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Introduction: The diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery. Objective: To characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1. Methods: Nuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis. Results: The results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power. Conclusions: This study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results. [ABSTRACT FROM AUTHOR]

Context In patients with GH deficiency (GHD) receiving GH treatment, IGF-1 concentrations are used by physicians to monitor treatment safety and efficacy and guide dosing decisions. Somatrogon is a long-acting GH approved as a once-weekly treatment for pediatric GHD. Somatrogon administration results in characteristic changes in the IGF-1 profile, with values measured at 96 hours postdose representing mean IGF-1 concentrations that best reflect overall somatrogon exposure. Objective To develop a simple method to enable physicians to predict mean IGF-1 concentrations following somatrogon dosing, based on a single IGF-1 measurement taken at any point during the 7-day dosing interval. Methods Data from phase 2 and phase 3 somatrogon studies were used to develop a 2-compartment pharmacokinetic model with delayed first-order absorption. An indirect-response pharmacokinetic/pharmacodynamic model was applied to the predicted somatrogon concentrations, and model simulations were used to predict IGF-1 and IGF-1 SD score (SDS) levels for participants in both studies. Results A total of 16,213 dosing records (from 42 and 109 participants in the phase 2 and 3 studies, respectively) were used for the simulations, generating predicted values for IGF-1 and IGF-1 SDS. Predicted values were scaled against the respective values at 96 hours (day 4). These values were used to create a table showing the adjustments required to predict mean IGF-1 and IGF-1 SDS values depending on time after dose. Conclusion We developed a simple method enabling physicians to predict mean weekly IGF-1 values using IGF-1 values measured at any point in the dosing interval. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the response to growth hormone (GH) therapy according to the presence of GH deficiency (GHD) in short-stature children born small for gestational age (SGA) in Korea and to present appropriate GH dose criteria. Methods: We evaluated 27 children born SGA with short stature and GHD (GHD group) and 23 without GHD (non-GHD group) registered in the LG Growth Study. Growth responses and changes in GH dose over a 2-year GH therapy period were compared, and the factors affecting growth response were investigated. Results: The standard deviation scores (SDSs) for baseline weight and body mass index (BMI) were significantly lower in boys without GHD than in boys with GHD. The SDS for insulin-like growth factor-1 (IGF-1) was lower among boys without GHD than among boys with GHD, while the SDS for insulin-like growth factor-binding protein-3 (IGFBP-3) was higher among girls without GHD than among girls with GHD; however, there was no significant difference when comparing all children with GHD to those without GHD. Regardless of the presence of GHD, the difference between chronological age and bone age decreased annually. Notably, there was significantly rapid bone age progression among patients without GHD. The findings showed differences in GH dose according to GHD starting from the 2nd year of therapy, with the non-GHD group receiving a significantly higher dose. Regarding the factors affecting growth response, younger age and bone age, higher height SDS, BMI SDS and MPH SDS were related to higher growth response (Δheight SDS and Δgrowth velocity), but there was no statistically significant correlation. Conclusion: GHD is rare among children born SGA. Nonetheless, if there are any signs of decreased growth velocity or hypopituitarism, the presence of GHD should be assessed before GH therapy, and personalized therapy based on the results is required. [ABSTRACT FROM AUTHOR]

Purpose: Craniopharyngiomas (CPs) often lead to growth hormone deficiency (GHD) in children. Growth hormone replacement therapy (GHRT) is essential for managing GHD but its impact on body mass index (BMI) and metabolic outcomes is controversial. Concerns exist that GHRT might contribute to tumor recurrence, with guidelines varying on when to start therapy post-surgery. This updated systematic review and meta-analysis explores the effects and timing of GHRT in children post-craniopharyngioma surgery. Methods: We systematically searched PubMed, Embase, and Cochrane Library databases. Included studies compared the effects of GHRT in childhood-onset craniopharyngioma patients who received GHRT versus those who did not. Random-effects meta-analyses were used to pool relative risk (RR) or mean difference (MD) for each outcome. Heterogeneity was assessed using the I² statistic. This study is registered with PROSPERO (CRD42024498082). Results: We included 11 studies in the meta-analysis. No differences in tumor progression/recurrence were found between the GHRT and no GHRT groups (RR 0.77, 95% CI 0.56–1.05, p = 0.10). The impact of timing of GHRT is less clear because of limited data and high heterogeneity. There were no differences in BMI between the GHRT and no GHRT (MD -0.94, 95% CI -1.88,0.00, p = 0.05). Two studies reported that GHRT might improve lipid profiles. Conclusion: Our study suggests that GHRT does not increase the risk of tumor progression/recurrence in CP patients. GHRT can improve linear growth, but its effects on the BMI and lipid profiles remain inconclusive, requiring further studies. [ABSTRACT FROM AUTHOR]

