Scientific letter
Hypothyroidism and protein-losing enteropathy: A case report
Hipotiroidismo y enteropatía pierde-proteínas: a propósito de un caso
Irene Berges-Raso
, Ismael Capel, Assumpta Caixàs, Roser Trallero, Mercedes Rigla
Corresponding author
Servicio de Endocrinología y Nutrición, Hospital Universitario Parc Taulí, Sabadell, Barcelona, Spain
Read
7702
Timeswas read the article
1047
Total PDF
6655
Total HTML
Share statistics
array:24 [ "pii" => "S2173509316000295" "issn" => "21735093" "doi" => "10.1016/j.endoen.2015.11.016" "estado" => "S300" "fechaPublicacion" => "2016-02-01" "aid" => "747" "copyright" => "SEEN" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Endocrinol Nutr. 2016;63:95-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2056 "formatos" => array:2 [ "HTML" => 1772 "PDF" => 284 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1575092215003265" "issn" => "15750922" "doi" => "10.1016/j.endonu.2015.11.001" "estado" => "S300" "fechaPublicacion" => "2016-02-01" "aid" => "747" "copyright" => "SEEN" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Endocrinol Nutr. 2016;63:95-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2600 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 2132 "PDF" => 466 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Hipotiroidismo y enteropatía pierde-proteínas: a propósito de un caso" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "95" "paginaFinal" => "96" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hypothyroidism and protein-losing enteropathy: A case report" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Irene Berges-Raso, Ismael Capel, Assumpta Caixàs, Roser Trallero, Mercedes Rigla" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Irene" "apellidos" => "Berges-Raso" ] 1 => array:2 [ "nombre" => "Ismael" "apellidos" => "Capel" ] 2 => array:2 [ "nombre" => "Assumpta" "apellidos" => "Caixàs" ] 3 => array:2 [ "nombre" => "Roser" "apellidos" => "Trallero" ] 4 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Rigla" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173509316000295" "doi" => "10.1016/j.endoen.2015.11.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000295?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1575092215003265?idApp=UINPBA00004N" "url" => "/15750922/0000006300000002/v1_201601290049/S1575092215003265/v1_201601290049/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173509316000258" "issn" => "21735093" "doi" => "10.1016/j.endoen.2016.02.004" "estado" => "S300" "fechaPublicacion" => "2016-02-01" "aid" => "742" "copyright" => "SEEN" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Endocrinol Nutr. 2016;63:96-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2350 "formatos" => array:3 [ "EPUB" => 1 "HTML" => 1991 "PDF" => 358 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Transient electrocardiographic abnormalities during hypoglycemia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "96" "paginaFinal" => "97" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Alteraciones electrocardiográficas transitorias durante un episodio de hipoglucemia" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 750 "Ancho" => 1000 "Tamanyo" => 72050 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Normalization of changes in the ST segment and repolarization after correction of hypoglycemia with intravenous hypertonic glucose.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Manuel José Fernández Anguita, Virgilio Martínez Mateo, Laura Cejudo del Campo Díaz, Miguel Ángel Villanueva Terrazas, Antonio Jesús Paule Sánchez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Manuel José" "apellidos" => "Fernández Anguita" ] 1 => array:2 [ "nombre" => "Virgilio" "apellidos" => "Martínez Mateo" ] 2 => array:2 [ "nombre" => "Laura" "apellidos" => "Cejudo del Campo Díaz" ] 3 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "Villanueva Terrazas" ] 4 => array:2 [ "nombre" => "Antonio Jesús" "apellidos" => "Paule Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1575092215002776" "doi" => "10.1016/j.endonu.2015.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1575092215002776?