Growth Hormone Deficiency Group Research Articles

Robust growth hormone responses to GH-releasing peptide 2 in adolescents.

GH-releasing peptide-2 (GHRP2) can be used for provocative growth hormone testing (GHT). Since it acts as a powerful stimulus for GH secretion, cut-off peak GH level in GHRP2 loading test (GHRP2T) is higher than in other GHT. Nevertheless, data on response at adolescents are limited. This report aimed to investigate peak GH levels in GHRP2T in adolescents. Clinical data of adolescents after onset of puberty who underwent GHRP2T at our institution from May 2010 to March 2023 were collected retrospectively. Subjects were classified into three groups according to underlying diseases. Total 23 patients were included: 12 in organic or genetic GHD (o/gGHD) group, three in idiopathic GHD (iGHD) group, and eight in short stature (SS) group. The median GH peak levels were 3.4 ng/mL in o/gGHD group, 88.9 ng/mL in iGHD group, and 90.1 ng/mL in SS group, indicating a robust response of GH peak levels in iGHD and SS groups. Two patients exceeded the cut-off for GHRP2T but below for other GHT, indicating the current cut-off for GHRP2T may miss some GHD patients. The GH response to GHRP2T in adolescents except the o/gGHD group may be robustly responsive. For the correct diagnosis of GHD, the cut-off peak GH levels in GHRP2T in adolescents may require revisiting.

Genetic Findings in Short Turkish Children Born to Consanguineous Parents.

The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented. This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height <-3.5 standard deviation score [SDS]) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c). In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively. Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.

Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency, Small for Gestational Age, and Turner Syndrome in Germany: Data from the PATRO® Children Study

Introduction: Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment. Methods: German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first-year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 to 2018 to determine specific parameters for GH treatment optimization. Results: All patient groups started GH treatment at a relatively high chronological age (2007–2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016–2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups, female patients were underrepresented compared to male patients (GHD 32.3%, SGA 43.6%) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients, GH therapy was started below the registered dose recommendation (30.0 μg/kg/day and 33.7 μg/kg/day, respectively). In the first year of treatment, the mean GH dose was increased moderately (GHD: 30.7, SGA: 35.7, TS: 40.8 μg/kg/day). There was no significant change of GH dosing over time from 2007 to 2018. The IoR was comparable between time-groups for all 3 diagnoses. Discussion: This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at the start of treatment. This is in accordance with important parameters used in prediction models.

Assessment of Quality of Life in a Sample of Short Stature Iraqi Children with Growth Hormone Deficiency

Background: Short stature (SS) is defined as a height of 2.0 or more standard deviations (SD) below the population-specific mean height for age and gender. 2.5% of children have short stature, and it is one of the most frequent causes for children to see a growth specialist during their childhood. It is challenging to generalize about the effect of short stature on psycho-social adaption given the data currently available. Health-related quality of life (HrQoL) was generally shown to be lower in clinically identified short stature children than in population-based normal-sized reference groups. Aim: Examine the behavioral pattern and mental health of SS and its psychological influence on QoL of children/adolescence. In addition, compare the behavioral response and QoL between growth hormone deficiency GHD and control groups. Methods: It is a cross sectional study, included 80 participants (60 with GHD and 20 with normal height as control group) between 4 and 18 years old. The parents of the participants were given a parent-reported version of the written Quality of Life in Short Stature Youth QoLISSY questionnaire in Arabic in order to examine the association with the socio-demographic characteristics of the participants. Results: 51.25% female and 48.75% male included in this study, the mean age at assessment was 12.1 ± 2.7, and 11.8 ± 2.6 of the GHD and control group, respectively. There was significant difference in QoLISSY total score between GHD and control groups. The association between socio-demographic characteristics of the participants was significantly different. Conclusion: The QoL of Iraqi children with GHD showed lower scores in all domains of QoLISSY compared to normal children.

