GH-deficient Children Research Articles

Dynamic Ghrelin and GH serum levels during combined simultaneous arginine clonidine stimulation test in children with dwarfism

BackgroundCombined simultaneous arginine clonidine stimulation (CSACS) test represents a more appropriate stimulus to detect Ghrelin, for it does not affect glucose metabolism.MethodsFifty prepubertal children with dwarfism were recruited and further classified into normal growth hormone (NGH) and growth hormone deficiency (GHD) group with growth hormone (GH) peak cut-off value of 10 μg/l. In both groups, GH and Ghrelin serum levels were determined after the GH provocation test at 30, 60, and 120 min and the height standard deviation score (SDS) for bone age was measured six months later.ResultsThe participants were classified into NGH (n = 24) and GHD group (n = 26). A decrease in the circulating Ghrelin levels prior to the GH peak was observed in the NGH children, whereas both GH and Ghrelin levels demonstrated a rise in the GHD children. Ghrelin level in GHD group was higher compared with NGH group and the GH peak in GHD group is lower than NGH group. The 6 months CSACS treatment could increase the height SDS in both groups.ConclusionAlthough analogous changes were not detected in GHD group, the inverse correlation between GH and Ghrelin in NGH indicates a negative feedback lying between GH and Ghrelin.

Changes in ghrelin and nesfatin-1 in children with growth hormone deficiency treated by recombinant human growth hormone

This study aims to investigate the effects of recombinant human growth hormone (rhGH) on serum nesfatin-1 and ghrelin in children with growth hormone deficiency (GHD), in order to provide a reliable basis for the effectiveness and safety of applying rhGH in treating GHD children in the clinic. A total of 30 GHD pediatric patients were selected as the observation group. According to the peak of GH, these patients were divided into two subgroups: complete absence of growth hormone (CGHD) group and partial absence of growth hormone (PGHD) group. At the same time, 20 healthy children of normal height with matching age and gender were randomly selected as a normal control group. Serum ghrelin and nesfatin-1 levels were detected in children in the control group and observation group before rhGH treatment, and at 3 and 6 months after treatment. After 3 and 6 months of treatment, the height and growth rate of children in the PGHD and CGHD groups significantly increased ( P < 0.05), but their body weights did not significantly change ( P > 0.05), compared with those before treatment. Before treatment, ghrelin was higher in the PGHD group than in the control group, while ghrelin was lower in the CGHD group than in the control group. In addition, nesfatin-1 was higher in these two subgroups, compared with that in the control group. At pretreatment, and after 3 and 6 months of treatment, ghrelin and nesfatin-1 both decreased in the PGHD group, while ghrelin increased and nesfatin-1 decreased in the CGHD group. It was confirmed that ghrelin and nesfatin-1 were closely correlated with GHD. Furthermore, rhGH has a significant effect on children with GHD, and can significantly accelerate the annual growth rate.

Poor growth response during the first year of growth hormone treatment in short prepubertal children with growth hormone deficiency and born small for gestational age: a comparison of different criteria

BackgroundThere is no consensus on the definition of poor growth response after the first year of growth hormone (GH) treatment. We determined the proportion of poor responders identified by different criteria in children with GH deficiency (GHD) and born small for gestational age (SGA). The second aim was to analyze the IGF-1 response in poor growth responders.MethodsFirst-year height data of 171 SGA and 122 GHD children who remained prepubertal during the first GH treatment year were retrieved from the BESPEED database and analyzed. Criteria for poor first-year response/responsiveness were: change in height (∆Ht) SDS<0.3 or<0.5, height velocity (HV) SDS<0.5 or <1 based on the population reference, HV SDS<− 1 based on the KIGS expected HV curve (HV Ranke SDS), studentized residual (SR) <− 1 in the KIGS first-year prediction model.Results∆Ht SDS<0.5 gave the highest percentage poor responders (37% SGA, 26% GHD). Although % poor responders were comparable for ∆Ht SDS<0.3, HV SDS<+ 0.5, HV SDS<+ 1, SR<− 1, and HV Ranke SDS<− 1, these criteria did not always identify the same patients as poor responders. Among the poor growth responders 24% SGA and 14% GHD patients had an IGF-1 increase < 40%.ConclusionsThe different response criteria yield high but comparable percentages poor responders, but identify different patients. This study does not provide evidence that one criterion is better than another. A limited IGF-1 generation is not the major reason for a poor growth response in the first year of GH treatment in SGA and GHD children.Trial registrationRetrospectively registered.

Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and Treatment of Growth Hormone Deficiency in Children

Background: The analysis of insulin-like growth factor I (IGF-I) is an important tool for pediatricians in the diagnosis and treatment of growth hormone deficiency in children. However, significant differences exist in IGF-I assays and normative datasets, which can have important clinical consequences. Methods: IGF-I analyses were performed using the IDS-iSYS platform on 1,897 samples from pediatric patients (0.5–18 years old). Z-scores were calculated based on normative IGF-I data from Bidlingmaier et al. (SD-BM) [J Clin Endocrinol Metab. 2014 May; 99(5): 1712–21] and normative IGF-I data from the IGF-I harmonization program in the Netherlands (SD-NL). The differences in Z-scores were analyzed at relevant clinical decision points (–2 SD, +2 SD). These normative datasets were also compared to normative data reported by Elmlinger et al. [Clin Chem Lab Med. 2004; 42(6): 654–64]. Results: The difference in Z-score between SD-BM and SD-NL was highest in males between 0 and 3 years old, exceeding 2 SD. Clinically relevant discordance between both Z-scores at –2 and +2 SD was found in 12.7% of all samples. The IGF-I levels at –2 and +2 SD reported in the normative dataset of Elmlinger et al. were up to 100% higher than the IGF-I levels reported by Bidlingmaier et al. or the Dutch harmonization program. Conclusion: Pediatricians and laboratory specialists should be aware of relevant differences that can exist between IGF-I assays and normative data. Well-defined pediatric reference ranges for the IDS-iSYS platform are highly desirable.

Reliability of clonidine testing for the diagnosis of growth hormone deficiency in children and adolescents.

The diagnosis of growth hormone deficiency (GHD) is currently based on clinical, auxological, biochemical and neuro-radiological investigation. Provocative tests of GH secretion using physiological/pharmacological stimuli are required to confirm GHD. The clonidine test (CT) is widely used to assess GH secretory status. In this retrospective study, we analyzed the reliability of CT and the effect of puberty in a large number of children with short stature who had been evaluated for suspected GHD. Data were collected retrospectively from 327 children and adolescents with short stature (204 boys and 123 girls, median age 10.5years (IQR 7.90-12.40) followed in four Italian Paediatric Endocrine Units (Cagliari, Genova, Napoli and Roma) between 2005 and 2013. All children underwent CT as the first GH stimulation test after exclusion of other known cause of their short stature. In 73 prepubertal children and 25 pubertal children, the GH peak after CT was <7μg/L. GHD was confirmed in 87 (37 organic, 50 idiopathic). Six prepubertal and five pubertal patients showed false positive responses. The median BMI-SDS in these children was similar to that of children with GH peak ≥7μg/L, and none were obese. Overall, the prevalence of false-positive responses was 3.3%. The median (IQR) peak GH after CT was similar between prepubertal and pubertal GHD (3.80μg/L [1.7-6.00] vs 3.51μg/L [0.76-5.74]) and non-GHD (13.70μg/L [10.70-18.40] vs 12.40μg/L [9.90-19.25]) children. Our results show that CT is a reliable and safe GH-releasing agent in both prepubertal and pubertal children.

Growth hormone and hematopoiesis: A retrospective analysis on a large cohort of children with growth hormone deficiency

ObjectiveFew large-scale studies regarding the impact of GH deficiency (GHD) on hematopoiesis in children have been reported. Our aim was to investigate hematopoiesis indices in a large cohort of GHD children at diagnosis and during GH treatment (GHT) and any correlation with hormonal parameters. DesignClinical and biochemical data of children with idiopathic GHD at diagnosis and annually up to 36 months of GHT were retrospectively evaluated. Overall, 255 children reached 12 months, 140 children 24 months and 86 children 36 months of follow-up during GHT. ResultsAt baseline, 18.4% of GHD children and 10.1% of controls showed normocytic anemia. GHD children showed lower hemoglobin (Hb) (p = 0.007), red blood cells (RBC) (p < 0.001) and hematocrit (Ht) (p = 0.001) than controls. During GHT, the percentage of anemic patients decreased from 18.4 to 5.4–3.5 and 4.6% after 12 (p = 0.001), 24 (p < 0.001) and 36 months (p < 0.001) of GHT, respectively. In both anemic and non-anemic patients, a significant increase in Hb (p < 0.001, <0.001 and 0.002), RBC (all p < 0.001) and Ht (all p < 0.001) was found after 12, 24 and 36 months of GHT. The Hb levels were significantly correlated with the GH peak after stimulation test (p < 0.001) at baseline and with IGF-I levels at 36 months of GHT (p = 0.002). ConclusionsA significant improvement in erythropoiesis indices occurs during GHT, regardless of any previous presence of anemia.

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.

