Original Article
The relationship between metabolic disorders and small for gestational age with idiopathic premature adrenarche
Estudio de la asociación de adrenarquia prematura idiopática con la presencia de alteraciones metabólicas y con antecedente de pequeño para edad gestacional
Francisco Javier Mejorado Molanoa, Laura Andrés Zallob, Marta Fornos Rodríguezb, Pilar Pérez Seguraa,c, Teresa Gavela Péreza,c,d, María Luisa Sanz Calvoe, Leandro Soriano Guilléna,c,d,
Corresponding author
a Servicio de Pediatría, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
b Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
c Unidad de Endocrinología Infantil, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
d Laboratorio de Lípidos, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
e Centro de Salud Palma Norte, Madrid, Spain
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Díaz, Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centro de Salud Palma Norte, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio de la asociación de adrenarquia prematura idiopática con la presencia de alteraciones metabólicas y con antecedente de pequeño para edad gestacional" ] ] "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" => 1510 "Ancho" => 1519 "Tamanyo" => 96375 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparison of normal weight, overweight and obesity in girls with IPA versus girls of similar age in the 2013 nationwide ALADINO study.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Premature adrenarche is defined as the development of pubic and/or axillary hair and/or adult-like apocrine odour before age 8 years in girls and 9 years in boys. Idiopathic premature adrenarche (IPA) is diagnosed after ruling out other causes of excessive androgen production, such as adrenocortical or gonadal sex hormone secreting tumours, late-onset congenital adrenal hyperplasia or exogenous sources of androgens.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> Therefore, IPA is a diagnosis of exclusion.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The exact prevalence of IPA in the general population is unknown,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a> but it is a fairly frequent reason for medical visits, with a female-to-male ratio of approximately 9:1.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">To date, studies have analysed potential associations of IPA with a history of small for gestational age (SGA) or the presence of obesity and various metabolic disorders.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> A physiological hypothesis that attempts to explain the association between SGA and IPA proposes that malnutrition in the prenatal period may trigger a series of epigenetic changes that would alter the function of the adrenal gland after birth. To this, we need to add the potential impact of the rapidity of catch-up weight and height gain in the postnatal period.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">2,5</span></a> This hypothesis has been evaluated in studies conducted in cohorts of Catalonian girls with metabolic disorders, a history of SGA and androgen excess in childhood.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6–9</span></a> Other studies have reported elevated serum levels of dehydroandrosterone sulfate (DHEA-S) during childhood and adolescence in girls with a history of SGA.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> However, there is no conclusive evidence that a history of SGA may directly predispose to the development of IPA. This may be due to the existing studies having been conducted in different populations, with different sample sizes and different criteria for the definition of SGA.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">2,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The potential association between metabolic disorders, blood pressure and IPA has not been studied thoroughly. Idiopathic premature adrenarche results from an excess of adrenal androgen precursors, mainly DHEA-S. Some studies have found an association between the development of insulin resistance with elevated levels of DHEA-S.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> In fact, the presence of insulin resistance is a consistent finding in studies of girls with IPA, but there is some controversy in regards to the association of IPA with dyslipidaemia and high blood pressure (BP).<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">There is also a degree of disagreement on the relationship that may exist in cases of obesity concurrent with IPA. For instance, on one hand, some studies have found an association between obesity and high serum or urine levels of DHEA-S. Furthermore, it seems that obesity and overweight are more prevalent in the IPA population compared with the general population. On the other hand, there are also studies that did not find evidence of these associations.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1,2,10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Some authors believe that polycystic ovary syndrome (PCOS) may originate during pregnancy but manifest starting in adolescence.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">2,12</span></a> Consistent with this hypothesis, 45% of a cohort of Catalonian girls with IPA and a history of SGA progressed to PCOS at a later age.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Considering the disparity in the evidence on the association between IPA with a history of SGA and metabolic disorders, we thought it would be relevant to analyse a sample of girls that met the diagnostic criteria for IPA. Thus, we hypothesised that girls with IPA would be more likely to have a history of SGA compared to the general population, and also be at higher risk of overweight or obesity and metabolic disorders. To evaluate this hypothesis, we set the following objectives: a) to analyse the association between IPA and a positive history of SGA; b) to assess the prevalence of overweight and obesity in girls with IPA; c) to determine the prevalence of high blood pressure and of changes in lipid and carbohydrate metabolism in girls with IPA.