Original Article
Efficacy and safety of replacement treatment in isolated growth hormone deficiency
Eficacia y seguridad del tratamiento sustitutivo en el déficit aislado de hormona del crecimiento
Ana Belén Ariza Jiménez
, María José Martínez-Aedo Ollero, Juan Pedro López-Siguero
Corresponding author
Hospital Materno-infantil de Málaga, Málaga, Spain
Read
5849
Timeswas read the article
1869
Total PDF
3980
Total HTML
Share statistics
array:25 [ "pii" => "S2341287919300511" "issn" => "23412879" "doi" => "10.1016/j.anpede.2018.05.007" "estado" => "S300" "fechaPublicacion" => "2019-05-01" "aid" => "2462" "copyright" => "Asociación Española de Pediatría" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2019;90:285-92" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 599 "formatos" => array:3 [ "EPUB" => 72 "HTML" => 382 "PDF" => 145 ] ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S1695403318302224" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2018.05.012" "estado" => "S300" "fechaPublicacion" => "2019-05-01" "aid" => "2462" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2019;90:285-92" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2412 "formatos" => array:3 [ "EPUB" => 137 "HTML" => 1645 "PDF" => 630 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Eficacia y seguridad del tratamiento sustitutivo en el déficit aislado de hormona del crecimiento" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "285" "paginaFinal" => "292" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Efficacy and safety of replacement treatment in isolated growth hormone deficiency" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 932 "Ancho" => 1248 "Tamanyo" => 167899 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Talla puberal y adulta de acuerdo al sexo en niños con déficit aislado de GH.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Belén Ariza Jiménez, María José Martínez-Aedo Ollero, Juan Pedro López-Siguero" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Ana Belén" "apellidos" => "Ariza Jiménez" ] 1 => array:2 [ "nombre" => "María José" "apellidos" => "Martínez-Aedo Ollero" ] 2 => array:2 [ "nombre" => "Juan Pedro" "apellidos" => "López-Siguero" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287919300511" "doi" => "10.1016/j.anpede.2018.05.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300511?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403318302224?idApp=UINPBA00005H" "url" => "/16954033/0000009000000005/v1_201905020855/S1695403318302224/v1_201905020855/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2341287919300493" "issn" => "23412879" "doi" => "10.1016/j.anpede.2018.05.005" "estado" => "S300" "fechaPublicacion" => "2019-05-01" "aid" => "2448" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2019;90:293-300" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1134 "formatos" => array:3 [ "EPUB" => 90 "HTML" => 789 "PDF" => 255 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "293" "paginaFinal" => "300" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Engrosamiento del tallo hipofisario en niños y adolescentes con diabetes insípida central: causas y consecuencias" ] ] "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" => 1547 "Ancho" => 2333 "Tamanyo" => 159794 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow chart of patients with a diagnosis of central diabetes insipidus, showing the presence of pituitary stalk thickening and its association with the aetiology of diabetes. CDI, central diabetes insipidus; ICDI, idiopathic central diabetes insipidus.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Beatriz Corredor Andrés, María Teresa Muñoz Calvo, Miguel Ángel López Pino, María Márquez Rivera, Lourdes Travieso Suárez, Jesús Pozo Román, Jesús Argente" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Beatriz" "apellidos" => "Corredor Andrés" ] 1 => array:2 [ "nombre" => "María Teresa" "apellidos" => "Muñoz Calvo" ] 2 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "López Pino" ] 3 => array:2 [ "nombre" => "María" "apellidos" => "Márquez Rivera" ] 4 => array:2 [ "nombre" => "Lourdes" "apellidos" => "Travieso Suárez" ] 5 => array:2 [ "nombre" => "Jesús" "apellidos" => "Pozo Román" ] 6 => array:2 [ "nombre" => "Jesús" "apellidos" => "Argente" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403318301826" "doi" => "10.1016/j.anpedi.2018.05.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403318301826?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300493?idApp=UINPBA00005H" "url" => "/23412879/0000009000000005/v1_201905020905/S2341287919300493/v1_201905020905/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2341287919300523" "issn" => "23412879" "doi" => "10.1016/j.anpede.2018.05.008" "estado" => "S300" "fechaPublicacion" => "2019-05-01" "aid" => "2466" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2019;90:280-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1026 "formatos" => array:3 [ "EPUB" => 67 "HTML" => 763 "PDF" => 196 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "<span class="elsevierStyleItalic">Erythrovirus</span> B19 infections. Six years of follow-up in adults and children" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "280" "paginaFinal" => "284" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infecciones por <span class="elsevierStyleItalic">Erythrovirus</span> B19. Seis años de seguimiento en población adulta y pediátrica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Natàlia Claver Belver, Isabel Sanfeliu Sala, M. Jesús Merino Asensio, Carla Monterde Pedra, Valentí Pineda Solas, Silvia Capilla Rubio, Dionisia Fontanals Aymerich" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Natàlia" "apellidos" => "Claver Belver" ] 1 => array:2 [ "nombre" => "Isabel" "apellidos" => "Sanfeliu Sala" ] 2 => array:2 [ "nombre" => "M. Jesús" "apellidos" => "Merino Asensio" ] 3 => array:2 [ "nombre" => "Carla" "apellidos" => "Monterde Pedra" ] 4 => array:2 [ "nombre" => "Valentí" "apellidos" => "Pineda Solas" ] 5 => array:2 [ "nombre" => "Silvia" "apellidos" => "Capilla Rubio" ] 6 => array:2 [ "nombre" => "Dionisia" "apellidos" => "Fontanals Aymerich" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403318302261" "doi" => "10.1016/j.anpedi.2018.05.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403318302261?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300523?idApp=UINPBA00005H" "url" => "/23412879/0000009000000005/v1_201905020905/S2341287919300523/v1_201905020905/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Efficacy and safety of replacement treatment in isolated growth hormone deficiency" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "285" "paginaFinal" => "292" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ana Belén Ariza Jiménez, María José Martínez-Aedo Ollero, Juan Pedro López-Siguero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Ana Belén" "apellidos" => "Ariza Jiménez" "email" => array:1 [ 0 => "micodemas@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "María José" "apellidos" => "Martínez-Aedo Ollero" ] 2 => array:2 [ "nombre" => "Juan Pedro" "apellidos" => "López-Siguero" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Materno-infantil de Málaga, Málaga, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia y seguridad del tratamiento sustitutivo en el déficit aislado de hormona del crecimiento" ] ] "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" => 919 "Ancho" => 1437 "Tamanyo" => 155320 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Height at onset of puberty and adult height by sex in children with isolated growth hormone deficiency.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Growth hormone deficiency (GHD) results in clinically significant growth retardation and metabolic disorders.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Early diagnosis of GHD is important so that replacement therapy can be initiated as soon as possible with the aim of achieving an adult height approximating the target height (if GHD is not treated, the adult height can end up being 4.7 standard deviations [SD] below the mean) and prevent metabolic disorders in the long term.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Since growth hormone (GH) secretion follows a pulsatile pattern, measuring its levels may not provide a reliable baseline, so instead pituitary stimulation tests are used to assess the secretion of GH.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3,4</span></a> If there is no response, this finding must be confirmed by a second test using a different provocative stimulus due to the high proportion of false positives.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Once GHD is diagnosed, treatment with recombinant human GH is initiated if the patient's height is 2 SD below the mean and the height velocity 1 SD below the mean.