID espec&#237;ficos para ros&#225;cea dos registros do hospital&#46; Al&#233;m disso&#44; todos os participantes foram avaliados quanto &#224; presen&#231;a de hipotireoidismo e hipertireoidismo&#46; A an&#225;lise de regress&#227;o log&#237;stica condicional foi utilizada para calcular o <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; dos casos e controles&#44; com intervalos de confian&#231;a de 95&#37;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 2&#46;091 pacientes com ros&#225;cea &#40;1&#46;546 mulheres&#44; 545 homens&#59; m&#233;dia 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;53 anos&#41; e 9&#46;572 controles &#40;7&#46;009 mulheres&#44; 2&#46;563 homens&#59; m&#233;dia 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;1 anos&#41;&#46; Ainda que a taxa de hipotireoidismo tenha sido significantemente maior em pacientes com ros&#225;cea &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;3&#59; IC 95&#37; de 1&#44;13&#8208;1&#44;49&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; n&#227;o houve diferen&#231;a significante na taxa de hipertireoidismo entre os grupos &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12&#59; IC 95&#37; de 0&#44;81&#8208;1&#44;53&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;497&#41;&#46; A estratifica&#231;&#227;o por g&#234;nero tamb&#233;m revelou associa&#231;&#227;o significante entre hipotireoidismo e ros&#225;cea em mulheres &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;27&#59; IC 95&#37; de 1&#44;1&#8208;1&#44;47&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; e em &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;58&#59; IC 95&#37; de 1&#44;04&#8208;2&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;032&#41;&#46; A frequ&#234;ncia de hipotireoidismo em pacientes com ros&#225;cea aumentou na faixa et&#225;ria de 40&#8208;49 anos e depois diminuiu&#44; paralelamente &#224; frequ&#234;ncia de hipotireoidismo da popula&#231;&#227;o do estudo&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">N&#227;o foi poss&#237;vel distinguir os diferentes subtipos e gravidades da ros&#225;cea&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O hipotireoidismo pode ser uma comorbidade da ros&#225;cea&#44; e a investiga&#231;&#227;o de hipotireoidismo pode ser apropriada na avalia&#231;&#227;o de pacientes com ros&#225;cea&#46;</p></span>"
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                  \t\t\t\t">2042 &#40;97&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Refer&#234;ncia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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Artigo original
Doenças da tireoide em pacientes com rosácea: um estudo caso‐controle
Asli Akin Bellia,
Corresponding author
dr_asliakin@hotmail.com

Autor para correspondência.
, Emine Tugba Alatasb, Asude Kara Polatc, Gulhan Akbabad
a Mugla Sitki Kocman University Training and Research Hospital, Departamento de Dermatologia, Mugla, Turquia
b Mugla Sitki Kocman University Medical School, Mugla, Turquia
c Istanbul Training and Research Hospital, Istambul, Turquia
d Mugla Sitki Kocman University Medical School, Departamento de Endocrinologia e Doenças Metabólicas, Mugla, Turquia
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ela ainda n&#227;o foi totalmente compreendida&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a> Al&#233;m disso&#44; constatou&#8208;se que v&#225;rias comorbidades&#44; como doen&#231;as cardiovasculares&#44; gastrintestinais&#44; neurol&#243;gicas e psiqui&#225;tricas&#44; aumentam em pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; a rela&#231;&#227;o entre a ros&#225;cea e doen&#231;as autoimunes envolvendo diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 1&#44; doen&#231;a cel&#237;aca&#44; artrite reumatoide e esclerose m&#250;ltipla tem sido enfatizada&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;7</span></a> Entretanto&#44; embora a frequ&#234;ncia de c&#226;ncer de tireoide tamb&#233;m tenha aumentado em pacientes com ros&#225;cea&#44; a autoimunidade da tireoide ainda n&#227;o foi estudada em detalhes na ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a> A rela&#231;&#227;o da autoimunidade da tireoide com o c&#226;ncer da tireoide &#233; conhecida h&#225; muito tempo&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> Al&#233;m disso&#44; de modo semelhante &#224;s doen&#231;as da tireoide&#44; a associa&#231;&#227;o entre ros&#225;cea e doen&#231;as metab&#243;licas foi relatada em detalhes nos &#250;ltimos anos&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">10&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A hip&#243;tese do presente estudo &#233; que