{"id":7171,"date":"2023-08-31T17:52:13","date_gmt":"2023-08-31T20:52:13","guid":{"rendered":"https:\/\/gastropedia.pub\/pt\/?p=7171"},"modified":"2023-09-02T09:10:29","modified_gmt":"2023-09-02T12:10:29","slug":"sindrome-de-gilbert-o-que-precisamos-saber","status":"publish","type":"post","link":"https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/sindrome-de-gilbert-o-que-precisamos-saber\/","title":{"rendered":"S\u00edndrome de Gilbert: o que precisamos saber?"},"content":{"rendered":"<div class=\"pdfprnt-buttons pdfprnt-buttons-post pdfprnt-top-right\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-json\/wp\/v2\/posts\/7171?print=pdf\" class=\"pdfprnt-button pdfprnt-button-pdf\" target=\"_blank\" ><img decoding=\"async\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/plugins\/pdf-print\/images\/pdf.png\" alt=\"image_pdf\" title=\"Ver PDF\" \/><\/a><a href=\"https:\/\/gastropedia.pub\/pt\/wp-json\/wp\/v2\/posts\/7171?print=print\" class=\"pdfprnt-button pdfprnt-button-print\" target=\"_blank\" ><img decoding=\"async\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/plugins\/pdf-print\/images\/print.png\" alt=\"image_print\" title=\"Conte\u00fado de impress\u00e3o\" \/><\/a><\/div>\n<p>A S\u00edndrome de Gilbert (SG) \u00e9 uma desordem hep\u00e1tica do metabolismo das bilirrubinas com redu\u00e7\u00e3o na glicuronida\u00e7\u00e3o da bilirrubina e consequente hiperbilirrubinemia indireta (n\u00e3o conjugada).<\/p>\n\n\n\n<p>\u00c9 uma condi\u00e7\u00e3o comum (3-10% da popula\u00e7\u00e3o), com redu\u00e7\u00e3o na atividade da UGT1A1 em 25-40%. As muta\u00e7\u00f5es ocorrem na sequ\u00eancia da regi\u00e3o promotora (TATA box) do gene UGT1A1, a qual tem a fun\u00e7\u00e3o de controlar os n\u00edveis da prote\u00edna normal produzida. Desta forma, na SG, a prote\u00edna produzida \u00e9 estruturalmente normal, por\u00e9m em menor quantidade.<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-regular has-normal-font-size\"><div class=\"pcrstb-wrap\"><table class=\"has-background\" style=\"background-color:#c9cee1\"><tbody><tr><td><strong>Gene UGT1A1<\/strong><br>Promove a produ\u00e7\u00e3o da enzima bilirrubina-UGT, respons\u00e1vel pela conjuga\u00e7\u00e3o de bilirrubina. Logo, muta\u00e7\u00f5es na UGT1A1 geram a produ\u00e7\u00e3o de uma prote\u00edna anormal, com perda completa ou n\u00edveis menores de atividade da bilirrubina-UGT.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-apresentacao-clinico-laboratorial\"><strong>Apresenta\u00e7\u00e3o cl\u00ednico-laboratorial<\/strong><\/h2>\n\n\n\n<p>Clinicamente, os pacientes costumam ser assintom\u00e1ticos e identificar eleva\u00e7\u00f5es nos n\u00edveis de bilirrubinas totais com predom\u00ednio de bilirrubina indireta (&lt;4-5mg\/dL), de forma incidental, ou podem apresentar quadros intermitentes de icter\u00edcia, em especial, desencadeados por gatilhos como exerc\u00edcio f\u00edsico intenso, baixa ingest\u00e3o cal\u00f3rica\/jejum, per\u00edodo menstrual, desidrata\u00e7\u00e3o e infec\u00e7\u00f5es.<\/p>\n\n\n\n<p>Laboratorialmente, n\u00e3o h\u00e1 eleva\u00e7\u00e3o de enzimas hep\u00e1ticas ou altera\u00e7\u00f5es nos demais exames de fun\u00e7\u00e3o hep\u00e1tica (tempo de protrombina e albumina), al\u00e9m de n\u00e3o haver ind\u00edcios de hem\u00f3lise ou doen\u00e7a estrutural f\u00edgado.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<details class=\"wp-block-details has-text-color is-layout-flow wp-block-details-is-layout-flow\" style=\"color:#005a8e\"><summary>Saiba mais sobre altera\u00e7\u00e3o de enzimas hep\u00e1ticas nesse post:<\/summary>\n<figure class=\"wp-block-embed is-type-wp-embed is-provider-gastropedia wp-block-embed-gastropedia\"><div class=\"wp-block-embed__wrapper\">\n<blockquote class=\"wp-embedded-content\" data-secret=\"si2Q2qKBL0\"><a href=\"https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/abordagem-de-pacientes-com-alteracoes-de-enzimas-hepaticas\/\">Abordagem de pacientes com altera\u00e7\u00f5es de enzimas hep\u00e1ticas<\/a><\/blockquote><iframe class=\"wp-embedded-content\" sandbox=\"allow-scripts\" security=\"restricted\" style=\"position: absolute; clip: rect(1px, 1px, 1px, 1px);\" title=\"&#8220;Abordagem de pacientes com altera\u00e7\u00f5es de enzimas