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In Spain, treatment with GH is restricted to hospital settings and is overseen by the Advisory Committee for Growth Hormone Treatment of the competent autonomous community.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment is maintained until the height velocity decreases to less than 2<span class="elsevierStyleHsp" style=""></span>cm/year and the bone age (BA) is greater than 16 years in male patients or 14 years in female patients. Nevertheless, GHD can continue to have an impact in adulthood due to its metabolic effects.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Growth hormone replacement therapy carries significant costs for health care systems, so it would be beneficial to establish predictors of response to treatment in order to optimise its effectiveness and safety. This justifies the investment on long-term studies of GH replacement, which would provide clinicians the information needed to identify the patients that would most benefit from treatment without long-term risks.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We aimed to conduct a study in our population to define GHD and the variables that influence adult height, for while similar studies have been conducted in countries such as Italy, France or the United States, none have been published in Spain on this subject.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Thus, starting from the hypothesis that GH replacement increases adult height in Spanish patients with isolated GHD without a significant frequency of adverse effects, we set the objective of evaluating the effectiveness and safety of GH replacement therapy in patients with idiopathic isolated GHD, assessing the impact of pubertal development during treatment, the variables associated with effectiveness, and which patients continued to have GHD as adults.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">We conducted a longitudinal retrospective and prospective descriptive study of children of both sexes aged 0–14 years given a diagnosis of GHD based on the results of 2 stimulation tests and that received GH replacement therapy until adulthood or the end of the period under in a tertiary hospital over a period of 14 years. In addition, after discontinuation of treatment upon reaching the adult height, all patients underwent a re-evaluation that included measurement of insulin-like growth factor 1 (IGF-1<span class="elsevierStyleSmallCaps">)</span> and a stimulation test, for which we obtained their informed consent.</p><p id="par0055" class="elsevierStylePara elsevierViewall">All anthropometric measurements were taken 3 times, with the patients barefoot and in their underwear, using a manual SECA scale accurate to 0.1<span class="elsevierStyleHsp" style=""></span>kg and a wall-mounted Holtain stadiometer accurate to 0.1<span class="elsevierStyleHsp" style=""></span>cm calibrated daily.</p><p id="par0060" class="elsevierStylePara elsevierViewall">To make the diagnosis, 2 tests were performed on different days: the exercise provocation test, on account of the few adverse events associated with it, and a clonidine stimulation test; when it came to the re-evaluation, the stimulation test was performed with insulin. We did not use sex steroid priming. The thresholds established based on the current literature<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">12</span></a> were 7.4<span class="elsevierStyleHsp" style=""></span>ng/mL for the initial diagnosis and 5.6<span class="elsevierStyleHsp" style=""></span>ng/mL for the re-evaluation. The levels of GH and IGF-1 were measured by qualified staff using a chemiluminescent immunoassay method (IMMULITE 2000).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The cohort was monitored from diagnosis until reaching the adult height, with collection of data for variables such as age at diagnosis, the SD of the weigh, height and body mass index at baseline and at 1, 2, 3 and 4 years of treatment, the bone age to chronological age ration (BA/CA) at baseline and at 1 year, predicted adult height (PAH) estimated according to the Bayley Pinneau method at baseline and at 1 year, IGF-1 at baseline and 1 year, target height, age at onset of puberty, height at onset of puberty (HOP), pubertal height gain (PHG), adult height and levels of GH and IGF-1 at the time of the re-evaluation.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Whenever possible, we adjusted the SD scores to the data of the cross-sectional growth studies conducted in Spain using the auxologic software AUXOTEC<span class="elsevierStyleSup">®</span>,<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> while levels IGF-1 were adjusted for age and sex using the software provided with the IMMULITE system.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Lastly, we performed a statistical analysis of the collected data with the software SPSS version 22. We compared 2 means using the Student t test if the variables followed a normal distribution or the Mann–Whitney <span class="elsevierStyleItalic">U</span> test otherwise and more than 2 means using ANOVA for normally distributed variables and the Kruskal Wallis test otherwise, and also calculated the Pearson correlation coefficient for comparison of quantitative data. We fitted a multiple regression model including the variables that had exhibited a significant association with final height in the previous analyses.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">We analysed the cases of 97 patients of both sexes with a diagnosis of GHD, treated with a mean dose of GH of 0.028<span class="elsevierStyleHsp" style=""></span>mg/kg/day (0.025–0.03) for 5 years (from diagnosis to adulthood). The mean age at diagnosis was 10.5 years (8.26–11.7). Sixty nine percent of the patients were male, and 89.58% had achieved their adult height by the end of the study. We did not identify a neoplastic aetiology in any of the cases, and none of the patients experienced adverse effects from treatment.</p><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the main descriptive characteristics of the sample.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The mean height gain standard deviation score (SDS) in the first year of treatment was 0.49 SD score. The PAH adjusted for BA/CA increased by 0.6 SD. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the progressive improvement in height gain. The height SDS improved by 0.79 from baseline to puberty in both sexes, and from puberty to reaching the adult height by 0.43 in male patients and 0.29 in female patients. The total increase in height SDS until achievement of the final height was greater in male compared to female patients: 1.22 SD versus 1.08 SD (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The increase in the actual adult weight relative to the initial PAH was of 0.1 SD, and the increase relative to the target height was of 0.28 SD.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">We found statistically significant differences (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic"><</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">.</span>05) based on sex in the variables shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">We found that adult height was associated with male sex, with male patients exhibiting greater heights throughout treatment and greater target heights, PAHs and PHG as well as earlier puberty, a lower BA/CA and lower levels of IGF-1 and GH in the re-evaluation (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic"><</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">.</span>05) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Lastly, we also observed a linear correlation between the body mass index and the dose of GH, and the dose of GH was higher at the end of treatment compared to the dose at treatment initiation (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic"><</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">.</span>05).</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Re-evaluation</span><p id="par0110" class="elsevierStylePara elsevierViewall">We re-evaluated 69 patients as adults (71.13%), and found that GHD persisted in 39.4%. Of all patients with persisting GHD, 69% were male.</p><p id="par0115" class="elsevierStylePara elsevierViewall">We measured the levels of IGF-1 in the re-evaluation of adult height in 87 patients (89.58%), and found a mean level corresponding to a SDS score of 0.023, with deficient levels of IGF-1, defined as at least 2 SD below the mean, in 11%, all of whom also had deficient GH level in the re-evaluation (GH<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>5.4<span class="elsevierStyleHsp" style=""></span>mg/dL) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic"><</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">.