Insulin-like Growth Factor-1 Standard Deviation Score Research Articles

Post hoc subgroup analysis of Asian children with paediatric GHD from the global phase 3 efficacy and safety study of once-weekly somatrogon vs. once-daily somatropin.

Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD. Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS. This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children. This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004.

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients.

The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients. Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents. Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001). Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT. This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.

Association of Body Mass Index with Insulin-like Growth Factor-1 Levels among 3227 Chinese Children Aged 2–18 Years

Insulin-like growth factor-1 (IGF-1) levels are affected by nutritional status, yet there is limited research exploring the association between body mass index (BMI) and IGF-1 levels among children. This cross-sectional study included 3227 children aged 2-18 years without specific diseases, whose height, weight, and pubertal stages were measured and assessed by pediatricians. BMI standard deviation scores (BMISDS) were used to categorize children as underweight (BMISDS < -2); normal-weight (-2 ≤ BMISDS ≤ 1); overweight (1 < BMISDS ≤ 2); and obese (BMISDS > 2). Children were divided into low-level (<-0.67 SD) and nonlow-level (≥-0.67 SD) groups based on IGF-1 standard deviation scores (IGF-1SDS). The association between IGF-1 and BMI as categorical and continuous variables was explored by Binary logistic regression, the restrictive cubic spline model, and the generalized additive model. Models were adjusted by height and pubertal development. Recursive algorithm and multivariate piecewise linear regression were further utilized to assess the threshold of the smooth curve. IGF-1 levels varied by BMI categories, with the highest levels observed in the overweight group. The proportion of low IGF-1 levels in underweight, normal-weight, overweight, and obese groups was 32.1%, 14.2%, 8.4%, and 6.5%, respectively. The risk odds of low IGF-1 levels in underweight children were 2.86-, 2.20-, and 2.25-fold higher than in children with normal weight before adjustment, after adjustment for height, and after adjustment for height and puberty, respectively. When analyzing the association between BMI and low IGF-1 levels, dose-response analysis demonstrated an inverted J-shaped relationship between BMISDS and low IGF-1 levels. Lower or higher BMISDS increased the odds of low IGF-1 levels, and significance was retained in underweight children but not in obese children. When BMI and IGF-1 levels were used as continuous variables, the relationship between the BMISDS and IGF-1SDS followed a nonlinear inverted U shape. IGF-1SDS increased with the increase of BMISDS (β = 0.174, 95% CI: 0.141 to 0.208, p < 0.01) when BMISDS was less than 1.71 standard deviation (SD) and decreased with the increase of BMISDS (β = -0.358, 95% CI: -0.474 to -0.241, p < 0.01) when BMISDS was greater than 1.71 SD. The relationship between BMI and IGF-1 levels was found to depend on the type of variable, and extremely low or high BMI values could result in a tendency toward low IGF-1 levels, emphasizing the importance of maintaining a normal BMI range for normal IGF-1 levels.

Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study.

This study investigated the association between insulin-like growth factor-1 and nutritional status indicators in patients undergoing maintenance hemodialysis (MHD). Patients undergoing MHD for > 3months were included in this single-center cross-sectional study in March 2021. Clinical, demographic, and body mass data and blood samples were collected before the hemodialysis sessions. Serum insulin-like growth factor-1 (IGF-1) levels were measured using a radioimmunoassay, and serum IGF-1 standard deviation score (SDS) was calculated for MHD patients according to age and sex. The nutritional status of patients was assessed using serum albumin, serum prealbumin, handgrip strength, pinching strength, upper arm muscle circumference, lean body mass, phase angle, seven-point subjective global assessment (SGA) score, and geriatric nutritional risk index (GNRI). The patients were divided into groups according to tertiles of serum IGF-1 SDS levels. Spearman correlation analyses and univariate and multivariate binary logistic regression analyses were used to determine the association between serum IGF-1 SDS and nutritional status parameters. A total of 155 MHD patients (male: female = 90:65) were enrolled in the study, witha median dialysis vintage of 28.0 (11.0, 55.0)months, and an average age of66 (65.5 ± 13.0)years. The median of IGF-1 SDS was - 0.1 (- 0.6 to 0.6). Compared to patients with higher IGF-1 SDSs, patients with lower IGF-1 SDSs had lower levels of serum ceruloplasmin (341.0 [287.5, 416.0] vs 395.0 [327.0, 451.0] vs 409.0 [349.5, 507.5], p = 0.002), serum albumin (34.7 ± 3.0 vs 37.0 ± 3.1 vs 37.8 ± 2.6, p < 0.001), serum prealbumin (270.3 [233.7, 327.8] vs 326.0 [279.3, 355.6] vs 363.0 [324.2, 398.2], p < 0.001), handgrip strength (13.8 [10.0, 20.7] vs 17.7 [10.7, 22.5] vs 23.3 [16.6, 27.8], p < 0.001), pinch strength (4.6 [3.9, 6.0] vs 4.9 (3.9, 6.9) vs 6.5 [4.7, 8.7], p = 0.002), phase angle (3.3 [3.0, 3.8] vs 3.9 [3.4, 4.7] vs 4.3 [3.6, 5.2, p < 0.001), modified Creatinine Index (83.1 ± 19.7 vs 93.1 ± 23.4 vs 113.9 ± 24.3, p < 0.001), intracellular water (14.5 ± 4.4 vs 16.1 ± 4.9 vs 16.9 ± 4.4, p = 0.031), higher extracellular water (26.9 ± 5.8 vs 25.7 ± 5.5 vs 25.1 ± 3.1, p = 0.042), and higher malnutrition risk as defined by GNRI (49.0% vs 15.7% vs 11.5%, p < 0.001) and SGA (53.9% vs 23.5% vs 7.7%, p < 0.001). Lower IGF-1 SDSs are independently associated with higher malnutrition risk in patients with MHD.

