Human growth hormone and Turner syndrome

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of the mean height standard deviation scores in the first four phases of the study. 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array:4 [ "autoresLista" => "Silvia Beatriz Sánchez Marco, Antonio de Arriba Muñoz, Marta Ferrer Lozano, José Ignacio Labarta Aizpún, Jesús María Garagorri Otero" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Silvia Beatriz" "apellidos" => "Sánchez Marco" "email" => array:1 [ 0 => "ssanchezmarco@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Antonio" "apellidos" => "de Arriba Muñoz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Marta" "apellidos" => "Ferrer Lozano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "José Ignacio" "apellidos" => "Labarta Aizpún" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Jesús María" "apellidos" => "Garagorri Otero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Endocrinología Pediátrica, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hormona de crecimiento y síndrome de Turner" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 902 "Ancho" => 1392 "Tamanyo" => 55665 ] ] "descripcion" => array:1 [ "en" => "Longitudinal changes in mean IGFBP3 levels (μg/mL)." ] ] ] "textoCompleto" => "IntroductionTurner syndrome is a chromosomal disorder that occurs in one of every 2500 live births, characterised by the complete or partial absence of a chromosome X (the complete monosomy [45,X] accounts for more than 50% of cases),<a class="elsevierStyleCrossRefs" href="#bib0160">1,2</a> although some studies have found evidence of a high prevalence of mosaicism.<a class="elsevierStyleCrossRef" href="#bib0170">3</a> It is associated with a range of phenotypic characteristics, chief of which are short stature, gonadal dysgenesis, hand and foot lymphoedema, pterygium colli, cubitus valgus and cardiovascular malformations, among others.<a class="elsevierStyleCrossRef" href="#bib0165">2</a>Since short stature is a common feature and the sole clinical manifestation in most cases,<a class="elsevierStyleCrossRefs" href="#bib0160">1–3</a> several studies have evinced the efficacy of treatment with recombinant human growth hormone (rhGH), with increases in final height of ∼7–10cm.<a class="elsevierStyleCrossRefs" href="#bib0175">4–6</a>Treatment with rhGH has to be initiated early when stature is more than two standard deviations (−2 SDS) below that of the general population or height velocity (HV) is below the tenth percentile for the patient's bone age. It should not be delayed past age 4 years nor initiated before age 2 years.<a class="elsevierStyleCrossRefs" href="#bib0160">1,4</a>Different studies have identified some predictors of adult height, such as height at initiation of treatment with rhGH, response in the first year of treatment, genetic height potential, age at initiation of treatment or mean weekly dose of rhGH.<a class="elsevierStyleCrossRefs" href="#bib0175">4,6,7</a>We present a study conducted in a Spanish cohort of patients with Turner syndrome with the aim of analysing the association between the response to treatment with rhGH and various factors.Materials and methodsWe conducted a retrospective study of 25 patients with a Turner syndrome diagnosis, 17 of who were treated with rhGH and followed up at the paediatric endocrinology unit of a tertiary level hospital until they reached their adult height. The patients treated with rhGH have been in followup from 1995 to present, and having reached adult height was an inclusion criterion. We also retrieved data for older cases that were not treated with rhGH on account of being diagnosed at older ages or the family refusing the treatment.We reviewed the medical records of patients with Turner syndrome, collecting data for auxological measurements, laboratory tests, karyotyping and pharmacological treatment throughout their followup in the unit. We informed the patients of the purpose of the study and obtained their informed consent.We assessed the short-term response to treatment with rhGH (12 months) based on changes in HV. We defined response to treatment as an increase in HV of more than three centimetres per year compared to the previous HV or an increase by three SDS at 12 months of treatment. To assess the long-term response to treatment (up to reaching adult height), we used five possible response variables: (1) an increase in height SDS compared to baseline SDS (delta HtSDS: adult height SDS− height at initiation of rhGH)<a class="elsevierStyleCrossRef" href="#bib0170">3</a>; (2) increase in height SDS compared to the baseline predicted adult height SDS (adult height SDS− 10th percentile SDS); (3) increase in height SDS compared to the height at initiation of oestrogen therapy as a response variable (adult height SDS− height at oestrogen initiation); (4) increase in height SDS compared to the difference of the height at initiation of treatment with rhGH and the height at initiation of oestrogen therapy (oestrogen initiation height SDS− rhGH initiation height SDS); (5) increase in height SDS relative to the duration of rhGH therapy prior to initiation of oestrogen therapy.We conducted a descriptive and inferential analysis with SPSS 18.0 for Windows using nonparametric tests: the Wilcoxon test for quantitative variables, Spearman's correlation test for analysing the linear correlation between quantitative variables, linear regression analysis for quantitative variables that had shown a linear correlation and for quantitative and qualitative variables; the Mann–Whitney U test to compare dichotomous qualitative variables with quantitative variables, and the Kruskal–Wallis test to compare nominal qualitative variables with quantitative variables. We defined statistical significance for all tests as a p-value of less than .05.ResultsOf the 25 patients under study, 17 (68%) received rhGH treatment, while eight did not.The most frequent karyotype in these patients was 45,X (42.9%) followed by isochromosome 46,X,i(Xq) (17.8%) and 46,X,i(Xq)/45,X mosaicism (14.3%). Other less frequent karyotypes found in the sample were mosaicisms such as 46,XX(r)/45,X; 47,XXX/45,X/46,XX; 45,X/46,X,der(X) and 45,X/47,XXX; 46,X,i/45,X/46,XX.When it came to phenotypic expression, we found that the classical presentation (short stature, pterygium colli, cubitus valgus, widely spaced nipples, etc.) was the most frequent phenotype (50%); while six patients did not have characteristic features (27.3%) and received the diagnosis when they underwent evaluation of short stature.The mean age at initiation of rhGH therapy was 7.90±4.13 years (range, 1.82–16.45 years) with a mean height SDS of −2.49±0.63.The mean initial dose of rhGH used for treatment was 0.048±0.01mg/kg/day and the mean duration of treatment was 7.36±3.88 years. At the time of treatment completion, patients had a mean age of 14.52±1.69 years and had reached a mean final adult height of 156.15±3.66cm (−1.23±0.62 SDS).At 12 months of treatment with rhGH, there was an increased HV of 8.21±2.22cm/year (2.5±2.55 SDS) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). At this time, the predicted adult height for the patients had increased by 4.39±3.14cm (144.98±7.99 vs 149.37±5.92cm) and 0.67±1.06 SDS (−2.92±1.21 vs −2.24±0.91 SDS) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). At two years of treatment, the mean predicted adult height increased to 150.56±5.17cm, with a slight decrease in HV to 6.73±1.63cm/year.