</span>05). Although these differences were not statistically significant, we found that patients with permanent GHD had received the diagnosis earlier, had had lower baseline levels of IGF-1, lower height and weight at diagnosis, and exhibited a greater response to treatment.</p><p id="par0120" class="elsevierStylePara elsevierViewall">If in the re-evaluation we were to use a threshold for the IGF-1 levels of −3.22 SDS rather than −2 SDS, the area under the receiver operating characteristic (ROC) curve would have been of 0.8, which indicates that the test is good and shows a stronger correlation with GH (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">Although GH has been used to treat short stature for over 40 years, there is no consensus on the criteria that should be applied to define a satisfactory response to treatment.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">One of the interesting aspects of our study was that nearly 90% of the recruited children achieved their adult height, so that we were able to re-evaluate a significant proportion of the patients to determine their evolution during treatment as well as the outcomes of treatment.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Other studies, like ours, reported diagnosis in prepubertal children with a predominance of the male sex, but with a mean age at diagnosis that is 2 years younger compared to our sample, where the mean age was 10.5 years, which could entail a poorer response to treatment.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">15</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The published data are heterogeneous as regards the onset of puberty, with some studies reporting delays in the onset of puberty in patients with GHD and others no difference, as was the case of our cohort. On the other hand, the evidence currently available shows positive correlations between the age at diagnosis and puberty and between initial height, height gain at 1 year, age, sex, duration of treatment, BA/CA and adult height, of which our study only corroborated the association between age and diagnosis and age at onset of puberty, on one hand, and sex and height at baseline, height at 1 year and adult height, on the other.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,15–18</span></a> Maghnie et al. also reported an association between adult height and PHG,<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">19</span></a> which has not been described by other authors, but which was consistent with our findings, in line with our objective of assessing the influence of puberty on adult height.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Furthermore, our analysis also revealed negative correlations between age at diagnosis and HOP, GH dose and HOP and the baseline level of IGF-1 and the PAH at 1 year, the HOP and the adult height, which had not been described to date. In addition, we found a statistically significant negative, rather than positive, correlation of BA with adult height, which seems logical given that greater delays in BA are associated with longer durations of growth, and that in the existing literature, duration of growth is either positively correlated with adult height or, as is the case of the Kabi International Growth Study (KIGS), not associated with it.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">20–22</span></a> Although there is no agreement between studies regarding the association of the age onset of puberty or the age at treatment initiation with adult height, we ought to mention that we did not find evidence of either.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,15–19,23,24</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">When it came to significant differences in height based on sex, we consider that while the literature and our own study have found an association between these variables,<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,14</span></a> these differences may be due to differences between the sexes in pubertal growth and to the fact that target heights are lower in female patients, and, in our study in particular, that some of the female patients were in the prepubertal stage at the time of diagnosis (38% had the onset of puberty within 1 year). We also found negative correlations between age at onset of puberty and duration of puberty, on one hand, and PHG on the other, as described in previous studies.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,20,21</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The KIGS found statistically significant associations of PHG with sex, target height, dose of GH, BA/CH, HOP and the age at onset and end of puberty,<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">20,22</span></a> whereas our study only found a statistically significant positive correlation between PHG and male sex. The authors also noted that despite the intersubject variability in linear growth during treatment in patients of either sex in the prepubertal stage, there was no evidence of differences between the sexes in height gain and linear growth velocity in the first 3 years of treatment.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">21,25</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">There is also evidence of a negative association with the difference between the initial and the target height and between the peak value in the GH stimulation test, the age at diagnosis and adult height. The correlation between the peak GH value and adult height is also consistent with our findings of baseline GH values, age at diagnosis and a higher adult height, although in our study the differences were not statistically significant.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,16–19,23,24</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The KIGS also reported an association of adult height with the frequency of GH injections, dose of GH, linear growth velocity in the previous year, current weight, birth weight and the severity of GHD. Neither our study or previous studies have found evidence of these associations, which denotes a need for further research on the subject.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,15–19,23</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In addition, our study has also found associations between adult height and the initial PAH, the target height and the heights at different time points during treatment, including the baseline and the HOP, which had not yet been clearly established in the previous literature. Thus, adult height is associated with response to treatment throughout the duration of GH replacement therapy.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Lastly, while most authors assert that the target height is not associated with the adult height, probably due to samples including patients that could have idiopathic short stature, the Nordinet International Outcome Study (IOS) and the KIGS found a positive correlation between them, as was also the case in our study.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,15–19,23–25</span></a> Also in agreement with our study, Aimaretti et al. found an increase in the IGF-1 levels in association with treatment. These authors also reported a fair level of agreement between stimulation tests, the levels of IGF-1 and the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">26</span></a> In light of this, we ought to underscore our findings for IGF-1 and GH in the re-evaluation, which supports the agreement reported by this group and suggests a potential concomitant role of IGF-1 in the re-evaluation of GHD. In every case that the levels of IGF-1 were deficient in the re-evaluation, there had been no response in the GH stimulation test; however, not all patients with deficient GH values in the stimulation test had deficient levels of IGF-1 at re-evaluation, a fact that had not been clearly specified to present in the literature.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">27</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Thus, in line with our set objectives, the published data and our experience, the target height, baseline PAH, HOP, age at onset of puberty, PHG, height gain at different points of treatment, BA/CA and level of IGF-1 could be predictors of the response to GH replacement therapy.</p><p id="par0185" class="elsevierStylePara elsevierViewall">When it comes to efficacy, the studies in the literature have reported increases in the height SDS ranging from +0.4 to +1.5, in agreement with the value observed in our study, of +1.17 SDS.