Proposed reference intervals of serum insulin-like growth factor-1 (IGF-1) levels in older Japanese populations.

Measurements of serum insulin-like growth factor 1 (IGF-1) levels are useful surrogate markers for the diagnosis and management of patients with growth hormone-related disorders. We have previously published normative data of serum IGF-1 levels for the Japanese population aged 0-77 years by combining and analyzing previously reported references, which were separately and independently constructed, to properly reflect data in the transition period. Although the reference is widely used in both clinical and research settings, the reference did not include data for those aged >77 years, raising the question of how we would evaluate patients over those ages. In this study, we extended the age- and sex-specific reference ranges of serum IGF-1 levels to the age of 80 years by reanalyzing combined data on serum IGF-1 levels from previously published references. Based on our results, we proposed that individuals aged >80 years can be evaluated using the references set at the age of 80 years. However, our proposal was based on a very limited number of participants. Therefore, physicians should exercise caution when interpreting IGF-1 standard deviation scores for those aged >80 years because they are not exactly correct but acceptable.

Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m2, with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ − 2.0 SDS and standard IGF-1 group; − 2.0 < and <  + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients.

ODP386 Growth Velocity and Growth Hormone Deficiency During Puberty

Abstract Background A subnormal growth velocity (GV) is a characteristic feature of growth hormone deficiency (GHD). During puberty growth hormone (GH) levels increase markedly in response to sex hormone secretion. The normal range for GV declines during childhood, increases during puberty with peak levels at mid-puberty. Hence, pubertal status rather than age alone must be considered in the evaluation of GV in children and adolescents. In most cases, a diagnosis of GHD is established by a subnormal response in GH levels following a stimulation with two pharmacological agents. Objective We determined the reliability of GV as a predictor of GHD during puberty. Methods We conducted a retrospective study of pubertal children and adolescents who underwent a GH stimulation test in our pediatric endocrinology clinic. Seventy-nine subjects (57 boys and 22 girls) were included in this study. Bone age was determined for all patients. Serum levels of insulin like growth factor-1 (IGF-1) were obtained prior to GH stimulation test. Serum IGF-1 levels, expressed as a standard deviation score were compared to the IGF-1 levels expected chronological age (CA), height age (HA), and bone age (BA). Serum GH levels were determined following the administration of arginine and levodopa. GHD was established by a peak GH level &amp;lt;10 ng/mL. IBM SPSS Statistics software version 28. 0. 0. 0 (190) was used for data analysis. Results Subjects ranged in age from 7.3-17.9 years. Thirty-nine patients (49.4%) had GV &amp;lt; 10 th percentile for CA; Forty patients (50.6%) had GV &amp;lt;10 th percentile for BA. Sixty percent of patients with GV &amp;lt;10 th percentile for CA had GHD. A similar number (59%) of patients with normal GV for CA also had GHD. Among patients with GV &amp;lt;10 th percentile for BA, 72.5% of subjects had GHD. By contrast, the percentage of patients who had normal GV for bone age and GHD (46.2%) was significantly less than that of subjects with GV &amp;lt;10 th percentile for BA (p = 0. 015). Positive predictive value, negative predictive value, sensitivity and specificity for GV &amp;lt;10 th percentile for BA in the diagnosis of GHD were 72.5%, 53.8%, 61.7%, and 65.6%, respectively. With respect to the diagnostic value of serum IGF-1, when the area under the ROC curve was used to measure how well the serum IGF-1 standard deviation score distinguished between GHD and normal, serum IGF-1 standard deviation score for CA, HA, and BA were not predictive of GHD (p = 0.1, 0.47, and 0.27, respectively). Conclusions During puberty, slow growth velocity for bone age (but not slow growth velocity for chronological age) was useful to predict a diagnosis of growth hormone deficiency. Presentation: No date and time listed