Objective: In boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa). Methods: Fifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n = 28) or the combination of GnRHa and rhGH (GnRHa group, n = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH). Results: The increase in height of the letrozole group was significantly more than the GnRHa group both in the first year [(10.37 ± 2.19) vs. (7.78 ± 1.55) cm] and at two years [(18.82 ± 2.49) vs. (13.84 ± 2.17) cm] (p < 0.05), however, there was no significant group difference in the advancement of bone age (BA) of in the first year or at two years (p > 0.05). The mean FAH in two groups were similar, but the treatment duration of the letrozole group was significantly less than GnRHa group. There was a significant body mass index (BMI) SDS increase in the letrozole vs. GnRHa groups. Of concern, bone mineral density (BMD) decreased in both groups after treatment, but more so in the letrozole cohort. Conclusion: The combination of letrozole/rhGH in pubertal GHD boys was similar to GnRHa/rhGH in terms of the progression of BA and FAH, but the former co-therapy was superior in the gain of height. Disconcertingly, however, this combination may adversely affect BMI and BMD. Clinical trial registration number: ChiCTR2300068405. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) is the most frequently occurring pituitary hormone deficiency. Lesions in the hypothalamo-pituitary region and their treatment, pituitary apoplexy, empty sella, Sheehan's syndrome, traumatic brain injury, infective, autoimmune, infiltrative, and genetic causes may contribute to the development of GHD. Diagnosis of GHD relies on serum insulin-like growth factor-1 (IGF-1) levels, which may be low based on age/gender reference levels. Insulin-like growth factor-1 may not be diagnostic alone, and stimulation tests may be needed. The insulin tolerance test is considered the gold standard, with the growth hormone-releasing hormone-arginine test and the glucagon stimulation test as primary alternatives. Recently, a novel test with high diagnostic accuracy, macimorelin, an oral growth hormone (GH) secretagogue receptor agonist and ghrelin-mimetic, has been used. Adult GHD does not have pathognomonic clinical features. Decreased energy, reduced quality of life, depressive mood, increased fat mass, dry skin, osteoporosis, hypertension, dysglycemia, dyslipidemia, and increased cardiovascular risks are the most commonly reported findings, which are all may be seen in several diseases. Recombinant human GH is an effective and safe treatment, beneficial for body composition, bone, lipid profile, and quality of life, but it is costly, and not all patients with GHD may require treatment. If there is no benefit after 6-12 months of treatment, it may be discontinued. The best follow-up parameters for GH treatment are clinical response and serum IGF-1 levels, which should be kept within the mid-normal range, adjusted for age and gender. In this review, we extensively discussed GHD in adults with current data. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to examine the correlation between the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after 1 year of treatment with GH to the initial clinical and biochemical parameters. Additionally, the secretion dynamics of GH was also studied by analyzing the GH stimulation test profiles in relation to the GH treatment response. Methods This retrospective study included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GH max , GH secretion rate, and GH secretion volume were analyzed in relation to the response to recombinant human growth hormone (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. ResultsIoR was negatively correlated with the age (r=–0.607, p<0.01) and positively with the distance of child's height from its midparental height (MPH) r=0.466 (p<0.01) and pretreatment growth velocity (r=0.247, p<0.05). GH secretory indexes were correlated, and the highest association was observed between GH max and GH secretion volume (r=0.883, p<0.01). Among the GH secretory indexes, GH max was the best predictor of IoR (β coef. = –0.514, p<0.001) followed by the GH secretion volume (β coef. = –0.47, p<0.001) and GH secretion rate (β coef. = –0.367 p<0.001). Conclusions The age and the distance of child's height from its MPH are major predictors of GH 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 GH than GH max. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment. [ABSTRACT FROM AUTHOR]

Objectives: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. Methods: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. Results: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). Conclusions: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. Clinical trial registration: . [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To evaluate the indications, population characteristics and latency between short stature diagnosis to treatment with recombinant growth hormone (GH) therapy in a large cohort of children in Israel.We performed a retrospective medical chart review of all children treated with GH for conditions associated with short stature in three central districts in Israel from 1 January 2010 to 31 December 2021. Data extracted from the medical files included demographics, time to diagnosis, treatment indications and GH therapy duration.The study group comprised 5148 children aged 1 day to 17 years. A total of 64.1% were diagnosed with idiopathic short stature (ISS), 31.1% with GH deficiency (GHD) and 2.5% with small‐for‐gestational age (SGA). Males were treated more than females (58.9% vs. 41.1%). The mean age at first documentation of short stature was 6.9 ± 3.5 years. GH therapy was initiated at a mean age of 9.8 ± 3.3 years. A total of 51.2% were of high socio‐economic status (SES); 78.2% were non‐ultraorthodox Jews, 13%, ultraorthodox Jews, and 8.8% were Arabs.Meticulous growth follow‐up from early childhood for all children, specifically females, those of low SES, and minorities is important to provide appropriate referral, treatment and final adult height outcomes. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the impact of polyethylene glycol - conjugated recombinant human growth hormone (PEG - rhGH) treatment on immune function in children with growth hormone deficiency (GHD), by analyzing changes in lymphocyte subsets, immunoglobulin levels, and T helper cell (Th1/Th2) cytokines before and after treatment. Methods: Fifty - five children diagnosed with GHD were enrolled as study participants from May 2022 to June 2023 at the Department of Pediatrics of Huai' an First People's Hospital and Hongze District People's Hospital. According to the preferences of the participants, they were allocated into a control group (n=25) and a PEG-rhGH group (n=30) . The control group received guidance on exercise, diet, and sleep, while the PEG-rhGH group received PEG-rhGH treatment in addition to these interventions. Measurements of height, bone age, BMI, insulin-like growth factor -1 (IGF -1), lymphocyte subsets, Th1/Th2 cytokines, and immunoglobulin (Ig) levels were conducted at baseline and 3 months post-treatment. The changes in various parameters before and after the intervention were compared. Results: Before treatment, there were no significant differences in the baseline levels of the various indicators between the two groups. After 3 months of treatment, the standard deviation of height, growth rate, and serum IGF - 1 level in the PEG - rhGH group significantly increased compared to pre - treatment levels and were notably higher than those in the control group. After treatment, the PEG - rhGH group demonstrated a significantly higher proportion of CD3+, CD4+ and CD4+ /CD8+ as well as elevated levels of IgA, IgM, and IgG compared to the control group, while the proportion of CD8+ cells was notably lower in the PEG-rhGH group than in the control group, There were no significant differences in the proportion of CD19 + and CD3- CD16 + CD56 + cells between the two groups. Additionally, the levels of Th1/Th2 cytokines, interleukin (IL) -2, IL-6, and tumor necrosis factor-α (TNF-α) in the PEG-rhGH group were significantly lower after treatment compared to before, and were significantly lower than those in the control group. There were still no significant differences in the levels of IL-4 and interferon-γ (IFN-γ) between the two groups. Conclusion: PEG-rhGH treatment not only improves the height of GHD children but also affects their cellular immunity and humoral immunity. [ABSTRACT FROM AUTHOR]