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0040" class="elsevierStylePara elsevierViewall">Cross-sectional descriptive study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Setting</span><p id="par0045" class="elsevierStylePara elsevierViewall">Paediatrics Department of the Hospital Universitario Fundación Jiménez Díaz.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Sample size calculation</span><p id="par0050" class="elsevierStylePara elsevierViewall">Considering that the prevalence of SGA in the general population is estimated at 3%–5%,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> obtaining a difference in prevalence of at least 10% between the general population and girls with IPA required the inclusion of at least 53 girls with diagnostic criteria for IPA in the study cohort, for an <span class="elsevierStyleItalic">α</span> level of 0.05 and a power <span class="elsevierStyleItalic">β</span> of 80%.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Inclusion criteria</span><p id="par0055" class="elsevierStylePara elsevierViewall">Girl without underlying disease and not undergoing chronic treatment that met the diagnostic criteria for IPA:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Development of pubic and/or axillary hair and/or adult-like apocrine odour before age 8 years.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Absence of the larche.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Normal ACTH levels (to rule out the presence of late-onset congenital adrenal hyperplasia).</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Absence of ovarian or adrenal tumour (normal abdominal and pelvic ultrasound, androgen levels within normal ranges).</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data collection</span><p id="par0080" class="elsevierStylePara elsevierViewall">We reviewed the medical records of patients managed in the Department of Paediatrics of the Hospital Universitario Fundación Jiménez Díaz between January 2007 and May 2015 with a diagnosis of suspected IPA, without introducing, modifying or removing any data in the IT system and not entering into direct contact with patients to gather information. The project was approved by the Clinical Research Ethics Committee of the Hospital Universitario Fundación Jiménez Díaz.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Variables for which data were collected</span><p id="par0085" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Family history</span>: height of both parents (cm), maternal age of menarche (years), family history of PCOS, family history of hyperandrogenism (considered positive if either a “history of hyperandrogenism” or a “history of female relatives with excessive body hair with a typically male distribution” was documented) and history of fertility problems in female relatives (considered positive if “sterility,” “infertility” or difficulties getting pregnant were documented).</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Personal history</span>: ethnicity, country of birth, pregnancy, gestational age (weeks), type of delivery (spontaneous vaginal, caesarean or instrumental delivery), birth weight (in grams), birth length (in cm). We calculated the <span class="elsevierStyleItalic">z</span>-scores for the birth weight and length using reference tables for the Spanish population<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Demographic data, anthropometric characteristics and BP at diagnosis</span>: chronological age (decimal age), age of onset of IPA (decimal age), height (cm), weight (kg), body mass index (BMI), BP (mm Hg), pubertal stage (based on the Tanner scale), bone age (assessed by the Greulichand Pyle method). We calculated the weight and height <span class="elsevierStyleItalic">z</span>-scores based on reference tables for the Spanish population.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> We also calculated the BP <span class="elsevierStyleItalic">z</span>-score using tables developed by an expert panel as reference.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Blood chemistry variables (after 12<span class="elsevierStyleHsp" style=""></span>h of fasting at the time of diagnosis)</span>: glucose (mg/dL), fasting insulin (μIU/mL), HbA1C (%), total cholesterol (mg/dL), LDL cholesterol (mg/dL), HDL cholesterol (mg/dL), triglycerides (mg/dL), transaminases (IU/L), androstenedione (ng/ml), testosterone (ng/mL) and DHEA-S (μg/dl), baseline and 30- and 60-min peak 17-OH-progesterone levels after stimulation with 250μg ACTH (ng/mL).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Criteria for SGA</span>: birth length and/or weight at least 2 SDs below the mean (<span class="elsevierStyleItalic">z</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic"><</span><span class="elsevierStyleHsp" style=""></span>−2).<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a></p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Criteria for overweight and obesity</span>:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">•</span><p id="par0120" class="elsevierStylePara elsevierViewall">Criteria set by the Spanish Ministry of Health in 2006 using BMI tables from the 1988 Spanish study<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a>: a) normal weight: BMI between 3rd and 90th percentiles; b) overweight: BMI between 90th and 97th percentiles; c) obesity: BMI above the 97th percentile.