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT). MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites. ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009). ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.

[Consistency evaluation of 2 methods in detecting serum insulin-like growth factorⅠ in children].

Objective: To evaluate the consistency of mass spectrometry (MS) and chemiluminescence immunoassay (CLIA) in detecting serum insulin-like growth factor-1 (IGF-1) and IGF-1 standard deviation score (SDS). Methods: This cross-sectional parallel control study prospectively collected the serum samples of 115 children with short stature disorders who were admitted in the Department of Endocrinology, Beijing Children's Hospital, Capital Medical University from February 2020 to December 2021. The serum IGF-1 level was detected by CLIA and MS, and converted to SDS for consistency analysis. Pearson analysis was used to analyze the correlation between the 2 methods, and Deming regression equation was established. Bland-Altman diagram and weighted Kappa coefficient were used to evaluate the consistency of the 2 methods. Results: There were 46 boys (40.0%) and 69 girls (60.0%), aged (8±3) years. Among the 115 cases, 37 were Turner syndrome, 59 were small for gestational age (SGA) at term, 1 was growth hormone deficiency (GHD) and 18 were other diseases. Pearson correlation analysis showed a preferable correlation between IGF-1 measured by the 2 detection methods (r=0.94, P<0.01), and IGF-1 SDS was also significantly correlated (r=0.92, P<0.01). Bland-Altman analysis showed that the consistency of serum IGF-1 levels detected by the 2 methods was poor, and the mean difference between CLIA and MS was 33.38 μg/L. The result detected by CLIA was significantly higher than that by MS, with SDS of 43.51 μg/L (95%CI -51.89-118.7 μg/L). After converting the results to SDS and removing 3 outliers (including 1 GHD patient), the weighted Kappa showed acceptable consistency (κ=0.68). Conclusion: In clinical application, after converting to IGF-1 SDS, IGF-1 detected by MS and CLIA can be used for cross-reference, but too high or too low levels should be cautious about.

Association Between the Growth Hormone/Insulin-Like Growth Factor-1 Axis and Muscle Density in Children and Adolescents of Short Stature.

ObjectiveTo evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature.MethodsParticipants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition.ResultsA total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2  = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (β = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (β = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (β = 0.180, P < .01 and β = 0.222, P < .01).ConclusionsA chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.

The Association Between Serum Zinc Levels and Anthropometric Measurements and Nutritional Indicators in Children With Idiopathic Short Stature.

BackgroundZinc (Zn) is an essential trace element, and its deficiency causes various symptoms, such as anemia, short stature, and poor weight gain, in children. Several studies have reported an association between Zn deficiency and short stature in children. However, few studies have reported on the relationship between serum Zn levels, body mass index (BMI), and nutritional indicators such as albumin, amino acids, and vitamin D.MethodsWe retrospectively analyzed the data of 56 children with idiopathic short stature. We investigated the mean serum Zn levels and the relationships among serum Zn levels and height standard deviation score (SDS), bodyweight SDS, BMI SDS, hemoglobin (Hb), albumin, alkaline phosphatase (ALP), insulin-like growth factor-1 (IGF-1), 25-hydroxyvitamin D (25(OH)D), and amino acid levels.ResultsThe mean serum Zn levels of the study participants were 70.3±10 µg/dL. Serum Zn levels correlated significantly with weight SDS (r=0.472, p<0.001) and BMI SDS (r=0.416, p<0.001). In contrast, no significant association was found between serum Zn levels and height SDS (r=0.217, p=0.078). We found significant positive correlations between serum Zn levels and Hb and IGF-1 SDS (Hb: r=0.333, p=0.012; IGF-1 SDS: r=0.372, p=0.00478). Serum Zn levels were not correlated with albumin, ALP, 25(OH)D, and amino acid levels.ConclusionsSerum Zn levels are associated with anthropometric measurements, especially body weight and BMI. It is important to evaluate Zn levels in children who fail to thrive, even in developed countries.