Purpose: There is controversy as to whether brain magnetic resonance imaging (MRI) should be performed on all children with growth hormone deficiency (GHD) including those judged to have mild GHD. This study was aimed to determine the frequency of pituitary or intracranial abnormalities in pediatric GHD and to identify risk factors that may predict pituitary or intracranial abnormalities. Methods: A total of 95 pediatric GHD patients were included. Their medical records and brain magnetic resonance (MR) images were reviewed retrospectively. Results: Abnormal pathogenic MR images were found in 14 patients (14.7%), including 10 (10.5%) with pituitary hypoplasia and 4 (4.2%) with pituitary stalk interruption syndrome. Serum levels of insulin-like growth factor-I (IGF-I), IGF-I standard deviation score (SDS), insulin-like growth factor binding protein 3 (IGFBP3), and growth hormone (GH) peak level of GH stimulation test were statistically significantly lower in the group with abnormal brain MRI. The frequency of abnormal MRI was statistically significantly higher in the complete GHD group. IGF-1 SDS showed the highest area under the curve which can predict the presence of brain abnormality with a sensitivity of 85% and a specificity of 71.4%, if IGF-1 SDS was less than -1.365. IGF-1, IGFBP3, and GH peak levels also showed good sensitivity of over 80% for predicting brain abnormalities with cutoff values of 70.285 ng/mL, 1,604 ng/mL, and 4.205 ng/mL, respectively. Conclusion: The sensitivity and specificity of each cutoff value of IGF-1, IGF-1 SDS, IGFBP3, and GH peak levels were good and statistically significant in predicting brain MRI abnormalities. However, it was insufficient to predict all brain abnormalities with these variables. Therefore, we would like to recommend performing a brain MRI if a child is diagnosed with GHD. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) diagnosis still lacks a gold standard or ideal diagnostic marker. Unlike other epigenetic mechanisms, non-coding RNAs regulate post-transcriptional levels. The information on non-coding RNAs in the field of GHD is limited. Therefore, this study aimed to explore the role of hsa_circ_0002473 as a competitive endogenous RNA for has-miR-4645-3p in attenuating the inhibitory effect of has-miR-4645-3p on SSTR2. In this study, we screened three significantly expressed circular RNAs (circRNAs) in five children with GHD, and selected the highest expressed hsa_circ_0002473 as the study object, and screened has-miR-4645-3p, which is the most likely to bind to hsa_circ_0002473, according to the microRNA (miRNA)-circRNA regulatory network, to study the role and mechanism of has-miR-4645-3p as a competitive endogenous RNA of has-miR-4645-3p on GH3 cells. Somatostatin receptor 2 (SSTR2) inhibits GH3 cell proliferation, and miRNA binding to SSTR2 inhibits the latter expression. Both bioinformatics and dual-luciferase reporter analyses showed targeting relationships between hsa_circ_0002473 and has-miR-4645-3p and between has-miR-4645-3p and SSTR2. We constructed the hsa_circ_0002473/has-miR-4645-3p axis and transfected it into GH3 cells and found that overexpression of hsa_circ_0002473 inhibited the proliferation and growth hormone (GH) secretion of GH3 cells, and that hsa-miR-4645-3p promoted the proliferation and GH secretion of GH3 cells by targeting SSTR2. Co-culture revealed that the inhibitory effect of hsa_circ_0002473 was reversed by has-miR-4645-3p. In conclusion, our findings suggest that hsa_circ_0002473 can act as a competitive endogenous RNA for has-miR-4645-3p to regulate GH3 cell proliferation and secretion by targeting SSTR2. [ABSTRACT FROM AUTHOR]

Background Growth hormone (GH)-related short stature is a rare but important problem during pediatric follow-up. The determination of pituitary anatomy via pituitary magnetic resonance imaging (MRI) is an important tool in the diagnosis of GH disorders and acquired pituitary diseases. Pituitary dimensions in children vary according to age, and clear limits are not known. In this study, we investigated the relationship between pituitary MRI findings and GH in patients with GH deficiency (GHD) and bioinactive GH. Materials and Methods A total of 306 pediatric patients with GHD and bioinactive GH were analyzed. Pituitary MRI was performed in all patients, and the diagnoses were divided into 3 groups: severe GHD, mild-moderate GHD, and bioinactive GH. Results According to pituitary size, 63.4% of patients had a normal pituitary MRI scan, 27.5% were hypoplastic, and 0.3% were hyperplastic. Pituitary height and volume were lower in patients with severe GHD than in the mild-moderate group (p<0.05). The most effective measurement of pituitary volume was the height of the pituitary gland. A significant correlation was observed between the height standard deviation score and pituitary height (r=0.824, p<0.001). The relationship between peak GH level and pathologic MRI was analyzed. Cut-off 14.5 area under the curve (AUC) (95%): 0.59 (0.52-0.67), sensitivity 97%, specificity 95% (p=0.007). Conclusion There was a strong correlation between GH and pituitary size measured by MRI for the estimation of pituitary volume. Pituitary height measurement alone is an important supportive finding for the diagnosis of isolated GHD in children with slow growth. Keywords:Bioinactive growth hormone, growth hormone deficiency, magnetic resonance imaging: [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA). Methods: A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion. Results: Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores. Conclusions: In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments. [ABSTRACT FROM AUTHOR]

Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates—and have protection from age-associated disease—they have become important fixtures in the aging field. On the other hand, the 12 "uncommon" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the central nervous system, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next-generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic. [ABSTRACT FROM AUTHOR]

Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome. [ABSTRACT FROM AUTHOR]

Abstract Objective In boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa). Methods Fifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n = 28) or the combination of GnRHa and rhGH (GnRHa group, n = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH). Results The increase in height of the letrozole group was significantly more than the GnRHa group both in the first year [(10.37 ± 2.19) vs. (7.78 ± 1.55) cm] and at two years [(18.82 ± 2.49) vs. (13.84 ± 2.17) cm] (p 0.05). The mean FAH in two groups were similar, but the treatment duration of the letrozole group was significantly less than GnRHa group. There was a significant body mass index (BMI) SDS increase in the letrozole vs. GnRHa groups. Of concern, bone mineral density (BMD) decreased in both groups after treatment, but more so in the letrozole cohort. Conclusion The combination of letrozole/rhGH in pubertal GHD boys was similar to GnRHa/rhGH in terms of the progression of BA and FAH, but the former co-therapy was superior in the gain of height. Disconcertingly, however, this combination may adversely affect BMI and BMD. Clinical trial registration number ChiCTR2300068405.