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11,15,17,24</span></a> In addition, Ranke et al. reported a height gain of +1.2<span class="elsevierStyleHsp" style=""></span>cm corresponding to +0.2 SDS at 1 year of treatment,<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">28</span></a> slightly lower compared to our sample (+0.49 SDS). In our sample, this improvement in adult height fell within the normal range of the Spanish population, which was consistent with the findings of the KIGS.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">29</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">When it comes to the PHG, previous studies have reported a gain of +0.8 SDS compared to +0.43 SDS in our sample, which could be explained by the BA/CA and the short delay in the onset of puberty, resistance to treatment or lack of adherence, none of which we are able to confirm.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">15,30</span></a> Kirk also noted an improvement in height relative to the target height of between +0.2 and +0.8 SDS,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">16</span></a> and Blethen et al. reported an improvement relative to the PAH of +0.7 SDS,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">11</span></a> consistent with the improvement observed in our sample of +0.28 SDS relative to the target height, but with a significant discrepancy in regard to the improvement found in our sample in relation to the PAH, of only +0.1 SDS, which is likely related to the mild delay in BA in our sample.</p><p id="par0195" class="elsevierStylePara elsevierViewall">Last of all, we ought to highlight that the proportion of patients with persistent GHD at the time of re-evaluation ranges from 44.4% to 71.9% in the literature, compared to 39.4% in our sample.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12,26,31</span></a> We also found a younger age at diagnosis, lower baseline IGF-1 levels and baseline heights and a greater response to treatment in patients with persisting GHD. The predominance of the male sex is also worth noting, which may be associated with the higher frequency of abnormalities detected by magnetic resonance imaging at the time of diagnosis in these patients.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Although some authors have described adverse effects of treatment, Sotos and Tokar reported the absence of adverse events associated to treatment in their patients,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a> which is consistent with the outcomes of GH replacement therapy observed in our patients and our hypothesis, although this could be due to differences in sample size. However, our results are also consistent with those of the study on the Safety and Appropriateness of Growth Hormone treatment in Europe (SAGhE) and the IOS, which had larger samples and longer durations of follow-up and found a low incidence of adverse events in these patients. Nevertheless, patients that have received this treatment in childhood should remain under follow-up to assess for potential long-term side effects that we may not yet be aware of.<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">25,31,33–35</span></a> Lastly, the studies published to date on GH replacement therapy in children with isolated GH, with the exception of a randomised controlled trial published by Ranke et al.,<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a> are observational studies without controls in samples of 20–2852 children of both sexes with followup periods ranging from 1 to 9 years, that is, shorter than our study. Only 40% of these studies had larger samples compared to ours, and in some instances the samples were very small. We also ought to mention that most of the studies with samples larger than ours were sponsored by pharmaceutical companies, which was not the case of our study, as we did not receive any support and had no conflicts of interest.</p><p id="par0205" class="elsevierStylePara elsevierViewall">That said, the factors that attest to the rigour of our study are its large sample size, the fact that it was conducted in a single centre, the careful methodology applied and the confirmation of statistical significance through the use of different tests.</p><p id="par0210" class="elsevierStylePara elsevierViewall">On the other hand, the main limitations of our study are the missing data for variables whose data were collected retrospectively and the fact that while most patients had achieved their adult height by the end of the followup, it was not 100% of the sample. We also ought to consider the ever-present risk of measurement error and poor interrater reliability. Furthermore, GHD may have been overdiagnosed due to the limitations of the tests currently available for diagnosis, including the fact that we did not use sex steroid priming.</p><p id="par0215" class="elsevierStylePara elsevierViewall">In short, in our sample the adult height after GH replacement therapy was similar to the target height, which supports our initial hypothesis regarding the effectiveness of this treatment. Of all patients, 39.4% exhibited persistent deficient levels of GH in the re-evaluation, of who 11.1% also exhibited deficient levels of IGF-1 at that time point. Furthermore, we found that patients with permanent GHD had received the diagnosis earlier, had had shorter stature and lower levels of IGF-1 at diagnosis and had exhibited a stronger response to treatment, which suggests that these patients may actually correspond to the true cases of GHD, although further research and better diagnostic tests are needed to confirm this hypothesis.</p><p id="par0220" class="elsevierStylePara elsevierViewall">None of the patients experienced adverse events with the dosage used for treatment during the follow-up; and while we cannot establish with absolute certainty the safety of GH replacement therapy, our findings are supported by other studies in the literature.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Last of all, the association of different variables with the response to treatment suggest possible predictors for the effectiveness of treatment, such as the target height, the initial PAH, the age at onset of puberty, the PHG, the heights during treatment and the HOP, which are positively correlated with the adult height, and the BA/CA and baseline IGF-1 level, which are negatively correlated.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1185915" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1105636" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1185916" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1105635" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Re-evaluation" ] ] ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-01-30" "fechaAceptado" => "2018-05-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1105636" "palabras" => array:4 [ 0 => "Growth hormone treatment" 1 => "Isolated growth hormone deficiency" 2 => "Efficacy" 3 => "Safety" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1105635" "palabras" => array:4 [ 0 => "Tratamiento hormona del crecimiento" 1 => "Déficit de hormona del crecimiento" 2 => "Eficacia" 3 => "Seguridad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Growth in patients with isolated growth hormone (GH) deficiency is heterogeneous despite treatment due to the low specificity of diagnostic tests, making it necessary to define efficacy variables.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate efficacy of hormone replacement therapy in children with isolated GH deficiency.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Observational-ambispective study of patients treated in our department in the last 14 years for isolated GH deficiency. This was defined as a GH level less than 7.4<span class="elsevierStyleHsp" style=""></span>mg/dL in response to 2 stimulation tests in patients with height<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2SD and a decreased growth rate.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The study included a total of 97 patients, of whom 69% were boys. The large majority (89.58%) achieved final height. None of them had side effects. The median dose of GH used was 0.028<span class="elsevierStyleHsp" style=""></span>mg/kg/day (0.03–0.025). There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of the patients were reassessed in adulthood, of whom 39.4% maintained the deficiency, and 79.31% achieved target range height. Target height, estimated height, and the total pubertal gain were positively correlated with final height, while the bone age/chronological age ratio and the initial insulin-like growth factor-1 showed a negative correlation.