Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency

Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency Aristeidis Giannakopoulos, Eleni Kallimani, Alexandra Efthymiadou, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4265731/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The aim of this study is to correlate the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after one year of treatment with growth hormone to the initial clinical and biochemical parameters. It also aims to study the secretory dynamics of GH by analyzing the profiles of GH stimulation tests in relation to the recombinant GH (rhGH) treatment response. Methods This a retrospective study which included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GHmax, GH secretion rate (GHSR) and GH secretion volume (GHSV) were analyzed in relation to the response to rhGH treatment as defined by the index of responsiveness (IoR). Correlation and regression models were used to identify the best clinical and biochemical predictors to rhGH treatment. Results IoR was correlated negatively with the age (r=-0.607, p < 0.01) and positively with the distance of child’s height from its MPH r = 0.466 (p < 0.01) and pretreatment growth velocity (r = 0.247, p < 0.05). GH secretory indexes correlated together, with the highest association being observed between GHmax and GHSV (r = 0.883, p < 0.01). Regarding the GH secretory indexes, GHmax was the best predictor of IoR (β coef. = -0.514, p < 0.001) followed by the GHSV (β coef. = -0.47, p < 0.001) and GHSR (β coef. = -0.367 p < 0.001). Conclusions The age and the distance of child’s height from its MPH are major predictors of rhGH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to rhGH than GHmax. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment. Growth hormone deficiency Index of Responsiveness GH stimulation test GH secretory indexes What is known Idiopathic GH deficiency is not an easy diagnosis to establish because no single test has increased specificity and sensitivity for GH deficiency. Prediction to treatment response with recombinant GH (rhGH) depends on multiple factors as well as the validity of the initial diagnosis. The age and the distance of child’s height from its mid-parental height are major predictors of rhGH treatment response in children with idiopathic GH deficiency. What is new The calculation of the GH secretory indexes, GH secretion rate and GH secretion volume are not better predictors of response to rhGH than GHmax currently used in pediatric practice. The combination of clinical and biochemical indexes (GHmax * Height dist. SDS) improve the pre-treatment estimation of response to rhGH treatment. Introduction In current clinical practice, the diagnosis of growth hormone (GH) deficiency in short stature is based on an integrated approach that assesses family history, auxological parameters of growth, baseline biochemical indices like IGF-I and the secretion of GH with dynamic tests [1]. Although the above diagnostic process has been standardized over the years with the help of consensus statements, diagnostic pitfalls are possible due to conditions such as constitutional delay of growth and puberty that phenotypically and biochemically overlaps with GH deficiency [2]. Many pediatric endocrinology centers use the GH stimulation tests as a key step in the diagnostic procedure of short stature. GH peaks after stimulation with a pharmacological agent that does not surpass a certain cut-off value, are considered indicative of a GH deficient state. However, several issues complicate the interpretation of GH test results. First, different stimulation agents generate different GH responses that poorly correlate with each other [3, 4]. Second, the GH peak is changing with advancing age [5] and is different between the prepubertal and pubertal children because of the effect that steroids have on GH secretion [6]. Third, obesity negatively effects GH secretion and is a confounding factor in the interpretation of GH stimulatory tests [7, 8]. After initiation of GH therapy, there is a high individual variability in height gain, suggesting variable responsiveness to rhGH treatment. While most subjects display an expected growth trajectory, some of them respond less well while others respond better than expected [9, 10]. Furthermore, a proportion of patients do not even reach an adult height within their MPH range after many years of GH treatment, questioning the diagnosis. Apart from its main target to improve the final height, treatment with rhGH should also be safe and cost-effective [11]. In monitoring the rhGH treatment effect, the deviation of the actual versus the expected course of height has been adequately described by growth prediction models (GPMs). GPMs, based on the auxological features and rhGH treatment doses, can predict the growth response of an individual. Over the last 3 decades, many GPMs for children with short stature, treated with rhGH have been developed [12, 13]. One of latest published, is the individualized growth response optimization (iGRO) model, which was based on the pharmaco-epidemiological survey KIGS (Pfizer® International Growth Database) that had 83,803 children/277,264 patient years who received rhGH therapy (mainly Genotropin™) [14]. This cloud-based model was developed to help physicians access the response to GH treatment and therefore to optimally manage their patients. It calculates an individual child’s level of responsiveness to rhGH treatment, termed the Index of Responsiveness (IoR). The IoR is the difference between observed (obs) and predicted (preTd) height velocity (HV) divided by the SD of the predicted HV during the first treatment year ([obsHV − predHV]/SD predHV). When using the SDS values of IoR, a positive value of the IoR SDS indicates a better growth response and a negative value indicates a reduced growth response in comparison to the reference cohort’s growth response contained in the database [15]. The aim of this study is to correlate the index of responsiveness (IoR) after one year of treatment in prepubertal children with GH deficiency to the basal anthropometric and laboratory values before and after treatment. It also aims to study the secretion dynamics of GH by analyzing the profiles of GH stimulation tests with clonidine in relation to the rhGH treatment response. Patients and Methods This is a retrospective cross-sectional and longitudinal study. The participants were 84 prepubertal children with short stature that after evaluation based on the current guidelines[1] were diagnosed with idiopathic GH deficiency. They received treatment with rhGH with a dose of 0.22 mg/week, as allowed by the Greek National Committee. Subjects with organic GH deficiency, combined pituitary deficiency, chronic disease or with a syndrome were excluded from the study. In addition, children who required priming with sex steroids before the clonidine test according to guidelines, or those who presented their GHmax value at t=0 since it was considered that the pharmaceutical agent acted on or shortly after the endogenous GH pulse, were also excluded from the study. Body height and weight were measured using standard anthropometric techniques. Height as the average of two measurements with a calibrated Harpenden stadiometer, was recorded to the nearest millimeter. Weight was measured on a calibrated scale (Seca, model 760) and recorded to the nearest 100 gr. MPH was calculated as (mothers’ height + fathers’ height ± 13 cm) ÷ 2. BMI was calculated using the formula weight/height ^ 2 (kg/m 2 ). BMI standard deviation score (SDS) was computed for each subject using the formula: BMI-SDS = (actual BMI-mean BMI for age, race and gender)/BMI SD for age and gender. SDS values for the heights, and BMI were calculated using the LMS data Centers for Disease Control and Prevention 2000 growth charts [16]. The study was approved by the local Ethics Committee of the