Abstract Background The purpose of this study is to evaluate the retinal and choroidal microvascular state in children with congenital isolated growth hormone deficiency (IGHD) and determine the effect of recombinant human growth hormone treatment on these structures compared with healthy controls. Methods The study included children with IGHD under recombinant human GH treatment as group one and another group of healthy controls. Both groups were examined using optical coherence tomography angiography (OCTA). Data concerning superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and retinal thickness were recorded. Results The study included two equal groups of 30 individuals. Both groups had no statistically significant differences in age, gender, weight, or spherical equivalent. However, subjects of group II were taller than those of group I (p = 0.011). OCTA images of the SCP, DCP, and CC vessel density revealed statistically non-significant differences between the two groups. Conclusion Children receiving recombinant growth hormone therapy showed no changes in the retinal and choroidal microvasculature or macular thickness. Trial registration number 1094/03/2024 by Minia University Faculty of Medicine Institutional Review Board. Another registration number is UMIN000055654.

Shahid Akhtar,1 Birgitte Berg,2 Johan Medina,3 Maya Nicole Gonczi,4 Sophie Hamilton,5 Emily Hildebrand,4 Nicky Kelepouris,6 Jesper Skov Neergaard,7 Claus Sværke,8 Gitte Ter-Borch,2 Niklas Kahr Rasmussen3 1Devices & Digital Health, Novo Nordisk A/S, Søborg, Denmark; 2Clinical Operations, Obesity, Liver Diseases & Devices, Novo Nordisk A/S, Søborg, Denmark; 3Medical & Science, Devices & Digital Health, Novo Nordisk A/S, Søborg, Denmark; 4Human Factors, Research Collective, Tempe, AZ, USA; 5Rare Endocrine Rare Renal Diseases, Novo Nordisk Inc, Plainsboro, NJ, USA; 6Rare Endocrine Disorders, Novo Nordisk Inc, Plainsboro, NJ, USA; 7Safety Surveillance, Cardiovascular Disease, Novo Nordisk A/S, Søborg, Denmark; 8Global Development, Novo Nordisk A/S, Søborg, DenmarkCorrespondence: Shahid Akhtar, Medical & Science, Devices & Digital Health, Novo Nordisk A/S, Vandtårnsvej 108– 110, Søborg, DK-2860, Denmark, Email SAHT@novonordisk.comPurpose: Adherence to growth hormone treatment is known to affect growth outcomes. Both device preference and ease of use have been shown to affect treatment adherence. In this study, we assessed device preference and ease of use with two long-acting growth hormones, somapacitan (Sogroya®, Novo Nordisk A/S) and somatrogon (Ngenla®, Pfizer).Patients and Methods: In a randomized, crossover study conducted between September 20 and November 2, 2023, we recruited 33 adolescents with a growth-related disorder, and 37 caregivers, at six locations in the United States. Each participant was trained in the use of both devices and asked to perform a simulated injection. Device training time, preparation and injection time, and injection completeness were recorded. Participants also completed the Device Handling and Preference Questionnaire (DHPAQ) to indicate their device preference and ease of use opinions. Following conclusion of the “standard” visit, 10 adolescents and 10 caregivers were randomly selected to participate in a sub-study to validate the relevance, comprehensiveness, and comprehension of the DHPAQ.Results: The majority of participants (84.3%; 95% confidence interval [CI]: 74;92) preferred the somapacitan device to the somatrogon device (p

Background: The purpose of this study is to evaluate the retinal and choroidal microvascular state in children with congenital isolated growth hormone deficiency (IGHD) and determine the effect of recombinant human growth hormone treatment on these structures compared with healthy controls. Methods: The study included children with IGHD under recombinant human GH treatment as group one and another group of healthy controls. Both groups were examined using optical coherence tomography angiography (OCTA). Data concerning superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and retinal thickness were recorded. Results: The study included two equal groups of 30 individuals. Both groups had no statistically significant differences in age, gender, weight, or spherical equivalent. However, subjects of group II were taller than those of group I (p = 0.011). OCTA images of the SCP, DCP, and CC vessel density revealed statistically non-significant differences between the two groups. Conclusion: Children receiving recombinant growth hormone therapy showed no changes in the retinal and choroidal microvasculature or macular thickness. Trial registration number: 1094/03/2024 by Minia University Faculty of Medicine Institutional Review Board. Another registration number is UMIN000055654. [ABSTRACT FROM AUTHOR]

Objective: To analyze the changes of vitamin D levels and prognostic factors in children with growth hormone deficiency before and after treatment with recombinant human growth hormone. Methods: 80 children with GH deficiency admitted during 2020.2-2023.2 were selected for recombinant human GH therapy. Compare relevant indicators and analyze prognostic factors. Results: The height, height standard deviation score and growth rate of children with GH deficiency increased compared with those before treatment (P<0.05); The serum expression levels of IGF-1 and IGFBP-3 in children with GH deficiency increased compared with those before treatment(P<0.05); Serum 25 (OH) D3,1, The expression level of 25-(OH) 2D3 was increased compared with that before treatment (P<0. 05); After the univariate and multivariate Logistic regression analysis, Pre-treatment growth rate, bone age maturity, and maternal pregnancy comorbidities were all independent factors for outcomes in children with GH deficiency (P<0.05). Conclusion: The growth-promoting effect of recombinant human growth hormone treatment helps to promote the metabolism of vitamin D, but the prognosis is influenced by pre-treatment growth rate, pre-treatment bone age maturity and maternal pregnancy comorbidities. [ABSTRACT FROM AUTHOR]