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000258?idApp=UINPBA00004N" "url" => "/21735093/0000006300000002/v1_201603200109/S2173509316000258/v1_201603200109/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173509316000246" "issn" => "21735093" "doi" => "10.1016/j.endoen.2016.02.003" "estado" => "S300" "fechaPublicacion" => "2016-02-01" "aid" => "741" "copyright" => "SEEN" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Endocrinol Nutr. 2016;63:87-94" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2412 "formatos" => array:3 [ "EPUB" => 1 "HTML" => 2123 "PDF" => 288 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitamin D" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "87" "paginaFinal" => "94" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Antibióticos humanos modulados por calcitriol: nuevos aspectos fisiopatológicos de la hipovitaminosis D" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1104 "Ancho" => 1639 "Tamanyo" => 92154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mechanism through which vitamin D modulates the secretion of cathelicidin and beta-2-defensin. Binding of some microbial antigens (Ag) to toll-like receptors (TLRs) activates 25-hydroxyvitamin D–1α-hydroxylase (CYP27b1), so that, depending on intracellular concentrations of 25-hydroxyvitamin D, local synthesis of 1,25-dihydroxyvitamin D is enhanced. The latter in turn binds to its receptor (VDR), and the intranuclear hormone-receptor complex activates the transcription of the cathelicidin and beta-2-defensin genes. Intracellular concentrations of 25-hydroxyvitamin D depend on plasma concentrations of this molecule, which is the most reliable marker of the nutritional status of this vitamin.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carlos Antonio Amado Diago, María Teresa García-Unzueta, María del Carmen Fariñas, Jose Antonio Amado" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Carlos Antonio" "apellidos" => "Amado Diago" ] 1 => array:2 [ "nombre" => "María Teresa" "apellidos" => "García-Unzueta" ] 2 => array:2 [ "nombre" => "María del Carmen" "apellidos" => "Fariñas" ] 3 => array:2 [ "nombre" => "Jose Antonio" "apellidos" => "Amado" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1575092215002764" "doi" => "10.1016/j.endonu.2015.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1575092215002764?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000246?idApp=UINPBA00004N" "url" => "/21735093/0000006300000002/v1_201603200109/S2173509316000246/v1_201603200109/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Hypothyroidism and protein-losing enteropathy: A case report" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "95" "paginaFinal" => "96" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Irene Berges-Raso, Ismael Capel, Assumpta Caixàs, Roser Trallero, Mercedes Rigla" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Irene" "apellidos" => "Berges-Raso" "email" => array:1 [ 0 => "inberges@tauli.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Ismael" "apellidos" => "Capel" ] 2 => array:2 [ "nombre" => "Assumpta" "apellidos" => "Caixàs" ] 3 => array:2 [ "nombre" => "Roser" "apellidos" => "Trallero" ] 4 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Rigla" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario Parc Taulí, Sabadell, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipotiroidismo y enteropatía pierde-proteínas: a propósito de un caso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 34-year-old female patient with a history of hypothyroidism, lymphangiectasia, and protein-losing enteropathy on treatment with levothyroxine (200<span class="elsevierStyleHsp" style=""></span>μg/day) who attended the emergency room complaining of dyspnea and fever. A chest X-ray showed bilateral pleural effusion and enlarged cardiac silhouette, while echocardiography revealed pericardiac effusion with systolic–diastolic collapse of the right chambers. The results of laboratory tests performed were as follows: TSH, 21.3<span class="elsevierStyleHsp" style=""></span>μU/mL (normal: 0.4–4); free thyroxine, 0.69<span class="elsevierStyleHsp" style=""></span>ng/dL (normal: 0.8–1.8); triiodothyronine, 0.62<span class="elsevierStyleHsp" style=""></span>pg/mL (normal: 2–4.4); serum albumin, 17.9<span class="elsevierStyleHsp" style=""></span>g/L (normal: 34–48); prealbumin, 11.4<span class="elsevierStyleHsp" style=""></span>mg/dL (normal: 20–40); total cholesterol, 118<span class="elsevierStyleHsp" style=""></span>mg/dL (normal: 150–200); triglycerides, 100<span class="elsevierStyleHsp" style=""></span>mg/dL (normal: 50–200); vitamin E 1.9<span class="elsevierStyleHsp" style=""></span>μg/mL (normal: 5–20) (corrected for cholesterol and triglyceride levels of 0.89<span class="elsevierStyleHsp" style=""></span>mg/g, in the lower limit of normal: normal: >0.8<span class="elsevierStyleHsp" style=""></span>mg/g); vitamin A, 0.09<span class="elsevierStyleHsp" style=""></span>mg/L (normal: 0.3–1); 25-OH vitamin D, <9<span class="elsevierStyleHsp" style=""></span>ng/mL; copper, 70<span class="elsevierStyleHsp" style=""></span>μg/dL (normal: 80–155); zinc 56<span class="elsevierStyleHsp" style=""></span>μg/dL (normal: 68–107); and serum selenium, 44<span class="elsevierStyleHsp" style=""></span>μg/dL (normal: 60–120).