University Hospital of Patras. Written informed consent from participants and their parents was obtained. All participants’ data were uploaded to the web-based platform of iGRO, and the output from the growth prediction model was the Index of Responsiveness (IoR) and IoR SDS at the end of 1 year after initiation of rhGH treatment [15]. The dynamics of stimulated GH secretion were characterized by the three following indices: The maximum value of GH (GHmax) of blood samples at 30’, 60’, 90’or 120’, obtained during the clonidine test. The GH secretion rate (GHSR) = \(\frac{{\text{G}\text{H}}_{\text{m}\text{a}\text{x} }-{ \text{G}\text{H}}_{(\text{t}=0)}}{{\text{T}\text{i}\text{m}\text{e}}_{\left(\text{G}\text{H}\text{m}\text{a}\text{x}\right)}}\) which is the variable derived by dividing the GH maximum value with the time class value. The latter was divided in the following 4 classes (1st class: GH peak at 30’, 2nd class: GH peak at 60’, 3rd class: GH peak at 90’, 4th class: GH peak at 120’). The GH secretion volume (GHSV) = Area under the Curve [GH=f(t 0-120 )] where AOC is calculated by the sum of all trapezoids formed by the function of GH values in the time points 30’,60’,90’or 120’ of the clonidine test. The above calculations were performed only on the GH stimulation profiles after the administration of clonidine as GH secretagogue. The cutoff for a “normal” GH peak was considered the 10 μg/L. All children with a subnormal GHmax value at two subsequent GH stimulation tests (clonidine 150 μg/m 2 and L-Dopa 10mg/kg) were subjected to magnetic resonance imaging of the hypothalamic/pituitary region. The diagnosis of idiopathic GH deficiency was proven only after the whole evaluation with a normal MRI scan was concluded. The IGF-I assay was performed with the IDS-Isys system (Immunodiagnostic Systems), in an automated procedure based on ELISA with detection by chemiluminescence. Serum IGF-I concentrations were interpreted by comparison with the reference intervals set up specifically for this iSYS device [17]. The intra-assay coefficient of variation for IGF-I was 3.1%. IGF-I levels are shown as standard deviation scores (SDS) due to their variability according to sex and age. The SDS conversion was performed using previously published LMS charts [17, 18]. Fasting blood samples were collected and after centrifugation, all samples were kept frozen at -7 C o until assayed. Statistical analysis Data were expressed as mean ± SD. Correlations between datasets were performed using the Pearson correlation coefficient. Classical tests of significance among the groups were done using ANOVA. Regression was performed using robust standard errors (to control for heteroskedasticity) and standardized beta coefficients after excluding in the same model independent variables with multicollinearity. A p value of < 0.05 was considered significant. Statistical analysis was performed by using Stata ver. 16. Results The anthropometric clinical parameters and IGF-I SDS levels of the eighty-four children (47 males and 37 females) with a mean age of 6.6 years are presented in Table 1. The correlations among the IoR and the other clinical and biochemical variables are shown in Table 2. IoR correlated significantly with age with a negative coefficient (r=-0.607, p<0.01). It was also significantly correlated to the height distance of the child from its mid-parental height (Height dist. SDS) with r=0.466 (p<0.01). In addition, pretreatment growth velocity (r=0.247, p<0.05) as well as posttreatment growth velocity (r=0.410, p<0.01) were significantly correlated to IoR. On the contrary, IoR was not correlated either to pre rhGH treatment IGF-I levels, nor to post treatment IGF-I SDS (Table 2). GH secretory indexes tightly correlated together, with the highest association being observed between GH max and GHSV (r=0.883, p<0.01), and followed by GH max and GHSR (r=0.558, p<0.01). GHSV was also significantly linked to GHSR, although with a lower strength, (r=0.403, p<0.001). GH max, GHSR and GHSV showed no significant association with pre or post rhGH treatment IGF-I SDS values (Table 3). To estimate the value of each GH secretory index in the prediction of IoR, we run three separate regression models (IoR model A, B and C) each for one for GH max, GHSR and GHSV including in each model all other common clinical and biochemical factors (Table 4). This was preformed to avoid the co-analysis of GHmax, GHSR and GHSV as variables with inherent collinearity in the same regression model. In all three models, the age, and the height distance from the mid-parental height (Height dist. SDS) were the best predictors of IoR one year after initiation of treatment with rhGH (Table 4). They were followed by the pre-treatment height SDS and BMI SDS. Pre-treatment growth velocity and IGF-I SDS levels did not have any statistical significance in predicting the IoR. Regarding the GH secretory indexes, it was observed that GH max was the best predictor of IoR (β coef. = -0.514, p<0.001) followed by the GHSV (β coef. = -0.47, p<0.001) and GHSR (β coef. = -0.367 p<0.001). Based on the observations that the best IoR predictors were the height dist. SDS and GH max after stimulation, we arbitrarily combined them by generating a new index calculated as follows: GHmax * Height dist. SDS. After using the new index into the same regression model, we found that GHmax * Height dist. SDS increased the predictability of GHmax considerably (β coef. =-0.68 p<0.001), meaning that this combined clinic-biochemical index may account for 68% of the variability of IoR (Table 5). Discussion In this study, we aimed to investigate the clinical and biochemical predictors of response to rhGH treatment in a very well characterized cohort of children with the diagnosis of short stature due to idiopathic GH deficiency. Treatment response was generated by the validated growth model prediction tool (iGRO). Our analysis showed a significant negative association between IoR and age at diagnosis, and a positive relation with the distance between the height of the child and its mid-parental height. As it is also expected, pre- and post-treatment growth velocity correlate very well with IoR. Age has been previously reported to be a basic predictor of rhGH treatment response [19]. The significant correlation of IoR to the distance in SD between the height of the child and its mid-parental height is observed in all regression models in our study and has been confirmed to be a principal predictor of growth response in other studies [14, 15]. Pretreatment height SDS is also associated well to the IoR. Interestingly, we found that, although IGF-I serum levels have a basic role in the diagnostic algorithm of short stature [1, 20], pretreatment as well as posttreatment IGF-I SDS did not show any statistical correlation to the IoR. Next, we investigated the potential of increasing the GH treatment response predictability of GH stimulation tests that we usually perform in current practice. It is known that the reproducibility of a GH stimulation test is low due to the temporal random action of the pharmacologic agent in relation to the spontaneous GH pulse that can be followed by a state of refractoriness [21]. Moreover, different pharmacological agents generate different mean GH peaks, with clonidine generating a higher GH response than arginine, insulin, or glucagon tests [22, 23], while puberty and obesity have their own effect on the pituitary GH secretion [6, 24]. We chose to include only prepubertal children to avoid the strong effect of sex steroids on GH levels after stimulation [24]. The calculated GHSR parameter aimed to incorporate into our evaluation the speed of pituitary gland response, which is how quickly can increase the GH levels after pharmacologic stimulation. GHSV index provides an indication of the somatotroph pituitary capacity. Above GH secretion values cannot be estimated by the GH max value of the stimulation