hep\u00e1ticas&#8221; &#8212; Gastropedia\" src=\"https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/abordagem-de-pacientes-com-alteracoes-de-enzimas-hepaticas\/embed\/#?secret=KjTEu1D7mq#?secret=si2Q2qKBL0\" data-secret=\"si2Q2qKBL0\" width=\"600\" height=\"338\" frameborder=\"0\" marginwidth=\"0\" marginheight=\"0\" scrolling=\"no\"><\/iframe>\n<\/div><\/figure>\n<\/details>\n\n\n\n<div style=\"height:45px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-diagnostico-diferencial\"><strong>Diagn\u00f3stico diferencial<\/strong><\/h2>\n\n\n\n<p>Dist\u00farbios na capta\u00e7\u00e3o hep\u00e1tica, armazenamento, conjuga\u00e7\u00e3o e excre\u00e7\u00e3o podem ocasionar hiperbilirrubinemia. Dentre as causas heredit\u00e1rias de hiperbilirrubinemia indireta, com exames normais de fun\u00e7\u00e3o hep\u00e1tica e sem altera\u00e7\u00e3o da histologia hep\u00e1tica, al\u00e9m da SG, faz-se o diagn\u00f3stico diferencial com:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>S\u00edndrome de Crigler-Najar tipo I<\/strong>: condi\u00e7\u00e3o muito rara com heran\u00e7a autoss\u00f4mica recessiva que se manifesta logo ap\u00f3s o nascimento. Pela aus\u00eancia da atividade UGT1A1 hep\u00e1tica, ocorre icter\u00edcia grave (20-45mg\/dL ou mais) e risco de dano neurol\u00f3gico e \u00f3bito por <em>kernicterus<\/em> (encefalopatia bilirrub\u00ednica) nos primeiros dias ap\u00f3s o nascimento. O tratamento precoce para a redu\u00e7\u00e3o dos n\u00edveis de bilirrubina indireta no sangue \u00e9 a fototerapia, devendo-se considerar a realiza\u00e7\u00e3o de transplante hep\u00e1tico como \u00fanica terapia curativa.<\/li>\n\n\n\n<li><strong>S\u00edndrome de Crigler-Najar tipo II<\/strong>: condi\u00e7\u00e3o rara com heran\u00e7a autoss\u00f4mica recessiva. H\u00e1 atividade UGT1A1 hep\u00e1tica de 10% ou menos, com icter\u00edcia cr\u00f4nica (6-20mg\/dL) e evolu\u00e7\u00e3o potencialmente benigna. O tratamento com fenobarbital propicia a redu\u00e7\u00e3o de cerca de 25-30% dos n\u00edveis de bilirrubina indireta pela indu\u00e7\u00e3o da atividade da UGT1A1 residual.<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-investigacao-diagnostica\"><strong>Investiga\u00e7\u00e3o diagn\u00f3stica<\/strong><\/h2>\n\n\n\n<p>Identificada a hiperbilirrubinemia indireta, recomenda-se anamnese e exame f\u00edsico detalhados, dosagem s\u00e9rica de enzimas hep\u00e1ticas (TGO, TGP, fosfatase alcalina e GGT) e fun\u00e7\u00e3o hep\u00e1tica (tempo de protrombina e albumina).<\/p>\n\n\n\n<p>Caso haja altera\u00e7\u00f5es nesta primeira etapa de avalia\u00e7\u00e3o, direciona-se a investiga\u00e7\u00e3o para a avalia\u00e7\u00e3o de hepatopatias, sendo prudente complementar com exame de imagem\/ultrassonografia de abdome superior e demais exames laboratoriais espec\u00edficos.<\/p>\n\n\n\n<p>Se n\u00e3o forem identificadas altera\u00e7\u00f5es na primeira etapa de avalia\u00e7\u00e3o, \u00e9 mandat\u00f3rio descartar hem\u00f3lise com a dosagem de DHL, haptoglobina e reticul\u00f3citos.<\/p>\n\n\n\n<p>Em adolescentes ou adultos, na aus\u00eancia de hem\u00f3lise e n\u00edveis de bilirrubina indireta &lt;5mg\/dL, presume-se o diagn\u00f3stico de s\u00edndrome de Gilbert. A confirma\u00e7\u00e3o \u00e9 feita pelo teste gen\u00e9tico para detectar muta\u00e7\u00f5es no gene UGT1A1\/TATA box.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38.jpeg\" data-rel=\"penci-gallery-image-content\" ><img fetchpriority=\"high\" decoding=\"async\" width=\"950\" height=\"534\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38.jpeg\" alt=\"\" class=\"wp-image-7175\" srcset=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38.jpeg?v=1692114589 950w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38-300x169.jpeg?v=1692114589 300w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38-768x432.jpeg?v=1692114589 768w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-12.48.38-585x329.jpeg?v=1692114589 585w\" sizes=\"(max-width: 950px) 100vw, 950px\" \/><\/a><figcaption class=\"wp-element-caption\"><br>Figura 1. Fluxograma de investiga\u00e7\u00e3o de hiperbulirrubinemia indireta.