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>As for laboratory parameters, there was a progressive increase in the levels of IGF1 and IGFBP3 until the end of treatment, with levels reaching up to three times their baseline values, but always remaining within normal ranges (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>The mean final height gain compared to baseline height at initiation of treatment was of 42.82±21.23cm (total gain of 1.25±0.76 SDS). When it came to the baseline predicted adult height, height gain in patients exceeded it by a mean of 9.59±5.39cm (1.68±1.51 SDS) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>After 12 months of treatment, patients had improvements in height (P=.011), HV (P=.004) and IGF1 levels (P=.043) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), and we also observed an improvement in the adult heights achieved (P=.028).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Our assessment of the short-term response to treatment based on increases in HV showed that in 66.6% of the patients, HV increased by more than 3cm/year at 12 months of treatment compared to baseline. Furthermore, we found a positive correlation between response to treatment and the dose of rhGH (P=.037; β=69.95), and response to treatment and increased levels of IGF1 and IGFBP3 (P=.000; r2 [IGF1]=0.846, r2 [IGFBP3]=0.809). When we analysed height gain relative to the interval between initiation of treatment with rhGH and initiation of oestrogen therapy, we found a positive correlation for auxological parameters such as height and HV both in cm and SDS at four months and one year of treatment (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The mean difference in final height between patients treated with rhGH and patients not treated with it was 10.69±2.63cm (P=.031; 156.15±3.66cm vs 145.44±3.69cm, respectively).Furthermore, we computed linear regression curves using the predictors for a favourable response identified in previous steps, but since the sample size was small, the results we obtained do not seem to be generalisable.We did not find any differences in response to treatment based on karyotype (P=.147).DiscussionShort stature is the key feature of Turner syndrome and may occur in the absence of other clinical manifestations.<a class="elsevierStyleCrossRef" href="#bib0170">3</a> Linear growth deceleration starts in infancy and early childhood, and becomes more marked in late childhood and adolescence, resulting in a significantly short stature in adulthood.<a class="elsevierStyleCrossRef" href="#bib0165">2</a> The indication of rhGH therapy to increase HV and adult height in patients with Turner syndrome is accepted and supported by various studies.<a class="elsevierStyleCrossRefs" href="#bib0160">1,2,4</a> There is evidence that this treatment results in increases of five to ten centimetres in the final adult height.<a class="elsevierStyleCrossRefs" href="#bib0175">4,5</a> Treatment should be initiated when the patient's height is two SDS below the population mean or when HV is below the tenth percentile for the patient's bone age.<a class="elsevierStyleCrossRefs" href="#bib0175">4,8</a>Several studies such as the one carried out by the Canadian Growth Hormone Advisory Committee<a class="elsevierStyleCrossRefs" href="#bib0200">9,10</a> and a few conducted in Spain have demonstrated the importance of rhGH treatment in these patients, as they have found increases in HV of 4.1–8.15cm at 12 months of treatment.<a class="elsevierStyleCrossRefs" href="#bib0210">11–13</a> There is great variability in the increases in HV reported in the literature, as they range from −1.69 to 1.97 SDS. The increase is greatest in the first year of treatment, and less significant in subsequent year.<a class="elsevierStyleCrossRef" href="#bib0225">14</a> In our study, at 12 months of treatment we found an increased HV of 8.21±2.22cm/year (2.5±2.55 SDS) with a difference compared to baseline of 3.22cm, which corresponds to a good initial increase in HV compared to what has been reported in previous studies.<a class="elsevierStyleCrossRefs" href="#bib0210">11–14</a>In addition, research in recent years has attempted to both assess response to treatment and determine the factors that promote a good response. Thus, for the purpose of assessing response to treatment in the short term, Quigley et al.<a class="elsevierStyleCrossRef" href="#bib0230">15</a> noted the increase in HV by ∼2cm a year. In our study, we assessed response to treatment with rhGH applying a threshold of 3cm a year for the increase in HV at 12 months of treatment, which was exceeded by 66.6% of the patients under study. Other authors<a class="elsevierStyleCrossRef" href="#bib0235">16</a> highlight a mean increase in height SDS in the first year of treatment of +0.50±0.03 SDS. In the short term, these parameters function as predictors of a long-term favourable response to treatment, although this remains controversial.<a class="elsevierStyleCrossRef" href="#bib0240">17</a> In the study that we present here, we observed that when it came to the longitudinal changes in the main auxological parameters, the largest changes in height, HV and predicted adult height took place in the first year (4–12 months from initiation), followed by lesser increases and an eventual plateau, except in HV.As to the findings concerning long-term response to treatment, Radetti et al. found increases in final height of up to 9.2cm, corroborated by more recent studies showing increases in final height of ∼7cm<a class="elsevierStyleCrossRef" href="#bib0245">18</a> and of more than 1 SDS.<a class="elsevierStyleCrossRefs" href="#bib0250">19,20</a> Our findings were similar, with a mean increase in final height compared to baseline height of 9.59±5.39cm (1.68±1.51 SDS).There is disagreement regarding the association between the dosage of rhGH and the improvement in clinical outcomes due to increased levels of growth factors; some authors have found such an association,<a class="elsevierStyleCrossRefs" href="#bib0235">16,20–22</a> while others, including García et al.