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">•</span><p id="par0125" class="elsevierStylePara elsevierViewall">Cole et al. criteria from 2000<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> and WHO criteria from 2007 modified according to BMI tables from a Spanish cross-sectional study published in 2008<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a>: a) normal weight: BMI between 3rd and 85thpercentiles; b) overweight: BMI between 85th and 95th percentiles; c) obesity: BMI above the 95th percentile.</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Criteria for alteration of lipid metabolism</span>: we calculated <span class="elsevierStyleItalic">z</span>-scores for total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides based on the reference tables.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a> Thus, we defined hypertryglyceridaemia as trigyceride levels above the 95th percentile, and low HDL cholesterol as levels of it below the 5th percentile.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Criteria for insulin resistance</span>: we calculated the HOMA index using the formula [(glucose (mmol/L)<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>baseline insulin (μIU/L)]/22.5. We defined insulin resistance as a baseline insulin of less than 15<span class="elsevierStyleHsp" style=""></span>μIU/mL and/or a HOMA index of less than 3.5.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">21</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Criteria for high blood pressure</span>: we defined high BP as a systolic BP (SBP) and/or diastolic BP (DBP) above the 95th percentile for age, sex and height.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a></p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0145" class="elsevierStylePara elsevierViewall">We used SPSS version 19.0 to build a database with the data obtained for all the variables. We then performed a descriptive analysis of quantitative variables, calculating the mean and expressing the results with their 95% confidence intervals. Subsequently, we used the Kolmogorov–Smirnov test to verify that the variables were normally distributed. For variables that were not normally distributed but whose histogram had a shape that was very similar to a Gaussian bell, we decided to use the mean and confidence intervals obtained in the descriptive analysis. However, for variables that did not follow a normal distribution and whose histogram revealed a clearly asymmetrical distribution, we thought it would be more appropriate to use the median and interquartile range. For qualitative variables, we performed a descriptive analysis to calculate the prevalence.</p><p id="par0150" class="elsevierStylePara elsevierViewall">We performed a bivariate analysis by means of the Student <span class="elsevierStyleItalic">t</span> test, dividing the sample into two groups for comparison: patients with normal weight, and patients with excess weight, with the latter including both overweight (BMI between the 90th and 97th percentiles) and obesity (BMI<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>97th percentile) based on Spanish reference tables.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> In addition, we compared the prevalence of overweight and obesity obtained in our study with the results reported in the most recent round of the ALADINO study, conducted in 2013.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0155" class="elsevierStylePara elsevierViewall">Of the total of 80 girls that sought care for premature adrenarche, 3 had results in the ACTH test that suggested the presence of congenital adrenal hyperplasia, and were therefore excluded from the study. Later on, this diagnosis was confirmed by genetic testing, which revealed changes in the 21-hydroxylase gene known to cause late-onset congenital adrenal hyperplasia. Another girl was also excluded because she had manifestations suggestive of premature adrenarche, but the data in her records was insufficient to establish a definitive diagnosis of IPA.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Thus, the final sample comprised a total of 76 girls. Of all of them, 74 had been born in Spain, 1 in Brazil and 1 in Bulgaria. As for ethnicity, 69 (90.7%) were Caucasian, while 5 were of Latin American, 1 of African and 1 of Indian descent. The median chronological age of the sample was 7.59 years (7.31–7.87).</p><p id="par0165" class="elsevierStylePara elsevierViewall">The mean maternal height was 162.94<span class="elsevierStyleHsp" style=""></span>cm (161.51–164.36) with a mean <span class="elsevierStyleItalic">z</span>-score of 0.29 (0.05–0.54); the mean paternal height was 175.85<span class="elsevierStyleHsp" style=""></span>cm (173.99–177.70) with a mean <span class="elsevierStyleItalic">z</span>-score of 0.15 (−0.16 to 0.45); the mean predicted genetic height was 163.04<span class="elsevierStyleHsp" style=""></span>cm (161.67–164.41) with a mean <span class="elsevierStyleItalic">z</span>-score of 0.28 (0.04–0.52).</p><p id="par0170" class="elsevierStylePara elsevierViewall">As for the maternal age at menarche, the mean was 12.2 years (11.86–12.54). There was a family history of PCOS in 27.3% of the patients, of hyperandrogenism in 37.5%, and of fertility problems in 16.7%.