Pediatric Continuous Reference Intervals of Serum Insulin-like Growth Factor 1 Levels in a Healthy Chinese Children Population – Based on PRINCE Study

ObjectivesWe aimed to establish age- and sex-dependent reference intervals for insulin-like growth factor 1 (IGF-1) based on the measurements of healthy Chinese children from the pediatric reference intervals in China study and to investigate whether body mass index (BMI) and height affect IGF-1 levels. MethodsA total of 3753 individuals with eligible blood specimens resampled from the pediatric reference intervals in China population were enrolled as reference individuals. IGF-1 levels were measured using a chemiluminescent immunoassay kit. The lower limit and upper limit values of the reference individuals were calculated by defining the 2.5th and 97.5th percentiles. The skewness-median-coefficient of variation method was used to calculate the standard deviation score (SDS) of serum IGF-1, and cubic spline curves were applied to depict a smoothed curve for each age- and sex-specific stratification of the L, M, and S parameters. ResultsSerum IGF-1 levels increased with age from the age of 1 year, peaking at around the age of 13 years in girls and 15 years in boys and then began to decline (both P <.001). Before 14 years, IGF-1 levels were higher in girls than in boys at the same age, and the difference was statistically significant (P < .05), but there was no significant difference in the IGF-1 levels between girls and boys aged 14 to 16 and 18 years. The Spearman correlation coefficients of height SDS, weight SDS, and BMI SDS with IGF-1 SDS were 0.29, 0.33, and 0.20, respectively (P < .001). ConclusionThis study established age- and sex-specific normative IGF-1 data for Chinese children and adolescents between the ages of 1 and 19 years. The BMI and height SDS had no effect on IGF-1 levels in healthy children.

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Evaluation of metabolic factors affecting the presence of hepatosteatosis and the effect of insulin like growth factor-1 level in overweight and obese children

Although previous studies related to non-alcoholic fatty liver disease (NAFLD) in childhood were predominantly ALT and uric acid level, the number of studies that have been handled in terms of insulin like growth factor-1 (IGF-1) level or IGF-1 standard deviation score (SDS) is limited. In this study, all factors that may affect NAFLD, including IGF-1 level and IGF-1 SDS, were evaluated in two groups of children who were not statistically different from each other in terms of age, gender, weight, height, body mass index and puberty. This study was a cross sectional study. 36 children with evidence of fatty liver disease on ultrasound imaging and 38 children without it were included in the study. Anthropometric data, laboratory measurements and radiological results of all participants were evaluated. All factors that could affect NAFLD were evaluated by binary logistic regression analysis. Weight, weight SDS, body mass index (BMI) SDS, homeostasis model assessment of insulin resistance (HOMA-IR), AST, ALT, GGT, uric acid, triglyceride, HDLcholesterol, IGF-1, IGF-1 SDS were evaluated in this model to predict NAFLD. In the statistical model, the percentage of predicting those with NAFLD, that is, the sensitivity, was 88.9%, while the detection rate of those without NAFLD, that is, the specificity, was 94.7%. IGF-1 level was found to be significantly lower in the group with NAFLD (p: 0.04), but there was no significant difference between the groups in terms of IGF-1 SDS (p: 0.10). There are conflicting results in studies examining the relationship between IGF-1 SDS and NAFLD. This may be due to ethnicity, regional differences, kit-specific laboratory reference ranges, or method of measurement. Laboratory measurements including appropriate parameters with a detailed physical examination can be used to predict the presence of NAFLD without the need for radiological examination.

Evaluation of early retinal vascular changes by optical coherence tomography angiography in children with type 1 diabetes mellitus without diabetic retinopathy.