<a class="elsevierStyleCrossRef" href="#bib0270">23</a> or Wetterau et al.,<a class="elsevierStyleCrossRef" href="#bib0275">24</a> believe that it has no impact on the final response to treatment. In our study, we found a positive correlation with the increase of growth factor levels (IGF1 and IGFBP3) at one year of treatment, which is strongly associated with the administered dose of rhGH and better clinical outcomes.<a class="elsevierStyleCrossRefs" href="#bib0225">14,25</a> Furthermore, studies conducted in recent years have attempted to identify the genes involved in the early response of these patients to rhGH. Some have identified polymorphisms in the CDK4 gene that may have an impact on IGF1 levels and therefore on the response to treatment with rhGH.<a class="elsevierStyleCrossRef" href="#bib0285">26</a> Ranke et al.<a class="elsevierStyleCrossRefs" href="#bib0175">4,25,27</a> found positive correlations with the administered dose (greater than 0.27mg/kg/day), frequency (more days per week) and age at initiation (some authors assert that adult height can reach the normal range if treatment is initiated between 2 and 4 years of age<a class="elsevierStyleCrossRefs" href="#bib0185">6,19</a>), with no consensus on the subject.<a class="elsevierStyleCrossRef" href="#bib0295">28</a>The duration of treatment with rhGH also seems to influence the final height gain. Chernausek et al.<a class="elsevierStyleCrossRefs" href="#bib0250">19,22,27</a> described this time interval as an important predictor of final height, and even produced an equation to estimate the approximate height gain: height gain (in cm=2.1× years of rhGH treatment prior to oestrogen initiation.The timing of initiation of oestrogen therapy continues to be debated; some authors<a class="elsevierStyleCrossRefs" href="#bib0290">27–29</a> have found greater height gains with initiation of oestrogen therapy at age 14 years; other studies suggest that low doses of oestrogen administered at earlier ages may lead to an increase of 0.37 SDS in adult height compared to patients in whom initiation of oestrogen therapy is delayed.<a class="elsevierStyleCrossRef" href="#bib0300">29</a> In our opinion, the timing of oestrogen initiation should be decided in agreement with the patient and the family, taking into account not only auxological parameters such as height or bone age, but also bone mineral density and the wishes expressed by the patient in relation to treatment initiation and pubertal development.Another controversial aspect is the use of anabolic steroids such as oxandrolone, as it seems to increase final height when combined with rhGH. Gault et al.<a class="elsevierStyleCrossRef" href="#bib0295">28</a> found a mean increase in final height of +4.6cm (range, 1.9–7.2cm) in a group treated with oxandrolone compared to a group treated with placebo. However, their study did not find a statistically significant positive additive effect for the combination of oxandrolone and late pubertal induction.Our comparison of patients treated with rhGH and patients not treated with rhGH was consistent with the findings of Paschino et al.<a class="elsevierStyleCrossRef" href="#bib0305">30</a> and Rosenfeld et al.,<a class="elsevierStyleCrossRef" href="#bib0310">31</a> with a mean difference in height between both groups of 10.69±2.63cm (P=.031), which evinces the importance of early treatment in these patients. Ranke et al.<a class="elsevierStyleCrossRef" href="#bib0245">18</a> studied the possibility of patients with specific karyotypes responding better to treatment with rhGH, but we found no differences based on karyotype.Based on the results of our study, we determined that the predictors for a long-term favourable response are, from most important to least: (A) dose of rhGH at treatment initiation, (B) duration of treatment with rhGH prior to initiation of oestrogen therapy, (C) increased levels of IGF1 and IGFBP3 during the first year of treatment and (D) HV in the first year of treatment.Conflict of interestsThe authors have no conflict of interests to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres794530" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec792853" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres794531" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec792854" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-11-28" "fechaAceptado" => "2016-02-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec792853" "palabras" => array:3 [ 0 => "Turner syndrome" 1 => "Short stature" 2 => "Growth hormone" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec792854" "palabras" => array:3 [ 0 => "Síndrome de Turner" 1 => "Talla baja" 2 => "Hormona de crecimiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveThe evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. Material and methodsA retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. ResultsA favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). ConclusionsPredictors of good response to growth hormone treatment are: (A) initial growth hormone dose, (B) time on growth hormone treatment until starting oestrogen therapy, (C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and (D) height gain velocity in the first year of treatment." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoEvaluación de parámetros clínicos y analíticos que actúen como predictivos de respuesta al tratamiento con hormona de crecimiento (rhGH) a largo plazo en pacientes con síndrome de Turner. Material y métodosEstudio retrospectivo de 25 niñas diagnosticadas de síndrome de Turner, de las cuales 17 recibieron tratamiento con rhGH y fueron controladas hasta alcanzar la talla adulta. Se determinaron diferentes variables auxológicas, analíticas, genéticas y farmacológicas a lo largo de su seguimiento en dichas consultas. Se realizó un estudio descriptivo y analítico mediante regresión lineal, con valoración de la respuesta al tratamiento a corto (12 meses) y a largo plazo. ResultadosSe observó una respuesta favorable a corto plazo valorada en ganancia de velocidad de crecimiento en el 66,6% de los casos (velocidad de crecimiento>3cm/año a los 12 meses de tratamiento respecto a la previa). También se evidenció una respuesta favorable a largo plazo, valorada en una ganancia de talla total de 42,82±21,23cm (1,25±0,76 SDS). Las pacientes ganaron una media de 9,59±5,39cm (1,68±1,51 SDS) respecto a su pronóstico de crecimiento previo al tratamiento. ConclusionesEl presente estudio evidencia como factores predictivos de buena respuesta al tratamiento con rhGH a largo plazo en orden de importancia: A) dosis de rhGH al inicio del tratamiento, B) tiempo de tratamiento con rhGH hasta inicio de terapia estrogénica, C) incremento en los niveles de IGF1 e IGFBP-3 durante el primer año de tratamiento y D) velocidad de crecimiento en el primer año de tratamiento." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Sánchez Marco SB, de Arriba Muñoz A, Ferrer Lozano M, Labarta Aizpún JI, Garagorri Otero JM. Hormona de crecimiento y síndrome de Turner. An Pediatr (Barc). 2017;86:81–86." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 810 "Ancho" => 1466 "Tamanyo" => 70423 ] ] "descripcion" => array:1 [ "en" => "Longitudinal changes in height velocity (SDS)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 737 "Ancho" => 1411 "Tamanyo" => 51416 ] ] "descripcion" => array:1 [ "en" => "Longitudinal changes in predicted adult height (SDS)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 927 "Ancho" => 1422 "Tamanyo" => 62128 ] ] "descripcion" => array:1 [ "en" => "Longitudinal changes in mean IGF1 levels (ng/mL)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 902 "Ancho" => 1392 "Tamanyo" => 55665 ] ] "descripcion" => array:1 [ "en" => "Longitudinal changes in mean IGFBP3 levels (μg/mL)." ] ] 4 => 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:1 [ "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" 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">Initiation of treatment \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">2 years of treatment \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">Adult age \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">Total gain \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">Height (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">113.32±22.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">124.18±17.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">156.15±3.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.82±21.23 \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 SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.49±0.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.93±0.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.23±0.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.25±0.76 \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 (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144.9±7.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">150.57±5.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.59±5.39 \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="char" valign="top">−2.92±1.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.05±0.81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.68±1.51 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328987.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Descriptive analysis of the long-term response to treatment with rhGH." ] ] 5 => 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:1 [ "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" 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">At treatment initiation, mean±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">At one year of treatment, mean±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">P \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.49±0.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.09±0.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.028 \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 velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.64±2.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.50±2.55 \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></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="char" valign="top">−2.92±1.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">− 2.24±0.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.075 \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">IGF1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">143.12±101.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">384.83±111.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.043 \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">IGFBP3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.25±1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.77±1.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.068 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328988.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analysis of the changes in studied parameters from baseline to one year after initiation of rhGH therapy." ] ] 6 => 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:1 [ "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" 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">P \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">R2 \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">R \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">β coefficient \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">Increase in height velocity at 1 year (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.094 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.75 \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><td class="td" title="table-entry " align="char" valign="top">0.134 \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">Increase in height velocity SDS at 1 year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.014 \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">0.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.189 \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 rhGH initiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.546 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.628 \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 gain SDS at 4 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.050 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.372 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.685 \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">rhGH dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.037 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.795 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.891 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328989.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Correlation between height gain parameters and duration of treatment with rhGH before initiation of oestrogen therapy." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0160" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nelson tratado de pediatría" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.M. 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Human growth hormone and Turner syndrome

Hormona de crecimiento y síndrome de Turner

Silvia Beatriz Sánchez Marcoa,

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ssanchezmarco@gmail.com

Corresponding author.