Evaluation of the growth response of children with growth hormone deficiency according to the peak growth hormone levels in provocation tests

BackgroundWe aimed to evaluate the relation between the peak growth hormone (GH) levels in provocation tests and response to recombinant human GH (rhGH) therapy in patients with GH deficiency (GHD). MethodsThis was a cross-sectional, single-center, and retrospective study. A total of 135 patients under the age of 16 years who were diagnosed with GHD through insulin tolerance tests and L-DOPA stimulation tests and who received rhGH therapy for at least 2 years in the Pediatric Endocrinology Clinic of Akdeniz University Hospital between 1997 and 2021 were included in the study. ResultsThe patients were divided into two groups: idiopathic GHD (group I, n = 119) and multiple pituitary hormone deficiencies or organic pathology on magnetic resonance imaging (group II, n = 16). The patients in group I were classified into three subgroups according to the peak GH values in the provocation tests (group Ia: peak GH <3 μg/L, n = 34; group Ib: peak GH between 3 and 7 μg/L, n = 71; group Ic: peak GH between 7 and 10 μg/L, n = 34). The median age was 11.5 years in group I (8.8 in group Ia, 12.1 in group Ib, 12.3 in group Ib) and 8.8 years in group II. The height standard deviation score (SDS) was −2.93 in group I (−2.85 in group Ia, −2.99 in group Ib, −2.94 in group Ic) and −3.79 in group II. The median Δheight SDS was 0.61 in group I and 1.05 in group II at the end of the first year of treatment and 0.31 in group I and 0.45 in group II at the end of the second year (p = 0.005 and p = 0.074, respectively). When the subgroups of group I were compared, height SDS, Δheight SDS, and height velocity (HV) SDS were all higher in group Ia at the end of the first year of rhGH therapy (p = 0.040, p = 0.029, and p = 0.005, respectively). The height SDS was still significantly higher in group Ia (p = 0.033) while the HV SDS and Δheight SDS were similar between the groups at the end of the second year of therapy (p = 0.164 and p = 0.522, respectively). There was a statistically significant association between the first-year HV SDS and the peak GH value in provocation tests in multiple regression analyses (p<0.001). In addition, the final model revealed that height SDS and weight SDS at the start of the treatment and the first-year HV SDS are the factors with a statistically significant effect on the second-year HV SDS (p = 0.022, p = 0.001, and p<0.001, respectively). ConclusionOur findings show that the lower the GH peak in provocation tests, the better the response to treatment. The best HV was observed in the first year of rhGH therapy, and the diagnosis should be checked in those patients who had a low first-year HV and did not have a severely low GH peak in provocation tests.

Developmental enamel defects and dental anomalies of number and size in children with growth hormone deficiency

Growth hormone is meaningfully involved in the processes of tooth cells differentiation and tissue formation. The aim of the study was to evaluate the occurrence of dental anomalies: microdontia, macrodontia, hypodontia and developmental defects of enamel (DDE) amongst a group of isolated growth hormone deficient (GHD) patients and healthy children. This cross-sectional study was based on a group of 101 Caucasian children: 33 with GHD (mean age 10.94, SD 2.51) and 68 being healthy, normal height subjects (mean age 10.4, SD 2.38). The dental examination in primary and permanent teeth was carried out by one trained and calibrated dentist, in accordance with the WHO guidelines. It was observed that 33% of GHD patients suffer from dental anomalies (hypodontia, microdontia or macrodontia), the difference between the study group and the control group was statistically significant (33% vs 4%, p < 0.001). Hypodontia and microdontia/macrodontia were the most common problems affecting 18% and 21% of the GHD individuals, respectively. The prevalence of DDE did not differ significantly between GHD group and the control group (58% vs 48%, p > 0.05). As children with GHD present more dental anomalies than their healthy coevals, clinicians should be aware of the possible oral health problems associated with GHD and consider dental screening and management as part of the patient’s overall health care plan.