mecanismos patog&#234;nicos compartilhados podem fornecer uma liga&#231;&#227;o entre a ros&#225;cea e doen&#231;as da tireoide e&#44; portanto&#44; objetivamos investigar se h&#225; rela&#231;&#227;o entre doen&#231;as da tireoide &#40;hipo&#8208; e hipertireoidismo&#41; e ros&#225;cea&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Conduzimos um estudo caso&#8208;controle em 2&#46;091 pacientes com ros&#225;cea e 9&#46;572 controles pareados por idade e sexo&#44; atendidos no Ambulat&#243;rio de Dermatologia do Mugla Sitki Kocman University Training and Research Hospital entre 1&#176; de janeiro de 2015 e 31 de dezembro de 2019&#46; Obteve-se aprova&#231;&#227;o do Comit&#234; de &#201;tica da Mugla Sitki Kocman University&#46; Identificamos pacientes com ros&#225;cea com c&#243;digos CID &#40;Classifica&#231;&#227;o Internacional de Doen&#231;as&#41; de ros&#225;cea &#40;L71&#46;8 e L71&#46;9&#41; nos prontu&#225;rios do hospital&#46; Os controles foram selecionados consecutivamente aos pacientes apresentando v&#225;rias queixas dermatol&#243;gicas&#44; exceto ros&#225;cea&#46; Cada paciente com ros&#225;cea foi pareado por idade e sexo &#40;no tempo de calend&#225;rio&#41; com aproximadamente cinco controles&#46; Tamb&#233;m avaliamos todos os participantes quanto &#224; presen&#231;a de hipotireoidismo &#40;c&#243;digos CID&#58; E03&#46;8 e E03&#46;9&#41; e hipertireoidismo &#40;c&#243;digos CID&#58; E05&#46;9 e E05&#46;2&#41; utilizando c&#243;digos CID doen&#231;a&#8208;espec&#237;ficos&#46; O crit&#233;rio de inclus&#227;o do estudo foi idade &#8805; 18 anos para os pacientes e controles&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O programa estat&#237;stico SPSS para Windows v&#46; 22&#46;0 foi utilizado na an&#225;lise estat&#237;stica&#46; As vari&#225;veis descritivas foram demonstradas como m&#233;dia&#44; desvio&#8208;padr&#227;o e frequ&#234;ncia&#46; A distribui&#231;&#227;o das vari&#225;veis foi verificada com o teste de Kolmogorov&#8208;Smirnov&#46; Como nem todas as vari&#225;veis num&#233;ricas apresentavam distribui&#231;&#227;o normal&#44; o teste U de Mann&#8208;Whitney foi utilizado para os dados quantitativos&#46; O teste de Qui&#8208;Quadrado foi utilizado para a an&#225;lise dos dados qualitativos&#46; A an&#225;lise de regress&#227;o log&#237;stica condicional foi usada para calcular o <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; de caso&#8208;controle com intervalos de confian&#231;a &#40;IC&#41; de 95&#37;&#59; valores de p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 foram considerados significantes&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0030" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos 2&#46;091 pacientes com ros&#225;cea &#40;1&#46;546 mulheres&#44; 545 homens&#59; faixa et&#225;ria de 18 a 89 anos&#44; m&#233;dia de idade de 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;53&#41; e 9&#46;572 controles &#40;7&#46;009 mulheres&#44; 2&#46;563 homens&#59; faixa et&#225;ria de 18 a 89 anos&#44; m&#233;dia de 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;1&#41; pareados por idade&#44; sexo e tempo de calend&#225;rio do estudo &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Enquanto a taxa de preval&#234;ncia de hipotireoidismo foi significantemente maior em pacientes com ros&#225;cea &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;3&#59; IC 95&#37; de 1&#44;13&#8208;1&#44;49&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; n&#227;o houve diferen&#231;a significante na taxa de hipertireoidismo entre pacientes com ros&#225;cea e controles &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12&#59; IC 95&#37; de 0&#44;81&#8208;1&#44;53&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;497 &#8211; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A estratifica&#231;&#227;o por sexo tamb&#233;m revelou uma associa&#231;&#227;o significante entre hipotireoidismo e ros&#225;cea em mulheres &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;27&#59; IC 95&#37; de 1&#44;1&#8208;1&#44;47&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; e em homens &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;58&#59; IC 95&#37; de 1&#44;04&#8208;2&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;032&#41;&#44; respectivamente&#44; enquanto n&#227;o houve associa&#231;&#227;o significante entre hipertireoidismo e ros&#225;cea em ambos os sexos &#40;p &#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia de hipotireoidismo em pacientes com ros&#225;cea aumentou na faixa et&#225;ria de 40&#8208;49 anos e depois diminuiu na faixa de 80&#8208;89 anos&#44; compat&#237;vel com a frequ&#234;ncia geral de hipotireoidismo da