test. For the reasons described above, we chose to calculate GHSR and GHSV only from the GH profiles generated by stimulation of clonidine. The potent stimulation of clonidine could accentuate any existing differences in GHSR and GHSV indices. Both GHSR and GHSV showed a good correlation to IoR. Although an earlier study had shown that GH peak at 45 min was associated with a better response to treatment [25], our results did not support that GHSR contributed additively to the diagnostic ability of the single GHmax value. We reached the same conclusion for the GHSV index, showing that the total GH secreted does not contribute to increased predictability of growth response to rhGH treatment. In addition, both GHSR and GHSV did not significantly correlate to pretreatment IGF-I SDS. Based on our results we combined the best predictor capabilities from clinics and laboratory by creating the variable of GHmax * Height dist. SDS derived from the arbitrary multiplication of GHmax and Height dist. SDS. In the application of the same regression model, the potential for prediction to rhGH response increased to 68.2 % of IoR variability compared to 51.2% of GHmax. In conclusion, we found that age and the distance of child’s height from its MPH are major predictors of rhGH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to rhGH than GHmax. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment. Declarations Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Aristeidis Giannakopoulos, Eleni Kallimani, Alexandra Efthymiadou and Dionisios Chrysis. . The first draft of the manuscript was written by Aristeidis Giannakopoulos and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics Approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Hospital of Patras (Date 16/2/2022 /No 262). Consent to participate Informed consent was obtained from the parents of all individual participants included in the study. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. 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SD 84 1.703 0.842 .21 4.05 PreT BMI (kg/m 2 ) 84 16.277 1.843 13.4 21 PreT BMI SDS 84 .128 0.993 -1.93 2.58 MPH (cm) 84 166.94 8.233 150.5 185.5 MPH SDS 84 − .6 0.838 -2.48 2.2 PreT IGF-I (µg/L) 84 66.145 47.793 5 284 PreT IGF-I SDS 84 -1.862 1.085 -4.21 1.72 PostT IGF-I (µg/L) 84 191.264 98.782 57 675 PostT IGF-I SDS 84 .321 1.944 -2.02 3.87 Table 2 Correlations among IoR and other clinico-biochemical pre and post rhGH treatment indices in children with idiopathic GH deficiency. Variables (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (1) IoR 1.000 (2) Age (years) -0.607*** 1.000 (3) PreT Height SDS 0.069 0.169 1.000 (4) PostT Height SDS 0.151 -0.073 0.159 1.000 (5) BMI SDS 0.202 -0.065 0.024 0.082 1.000 (6) PreT IGF-I SDS -0.074 0.008 -0.174 0.102 -0.091 1.000 (7) PostT IGF-I SDS 0.205 -0.183 -0.126 0.029 0.165 0.224** 1.000 (8) PreT Growth vel. (cm/y) 0.247** -0.433*** 0.111 0.112 0.086 0.071 0.142 1.000 (9) PostT Growth vel. (cm/y) 0.410*** -0.320*** -0.002 0.182 0.186 -0.156 0.131 0.096 1.000 (10) Height dist. SDS 0.466*** -0.317*** -0.273** -0.056 -0.191 0.049 0.177 0.016 0.165 1.000 *** p < 0.01, ** p < 0.05 referred to r coefficients Table 3 Correlation among the Growth Hormone Stimulation Dynamic Indices GH max , GHSR and GHSV and pre post rhGH treatment IGF-I SDS. Variables (1) (2) (3) (4) (5) (1) GH max 1.000 (2) GHSR 0.558*** 1.000 (3) GHSV 0.883*** 0.403*** 1.000 (4) PreT IGF-I SDS 0.065 -0.124 0.061 1.000 (5) PostT IGF-I SDS 0.048 -0.128 0.087 0.224** 1.000 *** p < 0.01, ** p < 0.05 Table 4 Regression models A, B and C of IoR for the Growth Hormone Stimulation Dynamic Indexes GH max , GHSR and GHSV, respectively. IoR model A CI (95%) IoR model B CI (95%) IoR model C CI (95%) (GH max ) (GHSR) (GHSV) Age -0.615 *** [-0.412, -0.246] -0.576 *** [-0.406, -0.225] -0.634 *** [-0.436, -0.243] Sex (male) 0.080 [-0.159, 0.571] 0.158 [-0.0737, 0.887] 0.067 [-0.239, 0.582] Height SDS 0.261 *** [0.444, 1.066] 0.331 *** [0.591, 1.293] 0.275 *** [0.425, 1.162] BMI SDS 0.175 *** [0.0954, 0.352] 0.145 * [0.0231, 0.341] 0.168 ** [0.0715, 0.356] IGF-I SDS 0.057 [-0.0381, 0.173] 0.044 [-0.118, 0.217] 0.039 [-0.0906, 0.183] PreT Growth vel. (cm/y) -0.020 [-0.161, 0.115] -0.053 [-0.209, 0.0855] 0.001 [-0.154, 0.156] Height dist. SD 0.354 *** [0.318, 0.774] 0.416 *** [0.390, 0.870] 0.426 *** [0.401, 0.915] GH max -0.514 *** [-0.348, -0.215] GHSR -0.367 *** [-0.538, -0.227] GHSV -0.470 *** [-0.126, -0.0628] N 84 84 84 Standardized beta coefficients; 95% confidence intervals in brackets * p < 0.05, ** p < 0.01, *** p < 0.001 Table 5 Regression model for the IoR incorporating the combined clinico-biochemical index [GHmax * Height Dist. SDS]. IoR model D CI (95%) ( GH max * Height Dist. SDS ) Age -0.581 *** [-0.407, -0.215] Sex (male) 0.116 [-0.123, 0.723] Height SDS 0.320 *** [0.552, 1.294] BMI SDS 0.194 *** [0.113, 0.381] PreT IGF-I SDS 0.084 [-0.0376, 0.234] PreT Growth vel. (cm/y) -0.013 [-0.174, 0.143] Height dist. SDS 0.916 *** [1.008, 1.818] GH max * Height Dist. SDS -0.682 *** [-0.183 -0.09] N 84 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4265731","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":293905665,"identity":"8133b632-a75d-47e9-a478-f72e3a7b5568","order_by":0,"name":"Aristeidis Giannakopoulos","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYJCCA0BswE+6FskGKItoYGBwgFgt/LOPXzzwc4edsfGN3IOfP+6xs2fgX/sArxaJczkFB3vPJJuZ3chLljjwLDmxQeK5AX5rzvAkHOBtY7Yxu5FjIHHgAHMCg8Qx/DrkgVoO/m2rtzGekWP848CBenuCWgzOsB84zNt22MxAIscMaMthxgb+NvxaDM/wMByWbTtuLHHmXZrFmQPHE9sk2PBrkTvD/vjj27Zqw/723MM3Kg5U2/PzE3AYAwMPLHx4IBSbRAIhLewPULUw8B8gpGUUjIJRMApGGAAA3z9L41d0HTgAAAAASUVORK5CYII=","orcid":"","institution":"University of Patras","correspondingAuthor":true,"prefix":"","firstName":"Aristeidis","middleName":"","lastName":"Giannakopoulos","suffix":""},{"id":293905666,"identity":"1009d0e1-88bf-4a8b-8419-c86c3340a991","order_by":1,"name":"Eleni Kallimani","email":"","orcid":"","institution":"University of Patras","correspondingAuthor":false,"prefix":"","firstName":"Eleni","middleName":"","lastName":"Kallimani","suffix":""},{"id":293905667,"identity":"3da5beb1-7e91-4ea1-8031-0c4edb4b0130","order_by":2,"name":"Alexandra Efthymiadou","email":"","orcid":"","institution":"University of Patras","correspondingAuthor":false,"prefix":"","firstName":"Alexandra","middleName":"","lastName":"Efthymiadou","suffix":""},{"id":293905669,"identity":"4d78f83c-f6de-4cce-a73b-16619da49f10","order_by":3,"name":"Dionisios Chrysis","email":"","orcid":"","institution":"University of Patras","correspondingAuthor":false,"prefix":"","firstName":"Dionisios","middleName":"","lastName":"Chrysis","suffix":""}],"badges":[],"createdAt":"2024-04-14 16:32:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4265731/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4265731/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55580307,"identity":"7d914b48-e98a-4ff6-b5ad-baf075404484","added_by":"auto","created_at":"2024-04-30 07:34:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":592993,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4265731/v1/94fdbfca-7649-47d8-a844-ce9621e96410.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency","fulltext":[{"header":"What is known","content":"\u003cul\u003e\n\u003cli\u003eIdiopathic GH deficiency is not an easy diagnosis to establish because no single test has increased specificity and sensitivity for GH deficiency.\u003c/li\u003e\n\u003cli\u003ePrediction to treatment response with recombinant GH (rhGH) depends on multiple factors as well as the validity of the initial diagnosis.\u003c/li\u003e\n\u003cli\u003eThe age and the distance of child\u0026rsquo;s height from its mid-parental height are major predictors of rhGH treatment response in children with idiopathic GH deficiency.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eThe calculation of the GH secretory indexes, GH secretion rate and GH secretion volume are not better predictors of response to rhGH than GHmax currently used in pediatric practice.