Assessment of anterior pituitary reserve capacity based on growth hormone response to growth hormone-releasing peptide-2 test in the elderly

ObjectiveThe growth hormone (GH)-releasing peptide-2 (GHRP-2) test is relatively safe among endocrine stimulation tests for the elderly. We investigated whether anterior pituitary function in elderly patients could be assessed on the basis of GH response to the GHRP-2 test. DesignSixty-five elderly patients aged 65 years and older with non-functioning pituitary neuroendocrine tumor (PitNET) who underwent pituitary surgery and preoperative endocrine stimulation tests were classified into the “GH normal group” and “GH deficiency group” based on GH response to the GHRP-2 test. The baseline characteristics and anterior pituitary function were compared between the groups. ResultsThirty-two patients were assigned to the GH normal group and 33 to the GH deficiency group. The cortisol and adrenocorticotropic hormone (ACTH) results in the corticotropin-releasing hormone test were significantly higher in the GH normal group than in the GH deficiency group (p < 0.001). The relationship between the cortisol and ACTH results and the GH response revealed significant correlations (p < 0.001). In addition, receiver operating characteristic curve analysis identified that the optimal cut-off point for a peak GH level in the correlation between adrenocortical function and GH response to the GHRP-2 test was 8.08 ng/mL (specificity 0.868, sensitivity 0.852). ConclusionThe present study indicated that adrenocortical function was significantly correlated with GH response to the GHRP-2 test in elderly patients before pituitary surgery. For elderly patients with non-functioning PitNET, GH response to the GHRP-2 test may support in diagnosing adrenocortical insufficiency.

A new Early–Middle Miocene phalangerid (Marsupialia: Phalangeridae) from the Riversleigh World Heritage Area, Boodjamulla (Lawn Hill) National Park, northwestern Queensland

Archerus johntoniae represents a new genus and species of phalangerid possum from the Early to Middle Miocene of the Riversleigh World Heritage Area, northwestern Queensland. The new taxon is the tenth extinct phalangerid species to be described and is the seventh species recognized from the diverse Riversleigh fossil assemblages. A. johntoniae has its closest morphometric affinities (such as relatively short molars, narrow premolars, an anteriorly narrow upper first molar, and posteriorly narrow fourth molars) with trichosurine and stem phalangerids. Morphologically, A. johntoniae has similarities to phalangerines and trichosurines, but is most dissimilar to other fossil phalangerids. The new species is one of the smallest (ca 1.3 kg) phalangerids known and may have occupied Early and Middle Miocene frugivorous/insectivorous niches demarcated from other phalangerids by body size and diet. A. johntoniae is one of a minority of Riversleigh species to have survived a significant decline in marsupial diversity associated with a rapid spike in global temperature at the Middle Miocene Climatic Optimum.Troy Myers [t.myers@unsw.edu.au], Earth and Sustainability Science Research Centre, School of Biological, Earth & Environmental Sciences, UNSW Sydney, NSW 2052, Australia; Kirsten Crosby [Kirsten.crosby@gmail.com], GHD Group Pty Ltd, Level 15, 133 Castlereagh St, Sydney, NSW, 2000 (currently), School of Biological, Earth & Environmental Sciences, UNSW Sydney, NSW 2052, Australia.

Treatment burden, adherence, and quality of life in children with daily GH treatment in France.

The objective of this study was to describe in a real-life setting the treatment burden and adherence and quality of life (QOL) of children treated with daily injections of growth hormone and their relationship with treatment duration. This non-interventional, multicenter, cross-sectional French study involved children aged 3-17 years treated with daily growth hormone injections. Based on a recent validated dyad questionnaire, the mean overall life interference total score (100 = most interference) was described, with treatment adherence and QOL, using the Quality of Life of Short Stature Youth questionnaire (100 = best). All analyses were performed according to treatment duration prior to inclusion. Among the 275/277 analyzed children, 166 (60.4%) had only growth hormone deficiency (GHD). In the GHD group, the mean age was 11.7 ± 3.2 years; median treatment duration was 3.3 years (interquartile range 1.8-6.4). The mean overall life interference total score was 27.7 ± 20.7 (95% CI (24.2; 31.2)), with non-significant correlation with treatment duration (P = 0.1925). Treatment adherence was good (95.0% of children reported receiving >80% of planned injections over the last month); it slightly decreased with treatment duration (P = 0.0364). Children's overall QOL was good (81.5 ± 16.6 and 77.6 ± 18.7 according to children and parents, respectively), but subscores of the coping and treatment impact domains were <50. Similar results were observed in all patients independently of the condition requiring treatment. This real-life French cohort confirms the treatment burden of daily growth hormone injections, as previously reported in an interventional study.