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Only 2 girls had a history of SGA, which amounted to a prevalence of 2.7% (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0180" class="elsevierStylePara elsevierViewall">None of the girls met the criteria for high blood pressure. We found insulin resistance in 21.2%. Of the patients in who a lipid profile had been performed, 13.95% met the criteria for hypertryglyceridaemia and/or HDL cholesterol below the 5th percentile (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">We found statistically significant differences in triglycerides, triglyceride <span class="elsevierStyleItalic">z</span>-scores, HDL cholesterol, HDL cholesterol <span class="elsevierStyleItalic">z</span>-score, the HOMA index and insulin in the group of girls with excess weight (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">Applying the BMI categories established by the modified 2000 Cole/2007 WHO criteria, we found a prevalence of 11.8% for overweight and of 11.8% for obesity, that is, a prevalence of excess weight of 23.6%. When we applied the BMI categories of the Spanish Ministry of Health,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> we found a prevalence of overweight of 6.6% and a prevalence of obesity of 18.4% (excess weight, 25%) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0195" class="elsevierStylePara elsevierViewall">The prevalence of SGA in the study sample did not exceed the prevalence reported for the general population, estimated at 3%–5%.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> When we reviewed the literature, we found inconsistent data regarding the association of IPA with SGA. Thus, a retrospective study that compared girls with premature pubarche (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>102) with girls who served as controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>83) found statistically significant differences in birth weight between the groups.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> The hypothesis that the authors proposed to explain this difference was that low birth weight could increase the risk of premature pubarche and other complications in the future. The same group of researchers designed a cohort composed of newborns meeting the criteria for SGA, defined as a birth weight <span class="elsevierStyleItalic">z</span>-score of less than −2, to analyse its causal relationship with the development of premature adrenarche and metabolic disorders.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> Along the same lines, an Australian study published in 2005<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a> that defined SGA as a birth weight and/or a ponderal index below the 10th percentile based on reference charts<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a> found a history of SGA in 35% of girls with IPA. Conversely, 3 studies (one conducted in France, one in Scotland and one in Finland) did not find a greater prevalence of SGA in girls with IPA compared to controls.<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">26–28</span></a> The discrepancies that exist between studies may be due to the application of different criteria to define IPA and SGA, as well as differences in sample size and the population under study.</p><p id="par0200" class="elsevierStylePara elsevierViewall">In the study presented here, we analysed the prevalence of overweight and obesity applying different criteria: on one hand, a combination of the criteria set by the WHO in 2007 and the criteria proposed by Cole et al. in 2000,<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> using as reference the BMI tables developed in a recent cross-sectional study conducted in Spain,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a> with the purpose of having results based on international criteria; on the other hand, the criteria set by the Spanish Ministry of Health, which allowed us to compare our results to those of the most recent study of the prevalence of overweight and obesity in Spain: the ALADINO study.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> When we pooled the data for girls with overweight and girls with obesity, we found a prevalence of excess weight of 23.6% applying the modified 2007 WHO/2000 Cole criteria and of 25% applying the criteria of the Spanish Ministry of Health. The prevalence found in our study did not exceed the prevalence reported in a nationwide study as large as the ALADINO study, in which the combined prevalence of overweight and obesity reached 40.4%. In addition, the prevalence of obesity in our sample based on the criteria of the Ministry of Health (18.4%) was slightly greater than the prevalence of obesity in the ALADINO study (15.5%). The Australian study we cited above also assessed the prevalence of excess weight in girls with premature pubarche. The authors of that study used a BMI above the 85th percentile to define overweight and a BMI above the 97th percentile to define obesity based on their reference tables.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a> Applying these criteria, they found overweight in 33.7% of the sample and obesity in 31.4%, that is, 65.1% of the girls had excess weight. These percentages were greater than those observed in the Australian general population. On the other hand, a study conducted in the Finnish population defined excess weight as a BMI above the 75th percentile. With this criterion, the authors found a significantly higher prevalence of excess weight in girls with IPA compared to controls.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a> The heterogeneity of the criteria used to define IPA, overweight and obesity may influence the lack of consistency in the results reported in the literature.