To evaluate macular and peripapillary vascular changes by optical coherence tomography angiography (OCTA) in children with type 1 diabetes mellitus (T1DM) without diabetic retinopathy (DR). This study included 46 patients with T1DM and 46 age-sex matched healthy subjects. All participants were evaluated in terms of macular and optic disk parameters by using AngioVue. Foveal avascular zone (FAZ) area, macular and optic disk vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as disease duration, mean hemoglobin A1c (HbA1c), insulin-like growth factor 1 (IGF-1) standard deviation score (SDS), homocysteine (Hcy) level, body mass index (BMI) SDS and daily insulin dose was also investigated in T1DM group. No significant difference was found in FAZ area and optic disk radial peripapillary capillary (RPC) VD comparing diabetic and control groups. In all macular regions, VD was significantly lower in T1DM versus control group both in superficial capillary plexus (SCP) and deep capillary plexus (DCP). None of the metabolic parameters was correlated with FAZ area and optic disk RPC-VD. Vascular density in SCP was negatively correlated with mean HbA1c and positively correlated with IGF-1 SDS. Homocysteine level was negatively correlated with DCP-VD in all areas. In children with T1DM without clinically apparent DR, VD in SCP and DCP was decreased and OCTA is a valuable imaging technique for detecting early vascular changes. The metabolic parameters such as mean HbA1c, IGF-1 SDS and Hcy affect the macular VD in diabetic children. 2011-KAEK-2, 2021/4, Trial registration date: 02.04.2021.

Thyroid function in children with short stature accompanied by isolated pituitary hypoplasia.

Few studies have focused on thyroid function in children with isolated pituitary hypoplasia (IPH). The purpose of this study was to investigate thyroid function in children with short stature accompanied by IPH and evaluate the values of thyroid function for the diagnosis of IPH. This was a retrospective observational study. A total of 100 children with short stature accompanied by IPH were enrolled. Among them, 68 children presenting with isolated growth hormone deficiency (IGHD) were chosen as the IPH group. Sixty-eight age-matched and sex-matched IGHD children without pituitary abnormalities were chosen as the control group. Clinical, hormonal, and imaging parameters were analyzed. The diagnostic value of thyroid function for IGHD children with IPH was evaluated. Children in the IPH group had significantly lower height standard deviation score (HSDS), HSDS-target height standard deviation score (THSDS), free thyroxine (FT4), insulin-like growth factor-1 standard deviation score (IGF-1SDS), and pituitary height than the control subjects (p = 0.027, p = 0.033, p < 0.001, p = 0.03, and p < 0.001, respectively). The value of the area under the curve (AUC) was 0.701 (95% CI 0.614-0.788, p < 0.001) when the cut-off value for FT4 was ≤ 16.43pmol/L and the sensitivity and specificity were 72.1 and 61.8%, respectively. FT4 levels were positively correlated with FT3, GH peak, and IGF-1 SDS levels in all children with short stature accompanied by IPH (p < 0.001, p = 0.009, and p = 0.01, respectively). IGHD children with IPH had lower FT4 levels than IGHD children without pituitary abnormalities. FT4 levels may have diagnostic value for IGHD children with IPH.

Vitamin D content in children with short stature due to intrauterine growth restriction against normosomatotropinemia

Background. There are no data about the status of vitamin D and its effect on the growth hormone/growth factors axis in prepubertal children with intrauterine growth restriction (IGR). Of particular interest is a group of patients who remain significantly short on the background of a decrease in insulin-like growth factor 1 (IGF-1) levels and normal stimulated release of growth hormone (GH). The purpose of our study was to determine the levels of 25-hydroxycalciferol in the blood plasma of prepubertal children with short stature due to IGR on the background of normosomatotropinemia. Materials and methods. We examined 34 prepubertal children (14 girls and 20 boys) with short stature (average age — 6.95 ± 0.46 years) who had signs of IGR at birth. A symmetrical type of IGR was found in 15 (44.2 %) patients, an asymmetrical type — in 19 (55.8 %). According to the results of functional tests all patients had a normal GH peak release (&gt; 10 ng/ml). Thyroid-stimulating hormone, free thyroxine levels in the blood plasma were determined by the immunoradiometric assay with standard Immunotech® kit (Czech Republic). At the time of examination, all patients were euthyroid. GH, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3) levels were determined by enzyme-linked immunosorbent assay using Immulite 2000 Xi kits (Siemens, USA). 25-hydroxycalciferol level was determined by the immunochemiluminescent method (Abbott, USA). The results were evaluated according to the guidelines of the International Society of Endocrinology (2011). Results. It was found that in prepubertal children with IGR signs at birth, the average height standard deviation score (SDS) at the time of the examination was –2.83 ± 0.12. There were no significant differences between the height and body weight in patients with a symmetrical and an asymmetrical types of IGR at the time of examination (p &gt; 0.05). Vitamin D content in the blood plasma of children with IGR signs was 49.70 ± 2.17 nmol/l in the whole group. Vitamin D insufficiency below 75 nmol/l was found in 16 (47 %) patients, and vitamin D deficiency below 50 nmol/l — in 18 (53 %). No significant differences were found between vitamin D values in girls and boys with signs of IGR (51.79 ± 3.38 nmol/l and 48.36 ± 2.86 nmol/l, respectively, p &gt; 0.05). Height SDS in the group of patients with an asymmetrical type of IGR weakly correlates (r = 0.38) with vitamin D content. Vitamin D level significantly differed depending on IGR type (in a symmetrical type — 44.1 ± 3.2 nmol/l, in an asymmetrical type — 54.20 ± 2.56 nmol/l, p &lt; 0.05). IGF-1 SDS in the group of patients with an asymmetrical type of IGR weakly correlated (r = 0.36) with vitamin D level. On the background of a significant decrease in IGFBP-3 content in children with an asymmetrical type of IGR compared to those with a symmetrical type (–1.32 ± 0.07 SDS and –1.00 ± 0.14 SDS, p &lt; 0.05), there was a reduction in IGF-1 levels (–1.62 ± 0.10 SDS and –1.34 ± 0.14 SDS, p = 0.05). Conclusions. Patients born with signs of IGR, even against normosomatotropinemia, may still have significant growth deficit, a sharp decrease in IGF-1 and IGFBP-3 for a long time after birth. The results obtained indicate the presence of hypovitaminosis D in all prepubertal patients who were born with the signs of intrauterine growth restriction. No correlation was found between vitamin D level and the maximum peak of stimulated growth hormone release. However, patients with an asymmetrical type of IGR have a weak correlation (r = 0.36) between IGF-1 SDS and vitamin D content, a significant decrease in the content of IGF-1, IGFBP-3, as well as vitamin D compared to its level in a symmetrical type of IGR. It is recommended to include the determination of vitamin D level in the blood plasma irrespective of the type of disease and the state of somatotropic function in the list of studies for the examination of children with short stature who were born with signs of intrauterine growth restriction.