, Antonio de Arriba Muñoza, Marta Ferrer Lozanoa, José Ignacio Labarta Aizpúna, Jesús María Garagorri Oterob

a Unidad de Endocrinología Pediátrica, Hospital Universitario Miguel Servet, Zaragoza, Spain

b Servicio de Pediatría, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Turner syndrome is a chromosomal disorder that occurs in one of every 2500 live births&#44; characterised by the complete or partial absence of a chromosome X &#40;the complete monosomy &#91;45&#44;X&#93; accounts for more than 50&#37; of cases&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#44;2</span></a> although some studies have found evidence of a high prevalence of mosaicism&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> It is associated with a range of phenotypic characteristics&#44; chief of which are short stature&#44; gonadal dysgenesis&#44; hand and foot lymphoedema&#44; pterygium colli&#44; cubitus valgus and cardiovascular malformations&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Since short stature is a common feature and the sole clinical manifestation in most cases&#44;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#8211;3</span></a> several studies have evinced the efficacy of treatment with recombinant human growth hormone &#40;rhGH&#41;&#44; with increases in final height of &#8764;7&#8211;10<span class="elsevierStyleHsp" style=""></span>cm&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment with rhGH has to be initiated early when stature is more than two standard deviations &#40;&#8722;2 SDS&#41; below that of the general population or height velocity &#40;HV&#41; is below the tenth percentile for the patient&#39;s bone age&#46; It should not be delayed past age 4 years nor initiated before age 2 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Different studies have identified some predictors of adult height&#44; such as height at initiation of treatment with rhGH&#44; response in the first year of treatment&#44; genetic height potential&#44; age at initiation of treatment or mean weekly dose of rhGH&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">We present a study conducted in a Spanish cohort of patients with Turner syndrome with the aim of analysing the association between the response to treatment with rhGH and various factors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We conducted a retrospective study of 25 patients with a Turner syndrome diagnosis&#44; 17 of who were treated with rhGH and followed up at the paediatric endocrinology unit of a tertiary level hospital until they reached their adult height&#46; The patients treated with rhGH have been in followup from 1995 to present&#44; and having reached adult height was an inclusion criterion&#46; We also retrieved data for older cases that were not treated with rhGH on account of being diagnosed at older ages or the family refusing the treatment&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We reviewed the medical records of patients with Turner syndrome&#44; collecting data for auxological measurements&#44; laboratory tests&#44; karyotyping and pharmacological treatment throughout their followup in the unit&#46; We informed the patients of the purpose of the study and obtained their informed consent&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We assessed the short-term response to treatment with rhGH &#40;12 months&#41; based on changes in HV&#46; We defined response to treatment as an increase in HV of more than three centimetres per year compared to the previous HV or an increase by three SDS at 12 months of treatment&#46; To assess the long-term response to treatment &#40;up to reaching adult height&#41;&#44; we used five possible response variables&#58; &#40;1&#41; an increase in height SDS compared to baseline SDS &#40;delta HtSDS&#58; adult height SDS&#8722; height at initiation of rhGH&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a>&#59; &#40;2&#41; increase in height SDS compared to the baseline predicted adult height SDS &#40;adult height SDS&#8722; 10th percentile SDS&#41;&#59; &#40;3&#41; increase in height SDS compared to the height at initiation of oestrogen therapy as a response variable &#40;adult height SDS&#8722; height at oestrogen initiation&#41;&#59; &#40;4&#41; increase in height SDS compared to the difference of the height at initiation of treatment with rhGH and the height at initiation of oestrogen therapy &#40;oestrogen initiation height SDS&#8722; rhGH initiation height SDS&#41;&#59; &#40;5&#41; increase in height SDS relative to the duration of rhGH therapy prior to initiation of oestrogen therapy&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We conducted a descriptive and inferential analysis with SPSS 18&#46;0 for Windows using nonparametric tests&#58; the Wilcoxon test for quantitative variables&#44; Spearman&#39;s correlation test for analysing the linear correlation between quantitative variables&#44; linear regression analysis for quantitative variables that had shown a linear correlation and for quantitative and qualitative variables&#59; the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test to compare dichotomous qualitative variables with quantitative variables&#44; and the Kruskal&#8211;Wallis test to compare nominal qualitative variables with quantitative variables&#46; We defined statistical significance for all tests as a <span class="elsevierStyleItalic">p</span>-value of less than &#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">Of the 25 patients under study&#44; 17 &#40;68&#37;&#41; received rhGH treatment&#44; while eight did not&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The most frequent karyotype in these patients was 45&#44;X &#40;42&#46;9&#37;&#41; followed by isochromosome 46&#44;X&#44;i&#40;Xq&#41; &#40;17&#46;8&#37;&#41; and 46&#44;X&#44;i&#40;Xq&#41;&#47;45&#44;X mosaicism &#40;14&#46;3&#37;&#41;&#46; Other less frequent karyotypes found in the sample were mosaicisms such as 46&#44;XX&#40;r&#41;&#47;45&#44;X&#59; 47&#44;XXX&#47;45&#44;X&#47;46&#44;XX&#59; 45&#44;X&#47;46&#44;X&#44;der&#40;X&#41; and 45&#44;X&#47;47&#44;XXX&#59; 46&#44;X&#44;i&#47;45&#44;X&#47;46&#44;XX&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">When it came to phenotypic expression&#44; we found that the classical presentation &#40;short stature&#44; pterygium colli&#44; cubitus valgus&#44; widely spaced nipples&#44; etc&#46;&#41; was the most frequent phenotype &#40;50&#37;&#41;&#59; while six patients did not have characteristic features &#40;27&#46;3&#37;&#41; and received the diagnosis when they underwent evaluation of short stature&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The mean age at initiation of rhGH therapy was 7&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;13 years &#40;range&#44; 1&#46;82&#8211;16&#46;45 years&#41; with a mean height SDS of &#8722;2&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;63&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The mean initial dose of rhGH used for treatment was 0&#46;048<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;01<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day and the mean duration of treatment was 7&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;88 years&#46; At the time of treatment completion&#44; patients had a mean age of 14&#46;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;69 years and had reached a mean final adult height of 156&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;66<span class="elsevierStyleHsp" style=""></span>cm &#40;&#8722;1&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;62 SDS&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">At 12 months of treatment with rhGH&#44; there was an increased HV of 8&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;22<span class="elsevierStyleHsp" style=""></span>cm&#47;year &#40;2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;55 SDS&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; At