<\/figcaption><\/figure>\n<\/div>\n\n\n<h2 class=\"wp-block-heading\" id=\"h-diagnostico-genetico\"><strong>Diagn\u00f3stico Gen\u00e9tico<\/strong><\/h2>\n\n\n\n<p>Diante da possibilidade de rea\u00e7\u00f5es adversas a algumas drogas metabolizadas pelo UGT1A1, a exemplo do irinotecano e atazanavir, recomenda-se considerar a confirma\u00e7\u00e3o da SG pela pesquisa da muta\u00e7\u00e3o UGT1A1 pelo m\u00e9todo de PCR em tempo real (Imagem 1).<\/p>\n\n\n\n<p>Quando em homozigose, n\u00e3o h\u00e1 necessidade de rastreamento adicional, entretanto, se o paciente possuir apenas um alelo da muta\u00e7\u00e3o UGT1A1 ou ambos os alelos forem normais, deve-se pesquisar as muta\u00e7\u00f5es G71R e Y486D, as quais tamb\u00e9m se associam com a SG.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43.png\" data-rel=\"penci-gallery-image-content\" ><img decoding=\"async\" width=\"914\" height=\"525\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43.png\" alt=\"\" class=\"wp-image-7181\" srcset=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43.png 914w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43-300x172.png 300w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43-768x441.png 768w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/08\/WhatsApp-Image-2023-08-15-at-13.08.43-585x336.png 585w\" sizes=\"(max-width: 914px) 100vw, 914px\" \/><\/a><figcaption class=\"wp-element-caption\"><br>Imagem 1. Resultado do teste gen\u00e9tico para S\u00edndrome de Gilbert com homozigose do alelo 28 no gene UGT1A1.<\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-tratamento\"><strong>Tratamento<\/strong><\/h2>\n\n\n\n<p>Por ser uma condi\u00e7\u00e3o benigna, o tratamento \u00e9 conservador apenas com observa\u00e7\u00e3o. O progn\u00f3stico dos pacientes com SG \u00e9 excelente e n\u00e3o exige tratamento espec\u00edfico.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-referencias\"><strong>Refer\u00eancias<\/strong><\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Thoguluva Chandrasekar V, Faust TW, John S. Gilbert Syndrome. 2023 Feb 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan\u2013. PMID: 29262099.<\/li>\n\n\n\n<li>Singh A, Koritala T, Jialal I. Unconjugated Hyperbilirubinemia. 2023 Feb 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan\u2013. PMID: 31747203.<\/li>\n\n\n\n<li>King D, Armstrong MJ. Overview of Gilbert&#8217;s syndrome. Drug Ther Bull. 2019 Feb;57(2):27-31. doi: 10.1136\/dtb.2018.000028. PMID: 30709860.<\/li>\n\n\n\n<li>Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC. Diagnostic criteria and contributors to Gilbert&#8217;s syndrome. Crit Rev Clin Lab Sci. 2018 Mar;55(2):129-139. doi: 10.1080\/10408363.2018.1428526. Epub 2018 Feb 1. PMID: 29390925.<\/li>\n\n\n\n<li>Rodrigues C, Vieira E, Santos R, de Carvalho J, Santos-Silva A, Costa E, Bronze-da-Rocha E. Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects. Blood Cells Mol Dis. 2012 Mar 15;48(3):166-72. doi: 10.1016\/j.bcmd.2012.01.004. Epub 2012 Feb 9. PMID: 22325916.<\/li>\n<\/ol>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-como-citar-este-artigo\">Como citar este artigo<\/h2>\n\n\n\n<p class=\"has-background\" style=\"background-color:#c9cbcd\">Oti KST, S\u00edndrome de Gilbert: o que precisamos saber? Gastropedia 2023, vol. 2. Dispon\u00edvel em: <br><a href=\"https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/sindrome-de-gilbert-o-que-precisamos-saber\/\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/sindrome-de-gilbert-o-que-precisamos-saber\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A S\u00edndrome de Gilbert (SG) \u00e9 uma desordem hep\u00e1tica do metabolismo das bilirrubinas com redu\u00e7\u00e3o na glicuronida\u00e7\u00e3o da bilirrubina e consequente hiperbilirrubinemia indireta (n\u00e3o conjugada). \u00c9 uma condi\u00e7\u00e3o comum (3-10%&hellip;<\/p>\n","protected":false},"author":5590,"featured_media":7244,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[21,18],"tags":[376,377],"ano":[137],"tipo":[121],"volume":[44],"class_list":["post-7171","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-figado","category-gastroenterologia","tag-enzimas-hepaticas","tag-sindrome-de-gilbert","ano-137","tipo-assuntos-gerais","volume-volume-ii"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.2 (Yoast SEO v27.3) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>S\u00edndrome de Gilbert: o que precisamos saber? 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