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A majority of patients reached target size, although only a few of them maintained the deficiency in adulthood. Target size, estimated adult height, and pubertal variables are directly related to adult height, while bone age/chronological age and insulin-like growth factor-1 were inversely related, and these can be used as efficacy variables. No adverse effects were observed in the sample with the doses used for the treatment.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Aims" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El crecimiento en pacientes con déficit aislado de hormona del crecimiento (GH) es heterogéneo a pesar del tratamiento, debido a la baja especificidad de las pruebas diagnósticas, por lo que es necesario definir las variables de eficacia.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia de la terapia de reemplazo hormonal en niños con déficit aislado de GH.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional-ambispectivo de pacientes tratados en nuestro servicio en los últimos 14 años por déficit aislado de GH, definido como GH inferior a 7,4<span class="elsevierStyleHsp" style=""></span>mg/dl en 2 pruebas de estímulo, en pacientes con talla<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−2DE y velocidad de crecimiento disminuida.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 97 pacientes. El 69% eran varones. Con el tratamiento hubo una ganancia de talla de 1,17DE. El 79,31% alcanzaron la talla diana. El 71,13% fueron reevaluados en la edad adulta, de los cuales el 39,4% mantuvo el déficit. La talla diana, el pronóstico de talla adulta y la ganancia puberal total se correlacionaron positivamente con la talla adulta, mientras que la relación edad ósea/edad cronológica y factor de crecimiento insulínico tipo 1 inicial mostraron una correlación negativa. Ninguno tuvo efectos secundarios.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La mayoría de los pacientes alcanzaron la talla diana, aunque no todos mostraron permanencia del déficit en edad adulta. La talla diana, el pronóstico de talla adulta y las variables de pubertad están directamente relacionados con la talla adulta; mientras que la edad ósea/edad cronológica y factor de crecimiento insulínico tipo 1 están inversamente relacionadas, pudiendo utilizarse estas como variables de eficacia. No se han observado efectos adversos en la muestra con las dosis utilizadas.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ariza Jiménez AB, Martínez-Aedo Ollero MJ, López-Siguero JP. Eficacia y seguridad del tratamiento sustitutivo en el déficit aislado de hormona del crecimiento. An Pediatr (Barc). 2019;90:285–292.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 840 "Ancho" => 1181 "Tamanyo" => 246597 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Height gain from initiation of treatment to adult height in children with isolated growth hormone deficiency.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 919 "Ancho" => 1437 "Tamanyo" => 155320 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Height at onset of puberty and adult height by sex in children with isolated growth hormone deficiency.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1391 "Ancho" => 1253 "Tamanyo" => 57291 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Sensitivity and specificity of the cut-off point of −3.22 SD for the level of IGF-1 in the evaluation based on the ROC curve.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; GH, growth hormone; IGF-1, insulin-like growth factor 1; SDS, standard deviation score.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Min \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Max \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SDS \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−5.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline weight (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline BMI (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment dose (mg/kg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.036 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">646 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">181.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">116.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−5.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Target height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age/chronological age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline predicted adult height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−4.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.44 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age to chronological at 1 year of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1347 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">378.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">228.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−4.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Predicted adult height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 2 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 3 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 4 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adult height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GH at re-evaluation (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at re-evaluation (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1045.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">362.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">173.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at re-evaluation (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−7.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2022435.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Descriptive statistics of the quantitative data collected during the followup through achievement of adult height in children with isolated growth hormone deficiency.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; GH, growth hormone; IGF-1, insulin-like growth factor 1; NS, not significant; SDS, standard deviation score.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Boys</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Girls</th><th class="td" title="table-head " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SDS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SDS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.989 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.696 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.154 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.771 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.659 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.863 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.511 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline weight (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.259 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.681 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.246 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.598 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline BMI (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.418 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.941 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.478 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.873 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment dose (mg/kg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">,0278 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.028 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">123.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">219.