this time&#44; the predicted adult height for the patients had increased by 4&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;14<span class="elsevierStyleHsp" style=""></span>cm &#40;144&#46;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;99 vs 149&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;92<span class="elsevierStyleHsp" style=""></span>cm&#41; and 0&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;06 SDS &#40;&#8722;2&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;21 vs &#8722;2&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;91 SDS&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; At two years of treatment&#44; the mean predicted adult height increased to 150&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;17<span class="elsevierStyleHsp" style=""></span>cm&#44; with a slight decrease in HV to 6&#46;73<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;63<span class="elsevierStyleHsp" style=""></span>cm&#47;year&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">As for laboratory parameters&#44; there was a progressive increase in the levels of IGF1 and IGFBP3 until the end of treatment&#44; with levels reaching up to three times their baseline values&#44; but always remaining within normal ranges &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">The mean final height gain compared to baseline height at initiation of treatment was of 42&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;23<span class="elsevierStyleHsp" style=""></span>cm &#40;total gain of 1&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;76 SDS&#41;&#46; When it came to the baseline predicted adult height&#44; height gain in patients exceeded it by a mean of 9&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;39<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;51 SDS&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">After 12 months of treatment&#44; patients had improvements in height &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;011&#41;&#44; HV &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004&#41; and IGF1 levels &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;043&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; and we also observed an improvement in the adult heights achieved &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;028&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Our assessment of the short-term response to treatment based on increases in HV showed that in 66&#46;6&#37; of the patients&#44; HV increased by more than 3<span class="elsevierStyleHsp" style=""></span>cm&#47;year at 12 months of treatment compared to baseline&#46; Furthermore&#44; we found a positive correlation between response to treatment and the dose of rhGH &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>037&#59; <span class="elsevierStyleItalic">&#946;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#46;95&#41;&#44; and response to treatment and increased levels of IGF1 and IGFBP3 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>000&#59; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span> &#91;IGF1&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;846&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span> &#91;IGFBP3&#93;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;809&#41;&#46; When we analysed height gain relative to the interval between initiation of treatment with rhGH and initiation of oestrogen therapy&#44; we found a positive correlation for auxological parameters such as height and HV both in cm and SDS at four months and one year of treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The mean difference in final height between patients treated with rhGH and patients not treated with it was 10&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;63<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;031&#59; 156&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;66<span class="elsevierStyleHsp" style=""></span>cm vs 145&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;69<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Furthermore&#44; we computed linear regression curves using the predictors for a favourable response identified in previous steps&#44; but since the sample size was small&#44; the results we obtained do not seem to be generalisable&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">We did not find any differences in response to treatment based on karyotype &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;147&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Short stature is the key feature of Turner syndrome and may occur in the absence of other clinical manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> Linear growth deceleration starts in infancy and early childhood&#44; and becomes more marked in late childhood and adolescence&#44; resulting in a significantly short stature in adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a> The indication of rhGH therapy to increase HV and adult height in patients with Turner syndrome is accepted and supported by various studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> There is evidence that this treatment results in increases of five to ten centimetres in the final adult height&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;5</span></a> Treatment should be initiated when the patient&#39;s height is two SDS below the population mean or when HV is below the tenth percentile for the patient&#39;s bone age&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;8</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Several studies such as the one carried out by the Canadian Growth Hormone Advisory Committee<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">9&#44;10</span></a> and a few conducted in Spain have demonstrated the importance of rhGH treatment in these patients&#44; as they have found increases in HV of 4&#46;1&#8211;8&#46;15<span class="elsevierStyleHsp" style=""></span>cm at 12 months of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">11&#8211;13</span></a> There is great variability in the increases in HV reported in the literature&#44; as they range from &#8722;1&#46;69 to 1&#46;97 SDS&#46; The increase is greatest in the first year of treatment&#44; and less significant in subsequent year&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> In our study&#44; at 12 months of treatment we found an increased HV of 8&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;22<span class="elsevierStyleHsp" style=""></span>cm&#47;year &#40;2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;55 SDS&#41; with a difference compared to baseline of 3&#46;22<span class="elsevierStyleHsp" style=""></span>cm&#44; which corresponds to a good initial increase in HV compared to what has been reported in previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In addition&#44; research in recent years has attempted to both assess response to treatment and determine the factors that promote a good response&#46; Thus&#44; for the purpose of assessing response to treatment in the short term&#44; Quigley et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a> noted the increase in HV by &#8764;2<span class="elsevierStyleHsp" style=""></span>cm a year&#46; In our study&#44; we assessed response to treatment with rhGH applying a threshold of 3<span class="elsevierStyleHsp" style=""></span>cm a year for the increase in HV at 12 months of treatment&#44; which was exceeded by 66&#46;6&#37; of the patients under study&#46; Other authors<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> highlight a mean increase in height SDS in the first year of treatment of &#43;0&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03 SDS&#46; In the short term&#44; these parameters function as predictors of a long-term favourable response to treatment&#44; although this remains controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a> In