\u003c/li\u003e\n\u003cli\u003eThe combination of clinical and biochemical indexes (GHmax * Height dist. SDS) improve the pre-treatment estimation of response to rhGH treatment.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn current clinical practice, the diagnosis of growth hormone (GH) deficiency in short stature is based on an integrated approach that assesses family history, auxological parameters of growth, baseline biochemical indices like IGF-I and the secretion of GH with dynamic tests [1]. Although the above diagnostic process has been standardized over the years with the help of consensus statements, diagnostic pitfalls are possible due to conditions such as constitutional delay of growth and puberty that phenotypically and biochemically overlaps with GH deficiency [2].\u003c/p\u003e\n\u003cp\u003eMany pediatric endocrinology centers use the GH stimulation tests as a key step in the diagnostic procedure of short stature. GH peaks after stimulation with a pharmacological agent that does not surpass a certain cut-off value, are considered indicative of a GH deficient state. However, several issues complicate the interpretation of GH test results. First, different stimulation agents generate different GH responses that poorly correlate with each other [3, 4]. Second, the GH peak is changing with advancing age [5] and is different between the prepubertal and pubertal children because of the effect that steroids have on GH secretion [6]. Third, obesity negatively effects GH secretion and is a confounding factor in the interpretation of GH stimulatory tests [7, 8].\u003c/p\u003e\n\u003cp\u003eAfter initiation of GH therapy, there is a high individual variability in height gain, suggesting variable responsiveness to rhGH treatment. While most subjects display an expected growth trajectory, some of them respond less well while others respond better than expected [9, 10]. Furthermore, a proportion of patients do not even reach an adult height within their MPH range after many years of GH treatment, questioning the diagnosis. Apart from its main target to improve the final height, treatment with rhGH should also be safe and cost-effective [11].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn monitoring the rhGH treatment effect, the deviation of the actual versus the expected course of height has been adequately described by growth prediction models (GPMs). GPMs, based on the auxological features and rhGH treatment doses, can predict the growth response of an individual. Over the last 3 decades, many GPMs for children with short stature, treated with rhGH have been developed [12, 13]. One of latest published, is the individualized growth response optimization (iGRO) model, which was based on the pharmaco-epidemiological survey KIGS (Pfizer\u0026reg; International Growth Database) that had 83,803 children/277,264 patient years who received rhGH therapy (mainly Genotropin\u0026trade;) [14]. This cloud-based model was developed to help physicians access the response to GH treatment and therefore to optimally manage their patients. It calculates an individual child\u0026rsquo;s level of responsiveness to rhGH treatment, termed the Index of Responsiveness (IoR). The IoR is the difference between observed (obs) and predicted (preTd) height velocity (HV) divided by the SD of the predicted HV during the first treatment year ([obsHV\u0026thinsp;\u0026minus;\u0026thinsp;predHV]/SD predHV). When using the SDS values of IoR, a positive value of the IoR SDS indicates a better growth response and a negative value indicates a reduced growth response in comparison to the reference cohort\u0026rsquo;s growth response contained in the database [15].\u003c/p\u003e\n\u003cp\u003eThe aim of this study is to correlate the index of responsiveness (IoR) after one year of treatment in prepubertal children with GH deficiency to the basal anthropometric and laboratory values before and after treatment. It also aims to study the secretion dynamics of GH by analyzing the profiles of GH stimulation tests with clonidine in relation to the rhGH treatment response.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eThis is a retrospective cross-sectional and longitudinal study. The participants were 84 prepubertal children with short stature that after evaluation based on the current guidelines[1] were diagnosed with idiopathic GH deficiency. They received treatment with rhGH with a dose of 0.22 mg/week, as allowed by the Greek National Committee. Subjects with organic GH deficiency, combined pituitary deficiency, chronic disease or with a syndrome were excluded from the study. In addition, children who required priming with sex steroids before the clonidine test according to guidelines, or those who presented their GHmax value at t=0 since it was considered that the pharmaceutical agent acted on or shortly after the endogenous GH pulse, were also excluded from the study. Body height and weight were measured using standard anthropometric techniques. Height as the average of two measurements with a calibrated Harpenden stadiometer, was recorded to the nearest millimeter. Weight was measured on a calibrated scale (Seca, model 760) and recorded to the nearest 100 gr. MPH was calculated as (mothers\u0026rsquo; height\u0026thinsp;+\u0026thinsp;fathers\u0026rsquo; height\u0026thinsp;\u0026plusmn;\u0026thinsp;13 cm) \u0026divide;\u0026thinsp;2. BMI was calculated using the formula weight/height ^ 2 (kg/m\u003csup\u003e2\u003c/sup\u003e). BMI standard deviation score (SDS) was computed for each subject using the formula: BMI-SDS = (actual BMI-mean BMI for age, race and gender)/BMI SD for age and gender. SDS values for the heights, and BMI were calculated using the LMS data Centers for Disease Control and Prevention 2000 growth charts [16]. The study was approved by the local Ethics Committee of the University Hospital of Patras. Written informed consent from participants and their parents was obtained. \u0026nbsp;All participants\u0026rsquo; data were uploaded to the web-based platform of iGRO, and the output from the growth prediction model was the Index of Responsiveness (IoR) and IoR SDS at the end of 1 year after initiation of rhGH treatment [15]. The dynamics of stimulated GH secretion were characterized by the three following indices:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003eThe maximum value of GH (GHmax) of blood samples at 30\u0026rsquo;, 60\u0026rsquo;, 90\u0026rsquo;or 120\u0026rsquo;, obtained during the clonidine test.\u003c/li\u003e\n\u003cli\u003eThe GH secretion rate (GHSR) =\u0026nbsp;\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{{\\text{G}\\text{H}}_{\\text{m}\\text{a}\\text{x} }-{ \\text{G}\\text{H}}_{(\\text{t}=0)}}{{\\text{T}\\text{i}\\text{m}\\text{e}}_{\\left(\\text{G}\\text{H}\\text{m}\\text{a}\\text{x}\\right)}}\\)\u003c/span\u003e\u003c/span\u003e\u0026nbsp;which is the variable derived by dividing the GH maximum value with the time class value. The latter was divided in the following 4 classes (1st class: GH peak at 30\u0026rsquo;, 2nd class: GH peak at 60\u0026rsquo;, 3rd class: GH peak at 90\u0026rsquo;, 4th class: GH peak at 120\u0026rsquo;).\u003c/li\u003e\n\u003cli\u003eThe GH secretion volume (GHSV) = Area under the Curve [GH=f(t\u003csub\u003e0-120\u003c/sub\u003e)] where AOC is calculated by the sum of all trapezoids formed by the function of GH values in the time points 30\u0026rsquo;,60\u0026rsquo;,90\u0026rsquo;or 120\u0026rsquo; of the clonidine test.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe above calculations were performed only on the GH stimulation profiles after the administration of clonidine as GH secretagogue. The cutoff for a \u0026ldquo;normal\u0026rdquo; GH peak was considered the 10 \u0026mu;g/L. All children with a subnormal GHmax value at two subsequent GH stimulation tests (clonidine 150 \u0026mu;g/m\u003csup\u003e2\u003c/sup\u003e and L-Dopa 10mg/kg) were subjected to magnetic resonance imaging of the hypothalamic/pituitary region. The diagnosis of idiopathic GH deficiency was proven only after the whole evaluation with a normal MRI scan was concluded.