We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children had a diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/− hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in the normal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group. [ABSTRACT FROM AUTHOR]

We compared the effects of growth hormone (GH) treatment on height and predicted adult height in children with short stature born small for gestational age (SGA-SS) vs. with a growth hormone deficiency (GHD). This retrospective study analyzed the background and clinical characteristics of children who presented to Tanaka Growth Clinic for short stature and were diagnosed with either SGA-SS or GHD and underwent treatment with GH. We compared differences in height, height velocity, GH dose increases, insulin-like growth factor-1 levels, and bone-age/chronological-age ratio between the two groups. Out of these children, 33 SGA-SS and 54 GHD children started GH treatment before the age of 8 years, with a mean dose of 0.25 mg/kg/week and 0.20 mg/kg/week, respectively. At treatment initiation, the age and height standard deviation scores (SDS) of the SGA-SS group were significantly lower than those of the GHD group. The height velocity was significantly greater in the SGA-SS group for 3 years owing to higher GH doses and younger age. No notable differences in puberty onset height or predicted adult height were observed between the two groups for boys or girls. The increase in height SDS from the start of GH treatment until the onset of puberty was substantially greater in the SGA-SS group than in the GHD group for both sexes. Adult height of patients with SGA-SS is expected to resemble that of patients with GHD but may not reach the −1.0 SD achieved with GH treatment of those patients in Western countries. [ABSTRACT FROM AUTHOR]

The combination of rhGH and vitamin D has been suggested as a potential therapeutic approach for children with GHD. This retrospective study aimed to investigate the impact of recombinant human growth hormone plus vitamin D on development and lipid metabolism in children with growth hormone deficiency. A total of 198 children treated in our hospital from December 2011 to December 2021 were recruited. The study assessed development-related indices, lipid metabolism indices, growth factor indices, thyroid indices, and adverse reactions. After treatment, the development-related indices of children in both groups improved (P < 0.05), but the experimental group showed significantly better HtSDS and annual height growth rate (P < 0.05). Moreover, the experimental group had lower levels of TG, T-CHO, and LDL-C versus the observation group (P < 0.05), while no significant difference was observed in HDL-C levels between the two groups before and after treatment (P > 0.05). Moreover, patients receiving recombinant human growth hormone plus vitamin D had significantly higher IGF-1 and IGFBP-3 levels than those receiving recombinant human growth hormone alone (P < 0.05). The T3, T4, and TSH levels of children in both groups increased after treatment (P < 0.05). The incidence of adverse events did not significantly differ between the two groups (P > 0.05). In conclusion, our findings suggest that recombinant human growth hormone plus vitamin D effectively improves the development and lipid metabolism of children with growth hormone deficiency. Additionally, it increases growth factor levels without compromising thyroid function or increasing the risk of adverse drug reactions. [ABSTRACT FROM AUTHOR]

Introduction: Since direct comparisons of long-acting growth hormones (LAGHs) are lacking, analyses were performed to indirectly compare the efficacy and safety of somapacitan versus somatrogon and lonapegsomatropin in children with growth hormone deficiency (GHD). Methods: A systematic literature review (SLR) identified studies of once-weekly LAGHs for the treatment of pediatric GHD. Indirect comparisons (ICs) using a Bayesian hierarchical network meta-analysis and a random effects model were performed using daily growth hormone (GH) 0.034 mg/kg/day (base case) or 0.024–0.034 mg/kg/day (alternative analyses) as the common comparator to compare height outcomes to 52 weeks [annualized height velocity, height velocity standard deviation score (SDS), and height SDS]. Identified evidence did not allow IC of safety or longer-term efficacy outcomes so these were qualitatively described. Results: The SLR identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only), and one lonapegsomatropin trial comparing the LAGH with daily GH in treatment-naïve pre-pubertal children for IC. ICs revealed no differences at 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH, with respect to all growth outcomes considered in children with GHD. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily GH, with the exception of observed injection site pain for somatrogon. Conclusion: No efficacy and safety differences were identified in comparisons of once weekly somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH. All treatments were generally well tolerated, with the exception of observed injection site pain for somatrogon. Plain Language Summary: It is valuable to compare similarly acting treatments to determine their relative benefits and risks. Direct comparisons of long-acting growth hormones (LAGHs) are lacking, so analyses were performed to indirectly compare the efficacy and safety of the LAGH somapacitan versus the LAGHs somatrogon and lonapegsomatropin in children with growth hormone deficiency. Studies of once-weekly LAGHs for the treatment of pediatric growth hormone deficiency were identified using a systematic literature review, then the data obtained were indirectly compared using standard statistical methods with daily growth hormone 0.034 mg/kg/day (base case) or 0.024–0.034 mg/kg/day (alternative analyses) as the common comparator. Height outcomes to 52 weeks (annualized height velocity, height velocity standard deviation score, and height standard deviation score) were compared between treatments. Sufficient information to allow indirect comparison of safety or longer-term efficacy outcomes were not found so these were qualitatively described. The systematic literature review identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only) and one lonapegsomatropin trial comparing the LAGH with daily growth hormone in previously untreated pre-pubertal children for inclusion in the indirect comparison. Indirect comparisons identified no differences to 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily growth hormone, with respect to all growth outcomes considered in children with growth hormone deficiency. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily growth hormone, with the possible exception of injection site pain with somatrogon. [ABSTRACT FROM AUTHOR]