Alterations in brain structure and function associated with pediatric growth hormone deficiency: A multi-modal magnetic resonance imaging study.

Pediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children's cognitive function, brain structure and brain function were not yet fully illustrated. Full Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls. (1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index. Multiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index.

Relationship Between the Serum FGF21 Level and Growth in Children of Short Stature.

This study investigated the relationship between fibroblast growth factor 21 (FGF21) levels and growth in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS), and the effects of the FGF21 level on response to growth hormone (GH) treatment. We included 171 pre-pubertal children with a GHD (n = 54), ISS (n = 46), and normal height (n = 71). Fasting FGF21 levels were measured at baseline and every 6 months during GH treatment. Factors associated with growth velocity (GV) after GH therapy were investigated. The FGF21 level was higher in short children than in the controls without significant difference between the GHD and ISS groups. In the GHD group, the FGF21 level was inversely associated with the free fatty acid (FFA) level at baseline (r = -0.28, P = 0.039), however, was positively correlated with the FFA level at 12 months (r = 0.62, P = 0.016). The GV over 12 months of GH therapy was positively associated with the delta insulin-like growth factor 1 level (β = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (β = -0.64, P = 0.070). The FGF21 level was higher in children of short stature, both those with GHD and the ISS, than in children with normal growth. The pretreatment FGF21 level negatively affected the GV of children with GH-treated GHD. These results suggest the existence of a GH/FFA/FGF21 axis in children.

Evaluation of cardiac structure, exercise capacity and electrocardiography parameters in children with partial and complete growth hormone deficiency and their changes with short term growth hormone replacement therapy.

To evaluate cardiac structure, exercise capacity and electrocardiography (ECG) parameters of children with complete and partial growth hormone (GH) deficiency (GHD) and the effect of 12 months GH treatment on these. M-mode echocardiography, ECG and exercise test expressed as metabolic equivalent (MET) were performed in children with GHD, aged 9-14 years, divided into those with a peak GH response < 7µg/L (complete GHD; n = 30) and 7-10µg/L (partial GHD; n = 17) after two GH stimulation tests, at baseline and 12 months after GH initiation. Forty-eight healthy peers underwent the same tests once. Left ventricular mass (LVM) was significantly lower before treatment in both groups with GHD compared to healthy peers (p = 0.015 and p = 0.032) but LVM in the GHD groups was similar to controls after 12 months of treatment. The increase in LVM in the complete GHD group was significant (p = 0.044). LVM index was significantly reduced with treatment in children with partial GHD (p = 0.035). Max METs, VO2max and exercise duration were significantly increased in children with complete GHD after treatment (p = 0.022, p = 0.015 and p = 0.002, respectively). Significant changes in P wave and QTc dispersion on ECG between groups were within physiological limits. This study showed that children with both partial and complete GHD had smaller cardiac structures and less exercise capacity compared to their healthy peers prior to GH treatment but this improved with 12 months of treatment. The cardiac trophic effect of GH, as well as the effect of increasing exercise capacity, is greater in those with complete GHD than in those with partial GHD.

The long-term growth, cost-effectiveness, and glycemic effects of growth hormone therapy on children born small for gestational age over 10years: a retrospective cohort study.