\u003c/p\u003e\n\u003cp\u003eThe IGF-I assay was performed with the IDS-Isys system (Immunodiagnostic Systems), in an automated procedure based on ELISA with detection by chemiluminescence. Serum IGF-I concentrations were interpreted by comparison with the reference intervals set up specifically for this iSYS device [17]. The intra-assay coefficient of variation for IGF-I was 3.1%. IGF-I levels are shown as standard deviation scores (SDS) due to their variability according to sex and age. The SDS conversion was performed using previously published LMS charts [17, 18]. Fasting blood samples were collected and after centrifugation, all samples were kept frozen at -7 C\u003csup\u003eo\u003c/sup\u003e until assayed.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as mean \u0026plusmn; SD. Correlations between datasets were performed using the Pearson correlation coefficient. Classical tests of significance among the groups were done using ANOVA. Regression was performed using robust standard errors (to control for heteroskedasticity) and standardized beta coefficients after excluding in the same model independent variables with multicollinearity. A p value of \u0026lt; 0.05 was considered significant. Statistical analysis was performed by using Stata ver. 16.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe anthropometric clinical parameters and IGF-I SDS levels of the eighty-four children (47 males and 37 females) with a mean age of 6.6 years are presented in Table 1. The correlations among the IoR and the other clinical and biochemical variables are shown in Table 2. IoR correlated significantly with age with a negative coefficient (r=-0.607, p\u0026lt;0.01). It was also significantly correlated to the height distance of the child from its mid-parental height (Height dist. SDS) with r=0.466 (p\u0026lt;0.01). In addition, pretreatment growth velocity (r=0.247, p\u0026lt;0.05) as well as posttreatment growth velocity (r=0.410, p\u0026lt;0.01) were significantly correlated to IoR. On the contrary, IoR was not correlated either to pre rhGH treatment IGF-I levels, nor to post treatment IGF-I SDS (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGH secretory indexes tightly correlated together, with the highest association being observed between GH\u003csub\u003emax\u0026nbsp;\u003c/sub\u003eand GHSV (r=0.883, p\u0026lt;0.01), and followed by GH\u003csub\u003emax\u0026nbsp;\u003c/sub\u003eand GHSR (r=0.558, p\u0026lt;0.01). GHSV was also significantly linked to GHSR, although with a lower strength, (r=0.403, p\u0026lt;0.001). GH\u003csub\u003emax,\u0026nbsp;\u003c/sub\u003eGHSR and GHSV showed no significant association with pre or post rhGH treatment IGF-I SDS values (Table 3). To estimate the value of each GH secretory index in the prediction of IoR, we run three separate regression models (IoR model A, B and C) each for one for GH\u003csub\u003emax,\u0026nbsp;\u003c/sub\u003eGHSR and GHSV including in each model all other common clinical and biochemical factors (Table 4). This was preformed to avoid the co-analysis of GHmax, GHSR and GHSV as variables with inherent collinearity in the same regression model. In all three models, the age, and the height distance from the mid-parental height (Height dist. SDS) were the best predictors of IoR one year after initiation of treatment with rhGH (Table 4). They were followed by the pre-treatment height SDS and BMI SDS. Pre-treatment growth velocity and IGF-I SDS levels did not have any statistical significance in predicting the IoR. Regarding the GH secretory indexes, it was observed that GH\u003csub\u003emax\u003c/sub\u003e was the best predictor of IoR (\u0026beta;\u0026nbsp;coef. = -0.514, p\u0026lt;0.001) followed by the GHSV (\u0026beta;\u0026nbsp;coef. = -0.47, p\u0026lt;0.001) and GHSR (\u0026beta;\u0026nbsp;coef. = -0.367 p\u0026lt;0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Based on the observations that the best IoR predictors were the height dist. SDS and GH\u003csub\u003emax\u0026nbsp;\u003c/sub\u003eafter stimulation, we arbitrarily combined them by generating a new index calculated as follows: GHmax * Height dist. SDS. After using the new index into the same regression model, we found that GHmax * Height dist. SDS increased the predictability of GHmax considerably (\u0026beta; coef. =-0.68 p\u0026lt;0.001), meaning that this combined clinic-biochemical index may account for 68% of the variability of IoR (Table 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we aimed to investigate the clinical and biochemical predictors of response to rhGH treatment in a very well characterized cohort of children with the diagnosis of short stature due to idiopathic GH deficiency. Treatment response was generated by the validated growth model prediction tool (iGRO). Our analysis showed a significant negative association between IoR and age at diagnosis, and a positive relation with the distance between the height of the child and its mid-parental height. As it is also expected, pre- and post-treatment growth velocity correlate very well with IoR. Age has been previously reported to be a basic predictor of rhGH treatment response [19]. The significant correlation of IoR to the distance in SD between the height of the child and its mid-parental height is observed in all regression models in our study and has been confirmed to be a principal predictor of growth response in other studies [14, 15]. Pretreatment height SDS is also associated well to the IoR. Interestingly, we found that, although IGF-I serum levels have a basic role in the diagnostic algorithm of short stature [1, 20], pretreatment as well as posttreatment IGF-I SDS did not show any statistical correlation to the IoR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNext, we investigated the potential of increasing the GH treatment response predictability of GH stimulation tests that we usually perform in current practice. It is known that the reproducibility of a GH stimulation test is low due to the temporal random action of the pharmacologic agent in relation to the spontaneous GH pulse that can be followed by a state of refractoriness [21]. Moreover, different pharmacological agents generate different mean GH peaks, with clonidine generating a higher GH response than arginine, insulin, or glucagon tests [22, 23], while puberty and obesity have their own effect on the pituitary GH secretion [6, 24]. We chose to include only prepubertal children to avoid the strong effect of sex steroids on GH levels after stimulation [24]. The calculated GHSR parameter aimed to incorporate into our evaluation the speed of pituitary gland response, which is how quickly can increase the GH levels after pharmacologic stimulation. GHSV index provides an indication of the somatotroph pituitary capacity. Above GH secretion values cannot be estimated by the GH\u003csub\u003emax\u0026nbsp;\u003c/sub\u003evalue of the stimulation test. For the reasons described above, we chose to calculate GHSR and GHSV only from the GH profiles generated by stimulation of clonidine. The potent stimulation of clonidine could accentuate any existing differences in GHSR and GHSV indices. Both GHSR and GHSV showed a good correlation to IoR. Although an earlier study had shown that GH peak at 45 min was associated with a better response to treatment [25], our results did not support that GHSR contributed additively to the diagnostic ability of the single GHmax value. We reached the same conclusion for the GHSV index, showing that the total GH secreted does not contribute to increased predictability of growth response to rhGH treatment. In addition, both GHSR and GHSV did not significantly correlate to pretreatment IGF-I SDS.