</p><p id="par0205" class="elsevierStylePara elsevierViewall">At the time of the study, patients overall did not present with changes in BP, 14% had an abnormal lipid profile and 21.1% met the criteria for insulin resistance. Utriainen et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a> analysed the prevalence of metabolic syndrome, assessed by means of the definition of the ATP III and the WHO 1998 criteria. They found that metabolic syndrome was more common in patients with IPA compared to controls, a difference that was statistically significant, and that the most significant factors associated with metabolic syndrome were excess weight and hyperinsulinism. Similarly, a study of Catalonian girls with a history of SGA, elevated levels of DHEA-S and low levels of SHBG (which, according to the authors’ hypothesis, are associated with IPA) found statistically significant differences in the ratio of the percentage of abdominal visceral fat to subcutaneous fat, hyperinsulinaemia and levels of IGF-1compared to the control group.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">9</span></a> Another study by the same research group<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a> found an association between a history of SGA and rapid weight gain between birth and age 2 years, which would predispose to and explain the greater percentage of visceral fat and prevalence of insulin resistance between ages 2 and 4 years. The main hypothesis of the authors is that the higher frequency of hyperinsulinaemia, hyperandrogenism and excess adiposity in girls with premature pubarche is associated with low birth weight.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> In our sample, the comparison of patients of IPA with normal weight and those with overweight and obesity showed significant differences in the levels of triglycerides, HDL cholesterol and baseline insulin and the HOMA index. This suggests that excess weight in girls with IPA is associated with changes in cardiovascular risk factors. However, determining whether these changes in cardiovascular risk factors are caused directly by IPA or result from excess weight would require further prospective studies with larger samples.</p><p id="par0210" class="elsevierStylePara elsevierViewall">The main limitation of this study is the lack of a control group with which to make comparisons. Other limitations include not having performed an assessment of body composition and not having measured the levels of peptides associated with the pathophysiology of obesity.</p><p id="par0215" class="elsevierStylePara elsevierViewall">We can conclude that in our study, girls with IPA are not more likely to have a history of SGA than the general population. On the other hand, the prevalence of overweight and obesity in girls with IPA is not greater than that in Spanish girls of similar age overall. Last of all, the changes we found in the lipid profile and carbohydrate metabolism of girls with IPA were significantly more prevalent in those that had overweight or obesity. In short, we think that it would be useful to contribute to the design of new multicentre studies with a larger number of patients from different regions in Spain and the establishment of homogeneous criteria for the definition of IPA, SGA and excess weight with the purpose of continuing to evaluate these potential associations.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0220" 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" => "xres932709" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec907138" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres932708" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec907139" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Setting" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Sample size calculation" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Inclusion criteria" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Data collection" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Variables for which data were collected" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-07" "fechaAceptado" => "2016-10-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec907138" "palabras" => array:3 [ 0 => "Idiopathic premature adrenarche" 1 => "Overweight" 2 => "Obesity and small for gestational age" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec907139" "palabras" => array:3 [ 0 => "Adrenarquia prematura idiopática" 1 => "Sobrepeso" 2 => "Obesidad y pequeño para edad gestacional" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the <span class="elsevierStyleItalic">Fundación Jiménez Díaz</span> (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Hasta la fecha hay datos contradictorios sobre la relación entre adrenarquia prematura idiopática (API) y el antecedente de pequeño para edad gestacional así como con la presencia de obesidad y otras alteraciones metabólicas. Es nuestra intención estudiar esa posible asociación en una cohorte de niñas con API de nuestro hospital.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio descriptivo transversal que incluyó a niñas diagnosticadas de API en el servicio de Pediatría de la Fundación Jiménez Díaz entre enero de 2007 y mayo de 2015. Se recogieron datos sobre antecedentes familiares, antecedentes personales que incluían datos perinatales así como datos antropométricos y datos bioquímicos al diagnóstico.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Del total de 76 niñas con API, un 2,7% presentaba antecedente de pequeño para edad gestacional. Utilizando la clasificación del índice de masa corporal según criterios modificados de OMS 2007/Cole 2000, un 11,8% tenían sobrepeso y un 11,8% obesidad al diagnóstico. Según los criterios del Ministerio de Sanidad, un 6,6% presentaban sobrepeso y un 18,4% obesidad. Un 21,2% evidenciaron insulinorresistencia y un 13,95% presentaban dislipidemia. Ninguna de las pacientes cumplía criterios de hipertensión arterial. En el análisis comparativo entre niñas con API que presentaban normopeso frente a las que tenían sobrepeso y obesidad, las segundas presentaban niveles significativamente más elevados de triglicéridos e insulina y más bajos de colesterol HDL.