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.209 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.849 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.026 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.951 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Target height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.253 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.773 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.618 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.700 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.027 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age/chronological age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.683 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.171 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.777 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.147 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline predicted adult height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.236 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.368 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.237 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.366 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.327 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.523 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.256 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.421 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.135 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.554 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.133 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.669 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.464 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.830 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.553 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.844 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age/chronological age at 1 year of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.750 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.201 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.813 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">335.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">199.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">473.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">260.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.183 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.697 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.367 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.975 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Predicted adult height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.707 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.265 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.499 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.879 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 2 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.959 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.643 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.037 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.503 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 3 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.689 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.744 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.759 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.458 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 4 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.548 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.835 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.690 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.655 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at onset of puberty (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.197 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.084 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at onset of puberty (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.964 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.689 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.127 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.630 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adult height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.533 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.937 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.834 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.596 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.034 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pubertal height gain (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.432 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.617 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GH at re-evaluation (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.142 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.433 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.419 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.284 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at re-evaluation (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">352.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">167.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">384.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">187.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at re-evaluation (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.146 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.251 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.403 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.293 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2022436.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Statistically significant differences based on sex in the followup through adult height in children with isolated growth hormone deficiency.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; GH, growth hormone; IGF-1, insulin-like growth factor 1; NS, not significant; SDS, standard deviation score.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline weight (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline BMI (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GH dose (mg/kg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline IGF-1 (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Target height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age/chronological age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Predicted adult height (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone age/chronological age at 1 year of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.036 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IGF-1 at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Predicted adult height at 1 year of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 2 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 3 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at 4 years of treatment (SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height at onset of puberty \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pubertal height gain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2022437.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Association of variables analysed during the follow-up of children with isolated growth hormone deficiency with adult height.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0185" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Growth Hormone Research Society" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Endocrinol Metab" "fecha" => "2000" "volumen" => "85" "paginaInicial" => "3990" "paginaFinal" => "3993" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0190" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Routine monitoring of growth in children of primary school age" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Fayter" 1 => "J. Nixon" 2 => "S. Hartley" 3 => "A. Rithalia" 4 => "G. Butler" 5 => "M. Rudolf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Health Technol Assess (Rockv)" "fecha" => "2007" "volumen" => "11" "paginaInicial" => "1" "paginaFinal" => "184" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0195" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estudio del paciente con talla baja" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Lopera" 1 => "G. Campuzano" 2 => "V. Balthazar" 3 => "J. Alfaro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med Lab" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "511" "paginaFinal" => "531" "itemHostRev" => array:3 [ "pii" => "S0896627318303295" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0200" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Guzzetti" 1 => "A. Ibba" 2 => "S. Pilia" 3 => "N. Beltrami" 4 => "N. di Iorgi" 5 => "A. Rollo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2016" "volumen" => "175" "paginaInicial" => "41" "paginaFinal" => "47" "itemHostRev" => array:3 [ "pii" => "S0896627318303222" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0205" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Murray" 1 => "M. Dattani" 2 => "P. Clayton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2016" "volumen" => "101" "paginaInicial" => "96" "paginaFinal" => "100" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0210" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Talla baja idiopática y hormona de crecimiento: bastantes dudas y algunas recomendaciones" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. López-Siguero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Evid Pediatr" "fecha" => "2011" "volumen" => "7" "paginaInicial" => "1" "paginaFinal" => "4" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0215" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Towards