popula&#231;&#227;o do estudo &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0050" class="elsevierStylePara elsevierViewall">A ros&#225;cea &#233; uma doen&#231;a cr&#244;nica e inflamat&#243;ria&#44; cuja patog&#234;nese ainda est&#225; sendo investigada&#46; Al&#233;m disso&#44; um n&#250;mero crescente de comorbidades est&#225; sendo relatado na ros&#225;cea&#44; sugerindo que os m&#233;dicos avaliem mais pormenorizadamente os pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#44;5</span></a> Dentre os fatores que nos incentivaram a conduzir o presente estudo&#44; em primeiro lugar est&#225; o fato de a ros&#225;cea ter sido associada a certas doen&#231;as autoimunes&#59; em segundo lugar&#44; o relatado aumento do c&#226;ncer de tireoide em pacientes com ros&#225;cea&#59; e&#44; por &#250;ltimo&#44; o fato de que doen&#231;as da tireoide tamb&#233;m est&#227;o associadas a processos inflamat&#243;rios&#44; bem como a doen&#231;as cardiovasculares&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;8&#44;10</span></a> No presente estudo&#44; relatou&#8208;se que a frequ&#234;ncia de hipotireoidismo aumentou significantemente em pacientes com ros&#225;cea&#44; e nenhuma associa&#231;&#227;o foi observada entre hipertireoidismo e ros&#225;cea&#46; Ap&#243;s estratifica&#231;&#227;o por sexo&#44; a associa&#231;&#227;o entre hipotireoidismo e ros&#225;cea se manteve em ambos os sexos&#46; A faixa et&#225;ria em que o hipotireoidismo foi mais comum&#44; entre 40 e 49 anos&#44; em pacientes com ros&#225;cea &#233; compat&#237;vel com toda a popula&#231;&#227;o do estudo em termos de frequ&#234;ncia de hipotireoidismo&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; v&#225;rios estudos sugeriram autoimunidade na ros&#225;cea&#46; Egeberg et al&#46; relataram que a ros&#225;cea est&#225; associada ao diabetes <span class="elsevierStyleItalic">mellitus</span> tipo 1&#44; esclerose m&#250;ltipla&#44; doen&#231;a cel&#237;aca e artrite reumatoide&#44; principalmente em mulheres&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a> A infec&#231;&#227;o por <span class="elsevierStyleItalic">Helicobacter pylori</span>&#44; cujo envolvimento com a patog&#234;nese da ros&#225;cea j&#225; foi relatado&#44; pode ser enfatizada como outro achado sugestivo de autoimunidade na ros&#225;cea&#46; De fato&#44; diversas doen&#231;as autoimunes&#44; como artrite reumatoide&#44; tireoidite autoimune e p&#250;rpura de Henoch&#8208;Sch&#246;nlein&#44; j&#225; foram associadas &#224; infec&#231;&#227;o por <span class="elsevierStyleItalic">H&#46; pylori</span> al&#233;m da ros&#225;cea&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">14&#44;15</span></a> Al&#233;m disso&#44; Wozniacka et al&#46; relataram que 53&#44;3&#37; de 101 pacientes com ros&#225;cea tinham um t&#237;tulo de ANA &#8805; 1&#58;160&#44; e nenhum dos pacientes com t&#237;tulos elevados de ANA desenvolveu doen&#231;a autoimune conhecida durante o per&#237;odo de seguimento de dois anos&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> Entretanto&#44; embora a maioria das doen&#231;as da tireoide seja autoimune&#44; as mesmas n&#227;o foram muito estudadas na ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">A rela&#231;&#227;o da ros&#225;cea com doen&#231;as da tireoide foi investigada em alguns estudos&#44; com resultados conflitantes&#46; James et al&#46; avaliaram o hipotireoidismo em pacientes com psor&#237;ase e ros&#225;cea e encontraram taxas de preval&#234;ncia de 17&#44;5&#37; e 19&#44;7&#37;&#44; respectivamente&#46; Embora tenha sido observado que a taxa de hipotireoidismo era relativamente baixa &#40;13&#44;8&#37;&#41; em pacientes com outras doen&#231;as dermatol&#243;gicas&#44; eles n&#227;o mencionaram essa diferen&#231;a como significante&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> Em outro estudo&#44; Berksoy Hayta et al&#46; investigaram os n&#237;veis s&#233;ricos de horm&#244;nios tireoidianos livres&#44; autoanticorpos tireoidianos&#44; prolactina&#44; sulfato de de&#8208;hidroepiandrosterona &#40;DHEA&#8208;S&#41;&#44; cortisol basal&#44; prote&#237;na C&#8208;reativa e taxas de hemossedimenta&#231;&#227;o em 72 pacientes com ros&#225;cea e 62 controles&#44; e n&#227;o relataram associa&#231;&#227;o significante entre os grupos em rela&#231;&#227;o &#224; presen&#231;a de doen&#231;a da tireoide&#46; No entanto&#44; eles relataram que os n&#237;veis de PCR&#44; anticorpo anti&#8208;microssomal &#40;anti&#8208;M&#41; e prolactina aumentaram em pacientes com ros&#225;cea&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> Artanta&#351; et al&#46; examinaram achados cut&#226;neos de 220 pacientes com doen&#231;a da tireoide e relataram a