Background: Adult growth hormone deficiency (GHD) has been recognized since the late 1980s. The clinical manifestations of adult GHD are often nonspecific, and diagnosis relies on GH stimulation tests, which are intricate, costly, time-consuming, and may carry the risk of adverse effects. Diagnosis is further complicated by factors like age, sex, and BMI, which affect GH response during testing. Therefore, GH replacement therapy remains challenging, requiring careful individualized evaluation of risks and benefits. The aim of this review is to provide an update on diagnosing and treating adult GHD, addressing current limitations and challenges based on recent studies. Methods: We conducted a comprehensive review of the literature regarding the diagnosis and management of adult GHD by searching PubMed and EMBASE. Only articles in English were included, and searches were conducted up to August 2024. Results: A review of guidelines and literature up to 2024 highlights the significant heterogeneity in the data and reveals various protocols for managing GHD, covering both diagnostic and therapeutic approaches. Conclusions: Despite diagnostic and treatment advances, managing adult GHD remains challenging due to variable presentation and the need for personalized GH therapy. Future efforts should aim to improve and standardize diagnostic and treatment protocols. [ABSTRACT FROM AUTHOR]

Objective: To explore the differences in general information and serological indicators in children with growth hormone deficiency (GHD), and to establish a predictive model for early diagnosis of GHD using a column chart. Methods: A retrospective analysis was conducted on the hospitalization data of 719 children who visited our hospital due to low height between July 2021 and October 2023. The 719 children were divided into GHD group (474 cases) and non GHD group (245 cases) according to the growth hormone stimulation test. The serum IGF-1 levels of the patients were measured, and LASSO regression analysis was used to screen for the best predictive factors. Multiple factor logistic regression analysis was used to establish a column chart prediction model. The ROC curve verifies the performance of this mode. Results: Compared with the GHD group, the age The differences in BMI, ALT, AST, ALKP, IGF-BP, FFA, and IGF-1 data were statistically significant (P<0.05). The results of logistic regression analysis indicate that age ALT, AST, ALKP, IGFBP, FFA, and IGF-1 are early predictors of growth hormone deficiency. The C-index for internal validation of the column chart prediction model is relatively high. The AUC of the prediction model is 0.845 (95% CI: 0.801-0.891), which proves that the model has good predictive performance and discriminative ability. Conclusion: Age ALT, AST, ALKP, IGFBP, FFA, and IGF-1 are predictive factors for early growth hormone deficiency. Based on the above indicators, a column chart prediction model for early diagnosis of growth hormone deficiency has been successfully established. Internal validation shows that the model has good performance and certain clinical diagnostic value. [ABSTRACT FROM AUTHOR]

The study endeavored to evaluate the prolonged efficacy and safety of PEGylated rhGH (PEG-rhGH) administration in Chinese children diagnosed with growth hormone deficiency (GHD) over a 5-year period. A retrospective analysis was conducted on children with GHD, who received a 0.2 mg/kg/week dose of PEG-rhGH between 2016 and 2023 in our department. The height standard deviation score (Ht SDS) exhibited a marked elevation post-PEG-rhGH administration (p<0.001), sustaining this enhancement beyond year 3, with increments recorded at 0.94±0.37, 1.49±0.48, 1.77±0.51, 2.12±0.65, and 2.15±0.58 across 5 years. Similarly, the height velocity (HV), insulin-like growth factor-1 standard deviation score (IGF-1 SDS), and bone age to chronological age ratio (BA/CA ratio) underwent significant augmentations (p<0.01). Remarkably, no signs of rapid bone maturation were detected during the 5-year observation. Among the participants, 31 patients (59.62 %) experienced adverse events, of which eight instances (15.38 %) were classified as treatment-related adverse events, but none were severe or unexpected. Additionally, high-density lipoprotein (HDL) levels rose while low-density lipoprotein (LDL) levels fell, both remaining within the standard range throughout the treatment phase. Administering PEG-rhGH at a dosage of 0.2 mg/kg/week proved both effective and well-tolerated in treating prepubertal children with GHD. This regimen also demonstrated positive impacts on lipid metabolism over an extended treatment period. [ABSTRACT FROM AUTHOR]

Pediatric growth hormone deficiency (PGHD) is a chronic condition where the pituitary gland fails to produce sufficient growth hormone, leading to delayed growth and developmental challenges. Patient journey maps can provide insight into pain points and potential opportunities for new or improved interventions to enhance care. However, a patient journey map does not yet exist for PGHD. Secondary data analysis was performed on interviews and focus groups from five cohorts in Sweden, the United Kingdom, Luxembourg, France, and The Netherlands. Participants included 62 patients and caregivers who used a prototype digital health solution, which was used to guide discussions. Grounded theory was used to analyze the data, resulting in a patient journey map comprising six stages: awareness, diagnosis, treatment planning, treatment initiation, treatment maintenance and transition. This provides the first detailed PGHD patient journey map, revealing emotional sensitivities and challenges at each stage, and suggesting areas for targeted interventions to improve adherence and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Brain magnetic resonance imaging (MRI) is mandatory or highly recommended in many pediatric endocrinological conditions to detect causative anatomic anomalies and rule out neoplastic lesions. However, MRI can also show findings associated with the underlying clinical condition, as well as unrelated "incidentalomas". These latter findings are often abnormalities with a high incidence in the general population for which there is no clear literature regarding their management, especially in pediatric patients. The present study aimed to evaluate the number of unnecessary performed MRIs in pediatric endocrinology. Methods: Retrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty). Results: The MRI scans were completely normal in 67% of the individuals, and the prevalence of individuals who underwent more than one MRI was 18%, with no significant differences among the groups. The overall prevalence of incidentalomas was 17%. Among 170 repeated MRI scans, 147 (86%) were not required according to a dedicated protocol. Only five patients (four GHD, one Noonan) correctly repeated the MRI. All the repeated MRI scans did not reveal any progression in the findings. If we include the MRIs performed in cases of OCSS other than Noonan syndrome (n=32) and girls with CPP older than 6 years (n=89), an additional 121 MRIs could have been avoided, leading to a total number of unnecessary MRIs to 268 (46%). Conclusions: Only a few specific neuroimaging findings in endocrinologic pediatric patients warrant further investigation, while too often repeated imaging is carried out unnecessarily. We advocate the importance of guidelines to reduce costs for both the healthcare system and patients' families, as well as to alleviate physical and psychological distress for patients and caregivers. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Among a significant number of existing polymorphisms of the COL1A1 gene, the most studied is the polymorphism in the transcription initiation site SpI (+1245 G/T, rs1800012), and the heterozygous polymorphism of the COL1A1 gene determines the degree of bone mineral density reduction and, accordingly, linear bone growth. The +1245G/T polymorphism of the COL1A1 gene in children with growth hormone (GH) deficiency was investigated by polymerase chain reaction. A genetic study of 28 children (21 boys, 7 girls) with GH deficiency was performed. The age of the children was 10.86 ± 3.15 years, and the growth retardation was -2.34 (±0.85) SDS. At the time of the study, the children were in a state of euthyroidism. They had a polymorphism of the COL1A1 gene, namely +1245 G/T (rs1800012). In the group of patients with GH deficiency, the proportion of the T/G genotype was 1.4 times higher than in the controls. The presence of homozygous TT and GG genotypes can be protective against GH deficiency (OR = 0.38, 95%CI 0.08-1.79; P = 0.22 and OR = 0.99, 95%CI 0.40-2.18; P = 0.88, respectively). The ratio of allele frequencies in children with GH deficiency (pT = 0.268, qC = 0,732) was significantly different from 1:1, indicating a bias in the study group, possibly due to small sample size. The allele frequencies in patients with GH deficiency were practically indistinguishable from the control group, and the distribution of genotypes corresponded to the Hardy-Weinberg equilibrium. The main allele in the control group was G (pT = 0.693), as well as in the group with GH deficiency (pT = 0.732). Thus, in children with GH deficiency, carrying the G allele of the polymorphic locus +1245G/T (rs1800012) of the COL1A1 gene prevails, which may be a prerequisite for the development of this pathology. [ABSTRACT FROM AUTHOR]