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Las niñas con API estudiadas no presentan mayor porcentaje de pequeño para edad gestacional que la población general. La prevalencia de sobrepeso y obesidad entre las niñas con API no es superior a la de la población de su entorno.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Mejorado Molano FJ, Andrés Zallo L, Fornos Rodríguez M, Pérez Segura P, Gavela Pérez T, Sanz Calvo ML, et al. Estudio de la asociación de adrenarquia prematura idiopática con la presencia de alteraciones metabólicas y con antecedente de pequeño para edad gestacional. An Pediatr (Barc). 2017;87:253–259.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1510 "Ancho" => 1519 "Tamanyo" => 96375 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparison of normal weight, overweight and obesity in girls with IPA versus girls of similar age in the 2013 nationwide ALADINO study.</p>" ] ] 1 => 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:3 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">CI, confidence interval; IPA, idiopathic premature adrenarche.</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">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean (95% CI)</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">Gestational age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">39.2 (38.86–39.53)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Birth weight (g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">3100 (630)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Birth weight <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">0.01 (−0.26 to 0.28)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Birth length (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">49.74 (49.23–50.24)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Birth length <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">0.21 (−0.08 to 0.50)</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Prevalence</td><td class="td" title="table-entry " align="left" valign="top">Type of delivery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Frequency \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">Spontaneous vaginal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46/76 \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">Caesarean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20/76 \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">Instrumental \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10/76 \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">Small for gestational age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/76 (2.72%) \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></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1576323.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Data expressed as median and interquartile range.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Perinatal characteristics of patients with IPA.</p>" ] ] 2 => 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:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">BA, bone age; BMI, body mass index; CA, chronological age; CH, carbohydrate; CI, confidence interval; DBP, diastolic blood pressure; IR, insulin resistance; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides.</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 " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Media (IC 95%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Decimal age (year)</td><td class="td" title="table-entry " align="left" valign="top">7.59 (7.32–7.87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Waist circumference (cm)</td><td class="td" title="table-entry " align="char" valign="top">77.8 (72.48–83.12) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Height (cm)</td><td class="td" title="table-entry " align="left" valign="top">131.83 (129.74–133.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Waist circumference <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="char" valign="top">2.19 (1.46–2.92) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Height <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="left" valign="top">1.65 (1.45–1.85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">SBP (mm Hg)</td><td class="td" title="table-entry " align="char" valign="top">100.35 (97.28–103.42) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Weight (kg)</td><td class="td" title="table-entry " align="left" valign="top">32.24 (30.43–34.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">SBP <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="char" valign="top">0.13 (−0.15 to 0.41) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Weight <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="left" valign="top">1.51 (1.20–1.82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">DBP (mm Hg)</td><td class="td" title="table-entry " align="char" valign="top">59.21 (57.19–61.23) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>)</td><td class="td" title="table-entry " align="left" valign="top">18.33 (17.67–18.99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">DBP <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="char" valign="top">0.08 (−0.11 to 0.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">BMI <span class="elsevierStyleItalic">z</span>-score</td><td class="td" title="table-entry " align="left" valign="top">0.54 (0.29–0.78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">BA (decimal age)</td><td class="td" title="table-entry " align="char" valign="top">8.56 (8.21–8.92) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Alkaline phosphatase (IU/L)</td><td class="td" title="table-entry " align="left" valign="top">285 (243.54–326.