</p><p id="par0010" class="elsevierStylePara elsevierViewall">Multifactorial pleural and pericardiac effusion in the setting of hypoproteinemia and hypothyroidism, with respiratory tract superinfection, was diagnosed, and was treated with evacuating pericardiocentesis, oxygen therapy, and intravenous ceftriaxone. Her weight during hospitalization was 70<span class="elsevierStyleHsp" style=""></span>kg, and a low-fat diet was started (20–30<span class="elsevierStyleHsp" style=""></span>g of lipids during her hospital stay), together with oral supplements to provide a total of 600<span class="elsevierStyleHsp" style=""></span>kcal/day, with 27<span class="elsevierStyleHsp" style=""></span>g of hydrolyzed protein and 22<span class="elsevierStyleHsp" style=""></span>g of lipids, of which 15.4<span class="elsevierStyleHsp" style=""></span>g were medium-chain triglycerides (MCTs). Thirty grams of oil with mCTs and supplements of vitamin A (50,000<span class="elsevierStyleHsp" style=""></span>IU/day), E (200<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h), and D (10,000<span class="elsevierStyleHsp" style=""></span>IU/week) were also added. Copper and zinc levels were considered moderately low in the context of the acute phase, and watchful waiting was decided upon. The patient reported good compliance with levothyroxine treatment, and low drug levels despite very high doses (approximately 2.8<span class="elsevierStyleHsp" style=""></span>μg/kg/day) were therefore attributed to the underlying gastrointestinal disease. The dose was increased to 250<span class="elsevierStyleHsp" style=""></span>μg/day. Some days later, the patient experienced a clinical improvement with decreased stool count and steatorrhea and was discharged.</p><p id="par0015" class="elsevierStylePara elsevierViewall">At an outpatient monitoring visit at three months, her clinical condition was much improved. She weighed 70.3<span class="elsevierStyleHsp" style=""></span>kg and reported a lower number of stools, with mild steatorrhea. She was still taking oral supplements, and laboratory tests showed an improvement in the nutritional parameters: prealbumin 18<span class="elsevierStyleHsp" style=""></span>mg/dL and albumin 27.2<span class="elsevierStyleHsp" style=""></span>g/L. Levels of copper 88<span class="elsevierStyleHsp" style=""></span>μg/dL, serum selenium 60<span class="elsevierStyleHsp" style=""></span>μg/L, vitamin A 0.5<span class="elsevierStyleHsp" style=""></span>mg/L, and vitamin E 2.9<span class="elsevierStyleHsp" style=""></span>μg/mL (corrected: 1.4<span class="elsevierStyleHsp" style=""></span>mg/g) were normalized. The zinc level was 59<span class="elsevierStyleHsp" style=""></span>μg/dL, and her vitamin D level continued to be less than 9<span class="elsevierStyleHsp" style=""></span>ng/mL despite supplementation. Thyroid hormone levels had normalized (TSH 2.27<span class="elsevierStyleHsp" style=""></span>μU/mL and free thyroxine 1.1<span class="elsevierStyleHsp" style=""></span>ng/dL).</p><p id="par0020" class="elsevierStylePara elsevierViewall">A review of the patient's clinical history during her hospitalization found that she was born with congenital lymphedema and intestinal lymphangiectasia that required surgery several times during childhood. However, she was not diagnosed with Hennekam syndrome until she was 28, based on dysmorphic signs and the delayed development of her daughter. Previously, at the age of 24, she had experienced pleuropericarditis in the context of myxedema with 226<span class="elsevierStyleHsp" style=""></span>μU/mL of TSH and 0.06<span class="elsevierStyleHsp" style=""></span>ng/dL of free T4. Subsequently, patient monitoring was irregular, but the levothyroxine dose was increased to 200<span class="elsevierStyleHsp" style=""></span>μg/day, due to the difficulty in normalizing TSH.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Hennekam syndrome is an extremely uncommon cause of hypothyroidism characterized by congenital lymphedema, mainly affecting the limbs and genitalia, and developmental delay. It is also related to dysmorphic traits (flattened face, broad and flattened nasal bridge, and hypertelorism), glaucoma, hypoacusis, and dental and renal abnormalities. It is characterized by lymphangiectasia in the bowel, pleura, pericardium, thyroid gland, and kidney. An intestinal biopsy shows a dilation of lymphatic vessels in the lamina propria that leads to protein-losing enteropathy and malabsorption. Thyroid lymphangiectasia is the cause of hypothyroidism.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–5</span></a> This genetic condition was described by Hennekam in 1989.