Reduced Insulin-Like Growth Factor 1 Is Associated with Insulin Resistance in Obese Prepubertal Boys.

As one of the most common features of obesity, insulin resistance is central to the pathogenesis of the metabolic syndrome. Low insulin-like growth factor 1 (IGF-1) levels have been proven to be associated with many traditional cardiovascular risk factors, but it still remains controversial with the relationship between IGF-1 and insulin resistance. Accordingly, the main purpose of this study is to investigate the relationship between IGF-1 and insulin resistance in obese prepubertal boys. We used the whole-body insulin sensitivity index (WBISI) to represent insulin resistance. 70 obese prepubertal boys were included in the study, and the obese subjects were divided into two groups by using 1.285 as a threshold value for WBISI. Clinical examination and laboratory examinations were assessed for all participants. Among obese boys, the group of children with WBISI ≤ 1.285 had lower IGF-1 standard deviation scores (SDS) (p = 0.021) than the WBISI > 1.285 group. The results of multiple linear analyses show that lg WBISI was positively correlated with IGF-1 SDS (p = 0.031) after adjusting for traditional cardiovascular risk factors. IGF-1 SDS was negatively associated with insulin resistance in obese prepubertal boys, independent of other traditional cardiovascular disease risk markers.

Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6–8 Years Old: A Retrospective Study

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. Objective: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6–8 years. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75–2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.

Important Tools for Use by Pediatric Endocrinologists in the Assessment of Short Stature

Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions. It was reported that electronic monitoring and new algorithms have been devised that are providing more sensitive referral for short stature. In addition, computer programs have improved ways in which diagnoses are coded for use by various groups including healthcare providers and government health systems. Innovative cranial imaging techniques have been devised that are considered safer than using gadolinium contrast agents and are also more sensitive and accurate. Deep-learning neural networks are changing the way that bone age and bone health are assessed, which are more objective than standard methodologies. Models for prediction of growth response to growth hormone (GH) treatment are being improved by applying novel artificial intelligence methods that can identify non-linear and linear factors that relate to response, providing more accurate predictions. Determination and interpretation of insulin-like growth factor-1 (IGF-1) levels are becoming more standardized and consistent, for evaluation across different patient groups, and computer-learning models indicate that baseline IGF-1 standard deviation score is among the most important indicators of GH therapy response. While physicians involved in child growth and treatment of disorders resulting in growth failure need to be aware of, and keep abreast of, these latest developments, treatment decisions and management should continue to be based on clinical decisions. New digital technologies and advancements in the field should be aimed at improving clinical decisions, making greater standardization of assessment and facilitating patient-centered approaches.