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">BA-CA</td><td class="td" title="table-entry " align="char" valign="top">0.96 (0.78–1.15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Baseline 17-OH-progesterone (ng/mL)</td><td class="td" title="table-entry " align="left" valign="top">0.79 (0.67–0.91) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Androstenedione (ng/mL)</td><td class="td" title="table-entry " align="char" valign="top">0.53 (0.44)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Peak 17-OH-progesterone (ng/mL)</td><td class="td" title="table-entry " align="left" valign="top">2.60 (2.52)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">DHEA-S (μg/dL)</td><td class="td" title="table-entry " align="char" valign="top">78.25 (66.81–89.69) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Testosterone (ng/mL)</td><td class="td" title="table-entry " align="left" valign="top">0.12 (0.10)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="9" align="left" valign="top">Lipid metabolism</td><td class="td" title="table-entry " align="left" valign="top">CT (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164.14 (154.74–173.54) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">CH metabolism</td><td class="td" title="table-entry " align="left" valign="top">Glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.58 (74.89–78.27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TC <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.48 (−0.78 to−0.18) \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 insulin (μIU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.22 (9.52–12.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HDL (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.8 (48.37–55.23) \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">Glycated haemoglobin (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.22 (5.11–5.33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HDL <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.65 (−0.92 to−0.39) \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">HOMA index \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.13 (1.78–2.48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LDL (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99.87 (90.87–108.86) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">IR</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Frequency (%)</td><td class="td" title="table-entry " align="left" valign="top">LDL <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.14 (−0.46 to −0.18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">21.2</td><td class="td" title="table-entry " align="left" valign="top">TG (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61.77 (55.37–68.16) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">ALAT (GPT) (IU/L)</td><td class="td" title="table-entry " align="left" valign="top">21.53 (19.23–23.83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TG<span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 (0.3–0.75) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">ASAT (GOT) (IU/L)</td><td class="td" title="table-entry " align="left" valign="top">29 (8)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \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="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1576321.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Median and interquartile range.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Anthropometric and blood chemistry values at the time of diagnosis.</p>" ] ] 3 => 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="spar0075" class="elsevierStyleSimplePara elsevierViewall">DBP, diastolic blood pressures; IPA, idiopathic premature adrenarche; NS, differences not statistically significant; SBP, systolic blood pressure.</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Statistically significant variables with <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05 are presented in italics.</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">Independent variable \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">Girls with normal weight<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>57 \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">Girls with overweight or obesity<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>19 \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">Statistical significance \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">Birth weight <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.06 (−0.36 to0.24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 (−0.43 to 0.86) \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">Chronological age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.55 (7.21–7.89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.74 (7.28–8.19) \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.43 (7.98–8.87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.97 (8.46–9.47) \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 (0.67–1.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.20 (0.8–1.6) \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">Total cholesterol (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">167.42 (157.5–177.35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">159.12 (139.46–178.78) \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">Total cholesterol <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.44 (−0.76 to−0.12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.55 (−1.16 to 0.07) \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">Triglycerides (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">55.81 (49.60–62.01)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">70.88 (58.10–83.66)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">Triglycerides <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">0.33 (0.10–0.56)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">0.82 (0.38–1.27)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">LDL cholesterol (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100.43 (91.62–109.24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99.06 (79.55–118.58) \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">LDL <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.16 (−0.47 to 0.14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.11 (−0.82 to 0.59) \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">HDL cholesterol (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">55.35 (50.52–60.17)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">47 (42.79–51.20)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">Z-score HDL <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">−0.42</span> (−<span class="elsevierStyleItalic">0.8 to</span> −<span class="elsevierStyleItalic">0.04)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">−0.96</span> (−<span class="elsevierStyleItalic">1.31 to</span>−<span class="elsevierStyleItalic">0.62)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">Hb1Ac (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.17 (5.02–5.32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.31 (5.16–5.46) \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">HOMA index \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">1.74 (1.39–2.09)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">2.93 (2.23–3.63)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">Glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75.77 (73.66–77.88) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.33 (75.43–81.24) \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">Insulin (μIU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">9.25 (7.57–10.93)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleItalic">15.28 (11.94–18.60)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.<span class="elsevierStyleItalic">05</span> \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">SBP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100.85 (97.11–104.59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99 (93.28–104.72) \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">SBP <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.21 (−0.13–0.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.09 (−0.61–0.43) \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">DBP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59.09 (56.62–61.57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59.53 (55.83–63.23) \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">DBP <span class="elsevierStyleItalic">z</span>-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 (−0.13–0.33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 (−0.31–0.37) \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 => "xTab1576322.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comparative analysis of girls with IPA and normal weight versus girls with IPA with overweight or obesity.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature adrenarche: etiology, clinical findings, and consequences" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. 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| Year/Month | Html | Total | |
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| 2024 November | 5 | 11 | 16 |
| 2024 October | 50 | 41 | 91 |
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| 2024 May | 45 | 32 | 77 |
| 2024 April | 62 | 35 | 97 |
| 2024 March | 55 | 22 | 77 |
| 2024 February | 39 | 24 | 63 |
| 2024 January | 30 | 16 | 46 |
| 2023 December | 35 | 23 | 58 |
| 2023 November | 45 | 30 | 75 |
| 2023 October | 32 | 20 | 52 |
| 2023 September | 41 | 22 | 63 |
| 2023 August | 38 | 17 | 55 |
| 2023 July | 37 | 24 | 61 |
| 2023 June | 48 | 28 | 76 |
| 2023 May | 49 | 20 | 69 |
| 2023 April | 50 | 13 | 63 |
| 2023 March | 83 | 20 | 103 |
| 2023 February | 54 | 17 | 71 |
| 2023 January | 28 | 30 | 58 |
| 2022 December | 75 | 37 | 112 |
| 2022 November | 81 | 37 | 118 |
| 2022 October | 94 | 39 | 133 |
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| 2021 December | 34 | 46 | 80 |
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| 2021 October | 53 | 60 | 113 |
| 2021 September | 56 | 41 | 97 |
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| 2021 July | 35 | 29 | 64 |
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| 2021 May | 45 | 44 | 89 |
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| 2021 March | 53 | 33 | 86 |
| 2021 February | 28 | 15 | 43 |
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| 2020 December | 19 | 17 | 36 |
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| 2020 September | 49 | 20 | 69 |
| 2020 August | 27 | 10 | 37 |
| 2020 July | 31 | 32 | 63 |
| 2020 June | 38 | 22 | 60 |
| 2020 May | 33 | 18 | 51 |
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| 2020 March | 37 | 15 | 52 |
| 2020 February | 57 | 20 | 77 |
| 2020 January | 20 | 17 | 37 |
| 2019 December | 37 | 15 | 52 |
| 2019 November | 24 | 8 | 32 |
| 2019 October | 23 | 14 | 37 |
| 2019 September | 25 | 14 | 39 |
| 2019 August | 33 | 24 | 57 |
| 2019 July | 22 | 18 | 40 |
| 2019 June | 46 | 28 | 74 |
| 2019 May | 65 | 26 | 91 |
| 2019 April | 67 | 29 | 96 |
| 2019 March | 30 | 12 | 42 |
| 2019 February | 32 | 26 | 58 |
| 2019 January | 36 | 27 | 63 |
| 2018 December | 38 | 25 | 63 |
| 2018 November | 97 | 38 | 135 |
| 2018 October | 159 | 28 | 187 |
| 2018 September | 97 | 24 | 121 |
| 2018 August | 16 | 0 | 16 |
| 2018 July | 19 | 0 | 19 |
| 2018 June | 8 | 0 | 8 |
| 2018 May | 72 | 0 | 72 |
| 2018 April | 18 | 0 | 18 |
| 2018 March | 14 | 0 | 14 |
| 2018 February | 3 | 0 | 3 |
| 2018 January | 17 | 0 | 17 |
| 2017 December | 16 | 0 | 16 |
| 2017 October | 0 | 10 | 10 |
Show all