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> To our knowledge, 36 cases have been reported worldwide to date.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–5</span></a> This is the first case reported in Spain. Twenty-five percent of patients have autosomal recessive mutations in the <span class="elsevierStyleItalic">CCBE1</span> gene, and more than 20% in the <span class="elsevierStyleItalic">FAT4</span> gene. <span class="elsevierStyleItalic">CCBE1</span> is a key gene for the development of lymphatic system. However, the relationship with <span class="elsevierStyleItalic">FAT4</span> has not yet been elucidated.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> Other genes involved include <span class="elsevierStyleItalic">VEGFR3</span> and <span class="elsevierStyleItalic">GJC2</span>.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> In this patient, diagnosis was initially based on the clinical history and phenotype.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Hypothyroidism occurring in this syndrome is difficult to manage due to decreased levothyroxine absorption secondary to intestinal lymphangiectasia, which may require very high thyroid hormone doses. The treatment of malabsorption syndromes depends on symptom severity. It usually consists of a low-fat, protein- and mCT-rich diet, in addition to supplements of lipid soluble vitamins and electrolytes. Home enteral nutrition by mouth or tube using products specifically designed for malabsorption syndromes (with fat mainly as mCTs and partially hydrolyzed protein) may sometimes be required. Subcutaneous octreotide treatment<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> or parenteral nutrition may be required in very severe cases.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> If pleural or pericardiac effusion occurs, drainage may be needed. Lymphedema may be very disabling, requiring surgery and diuretics.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2–4</span></a> Its prognosis is highly variable, and if severe complications occur, life expectancy may be decreased.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,5</span></a> Differential diagnosis includes other syndromes causing congenital lymphedema such as Noonan syndrome, Aagenaes cholestasis-lymphedema syndrome, Milroy's disease, or Turner syndrome.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2,5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, Hennekam syndrome is a rare cause of hypothyroidism and intestinal malabsorption secondary to lymphangiectasia that requires adequate nutritional treatment with low-fat diet, protein supplementation, and deficient lipid soluble vitamins, and careful, possibly high levothyroxine dosage.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Berges-Raso I, Capel I, Caixàs A, Trallero R, Rigla M. Hipotiroidismo y enteropatía pierde-proteínas: a propósito de un caso. Endocrinol Nutr. 2016;63:95–96.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.C. Hennekam" 1 => "R.A. Geerdink" 2 => "B.C. Hamel" 3 => "F.A. Hennekam" 4 => "P. Kraus" 5 => "J.A. Rammeloo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.1320340429" "Revista" => array:5 [ "tituloSerie" => "Am J Med Genet" "fecha" => "1989" "volumen" => "34" "paginaInicial" => "593-600" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2624276" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lymphedema–lymphangiectasia–mental retardation (Hennekam) syndrome: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.D. Van Balkom" 1 => "M. Alders" 2 => "J. Allanson" 3 => "C. Bellini" 4 => "U. Frank" 5 => "G. de Jong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.10707" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "412" "paginaFinal" => "421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12376947" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variable clinical presentation in primary lymphoedema: report of two cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Ozyurt" 1 => "E. Sevinc" 2 => "A. Baykan" 3 => "D. Arslan" 4 => "M. Argun" 5 => "O. Pamukcu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCD.0000000000000036" "Revista" => array:6 [ "tituloSerie" => "Clin Dysmorphol" "fecha" => "2014" "volumen" => "23" "paginaInicial" => "83" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24619057" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hennekam syndrome: a rare cause of primary lymphedema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "I. Elmansour" 1 => "S. Chiheb" 2 => "H. Benchikhi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2014" "paginaInicial" => "20" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel CCBE1 mutation leading to a mild