frequ&#234;ncia de acne ros&#225;cea de 3&#44;6&#37; em geral&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a> No presente estudo&#44; uma taxa significantemente maior de hipotireoidismo foi observada no grupo ros&#225;cea &#40;14&#44;3&#37;&#41; em compara&#231;&#227;o ao grupo controle &#40;11&#44;3&#37;&#41;&#44; tanto no sexo masculino&#44; quanto no feminino&#46; Entretanto&#44; como os autoanticorpos s&#233;ricos da tireoide n&#227;o foram avaliados nos participantes&#44; n&#227;o foi poss&#237;vel demonstrar os dados sobre quantos dos participantes tinham doen&#231;as autoimunes da tireoide&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Embora as comorbidades tenham sido investigadas na ros&#225;cea&#44; a frequ&#234;ncia do c&#226;ncer de tireoide foi avaliada apenas em alguns estudos&#46; Considerando que Li et al&#46; relataram um risco aumentado de c&#226;ncer de tireoide em pacientes com ros&#225;cea nos Estados Unidos&#44; Egeberg et al&#46; n&#227;o observaram risco aumentado de c&#226;ncer de tireoide em pacientes com ros&#225;cea em seu estudo de coorte na popula&#231;&#227;o dinamarquesa&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">8&#44;21</span></a> A resposta inflamat&#243;ria e a fun&#231;&#227;o imune desempenham um papel fundamental na patog&#234;nese do c&#226;ncer de tireoide&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> De fato&#44; a autoimunidade da tireoide e o c&#226;ncer de tireoide&#44; particularmente o carcinoma papil&#237;fero de tireoide&#44; foram estudados e associados h&#225; v&#225;rias d&#233;cadas&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> A inflama&#231;&#227;o pode ser um elo potencial entre a ros&#225;cea e o c&#226;ncer de tireoide&#46; A associa&#231;&#227;o relatada entre ros&#225;cea e c&#226;ncer de tireoide pode dar suporte aos nossos resultados&#44; considerando que o hipotireoidismo autoimune &#233; a causa mais comum de hipotireoidismo&#44; assim como a autoimunidade da tireoide e o c&#226;ncer de tireoide est&#227;o altamente correlacionados&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;22</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Ros&#225;cea e doen&#231;as da tireoide tamb&#233;m s&#227;o semelhantes em termos de condi&#231;&#245;es metab&#243;licas e vias inflamat&#243;rias que as acompanham&#46; Os horm&#244;nios tireoidianos t&#234;m um papel fundamental no metabolismo de lip&#237;dios e glicose&#44; na homeostase energ&#233;tica e tamb&#233;m na press&#227;o arterial&#46; Portanto&#44; um dist&#250;rbio do metabolismo glicose&#8208;lip&#237;deo&#44; hipercolesterolemia e a forma&#231;&#227;o de aterosclerose s&#227;o mais frequentes em pacientes com hipotireoidismo&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> A ros&#225;cea tamb&#233;m foi associada a doen&#231;as cardiovasculares em v&#225;rios estudos com altera&#231;&#245;es metab&#243;licas semelhantes ao hipotireoidismo&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#8211;13</span></a> Al&#233;m disso&#44; o aumento da express&#227;o de marcadores inflamat&#243;rios&#44; incluindo metaloproteinases da matriz&#44; particularmente MMP&#8208;9&#44; foi demonstrado na ros&#225;cea&#44; bem como no hipotireoidismo&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">23&#8211;26</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">O presente estudo tem algumas limita&#231;&#245;es&#46; Em primeiro lugar&#44; ele foi baseado em banco de dados e&#44; portanto&#44; est&#225; sujeito a erros de codifica&#231;&#227;o&#46; N&#227;o foi poss&#237;vel distinguir os diferentes subtipos e gravidades da ros&#225;cea&#44; e tamb&#233;m as doen&#231;as da tireoide como autoimunes ou n&#227;o autoimunes&#46; Outra limita&#231;&#227;o do estudo foi o fato de incluir apenas indiv&#237;duos turcos&#44; bem como sua realiza&#231;&#227;o em um centro &#250;nico e&#44; portanto&#44; a incapacidade de generaliza&#231;&#227;o do estudo&#46; Al&#233;m disso&#44; como o presente estudo &#233; do tipo observacional&#44; n&#227;o &#233; poss&#237;vel determinar a causalidade&#44; se a ros&#225;cea leva ao hipotireoidismo ou vice&#8208;versa&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">Doen&#231;as da tireoide foram investigadas em pacientes com ros&#225;cea&#44; considerando que ambas as doen&#231;as t&#234;m origens inflamat&#243;rias e autoimunes&#46; Foi observado que a taxa de hipotireoidismo estava significantemente aumentada em pacientes com ros&#225;cea&#44; em ambos os sexos&#46; A frequ&#234;ncia de hipotireoidismo foi maior na faixa et&#225;ria de 40 a 49 anos em pacientes com ros&#225;cea&#44; compat&#237;vel com a popula&#231;&#227;o estudada&#46; O hipotireoidismo