We aimed to report our 10-year experience of treating short children born small for gestational age (SGA) by comparing the long-term growth, metabolic safety, and cost-effectiveness of recombinant human growth hormone (rhGH) therapy in short children born SGA with those in rhGH-treated children with growth hormone deficiency (GHD) and Turner syndrome. We performed a 10-year retrospective cohort study at King Saud University Medical City. We included children aged 3-16years who received rhGH for GHD, SGA, or Turner syndrome for >1year. A total of 166 children received rhGH therapy for GHD, 58 for SGA, and 16 for Turner syndrome. During the last study visit, the average height change was 21cm for GHD children and 14cm for children born SGA (p-value <0.001). The height SDS change was 0.84 forGHD children and 0.55 for SGA children (p-value=0.004). The average cost-effectiveness ratios for treating GHD and SGA children were USD 1,717.22 and USD 1,157.19 per centimeter gained, respectively. Moreover, the mean incremental cost-effectiveness ratio for GHD vs. SGA patients was USD 2,820.39 per centimeter gained. Dysglycemia developed in 70 patients: 43 (36.44%), 22 (40.74%), and 5 (13%) in the GHD, SGA, and Turner syndrome groups, respectively. rhGH is effective in height improvement of short children. However, pursuing rhGH treatment for children born SGA requires a shared decision-making approach to balance the modest benefit of final adult height gain with the long-term metabolic effects, considering the acceptable costs on the Saudi healthcare system.

Growth Hormone Secretory Capacity Is Associated with Cardiac Morphology and Function in Overweight and Obese Patients: A Controlled, Cross-Sectional Study

Obesity is associated with increased cardiovascular morbidity. Adult patients with growth hormone deficiency (GHD) show morpho-functional cardiological alterations. A total of 353 overweight/obese patients are enrolled in the period between 2009 and 2019 to assess the relationships between GH secretory capacity and the metabolic phenotype, cardiovascular risk factors, body composition and cardiac echocardiographic parameters. All patients underwent GHRH + arginine test to evaluate GH secretory capacity, DEXA for body composition assessment and transthoracic echocardiography. Blood samples are also collected for the evaluation of metabolic parameters. In total, 144 patients had GH deficiency and 209 patients had normal GH secretion. In comparing the two groups, we found significant differences in body fat distribution with predominantly visceral adipose tissue accumulation in GHD patients. Metabolic syndrome is more prevalent in the GHD group. In particular, fasting glycemia, triglycerides and systolic and diastolic blood pressure are found to be linearly correlated with GH secretory capacity. Epicardial fat thickness, E/A ratio and indexed ventricular mass are worse in the GHD group. In the population studied, metabolic phenotype, body composition, cardiovascular risk factors and cardiac morphology are found to be related to the GH secretory capacity. GH secretion in the obese patient seems to be an important determinant of metabolic health.

Vitamin D and Parathyroid Hormone during Growth Hormone Treatment.

Background. There is some controversy concerning a potential interaction between vitamin D and PTH and the GH/IGF-1 axis. The goal of this study is to assess vitamin D and PTH status in children with GH deficiency at diagnostic and during treatment with rhGH. Methods. Longitudinal and descriptive study in 110 patients, aged 3.3–9.1 years, with GH deficiency (GHD group) treated with rhGH. At diagnosis and after 12, 24, 36, and 48 months of treatment, a clinical (height, weight, and bone age) and laboratory (phosphorus, calcium, calcidiol, PTH, IGF-1) evaluation was performed. Concurrently, 377 healthy children, aged 3.8–9.7 years, were enrolled and constituted a control group. Vitamin D status was stated in accordance to the U.S. Endocrine Society criteria. Results. No significant differences were found in the prevalence of vitamin D deficiency among control (11.43%) and GHD (13.6%) groups at the moment of diagnosis, remaining without significant changes at 12 (12.9%), 24 (14.6%), 36 (13.1%), and 48 months (13.3%) of treatment. There were not any significant differences in serum levels of calcium, phosphorus, and calcidiol, but a steady increase (p < 0.001) in PTH was detected. Conclusions. Prepubertal patients with GH deficient do not appear to have a higher risk of vitamin D deficiency than healthy subjects, and with treatment with rhGH, no changes in the organic content of vitamin D were observed although a significant increase in PTH levels was detected.