form of Hennekam syndrome: case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Frosk" 1 => "B. Chodirker" 2 => "L. Simard" 3 => "W. El-Matary" 4 => "A. Hanlon-Dearman" 5 => "J. Schwartzentruber" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12881-015-0175-0" "Revista" => array:5 [ "tituloSerie" => "BMC Med Genet" "fecha" => "2015" "volumen" => "16" "paginaInicial" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25925991" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Al Sinani" 1 => "Y. Al Rawahi" 2 => "H. Abdoon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v18.i43.6333" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "6333" "paginaFinal" => "6337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23180957" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein-losing enteropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Amiot" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.revmed.2014.12.001" "Revista" => array:6 [ "tituloSerie" => "Rev Med Interne" "fecha" => "2015" "volumen" => "36" "paginaInicial" => "467" "paginaFinal" => "473" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25618488" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735093/0000006300000002/v1_201603200109/S2173509316000295/v1_201603200109/en/main.assets" "Apartado" => array:4 [ "identificador" => "5823" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735093/0000006300000002/v1_201603200109/S2173509316000295/v1_201603200109/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000295?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 15 | 0 | 15 |
| 2024 October | 108 | 12 | 120 |
| 2024 September | 119 | 15 | 134 |
| 2024 August | 91 | 21 | 112 |
| 2024 July | 94 | 11 | 105 |
| 2024 June | 95 | 10 | 105 |
| 2024 May | 75 | 9 | 84 |
| 2024 April | 105 | 10 | 115 |
| 2024 March | 100 | 11 | 111 |
| 2024 February | 79 | 16 | 95 |
| 2024 January | 99 | 12 | 111 |
| 2023 December | 97 | 19 | 116 |
| 2023 November | 103 | 23 | 126 |
| 2023 October | 147 | 26 | 173 |
| 2023 September | 99 | 10 | 109 |
| 2023 August | 115 | 4 | 119 |
| 2023 July | 133 | 9 | 142 |
| 2023 June | 119 | 3 | 122 |
| 2023 May | 158 | 6 | 164 |
| 2023 April | 106 | 21 | 127 |
| 2023 March | 83 | 18 | 101 |
| 2023 February | 82 | 22 | 104 |
| 2023 January | 106 | 12 | 118 |
| 2022 December | 83 | 10 | 93 |
| 2022 November | 77 | 17 | 94 |
| 2022 October | 52 | 16 | 68 |
| 2022 September | 82 | 21 | 103 |
| 2022 August | 64 | 27 | 91 |
| 2022 July | 56 | 11 | 67 |
| 2022 June | 56 | 13 | 69 |
| 2022 May | 48 | 17 | 65 |
| 2022 April | 56 | 11 | 67 |
| 2022 March | 92 | 13 | 105 |
| 2022 February | 54 | 6 | 60 |
| 2022 January | 90 | 5 | 95 |
| 2021 December | 55 | 7 | 62 |
| 2021 November | 71 | 7 | 78 |
| 2021 October | 76 | 21 | 97 |
| 2021 September | 73 | 18 | 91 |
| 2021 August | 96 | 20 | 116 |
| 2021 July | 49 | 5 | 54 |
| 2021 June | 56 | 14 | 70 |
| 2021 May | 92 | 17 | 109 |
| 2021 April | 158 | 22 | 180 |
| 2021 March | 123 | 19 | 142 |
| 2021 February | 76 | 12 | 88 |
| 2021 January | 88 | 14 | 102 |
| 2020 December | 73 | 8 | 81 |
| 2020 November | 86 | 13 | 99 |
| 2020 October | 67 | 10 | 77 |
| 2020 September | 60 | 15 | 75 |
| 2020 August | 93 | 11 | 104 |
| 2020 July | 74 | 16 | 90 |
| 2020 June | 70 | 16 | 86 |
| 2020 May | 72 | 13 | 85 |
| 2020 April | 43 | 8 | 51 |
| 2020 March | 56 | 8 | 64 |
| 2020 February | 64 | 3 | 67 |
| 2020 January | 80 | 10 | 90 |
| 2019 December | 73 | 9 | 82 |
| 2019 November | 65 | 8 | 73 |
| 2019 October | 79 | 3 | 82 |
| 2019 September | 68 | 5 | 73 |
| 2019 August | 77 | 9 | 86 |
| 2019 July | 63 | 12 | 75 |
| 2019 June | 75 | 16 | 91 |
| 2019 May | 116 | 55 | 171 |
| 2019 April | 104 | 13 | 117 |
| 2019 March | 48 | 3 | 51 |
| 2019 February | 40 | 4 | 44 |
| 2019 January | 40 | 1 | 41 |
| 2018 December | 37 | 6 | 43 |
| 2018 November | 44 | 5 | 49 |
| 2018 October | 60 | 11 | 71 |
| 2018 September | 31 | 3 | 34 |
| 2018 August | 22 | 0 | 22 |
| 2018 July | 19 | 1 | 20 |
| 2018 June | 31 | 0 | 31 |
| 2018 May | 28 | 1 | 29 |
| 2018 April | 28 | 1 | 29 |
| 2018 March | 14 | 2 | 16 |
| 2018 February | 25 | 1 | 26 |
| 2018 January | 25 | 1 | 26 |
| 2017 December | 26 | 0 | 26 |
| 2017 November | 24 | 1 | 25 |
| 2017 October | 16 | 6 | 22 |
| 2017 September | 21 | 3 | 24 |
| 2017 August | 29 | 14 | 43 |
| 2017 July | 24 | 1 | 25 |
| 2017 June | 39 | 7 | 46 |
| 2017 May | 30 | 11 | 41 |
| 2017 April | 24 | 9 | 33 |
| 2017 March | 34 | 30 | 64 |
| 2017 February | 39 | 3 | 42 |
| 2017 January | 18 | 2 | 20 |
| 2016 December | 28 | 4 | 32 |
| 2016 November | 21 | 1 | 22 |
| 2016 October | 25 | 6 | 31 |
| 2016 September | 36 | 2 | 38 |
| 2016 August | 20 | 1 | 21 |
| 2016 May | 0 | 1 | 1 |
| 2016 March | 0 | 1 | 1 |
Show all