pode ser uma comorbidade da ros&#225;cea e a investiga&#231;&#227;o de um poss&#237;vel hipotireoidismo pode ser uma abordagem apropriada na avalia&#231;&#227;o de pacientes com ros&#225;cea&#46; Estudos futuros s&#227;o necess&#225;rios para confirmar a associa&#231;&#227;o entre ros&#225;cea e hipotireoidismo em outras popula&#231;&#245;es&#44; para explicar as vias comuns dessas doen&#231;as em detalhes e recomendar exames de rotina no seguimento de doen&#231;as da tireoide em pacientes com ros&#225;cea&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0085" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0090" class="elsevierStylePara elsevierViewall">Asli Akin Belli&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; an&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Emine Tugba Alatas&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; an&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Asude Kara Polat&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Gulhan Akbaba&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o de dados&#59; revis&#227;o cr&#237;tica do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflito de interesses</span><p id="par0110" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A frequ&#234;ncia de doen&#231;as autoimunes e c&#226;ncer da tireoide tem aumentado em pacientes com ros&#225;cea&#46; Entretanto&#44; os estudos que investigam doen&#231;as da tireoide na ros&#225;cea s&#227;o escassos&#44; com resultados conflitantes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Investigar a rela&#231;&#227;o entre doen&#231;as da tireoide e ros&#225;cea&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Um estudo caso&#8208;controle foi conduzido com 2&#46;091 pacientes com ros&#225;cea&#44; pareados por idade e sexo com 9&#46;572 controles&#46; Os pacientes com ros&#225;cea foram identificados pelos c&#243;digos CID espec&#237;ficos para ros&#225;cea dos registros do hospital&#46; Al&#233;m disso&#44; todos os participantes foram avaliados quanto &#224; presen&#231;a de hipotireoidismo e hipertireoidismo&#46; A an&#225;lise de regress&#227;o log&#237;stica condicional foi utilizada para calcular o <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; dos casos e controles&#44; com intervalos de confian&#231;a de 95&#37;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 2&#46;091 pacientes com ros&#225;cea &#40;1&#46;546 mulheres&#44; 545 homens&#59; m&#233;dia 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;53 anos&#41; e 9&#46;572 controles &#40;7&#46;009 mulheres&#44; 2&#46;563 homens&#59; m&#233;dia 48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;1 anos&#41;&#46; Ainda que a taxa de hipotireoidismo tenha sido significantemente maior em pacientes com ros&#225;cea &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;3&#59; IC 95&#37; de 1&#44;13&#8208;1&#44;49&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; n&#227;o houve diferen&#231;a significante na taxa de hipertireoidismo entre os grupos &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;12&#59; IC 95&#37; de 0&#44;81&#8208;1&#44;53&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;497&#41;&#46; A estratifica&#231;&#227;o por g&#234;nero tamb&#233;m revelou associa&#231;&#227;o significante entre hipotireoidismo e ros&#225;cea em mulheres &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;27&#59; IC 95&#37; de 1&#44;1&#8208;1&#44;47&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; e em &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;58&#59; IC 95&#37; de 1&#44;04&#8208;2&#44;4&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;032&#41;&#46; A frequ&#234;ncia de hipotireoidismo em pacientes com ros&#225;cea aumentou na faixa et&#225;ria de 40&#8208;49 anos e depois diminuiu&#44; paralelamente &#224; frequ&#234;ncia de hipotireoidismo da popula&#231;&#227;o do estudo&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">N&#227;o foi poss&#237;vel distinguir os diferentes subtipos e gravidades da ros&#225;cea&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O hipotireoidismo pode ser uma comorbidade da ros&#225;cea&#44; e a investiga&#231;&#227;o de hipotireoidismo pode ser apropriada na avalia&#231;&#227;o de pacientes com ros&#225;cea&#46;</p></span>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col">Grupo ros&#225;cea&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;091&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col">Grupo controle&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;572&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&#47;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&#47;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Idade &#40;anos&#41;</span>&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">48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;53&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">48&#44;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;1&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">0&#44;942&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="4" align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&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">1546 &#40;73&#44;9&#41;&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">7009 &#40;73&#44;2&#41;&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">0&#44;505&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&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">545 &#40;26&#44;1&#41;&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">2563 &#40;26&#44;8&#41;&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2743956.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas da popula&#231;&#227;o do estudo</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
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          0 => array:3 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Regress&#227;o log&#237;stica condicional&#46; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#59; IC&#44; intervalo de confian&#231;a&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="6" align="left" valign="\n
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                  \t\t\t\t">1083 &#40;11&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ausente&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">1791 &#40;85&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">Refer&#234;ncia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="elsevierStyleHsp" style=""></span>Presente&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">49 &#40;2&#44;3&#41;&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
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                  \t\t\t\t">204 &#40;2&#44;1&#41;&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
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                  \t\t\t\t">1&#44;12&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">0&#44;81&#8208;1&#44;53&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">0&#44;497&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ausente&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">2042 &#40;97&#44;7&#41;&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">9368 &#40;97&#44;9&#41;&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">Refer&#234;ncia&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab2743959.png"
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          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Valores de <span class="elsevierStyleItalic">odds ratio</span> associando a ros&#225;cea com a ocorr&#234;ncia de hipotireoidismo e hipertireoidismo</p>"
        ]
      ]
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          0 => array:3 [
            "identificador" => "at3"
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            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Regress&#227;o log&#237;stica condicional&#46; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#59; IC&#44; intervalo de confian&#231;a&#46;</p>"
          "tablatextoimagen" => array:1 [
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \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" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Valores de <span class="elsevierStyleItalic">odds ratios</span> associando a ros&#225;cea com a ocorr&#234;ncia de hipotireoidismo e hipertireoidismo estratificado por sexo</p>"
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                  \t\t\t\t">7 &#40;0&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Frequ&#234;ncia de hipotireoidismo nos participantes por intervalos de aproximadamente 10 anos de idade</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rosacea &#8208; global diversity and optimized outcome&#58; proposed international consensus from the Rosacea International Expert Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46;E&#46; Elewski"
                            1 => "Z&#46; Draelos"
                            2 => "B&#46; Dr&#233;no"
                            3 => "T&#46; Jansen"
                            4 => "A&#46; Layton"
                            5 => "M&#46; Picardo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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Article information
ISSN: 26662752
Original language: Portuguese
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