Growth hormone deficiency interferes with dynamic brain networks in short children

PurposeThis study aimed to explore the disparities in dynamic brain networks between children with growth hormone deficiency (GHD) and idiopathic short stature (ISS, non-growth hormone deficiency). MethodsThis study enrolled 65 children with GHD and 60 sex- and age-matched children with ISS. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed for all participants to obtain information on dynamic regional homogeneity (dReHo) and functional connectivity (FC) in dynamic (dFC) or static (sFC) state. The rs-fMRI metrics were subsequently compared between the GHD and ISS groups. ResultsCompared to the ISS group, the GHD group showed significant dynamic abnormalities in intra-networks of the central executive and cerebellar networks and in inter-networks of the central executive network to attentional, sensorimotor, and visual networks, as well as cerebellar network to default mode, sensorimotor, and visual networks. In addition, FC changes in the dynamic state were different from those in the static state. ConclusionsThe abnormal dynamics in intra- and inter-networks involved in cognitive, emotional, and motor functions in children with GHD extend the knowledge on brain functional alterations in children with GHD as reflected by dynamic changes in macroscopic neural activity patterns. These findings may help explain how GHD leads to various behavioral and cognitive deficits in children with short stature.

Common Polymorphisms of Growth Hormone: Growth Hormone Receptor Axis in Turkish Children with Short Stature.

Objective: A single-nucleotide polymorphism of the growth hormone 1 gene, GH1IVS4+90A>T (rs2665802), associated with short stature and a polymorphism of the growth hormone receptor gene, exon 3 deleted variant, associated with increased responsiveness to growth hormone have been reported previously. We aimed to investigate the frequency of both polymorphisms and their correlation to height in Turkish short children. Also, we aimed to evaluate the effect of exon 3 deleted variant on response to 1-year growth hormone therapy.Materials and Methods: Children with idiopathic isolated growth hormone deficiency (n = 39) and with idiopathic short stature (n = 10) and 50 control subjects were evaluated for anthropometric parameters, annual growth velocity, and annual height gain. Growth hormone receptor gene polymorphisms were analyzed via multiplex polymerase chain reaction; growth hormone 1 gene polymorphism was analyzed via polymerase chain reaction and single-strand conformation polymorphism techniques.Results: The frequency of genotypes carrying the “A” allele was not significantly higher in the idiopathic isolated growth hormone deficiency group than in the idiopathic short stature and control groups (P = .03 for each). The exon 3 deleted variant genotype was significantly lower in the idiopathic short stature group compared to the control group (P = .01). There was no effect of exon 3 deleted variant, on response to the first-year growth hormone therapy.Conclusion: In Turkish population, no correlation was found between the “A” allele of GH1IVS4+90A>T polymorphism and idiopathic isolated growth hormone deficiency and short stature, and a significant negative correlation was found between exon 3 deleted variant and idiopathic short stature and short stature. Exon 3 deleted variant has no effect on response to growth hormone treatment.

Adherence and growth outcomes in children with growth disorders: results from the Easypod™ Connect Observational Study (ECOS) in Indonesia, Singapore, and Taiwan

Background Non-objective assessments indicate poor patient adherence to growth hormone (GH) prescribed for growth failure, with sub-optimal growth response. The easypod™ connect device for GH administration enables real-time, objective assessment of adherence.&#x0D; Objective To examine adherence with pediatric GH therapy in Asia-Pacific countries and relationship with growth outcomes.&#x0D; Methods Subjects were children in Indonesia, Singapore, Taiwan enrolled in the multi-national, open-label Easypod Connect Observational Study (ECOS). Adherence during follow-up was the primary endpoint and a relationship with 1-year growth outcomes was assessed by Spearman’s product-moment correlations.&#x0D; Results Over a 1-year time frame, median overall patient adherence was ≥89%; rates were similar for children with GH deficiency (GHD; n=17) and those born small-for-gestational age (SGA; n=5), except that median adherence dropped between 9 months (94%) and 1 year (83%) for SGA subjects. Median initial GH dose was 42.3µg/kg/day for GHD subjects and 31.4µg/kg/day for SGA subjects. Median age (12 years) and bone age (13 years) indicated that most children had entered puberty at treatment onset. Clinically meaningful improvements in growth were observed at 1 year in the GHD group, but not the SGA group. Statistically significant correlations between adherence and height change (P=0.039) as well as height velocity (P=0.004) were observed.&#x0D; Conclusions Children in Asia-Pacific countries show high adherence over the first year of GH therapy with easypod. The easypod study also shows that adherence is correlated to good growth outcomes.