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Based on our results we combined the best predictor capabilities from clinics and laboratory by creating the variable of GHmax * Height dist. SDS derived from the arbitrary multiplication of GHmax and Height dist. SDS. In the application of the same regression model, the potential for prediction to rhGH response increased to 68.2 % of IoR variability compared to 51.2% of GHmax.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; In conclusion, we found that age and the distance of child\u0026rsquo;s height from its MPH are major predictors of rhGH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to rhGH than GHmax. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by\u0026nbsp;Aristeidis Giannakopoulos, Eleni Kallimani, Alexandra Efthymiadou and Dionisios Chrysis.\u0026nbsp;. The first draft of the manuscript was written by\u0026nbsp;Aristeidis Giannakopoulos\u0026nbsp;and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Hospital of Patras (Date 16/2/2022 /No 262).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the parents of all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWit JM, Kamp GA, Oostdijk W, on behalf of the Dutch Working Group on Triage and Diagnosis of Growth Disorders in Children (2019) Towards a Rational and Efficient Diagnostic Approach in Children Referred for Growth Failure to the General Paediatrician. 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J Clin Endocrinol Metab 99:1712\u0026ndash;1721. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1210/jc.2013-3059\u003c/span\u003e\u003cspan address=\"10.1210/jc.2013-3059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedrich N, Wolthers OD, Arafat AM et al (2014) Age- and Sex-Specific Reference Intervals Across Life Span for Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 Ratio Measured by New Automated Chemiluminescence Assays. J Clin Endocrinol Metab 99:1675\u0026ndash;1686. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1210/jc.2013-3060\u003c/span\u003e\u003cspan address=\"10.1210/jc.2013-3060\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePozzobon G, Partenope C, Mora S et al (2019) Growth hormone therapy in children: predictive factors and short-term and long-term response criteria. 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Front Endocrinol 11:584906. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fendo.2020.584906\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2020.584906\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZADIK Z, CHALEW SA, KOWARSKI A (1990) Assessment of Growth Hormone Secretion in Normal Stature Children Using 24-Hour Integrated Concentration of GH and Pharmacological Stimulation. 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Horm Res Paediatr 93:470\u0026ndash;476. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000513393\u003c/span\u003e\u003cspan address=\"10.1159/000513393\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eROSE SR, MUNICCHI G, BARNES KM et al (1991) Spontaneous Growth Hormone Secretion Increases during Puberty in Normal Girls and Boys*. J Clin Endocrinol Metab 73:428\u0026ndash;435. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1210/jcem-73-2-428\u003c/span\u003e\u003cspan address=\"10.1210/jcem-73-2-428\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastagno M, Monzani A, Zanetta S et al (2018) Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time. J Endocrinol Investig 41:977\u0026ndash;983. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s40618-017-0824-6\u003c/span\u003e\u003cspan address=\"10.1007/s40618-017-0824-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eClinical and biochemical indexes of GHD children pre- and 1-year post GH treatment (preT: pre-treatment, postT: post-treatment, BMI: body mass index, MPH: mid-parental height)\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMean\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eStd. Dev.\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMin\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMax\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAge (years)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6.607\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.443\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.75\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e11.9\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT Height (cm)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e106.753\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e13.206\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e77\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e132.3\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT Height SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-2.303\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.442\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-3.51\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-1.53\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePostT Height (cm)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e113.767\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e17.005\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e82.2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e141.5\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePostT Height SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026minus;\u0026thinsp;.855\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.895\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-1.38\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.1\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.49\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.102\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.9\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePostT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.137\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.420\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12.5\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHeight dist. SD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.703\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.842\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.21\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.05\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT BMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16.277\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.843\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e13.4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT BMI SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.128\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-1.93\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.58\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMPH (cm)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e166.94\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.233\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e150.5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e185.5\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMPH SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026minus;\u0026thinsp;.6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.838\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-2.48\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.2\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT IGF-I (\u0026micro;g/L)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e66.145\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e47.793\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e284\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-1.862\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.085\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-4.21\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.72\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePostT IGF-I (\u0026micro;g/L)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e191.264\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e98.782\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e57\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e675\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePostT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.321\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.944\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-2.02\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.87\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCorrelations among IoR and other clinico-biochemical pre and post rhGH treatment indices in children with idiopathic GH deficiency.