The metabolic outcomes of growth hormone treatment in children are gender specific.

ObjectiveTo evaluate the impact of gender on the clinical and metabolic parameters in prepubertal growth hormone deficiency (GHD) children at diagnosis and during GH treatment (GHT).DesignThe data of 105 prepubertal children (61 males, 44 females, mean age 6.8 ± 0.7 years) affected by idiopathic GHD were retrospectively evaluated.MethodsBody height, BMI, waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after-OGTT glucose and insulin levels, insulin sensitivity and secretion indices were evaluated at baseline and after 24 months of GHT.ResultsAt baseline, no significant difference was found in all clinical, hormonal and metabolic parameters between males and females. After 24 months of GHT, both males and females showed a significant increase in height (both P < 0.001), BMI (both P < 0.001), WC (P < 0.001 and P = 0.004, respectively), IGF-I (both P < 0.001), fasting glucose (P < 0.001 and P = 0.001, respectively), fasting insulin (both P < 0.001) and Homa-IR (both P < 0.001), with a concomitant significant decrease in insulin sensitivity index (ISI) (both P < 0.001) and oral disposition index (DIo) (P = 0.001 and P < 0.001, respectively). At 24 months of GHT, females showed significantly higher BMI (P = 0.027), lower ISI (P < 0.001) and DIo (P < 0.001), in concomitance with a significant greater change from baseline to 24 months of BMI (P = 0.013), WC (P < 0.001), ISI (P = 0.002) and DIo (P = 0.072), although the latter does not reach statistical significance.ConclusionsTwenty-four months of GHT in prepubertal children leads to different metabolic outcomes according to gender, with a greater reduction in insulin sensitivity in females, regardless of auxological and hormonal parameters. Therefore, prepubertal GHD females should probably need a more proper monitoring in clinical practice.

Glucose Metabolism in Children With Growth Hormone Deficiency.

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis has a fundamental impact on glucose metabolism. Therefore, both untreated GH deficiency (GHD) and GH treatment (GHT) may be associated with some metabolic alterations, although the abnormalities of glucose metabolism have been investigated by relatively few studies as main outcomes. The present review summarizes the available data on glucose metabolism in children with GHD, providing an overview of the current state of the art in order to better clarify the real metabolic impact of GHD and GHT. Among all the existing studies, we evaluated all original studies that fulfilled our criteria for analysis reporting parameters of glucose metabolism as the primary or secondary objective. The reported impact of GHD per se on glucose metabolism is quite homogeneous, with the majority of studies reporting no significant difference in metabolic parameters between GHD children and controls. Conversely, GHT proves to be more frequently associated with a subtle form of insulin resistance, while both fasting glucose and HbA1c levels remain almost always within the normal range. The different methods to study glucose metabolism, the heterogeneity of the populations evaluated, the different doses of GH used together with the variable duration of follow-up may be responsible for discrepancy in the results. Long-term longitudinal studies having glucose homeostasis as their primary outcome are still needed in order better to clarify the real metabolic impact of GHD and GHT in children.

GH deficiency in children

GH deficiency in children

Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis

Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). For both aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. 47 pre-pubertal GHD children (aged 5-14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https://cran.r-project.org/mirrors.html). A p-value <0.05 was considered significant. At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV1, FEF25-75% and TLC were <50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant. The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT.

Effect of recombinant human growth hormone therapy on blood lipid and carotid intima-media thickness in children with growth hormone deficiency

BackgroundReports on the association between growth hormone deficiency (GHD) and cardiovascular risk factors in children are limited. We aim to investigate the effect of different doses of recombinant human growth hormone (rhGH) therapy on blood lipid and carotid intima-media thickness (cIMT) in Chinese GHD children.MethodsNinety children, including sixty isolated GHD children and thirty healthy children, were enrolled. GHD children were randomly divided into two groups (A and B) according to the rhGH dose given: group A received 0.23 mg/kg/week and group B received 0.35 mg/kg/week for 12 months. The TC, TG, LDL-C, HDL-C, and cIMT at baseline and after treatment were measured.ResultsThe height, weight, and height velocity improved significantly over 12 months of rhGH therapy in all GHD children. At baseline, GHD children in both the treatment groups showed significantly higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), cIMT, and lower high-density lipoprotein-cholesterol (HDL-C) than healthy children (all P≤0.033). After the 12-month rhGH therapy, a significant decrease in the TC, TG, LDL-C, and cIMT, as well as a significant increase in the HDL-C (P≤0.046), was observed in the GHD children, with change in the group B being even more marked.ConclusionsThe RhGH replacement therapy in GHD children can improve both the blood lipid profile and carotid intima-media thickness, with higher-dose rhGH therapy showing superior effects.

Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection

A typical clinical manifestation of growth hormone deficiency (GHD) is a short stature resulting from delayed growth, but GHD affects bone health, cardiovascular function and metabolic profile and therefore quality of life. Although early GH treatment during childhood has been shown to improve outcomes, no single biochemical parameter is currently available for the accurate diagnosis of GHD in children. There is hence a need for non-invasive biomarkers. In this study, the relative abundance of serum proteins from GHD children and healthy controls was measured by next-generation proteomics SWATH-MS technology. The data generated was analysed by machine-learning feature-selection algorithms in order to discover the minimum number of protein biomarkers that best discriminate between both groups. The analysis of serum proteins by a SWATH-MS approach yielded a useful method for discovering potential biomarkers of GHD in children. A total of 263 proteins were confidently detected and quantified in each sample. Pathway analysis indicated an effect on tissue/organ structure and morphogenesis. The top ten serum protein biomarker candidates were identified after applying feature-selection data analysis. The combination of three proteins – apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein – demonstrated the best classification performance for our data. In addition, the apolipoprotein group resulted in strong over-representation, thus highlighting these proteins as an additional promising biomarker panel. SignificanceCurrently there is no single biochemical parameter available for the accurate diagnosis of growth hormone (GH) deficiency (GHD) in children. Simple GH measurements are not an option: because GH is released in a pulsatile action, its blood levels fluctuate throughout the day and remain nearly undetectable for most of that time. This makes measurements of GH in a single blood sample useless for assessing GH deficiency. Actually, the diagnosis of GHD includes a combination of direct and indirect non-accurate measurements, such as taking several body measurements, testing GH levels in multiple blood samples after provocative tests (GH peak <7.3ng/mL, using radioimmunoassay), and conducting magnetic resonance imaging (MRI), among others. Therefore, there is a need for simple, non-invasive, accurate and cost-effective biomarkers. Here we report a case-control study, where relative abundance of serum proteins were measured by next-generation proteomics SWATH-MS technology in 15 GHD children and 15healthy controls matched by age, sex, and not receiving any treatment. Data generated was analysed by machine learning feature selection algorithms. 263 proteins could be confidently detected and quantified on each sample. The top 10 serum protein biomarker candidates could be identified after applying a feature selection data analysis. The combination of three proteins, apolipoprotein A-IV, complement factor H-related protein 4 and platelet basic protein, showed the best classification performance for our data. In addition, the fact that the pathway and GO analysis we performed pointed to the apolipoproteins as over-represented highlights this protein group as an additional promising biomarker panel for the diagnosis of GHD and for treatment evaluation.

Pons ratio as a potential diagnostic biomarker for the detection of growth hormone deficiency in children.

Pituitary insufficiency (PI) needs further research to optimize treatment. Growth hormone deficiency (GHD) is a subtype of PI. The purpose of the present study is to investigate the possible relationship between GHD and the anatomical position of the pons as revealed by magnetic resonance imaging (MRI) in the pediatric age group. In the current study, we developed a novel and simple index using MRI that could provide an alternative to other indexes in the classical literature. Brain MRI and clinical data of 48 children with suspected PI (22 females, 26 males; mean age 11.6 ± 2.2 years) were examined retrospectively. To estimate the location of the pons, the ratio of pons height over the axis between the dorsum sellae and the fourth ventricular hill in the sagittal plane (A) to the total height of the pons (B) was calculated (A/B). It was termed the pons ratio (PR). The PRs of children with or without a diagnosis of GHD were then compared statistically. Fifteen children were diagnosed with GHD and treated with growth hormone (GH), whereas the remaining 33 were reported normal. The mean PRs of the children diagnosed with GHD and given GH treatment (0.31 ± 0.07, range: 0.18-0.42) differed significantly from those without PI (0.26 ± 0.06, range: 0.17-0.44; P = 0.018). There appears to be an association between GHD and decreased PR in children receiving GH treatment. Spatial measurements of posterior fossa in radiological examinations may provide additional information that is helpful in the diagnosis of suspected cases of GHD.

Osteoprotegerin, Receptor Activator of Nuclear Factor Kappa B Ligand, and Growth Hormone/Insulin-Like Growth Factor-1 Axis in Children with Growth Hormone Deficiency.