A Real-World Study of Recombinant Human Growth Hormone in the Treatment of Idiopathic Short Stature and Growth Hormone Deficiency.

ObjectiveThis study aimed to evaluate the clinical efficacy of recombinant human growth hormone (rhGH) in the treatment of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) and to explore the related factors affecting treatment efficacy.MethodsThe current research reflects a real-world study. A total of 79 patients with ISS and 95 patients with GHD (both groups pre-puberty) who had been treated with rhGH for more than one year from January 2010 to September 2019 were included in this study. The patients were divided into two groups, ie, an ISS and a GHD group, respectively. The growth indexes, such as chronological age (CA), bone age (BA), height standard deviation score (HtSDS), insulin-like growth factor-1 (IGF-1) SDS, and body mass index were recorded and compared between the two groups before and after treatment. The treatment efficacy was evaluated according to changes in HtSDS before and after treatment, and the influencing factors of clinical efficacy were analyzed using a multivariate regression model.ResultsAt the start of treatment, the differences in CA, BA, height, weight, sexual development stage, HtSDS, mid-parental height SDS, and IGF-1 SDS between the two groups were not statistically significant (P > 0.05). However, the initial dose of rhGH in the GHD group was significantly lower than in the ISS group (P < 0.001). Following rhGH treatment, the differences in CA, BA, BA/CA ratio, and IGF-1 SDS measured at 6, 12, 18, and 24 months between the ISS and GHD groups were not statistically significant, while the difference in HtSDS measured at 6 months was statistically significant. With the extension of rhGH treatment time, the annual growth rate (GV) gradually decreased, and the difference between HtSDS and the baseline gradually increased; however, the differences between the ISS and GHD groups were not statistically significant. The most important factor affecting the treatment efficacy for patients with ISS was age at the start of treatment; the most important factors affecting the treatment efficacy for patients with GHD were age and IGF-1 SDS.ConclusionRecombinant human growth hormone treatment can significantly improve the height of patients with ISS and GHD. There was no significant difference in growth rate between patients with ISS and those with GHD at relatively high doses. The common factor affecting the treatment efficacy of the two groups was the age at the start of treatment. During treatment, monitored data indicated that rhGH treatment of GHD and ISS thyroid function showed a clinical phenomenon in the form of increased free triiodothyronine, rather than hypothyroidism, which was rarely reported in existing studies.

Brachydactyly Type A3 Is More Commonly Seen in Children With Short Stature But Does Not Affect Their Height Improvement by Growth Hormone Therapy.

IntroductionTo analyze the prevalence of brachydactyly type A3 (BDA3) in children with short stature and the effect on growth hormone (GH) therapy.MethodsWe analyzed the medical records of pediatric patients from July 2009 to July 2021. We included children with short stature defined as their height standard deviation score (HtSDS) < -2 and normal short height as their HtSDS between -2 and -1. We calculated the prevalence of BDA3 in different groups and compared the differences in children’s characteristics and the therapeutic effect of GH therapy between the BDA3 and no BDA3 groups.ResultsA total of 752 cases were included. The overall prevalence of BDA3 was 23.1%; with a female predominance (30.8% vs. 16.1%, P < 0.01). BDA3 was more prevalent in the short stature group (27.2%) than in the normal short stature group (16.7%) and growth hormone deficiency group (16.5%). Birth length, birth weight, HtSDS, and mid-parental height of children with BDA3 were lower than those without BDA3, but there were no significant differences. In patients with Turner syndrome and idiopathic short stature, the HtSDS of the BDA3 group was significantly lower than that of the no BDA3 group (P < 0.01). During four years of GH therapy, the HtSDS improvement per year in the BDA3 group were 0.79 ± 0.29, 0.50 ± 0.31, 0.20 ± 0.30, and 0.10 ± 0.22, which were not significantly different from those in the no BDA3 group. At the end of treatment, there were no significant differences in the duration of treatment and total HtSDS improvement between these two groups.ConclusionsBDA3 is more commonly seen in children with short stature with a female predominance. BDA3 occurrence is independent of the GH pathway and does not affect the therapeutic effect of GH on short stature children.