\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(3)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(6)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(7)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(8)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(9)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(10)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1) IoR\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2) Age (years)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.607***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(3) PreT Height SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.069\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.169\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4) PostT Height SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.151\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.073\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.159\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5) BMI SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.202\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.065\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.024\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.082\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(6) PreT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.074\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.008\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.174\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.102\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.091\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(7) PostT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.205\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.183\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.126\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.029\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.165\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.224**\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(8) PreT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.247**\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.433***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.111\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.112\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.086\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.071\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.142\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(9) PostT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.410***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.320***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.002\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.182\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.186\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.156\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.131\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.096\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(10) Height dist. SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.466***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.317***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.273**\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.056\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.191\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.049\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.177\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.016\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.165\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"12\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e*** p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ** p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 referred to r coefficients\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCorrelation among the Growth Hormone Stimulation Dynamic Indices GH\u003csub\u003emax\u003c/sub\u003e, GHSR and GHSV and pre post rhGH treatment IGF-I SDS.\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(3)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5)\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(1) GH\u003csub\u003emax\u003c/sub\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(2) GHSR\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.558***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(3) GHSV\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.883***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.403***\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(4) PreT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.065\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.124\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.061\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(5) PostT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.048\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.128\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.087\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.224**\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.000\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e*** p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ** p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eRegression models A, B and C of IoR for the Growth Hormone Stimulation Dynamic Indexes GH\u003csub\u003emax\u003c/sub\u003e, GHSR and GHSV, respectively.\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIoR model A\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCI (95%)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIoR model B\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCI (95%)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIoR model C\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCI (95%)\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(GH\u003csub\u003emax\u003c/sub\u003e)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(GHSR)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e(GHSV)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAge\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.615\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.412, -0.246]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.576\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.406, -0.225]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.634\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.436, -0.243]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSex (male)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.080\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.159, 0.571]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.158\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.0737, 0.887]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.067\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.239, 0.582]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHeight SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.261\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.444, 1.066]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.331\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.591, 