the study that we present here&#44; we observed that when it came to the longitudinal changes in the main auxological parameters&#44; the largest changes in height&#44; HV and predicted adult height took place in the first year &#40;4&#8211;12 months from initiation&#41;&#44; followed by lesser increases and an eventual plateau&#44; except in HV&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">As to the findings concerning long-term response to treatment&#44; Radetti et al&#46; found increases in final height of up to 9&#46;2<span class="elsevierStyleHsp" style=""></span>cm&#44; corroborated by more recent studies showing increases in final height of &#8764;7<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">18</span></a> and of more than 1 SDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">19&#44;20</span></a> Our findings were similar&#44; with a mean increase in final height compared to baseline height of 9&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;39<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;51 SDS&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">There is disagreement regarding the association between the dosage of rhGH and the improvement in clinical outcomes due to increased levels of growth factors&#59; some authors have found such an association&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;20&#8211;22</span></a> while others&#44; including Garc&#237;a et al&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">23</span></a> or Wetterau et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">24</span></a> believe that it has no impact on the final response to treatment&#46; In our study&#44; we found a positive correlation with the increase of growth factor levels &#40;IGF1 and IGFBP3&#41; at one year of treatment&#44; which is strongly associated with the administered dose of rhGH and better clinical outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">14&#44;25</span></a> Furthermore&#44; studies conducted in recent years have attempted to identify the genes involved in the early response of these patients to rhGH&#46; Some have identified polymorphisms in the <span class="elsevierStyleItalic">CDK4</span> gene that may have an impact on IGF1 levels and therefore on the response to treatment with rhGH&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a> Ranke et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;25&#44;27</span></a> found positive correlations with the administered dose &#40;greater than 0&#46;27<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41;&#44; frequency &#40;more days per week&#41; and age at initiation &#40;some authors assert that adult height can reach the normal range if treatment is initiated between 2 and 4 years of age<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">6&#44;19</span></a>&#41;&#44; with no consensus on the subject&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The duration of treatment with rhGH also seems to influence the final height gain&#46; Chernausek et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">19&#44;22&#44;27</span></a> described this time interval as an important predictor of final height&#44; and even produced an equation to estimate the approximate height gain&#58; height gain &#40;in cm<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;1&#215; years of rhGH treatment prior to oestrogen initiation&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The timing of initiation of oestrogen therapy continues to be debated&#59; some authors<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">27&#8211;29</span></a> have found greater height gains with initiation of oestrogen therapy at age 14 years&#59; other studies suggest that low doses of oestrogen administered at earlier ages may lead to an increase of 0&#46;37 SDS in adult height compared to patients in whom initiation of oestrogen therapy is delayed&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a> In our opinion&#44; the timing of oestrogen initiation should be decided in agreement with the patient and the family&#44; taking into account not only auxological parameters such as height or bone age&#44; but also bone mineral density and the wishes expressed by the patient in relation to treatment initiation and pubertal development&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Another controversial aspect is the use of anabolic steroids such as oxandrolone&#44; as it seems to increase final height when combined with rhGH&#46; Gault et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a> found a mean increase in final height of &#43;4&#46;6<span class="elsevierStyleHsp" style=""></span>cm &#40;range&#44; 1&#46;9&#8211;7&#46;2<span class="elsevierStyleHsp" style=""></span>cm&#41; in a group treated with oxandrolone compared to a group treated with placebo&#46; However&#44; their study did not find a statistically significant positive additive effect for the combination of oxandrolone and late pubertal induction&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our comparison of patients treated with rhGH and patients not treated with rhGH was consistent with the findings of Paschino et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">30</span></a> and Rosenfeld et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">31</span></a> with a mean difference in height between both groups of 10&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;63<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;031&#41;&#44; which evinces the importance of early treatment in these patients&#46; Ranke et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">18</span></a> studied the possibility of patients with specific karyotypes responding better to treatment with rhGH&#44; but we found no differences based on karyotype&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Based on the results of our study&#44; we determined that the predictors for a long-term favourable response are&#44; from most important to least&#58; &#40;A&#41; dose of rhGH at treatment initiation&#44; &#40;B&#41; duration of treatment with rhGH prior to initiation of oestrogen therapy&#44; &#40;C&#41; increased levels of IGF1 and IGFBP3 during the first year of treatment and &#40;D&#41; HV in the first year of treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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          "titulo" => "Introduction"
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    "fechaAceptado" => "2016-02-24"
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          "clase" => "keyword"
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            0 => "Turner syndrome"
            1 => "Short stature"
            2 => "Growth hormone"
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          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "S&#237;ndrome de Turner"
            1 => "Talla baja"
            2 => "Hormona de crecimiento"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study was performed on 25 girls with Turner syndrome &#40;17 treated with growth hormone&#41;&#44; followed-up until adult height&#46; Auxological&#44; analytical&#44; genetic and pharmacological parameters were collected&#46; A descriptive and analytical study was conducted to evaluate short &#40;12 months&#41; and long term response to treatment with growth hormone&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66&#46;6&#37; of cases &#40;height-gain velocity &#62;3<span class="elsevierStyleHsp" style=""></span>cm&#47;year&#41;&#46; A favourable long-term treatment response was also observed in terms of adult height&#44; which increased by 42&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;23<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;76 SDS&#41;&#44; with an adult height gain of 9&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;39<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;51 SDS&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Predictors of good response to growth hormone treatment are&#58; &#40;A&#41; initial growth hormone dose&#44; &#40;B&#41; time on growth hormone treatment until starting oestrogen therapy&#44; &#40;C&#41; increased IGF1 and IGFBP-3 levels in the first year of treatment&#44; and &#40;D&#41; height gain velocity in the first year of treatment&#46;</p></span>"