We report growth hormone (GH) deficiency due to presumed GH releasing hormone (GHRH) resistance in an adolescent with pseudohypoparathyroidism type 1B (PHP1B) due to paternal uniparental disomy of chromosome 20 (patUPD20). A male patient aged 11 years 10 months with obesity and mild developmental delay was found to have hypocalcemia, hyperphosphatemia, and an elevated parathyroid hormone level. History included muscle cramps and leg pain with activity. Examination showed round facies, short stature, and obesity. He was in puberty and bone age was advanced by > 2 years. Detailed genetic workup, including nucleotide sequence analysis of GNAS exons 1-13 and STX16 , methylation-sensitive multiplex ligation-dependent probe amplification and analysis of several microsatellite markers for chromosome 20, established the diagnosis of PHP1B due to patUPD20. Muscle cramps and hypocalcemia resolved with calcium carbonate, ergocalciferol, and calcitriol treatment. He was short with linear growth deceleration at around age 13 years. Peak GH concentration was insufficient following stimulation testing. Growth velocity improved with human GH treatment. Although rare, resistance to GHRH can occur in PHP1B and patients with this disorder should be evaluated for GH insufficiency if they present with short stature and reduced growth velocity. Treatment with recombinant human GH may improve growth velocity in such patients. [ABSTRACT FROM AUTHOR]

Background: Short stature can generate emotional and social stress in children and adolescents and their parents. Aim: To assess the effect of growth hormone (GH) therapy on quality of life (QoL) among growth hormone deficiency (GHD) and idiopathic short stature (ISS) children. Patients and methods: This cross–sectional study was conducted at the Suez Canal University endocrinology outpatient clinic in Ismailia City, Egypt, 194 children participated in this study. After receiving GH therapy for a year, children with ISS and GHD who met the inclusion and exclusion criteria were selected at random from the endocrinology outpatient clinic at Suez Canal University in Ismailia City, Egypt. A WHOQoL-BREF QoL evaluation was utilized in conjunction with health-related quality of life, and an Arabic translation of the questionnaire was used. Results: This study included 194 children, 107 children with ISS, and 87 children with GHD. Group with ISS had a significantly higher mean of age (13.5±2.8) years than the GHD group (8.5±1.5) years with P value less than 0.001. So, most of the children in ISS group at preparatory school (11–14 years old), while GHD group were at primary school (8–10 years old) with statistically significant difference (P <0.001). So, most of children in ISS group at preparatory school, while GHD group were at primary school with statistical significant difference (P <0.001). Most of children in ISS group have rural residence, positive consanguinity and positive family history of short stature, while GHD group had urban residence, negative consanguinity, and negative family history of short stature with statistical significant differences (P <0.001). Children with ISS had significantly lower height Z score before and after GH therapy as P value less than 0.001. Both groups showed statistically significant increase in height Z score after versus before GH therapy as P value less than 0.001. Mean WHOQoL-BREF domains scores showed a statistical significant increase after GH TTT, in both groups. Conclusion: Our findings indicate that a year of GH treatment significantly improved physical, social, psychological and environmental QoL, whereas the physical effects—which are to be expected given the noticeable increase in height—seem to have less of an influence. This is probably connected to the mild physical effects of baseline short height. But there is a correlation between the change in QoL and the height gain in SD, which amply illustrates the role of statural rise in improving QoL. [ABSTRACT FROM AUTHOR]

This retrospective analysis aimed to evaluate the potential benefits of integrating transdermal acupoint therapy with the tonifying spleen and kidney method alongside growth hormone (GH) treatment for pediatric patients suffering from growth hormone deficiency (GHD). Clinical data of 115 pediatric patients with GHD were retrospectively analyzed. Patients were categorized into two distinct groups for the analysis: the conventional GH treatment group (n=62) and the combined group of acupoint transdermal therapy alongside GH treatment (n=53). Baseline characteristics, hormone levels, bone mineral density (BMD), physical growth parameters, and adverse events were compared. The baseline characteristics of the two groups were well-matched. After one year of treatment, the combined group showed significantly lower levels of insulin-like growth factor-1 (P<0.001), testosterone (P<0.001), estrogen (P<0.001), thyroid-stimulating hormone (P<0.001), insulin-like growth factor binding protein-3 (P=0.009) and free thyroxine (P<0.001) compared to the conventional group. The transdermal treatment group demonstrated significantly higher BMD at multiple sites (P<0.05) and improved physical growth parameters (P<0.05) compared to the conventional group. Furthermore, the transdermal treatment was not linked to a higher occurrence of adverse incidents and showed significant correlations with various growth and development indexes (P<0.05). Combined therapy showed promising effects on endocrine function and physical growth. [ABSTRACT FROM AUTHOR]