The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is involved in the regulation of the receptor activator of nuclear factor kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system, but the exact mechanism of the associations is not fully explained. In this study we investigated the serum OPG and total sRANKL concentrations in short children who had differences in GH secretory status. We also investigated the associations between the GH/IGF-1 and OPG/RANKL systems in GH-deficient children during GH treatment. There were no significant differences in any anthropometric or biochemical parameters evaluated between the GH-deficient and GH-sufficient children. The OPG content and total alkaline phosphatase (ALP) activity increased significantly after the initiation of GH treatment, while total sRANKL remained unchanged. The variables baseline BMI SDS for height-age (β=0.42; p<0.05), baseline ALP activity (β=0.36; p<0.05), weight SDS for height-age at 6months of GH treatment (β=1.86; p<0.01), and total ALP activity at 6months of GH treatment (β=0.48, p<0.01) were identified as independent predictors of ΔOPG6-month-baseline. We conclude that OPG and total sRANKL concentrations are independent from GH secretory status in short children. OPG elevation during GH treatment is independently associated with total ALP activity and nutritional status in GH-deficient children.

Diagnosis of childhood growth hormone deficiency: Controversies, consensus and the need for new diagnostic tools.

Diagnosis of childhood growth hormone deficiency: Controversies, consensus and the need for new diagnostic tools.

Gender-Dependent Growth and Insulin-Like Growth Factor-1 Responses to Growth Hormone Therapy in Prepubertal Growth Hormone-Deficient Children.

Gender seems to be an important factor influencing the response to recombinant human growth hormone (rhGH) therapy in GH-deficient adolescents and adults. The results of studies evaluating gender-specific response to rhGH therapy in prepubertal GH-deficient children are divergent. The aim of this study was to determine the effect of gender on the growth and insulin-like growth factor-1 (IGF-1) responses in 75 prepubertal GH-deficient children during the first 2 years of rhGH therapy. There were no baseline gender differences in age, bone age, anthropometrical parameters, and IGF-1 SDS for bone age. After the initiation of rhGH therapy, there were no gender-specific differences concerning the reduction of height deficit. Serum IGF-1 levels were higher in the prepubertal GH-deficient girls than in the age-matched boys, but the difference was not significant when expressed as IGF-1 SDS for bone age. The increase in IGF-1 SDS for bone age was significantly greater in girls versus boys after the first 6 months of therapy, comparable between girls and boys after the first year of therapy, and tended to be higher in boys after the second year of therapy. In conclusion, prepubertal GH-deficient girls and boys do not differ significantly in growth response in the first 2 years of rhGH therapy.

RESULTS OF A 20-YEAR FOLLOW-UP OF CHILDREN WITH GROWTH HORMONE DEFICIENCY IN THE REPUBLIC OF TATARSTAN

One of the most important parameters of health in children is growth. Stunted growth leads to the development of inferiority complex in patients and often hampers social self-realization. Over the past two decades, the Republic of Tatarstan has been actively diagnosing and treating growth hormone deficiency in children with short stature. Children with isolated growth hormone deficiency receive monotherapy with recombinant growth hormone. Early treatment of children with growth hormone deficiency led to an improvement in anthropometric parameters and, consequently, psychological and social adaptation of this group of patients.

Growth Hormone Deficiency in Children and Adult Patients with Hypopituitarism: Challenges in the Diagnosis and Management

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used. Hypopituitarism is a complex medical condition associated with increased morbidity and mortality, requires complicated treatment regimens, and necessitates lifelong follow up by the endocrinologist.

Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency

ObjectiveData about the impact of growth hormone treatment (GHT) on insulin sensitivity in children are quite controversial, due to the different surrogate indices that have been used. DesignWe evaluated insulin sensitivity through the euglycemic hyperinsulinemic clamp, considered the gold standard technique, in 23 children affected by growth hormone deficiency (GHD) at baseline and after 12months of GHT and in 12 controls with short stature at baseline, and we compared the clamp-derived index (M-value) with the most commonly used surrogate index of insulin sensitivity, as ISI Matsuda, and with circulating plasma markers of insulin sensitivity, as adiponectin and resistin levels. ResultsAt baseline, no significant difference in all metabolic parameters between GHD children and control subjects was found. After 12months of GHT, GHD children showed a significant increase in fasting insulin (p<0.001) and resistin (p=0.028) and a decrease in ISI Matsuda (p<0.001) and M-value (p<0.001), without significant change in fasting glucose, HbA1c and adiponectin. In GHD children, M-value showed a significant but weak correlation with ISI Matsuda (rho 0.418, p=0.047) at baseline, while no correlation with other parameters was found. After 12months of GHT, M-value did not show any significant correlation with any other metabolic parameter analyzed. ConclusionsThis study highlights the limit of the evaluation of insulin sensitivity performed through surrogate indices or circulating markers, which may lead to controversial data and do not correlate with the gold standard technique to evaluate insulin sensitivity.