1.293]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.275\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.425, 1.162]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBMI SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.175\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.0954, 0.352]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.145\u003csup\u003e*\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.0231, 0.341]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.168\u003csup\u003e**\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.0715, 0.356]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.057\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.0381, 0.173]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.044\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.118, 0.217]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.039\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.0906, 0.183]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.020\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.161, 0.115]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.053\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.209, 0.0855]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.001\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.154, 0.156]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHeight dist. SD\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.354\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.318, 0.774]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.416\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.390, 0.870]\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.426\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.401, 0.915]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eGH\u003c/span\u003e\u003csub\u003e\u003cspan class=\"Bold\"\u003emax\u003c/span\u003e\u003c/sub\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e-0.514\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Bold\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e[-0.348, -0.215]\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eGHSR\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e-0.367\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Bold\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e[-0.538, -0.227]\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eGHSV\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e-0.470\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Bold\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e[-0.126, -0.0628]\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003eStandardized beta coefficients; 95% confidence intervals in brackets\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e\u003csup\u003e*\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003e**\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, \u003csup\u003e***\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eRegression model for the IoR incorporating the combined clinico-biochemical index [GHmax * Height Dist. SDS].\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIoR model D\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCI (95%)\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e( GH\u003csub\u003emax\u003c/sub\u003e * Height Dist. SDS )\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAge\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.581\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.407, -0.215]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSex (male)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.116\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.123, 0.723]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHeight SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.320\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.552, 1.294]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBMI SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.194\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[0.113, 0.381]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT IGF-I SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.084\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.0376, 0.234]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreT Growth vel. (cm/y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e-0.013\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[-0.174, 0.143]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHeight dist. SDS\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.916\u003csup\u003e***\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e[1.008, 1.818]\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eGH\u003c/span\u003e\u003csub\u003e\u003cspan class=\"Bold\"\u003emax\u003c/span\u003e\u003c/sub\u003e \u003cspan class=\"Bold\"\u003e* Height Dist. SDS\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e-0.682\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Bold\"\u003e***\u003c/span\u003e\u003c/sup\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003e[-0.183 -0.09]\u003c/span\u003e\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Growth hormone deficiency, Index of Responsiveness, GH stimulation test, GH secretory indexes","lastPublishedDoi":"10.21203/rs.3.rs-4265731/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4265731/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe aim of this study is to correlate the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after one year of treatment with growth hormone to the initial clinical and biochemical parameters. It also aims to study the secretory dynamics of GH by analyzing the profiles of GH stimulation tests in relation to the recombinant GH (rhGH) treatment response.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis a retrospective study which included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GHmax, GH secretion rate (GHSR) and GH secretion volume (GHSV) were analyzed in relation to the response to rhGH treatment as defined by the index of responsiveness (IoR). Correlation and regression models were used to identify the best clinical and biochemical predictors to rhGH treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIoR was correlated negatively with the age (r=-0.607, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and positively with the distance of child\u0026rsquo;s height from its MPH r\u0026thinsp;=\u0026thinsp;0.466 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and pretreatment growth velocity (r\u0026thinsp;=\u0026thinsp;0.247, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). GH secretory indexes correlated together, with the highest association being observed between GHmax and GHSV (r\u0026thinsp;=\u0026thinsp;0.883, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Regarding the GH secretory indexes, GHmax was the best predictor of IoR (β coef. = -0.514, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) followed by the GHSV (β coef. = -0.47, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and GHSR (β coef. = -0.367 p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe age and the distance of child\u0026rsquo;s height from its MPH are major predictors of rhGH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to rhGH than GHmax. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment.\u003c/p\u003e","manuscriptTitle":"Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-23 10:22:48","doi":"10.21203/rs.3.rs-4265731/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"254c8f33-e6ee-471c-8a46-bc8f2162ea53","owner":[],"postedDate":"April 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-30T07:26:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-23 10:22:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4265731","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4265731","identity":"rs-4265731","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}