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Short stature is a common complaint among pediatric visits and the differential diagnosis is extensive. Although some variations in growth are normal, deviation from normal growth is often the first symptom of chronic disease in children. This is true for hormone abnormalities including growth hormone deficiency, hypothyroidism and glucocorticoid excess. However, reduced growth velocity can also occur as the first sign of chronic anemia, malnutrition, deprivation (psychosocial dwarfism), chromosomal abnormalities, genetic syndromes and inflammatory bowel diseases. For the primary care provider, simple measures of standing height, sitting height, arm span, weight, body mass index (BMI) and bone age (BA) will lead to the correct diagnosis in most short children. Screening laboratory studies for endocrine disorders, a skeletal survey if skeletal disproportion is evident, a karyotype or microarray (microarray favored if developmental delay is also present) and genetic testing for monogenic disorders will lead to a specific diagnosis in an additional subset of short children. This case presented a diagnostic dilemma that spanned all these possibilities and served as a focal point for the review of normal growth and growth abnormalities.

The article "Sex Difference in Paediatric Growth Hormone Deficiency: Fact or Fiction?" published in Clinical Endocrinology explores biases impacting the diagnosis of growth hormone deficiency (GHD) in children, particularly the historically reported male predominance. The text discusses various factors contributing to this bias, such as societal perceptions, familial concerns, and provider referrals. It also highlights the need for accurate assessment of GHD frequencies in males and females, suggesting changes in diagnostic criteria and medical practices to address inequities in access to care. The authors emphasize the importance of multi-center studies and medical education campaigns to achieve improved health equity in managing children with short stature. [Extracted from the article]

Because the causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled in the study. Their median age was 11.2 years, pre-treatment height was −3.2 s.d., and maximal stimulated GH was 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 had central hypothyroidism, ten had hypogonadotropic hypogonadism, and three had central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with clinical suspicion of a specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without a detected causal variant after the first-tier testing or with no suspicion of a specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving the OTX2 gene). The remaining 6 children had causative genetic variants in the GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated the cause of CPHD in a fifth of the patients. Moreover, our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD.

Abstract Background Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear. Objective To investigate the topological organization of individual-level MBNs in pediatric GHD. Methods Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed. Results Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all P FDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all P FDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all P FDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected). Conclusion GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance.

Resumen: Introducción: La hormona de crecimiento (GH) y el factor de crecimiento similar a la insulina tipo 1 (IGF-1) tienen efecto modulador sobre la funcionalidad intestinal y la microbiota. Nuestro objetivo fue investigar si los pacientes con déficit de GH y, por lo tanto, con niveles bajos de GH e IGF-1 se asocian con cambios en la fisiología/integridad intestinal, así como en la composición de la microbiota intestinal. Material y métodos: Se realizó un estudio de casos y controles en 21 pacientes con déficit de GH previo al inicio y tras 6 meses de tratamiento con GH y en 20 controles sanos. Se estudiaron los cambios antropométricos, analíticos, de translocación bacteriana y también se determinó la composición del microbioma mediante secuenciación masiva del gen del ARNr 16S. Resultados: El déficit de GH se acompañó de un incremento significativo en los niveles séricos de sCD14, un marcador de translocación bacteriana (p

Background. The significance of this study lies in the fact that short stature is highly prevalent among children, affec­ting 1–5 % of the population and having diverse causes. The child’s growth potential in the long term is largely depends on the effectiveness of the diagnostic system and the level of adherence to the prescribed therapy. The purpose was to improve the diagnosis of growth hormone deficiency (GHD) in children and adherence to recombinant human growth hormone (rhGH) therapy based on information about the regional prevalence of the disease and barriers to adherence. Materials and methods. A follow-up study was conducted from 2012 to 2020 at the Odesa Regional Children’s Hospital. The cohort included 94 children with GHD. The prevalence was determined by calculating the ratio of the number of all detected GHD cases to the children population per 100,000. Adherence was measured using the Morisky Medication Adherence Scale. The statistical processing of the results was done using t-test and chi-square methods, and p-values less than 0.05 were considered statistically significant. Results. An assessment of GHD prevalence, the level of adherence and the frequency of continuity of rhGH therapy in children in the Odesa region at the end of 2014 revealed the incompleteness of regional diagnosis of the disease (in Odesa, 1 : 11,200; in the Odesa region, 1 : 10,800), as well as a low level of acceptable adhe­rence (in 57.4 %) and insufficient frequency of continuity of therapy (in 76.9 %). These data formed the basis of the regional program for optimizing the identification and management of GHD in children, which included organizational, medical and social measures. By the end of 2020, the prevalence of GHD in Odesa was 1 : 4,300, and in the Odesa region, 1 : 5,100. The rate of acceptable adherence to rhGH therapy increased to 80.0 %, and frequency of continuity of therapy to 91.1 %. Conclusions. The regional program designed to improve the detection and management of GHD in children has been found to improve the diagnosis of the disease, increase adhe­rence to rhGH therapy, and the frequency of continuity of treatment. High adherence to treatment is a bioethical issue because it signifies a good partnership between physicians, children, and parents and indicates respect for patient autonomy.

Background: Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear. Objective: To investigate the topological organization of individual-level MBNs in pediatric GHD. Methods: Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed. Results: Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all PFDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all PFDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all PFDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected). Conclusion: GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance. Key points: 1. GHD children undergo an extensive and significant reorganization in large-scale individual-level MBNs. 2. Abnormal morphological connectivity was found in cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry underlying pediatric GHD. [ABSTRACT FROM AUTHOR]