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            "titulo" => "Objective"
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            "identificador" => "abst0010"
            "titulo" => "Material and methods"
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            "titulo" => "Results"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n de par&#225;metros cl&#237;nicos y anal&#237;ticos que act&#250;en como predictivos de respuesta al tratamiento con hormona de crecimiento &#40;rhGH&#41; a largo plazo en pacientes con s&#237;ndrome de Turner&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 25 ni&#241;as diagnosticadas de s&#237;ndrome de Turner&#44; de las cuales 17 recibieron tratamiento con rhGH y fueron controladas hasta alcanzar la talla adulta&#46; Se determinaron diferentes variables auxol&#243;gicas&#44; anal&#237;ticas&#44; gen&#233;ticas y farmacol&#243;gicas a lo largo de su seguimiento en dichas consultas&#46; Se realiz&#243; un estudio descriptivo y anal&#237;tico mediante regresi&#243;n lineal&#44; con valoraci&#243;n de la respuesta al tratamiento a corto &#40;12 meses&#41; y a largo plazo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; una respuesta favorable a corto plazo valorada en ganancia de velocidad de crecimiento en el 66&#44;6&#37; de los casos &#40;velocidad de crecimiento<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm&#47;a&#241;o a los 12 meses de tratamiento respecto a la previa&#41;&#46; Tambi&#233;n se evidenci&#243; una respuesta favorable a largo plazo&#44; valorada en una ganancia de talla total de 42&#44;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#44;23<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#44;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;76 SDS&#41;&#46; Las pacientes ganaron una media de 9&#44;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;39<span class="elsevierStyleHsp" style=""></span>cm &#40;1&#44;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;51 SDS&#41; respecto a su pron&#243;stico de crecimiento previo al tratamiento&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El presente estudio evidencia como factores predictivos de buena respuesta al tratamiento con rhGH a largo plazo en orden de importancia&#58; A&#41; dosis de rhGH al inicio del tratamiento&#44; B&#41; tiempo de tratamiento con rhGH hasta inicio de terapia estrog&#233;nica&#44; C&#41; incremento en los niveles de IGF1 e IGFBP-3 durante el primer a&#241;o de tratamiento y D&#41; velocidad de crecimiento en el primer a&#241;o de tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; S&#225;nchez Marco SB&#44; de Arriba Mu&#241;oz A&#44; Ferrer Lozano M&#44; Labarta Aizp&#250;n JI&#44; Garagorri Otero JM&#46; Hormona de crecimiento y s&#237;ndrome de Turner&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;86&#58;81&#8211;86&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Longitudinal changes in mean IGF1 levels &#40;ng&#47;mL&#41;&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">Initiation of treatment&nbsp;\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">2 years of treatment&nbsp;\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">Adult age&nbsp;\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">Total gain&nbsp;\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">Height &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">113&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">124&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">156&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;23&nbsp;\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 SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;62&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">150&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;39&nbsp;\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&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;81&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;004&nbsp;\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&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722; 2&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;037&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&#46;52&nbsp;\t\t\t\t\t\t\n
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:31 [
            0 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nelson tratado de pediatr&#237;a"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;M&#46; Kliegman"
                            1 => "B&#46;F&#46; Stanton"
                            2 => "J&#46;W&#46; St&#46; Geme"
                            3 => "N&#46;F&#46; Schor"
                            4 => "R&#46;E&#46; Behrman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:6 [
                        "edicion" => "19&#46;&#170; edici&#243;n"
                        "fecha" => "2012"
                        "paginaInicial" => "2024"
                        "paginaFinal" => "2027"
                        "editorial" => "Elsevier"
                        "editorialLocalizacion" => "Barcelona"
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "2"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "S&#237;ndrome de turner"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;C&#46; Barreda Bonis"
                            1 => "I&#46; Gonzalez Casado"
                            2 => "R&#46; Gracia Bouthelier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2016.02.004

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Year/Month	Html	Pdf	Total

2024 November	6	14	20
2024 October	69	40	109
2024 September	73	34	107
2024 August	80	60	140
2024 July	61	34	95
2024 June	58	36	94
2024 May	62	39	101
2024 April	58	42	100
2024 March	51	31	82
2024 February	41	34	75
2024 January	47	30	77
2023 December	50	18	68
2023 November	41	29	70
2023 October	51	40	91
2023 September	30	29	59
2023 August	62	25	87
2023 July	54	34	88
2023 June	83	32	115
2023 May	65	30	95
2023 April	68	23	91
2023 March	56	31	87
2023 February	55	13	68
2023 January	51	31	82
2022 December	91	44	135
2022 November	93	67	160
2022 October	107	94	201
2022 September	108	43	151
2022 August	110	50	160
2022 July	86	50	136
2022 June	62	40	102
2022 May	68	44	112
2022 April	59	78	137
2022 March	99	70	169
2022 February	72	36	108
2022 January	78	37	115
2021 December	66	46	112
2021 November	75	52	127
2021 October	110	97	207
2021 September	61	43	104
2021 August	67	45	112
2021 July	51	40	91
2021 June	63	39	102
2021 May	68	42	110
2021 April	154	24	178
2021 March	90	80	170
2021 February	52	24	76
2021 January	97	31	128
2020 December	54	27	81
2020 November	65	32	97
2020 October	50	22	72
2020 September	67	39	106
2020 August	59	35	94
2020 July	64	55	119
2020 June	53	22	75
2020 May	70	28	98
2020 April	51	20	71
2020 March	61	29	90
2020 February	47	20	67
2020 January	67	25	92
2019 December	76	23	99
2019 November	89	26	115
2019 October	98	24	122
2019 September	48	18	66
2019 August	92	32	124
2019 July	60	29	89
2019 June	51	36	87
2019 May	81	34	115
2019 April	91	32	123
2019 March	43	24	67
2019 February	57	17	74
2019 January	59	31	90
2018 December	70	30	100
2018 November	116	42	158
2018 October	179	24	203
2018 September	88	19	107
2018 August	4	0	4
2018 July	1	0	1
2018 June	5	0	5
2018 May	5	0	5
2018 April	30	0	30
2018 March	27	0	27
2018 February	22	0	22
2018 January	36	0	36
2017 December	31	0	31
2017 November	20	0	20
2017 October	15	0	15
2017 September	36	0	36
2017 August	28	0	28
2017 July	25	3	28
2017 June	55	13	68
2017 May	57	18	75
2017 April	99	90	189
2017 March	24	8	32
2017 February	35	23	58
2017 January	6	7	13

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