optimal treatment with growth hormone in short children and adolescents: evidence and theses" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.B. Ranke" 1 => "A. Lindberg" 2 => "P.E. Mullis" 3 => "M.E. Geffner" 4 => "T. Tanaka" 5 => "W.S. Cutfield" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2013" "volumen" => "79" "paginaInicial" => "51" "paginaFinal" => "67" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0220" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endocrinología pediátrica. Manual práctico. Primera. Panamericana, editor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.P. Lopez Siguero" 1 => "B. Garcia Cuartero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:5 [ "fecha" => "2013" "paginaInicial" => "3" "paginaFinal" => "41" "editorial" => "Sociedad Española de Endocrinologia Pediátrica" "editorialLocalizacion" => "Madrid" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0225" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hormone replacement therapy in children: the use of growth hormone and IGF-I" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Pfäffle" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Best Pr Res Clin Endocrinol Metab" "fecha" => "2015" "volumen" => "29" "paginaInicial" => "339" "paginaFinal" => "352" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0230" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Revaluation of the clinical and metabolic behavior of children with isolated growth hormone deficiency during GH treatment according to newly proposed note 39 of the Italian Medicines Agency (AIFA)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Ciresi" 1 => "F. Cicciò" 2 => "M. Amato" 3 => "C. Giordano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Endocrinol Invest" "fecha" => "2015" "volumen" => "38" "paginaInicial" => "1301" "paginaFinal" => "1307" "itemHostRev" => array:3 [ "pii" => "S0896627318304185" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0235" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. The Genentech Groeth Study Group" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.L. Blethen" 1 => "J. Baptista" 2 => "J. Kuntze" 3 => "T. Foley" 4 => "S. LaFranchi" 5 => "A. Johanson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1997" "volumen" => "82" "paginaInicial" => "418" "paginaFinal" => "420" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0240" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reassessment of the growth hormone status in young adults with childhood-onset growth hormone deficiency: reappraisal of insulin tolerance testing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Secco" 1 => "N. di Iorgi" 2 => "F. Napoli" 3 => "E. Calandra" 4 => "A. Calcagno" 5 => "M. Ghezzi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2009" "volumen" => "94" "paginaInicial" => "4195" "paginaFinal" => "4204" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0245" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estudios españoles de crecimiento: situación actual, utilidad y recomendaciones de uso" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Sánchez González" 1 => "A. Carrascosa Lezcano" 2 => "J.M. Fernández García" 3 => "A. Ferrández Longás" 4 => "D. López de Lara" 5 => "J.P. López-Siguero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "An Pediatr" "fecha" => "2011" "volumen" => "74" "paginaInicial" => "193e1" "paginaFinal" => "193e16" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0250" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Height velocity targets from the national cooperative growth study for first-year growth hormone responses in short children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Bakker" 1 => "J. Frane" 2 => "H. Anhalt" 3 => "B. Lippe" 4 => "R. Rosenfeld" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2008" "volumen" => "93" "paginaInicial" => "352" "paginaFinal" => "357" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0255" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth, development, puberty and adult height before and during treatment in children with congenital isolated growth hormone deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K. Smuel" 1 => "R. Kauli" 2 => "P. Lilos" 3 => "Z. Laron" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Growth Horm IGF Res" "fecha" => "2015" "volumen" => "25" "paginaInicial" => "182" "paginaFinal" => "188" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0260" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indications for growth hormone therapy in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Kirk" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2012" "volumen" => "97" "paginaInicial" => "63" "paginaFinal" => "68" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0265" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term safety and efficacy of the recombinant human growth hormone Omnitrope<span class="elsevierStyleSup">®</span> in the treatment of Spanish growth hormone deficient children: results of a phase <span class="elsevierStyleSmallCaps">iii</span> study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. López-Siguero" 1 => "M.V. Borrás Pérez" 2 => "S. Balser" 3 => "J. Khan-Boluki" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Adv Ther" "fecha" => "2011" "volumen" => "28" "paginaInicial" => "879" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0270" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult height after growth hormone treatment in Japanese children with idiopathic growth hormone deficiency: analysis from the KIGS Japan database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Fujieda" 1 => "T. Tanaka" 2 => "K. Takano" 3 => "K. Chihara" 4 => "Y. Seino" 5 => "M. Irie" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Pediatr Endocrinol Metab" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "457" "paginaFinal" => "462" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0275" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult height in patients with permanent growth hormone deficiency with and without multiple pituitary hormone deficiencies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Maghnie" 1 => "L. Ambrosini" 2 => "M. Cappa" 3 => "G. Pozzobon" 4 => "L. Ghizzoni" 5 => "M. Ubertini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "2900" "paginaFinal" => "2905" "itemHostRev" => array:3 [ "pii" => "S0896627318303714" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0280" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GH use in the transition of adolescence to adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N. Mauras" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Endocr Dev" "fecha" => "2010" "volumen" => "18" "paginaInicial" => "109" "paginaFinal" => "125" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0285" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "CD003887CD38872009" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recombinant growth hormone for children and adolescents with Turner syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Baxter" 1 => "J. Bryant" 2 => "C. Cave" 3 => "R. Milne" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2007" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0290" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency idiopathic short stature, and primary insulin-like growth factor-I deficiency" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society" "etal" => true "autores" => array:6 [ 0 => "A. Grimberg" 1 => "S.A. Divall" 2 => "C. Polychronakos" 3 => "D.B. Allen" 4 => "L.E. Cohen" 5 => "J.B. Quintos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2016" "volumen" => "86" "paginaInicial" => "361" "paginaFinal" => "397" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0295" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reference curve for the first-year growth response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency: validation of the KIGS first-year growth response curve using the Belgian Register for the Study of Growth an" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Straetemans" 1 => "M. Roelants" 2 => "M. Thomas" 3 => "R. Rooman" 4 => "J. De Schepper" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2014" "volumen" => "81" "paginaInicial" => "343" "paginaFinal" => "349" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0300" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased height standard deviation scores in response to growth hormone therapy to near-adult height in older children with delayed skeletal maturation: results from the ANSWER Program" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Ross" 1 => "P. Lee" 2 => "R. Gut" 3 => "J. Germak" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Int J Pediatr Endocrinol" "fecha" => "2015" "volumen" => "2015" "paginaInicial" => "1" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0305" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Presentation number SAT-041" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age at treatment start is associated with normalisation of Near Adult Height (NAH) in growth hormone (GH)-treated children with isolated growth hormone deficiency (iGHD): an analysis from Nordinet<span class="elsevierStyleSup">®</span> International Outcome Study (IOS)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Polak" 1 => "J. Blair" 2 => "P. Kotnik" 3 => "E. Pournara" 4 => "B. Pedersen" 5 => "T. Rohrer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "titulo" => "Endocrine Society's 98th Annual Meeting and Expo" "conferencia" => "April 1–4, 2016. Boston" "serieFecha" => "2016" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0310" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE SIMA" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Aimaretti" 1 => "R. Attanasio" 2 => "S. Cannavò" 3 => "M.C. Nicoletti" 4 => "R. Castello" 5 => "C. Di Somma" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Endocrinol Invest" "fecha" => "2015" "volumen" => "38" "paginaInicial" => "377" "paginaFinal" => "382" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0315" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variable degree of growth hormone (GH) and insulin-like growth factor (IGF). sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Cohen" 1 => "J. Germak" 2 => "A. Rogol" 3 => "W. Weng" 4 => "A. Kappelgaard" 5 => "R. Rosenfeld" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2010" "volumen" => "95" "paginaInicial" => "2089" "paginaFinal" => "2098" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0320" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Observed and predicted total pubertal growth during treatment with growth hormone in adolescents with idiopathic growth hormone deficiency Turner syndrome, short stature, born small for gestational age and idiopathic short stature: KIGS analysis & revision" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Ranke" 1 => "A. Lindberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2011" "volumen" => "75" "paginaInicial" => "423" "paginaFinal" => "432" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0325" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Swedish KIGS National Board Final height in Swedish children with idiopathic growth hormone deficiency enrolled in KIGS treated optimally with growth hormone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O. Westphal" 1 => "A. Lindberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr" "fecha" => "2008" "volumen" => "97" "paginaInicial" => "1698" "paginaFinal" => "1706" "itemHostRev" => array:3 [ "pii" => "S089662731830179X" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0330" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Strategies for maximizing growth in puberty in children with short stature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N. Mauras" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Endocrinol Metab Clin North Am" "fecha" => "2009" "volumen" => "38" "paginaInicial" => "613" "paginaFinal" => "624" "itemHostRev" => array:3 [ "pii" => "S0896627318303817" "estado" => "S300" "issn" => "08966273" ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0335" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth hormone (GH) retesting and final adult height in childhood-onset GH deficiency (CO-GHD): experiences from King Chulalongkorn Memorial Hospital Thailand" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Wacharasindhu" 1 => "S. Aroonparkmongkol" 2 => "T. Sahakitrungrueng" 3 => "V. Supornsilchai" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Med Assoc Thai" "fecha" => "2015" "volumen" => "98" "paginaInicial" => "542" "paginaFinal" => "548" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0340" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.F. Sotos" 1 => "N.J. Tokar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Int J Pediatr Endocrinol" "fecha" => "2014" "volumen" => "2014" "paginaInicial" => "15" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0345" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Description of the SAGhE Cohort: a large European study of mortality and cancer incidence risks after childhood treatment with recombinant growth hormone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.J. Swerdlow" 1 => "R. Cooke" 2 => "K. Albertsson-Wikland" 3 => "B. Borgström" 4 => "G. Butler" 5 => "S. Cianfarani" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2015" "volumen" => "84" "paginaInicial" => "172" "paginaFinal" => "183" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0350" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimal therapy of growth hormone deficiency in the child and adolescent" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.R. Rose" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Endocrinol" "fecha" => "2011" "volumen" => "7" "paginaInicial" => "40" "paginaFinal" => "46" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0355" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is safety of childhood growth hormone therapy related to dose? Data from a large observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Sävendahl" 1 => "E. Pournara" 2 => "B. Pedersen" 3 => "O. Blankenstein" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2016" "volumen" => "174" "paginaInicial" => "681" "paginaFinal" => "691" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0360" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "KIGS International Board Height at start, first-year growth response and cause of shortness at birth are major determinants of adult height outcomes of short children born small for gestational age and Silver-Russell syndrome treated with growth hormone: analysis of data from KIG" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Ranke" 1 => "A. Lindberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Horm Res Paediatr" "fecha" => "2010" "volumen" => "74" "paginaInicial" => "259" "paginaFinal" => "266" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000009000000005/v1_201905020905/S2341287919300511/v1_201905020905/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000009000000005/v1_201905020905/S2341287919300511/v1_201905020905/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300511?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 10 | 15 |
| 2024 October | 34 | 30 | 64 |
| 2024 September | 47 | 29 | 76 |
| 2024 August | 67 | 46 | 113 |
| 2024 July | 46 | 26 | 72 |
| 2024 June | 52 | 25 | 77 |
| 2024 May | 47 | 23 | 70 |
| 2024 April | 41 | 31 | 72 |
| 2024 March | 39 | 25 | 64 |
| 2024 February | 32 | 29 | 61 |
| 2024 January | 39 | 12 | 51 |
| 2023 December | 57 | 20 | 77 |
| 2023 November | 67 | 38 | 105 |
| 2023 October | 64 | 22 | 86 |
| 2023 September | 51 | 22 | 73 |
| 2023 August | 33 | 19 | 52 |
| 2023 July | 45 | 22 | 67 |
| 2023 June | 47 | 29 | 76 |
| 2023 May | 71 | 26 | 97 |
| 2023 April | 43 | 20 | 63 |
| 2023 March | 69 | 17 | 86 |
| 2023 February | 69 | 11 | 80 |
| 2023 January | 49 | 24 | 73 |
| 2022 December | 65 | 31 | 96 |
| 2022 November | 56 | 34 | 90 |
| 2022 October | 73 | 51 | 124 |
| 2022 September | 54 | 57 | 111 |
| 2022 August | 50 | 70 | 120 |
| 2022 July | 47 | 53 | 100 |
| 2022 June | 42 | 37 | 79 |
| 2022 May | 37 | 53 | 90 |
| 2022 April | 56 | 35 | 91 |
| 2022 March | 89 | 43 | 132 |
| 2022 February | 69 | 30 | 99 |
| 2022 January | 52 | 27 | 79 |
| 2021 December | 57 | 37 | 94 |
| 2021 November | 50 | 47 | 97 |
| 2021 October | 116 | 60 | 176 |
| 2021 September | 43 | 37 | 80 |
| 2021 August | 51 | 44 | 95 |
| 2021 July | 84 | 28 | 112 |
| 2021 June | 83 | 36 | 119 |
| 2021 May | 74 | 36 | 110 |
| 2021 April | 132 | 79 | 211 |
| 2021 March | 68 | 24 | 92 |
| 2021 February | 70 | 22 | 92 |
| 2021 January | 73 | 21 | 94 |
| 2020 December | 82 | 16 | 98 |
| 2020 November | 82 | 23 | 105 |
| 2020 October | 127 | 21 | 148 |
| 2020 September | 128 | 19 | 147 |
| 2020 August | 96 | 8 | 104 |
| 2020 July | 100 | 16 | 116 |
| 2020 June | 80 | 8 | 88 |
| 2020 May | 87 | 25 | 112 |
| 2020 April | 73 | 16 | 89 |
| 2020 March | 27 | 18 | 45 |
| 2020 February | 30 | 10 | 40 |
| 2020 January | 16 | 12 | 28 |
| 2019 December | 38 | 9 | 47 |
| 2019 November | 30 | 10 | 40 |
| 2019 October | 37 | 9 | 46 |
| 2019 September | 25 | 11 | 36 |
| 2019 August | 23 | 16 | 39 |
| 2019 July | 31 | 16 | 47 |
| 2019 June | 40 | 21 | 61 |
| 2019 May | 67 | 24 | 91 |
| 2019 April | 56 | 13 | 69 |
Show all
