Received Growth Hormone Treatment Research Articles

Noonan Syndrome Growth Charts and Genotypes: 15-year Longitudinal Single-centre Study.

Growth patterns in Noonan syndrome (NS) remain relatively unknown. The objective of this study was to provide growth reference curves for patients with NS and identify correlations between their growth, genotype, and clinical features. This was a 15-year-long, monocentric, observational, retrospective, non-interventional study. Children with NS followed up between 2005 and 2022 at 'Bambino Gesù' Children's Hospital, Italy, were included, and excluded if they had received growth hormone treatment. Comparison of growth curves of participants with NS versus the general Italian population and further genotypic analyses were performed. Overall, 190 eligible participants with NS were identified, with median (interquartile range) age of 14.01 (9.05-19.25) years, (55.8% male). Cardiovascular anomalies were present in 85.3% of participants, most commonly pulmonary stenosis (52.6%) and atrial septal defects (36.8%); 48.1% of male participants had cryptorchidism. The most frequently detected mutations were in PTPN11 (66.3%) and SOS1 (13.9%). NS-sex-specific centile curves for height, weight, body mass index, and height velocity were produced. For both sexes, the 50th percentile of height and weight for participants with NS overlapped with the 3rd percentile for the general Italian population. Both sexes with a PTPN11 mutation had a significantly lower height and weight than those with 'other mutations' at 5 years old. No significant associations were observed between cardiac anomalies and PTPN11 mutation status. We present longitudinal data describing growth curves and trends, the natural history, and genotypes of the NS population, which provide a useful tool for clinicians in the management of NS.

Relationship of thyroid function with genetic subtypes and treatment with growth hormone in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is the most common genetic syndrome with obesity and results from loss of expression of paternally inherited genes on chromosome 15q11-q13 by a variety of mechanisms which include large deletions (70%-75%), maternal uniparental disomy (UPD) (20%-30%), and imprinting defects (2%-5%) or balanced translocations. Individuals often have a characteristic behavior disorder with mild intellectual disability, infantile hypotonia associated with poor sucking, short stature, and obesity. PWS is characterized by hypothalamic-pituitary axis dysfunction with growth hormone (GH) deficiency, hypogonadism, and several other hormonal deficiencies resulting in short stature, centrally driven excessive appetite (hyperphagia), central obesity, cryptorchidism, and decreased lean body mass. In this study, we determined and sought differences in the incidence of thyroid abnormalities among the common genetic subtypes in a cohort of 52 subjects with PWS because there was limited literature available. We also sought the effects of growth hormone (GH) treatment on the thyroid profile. Fifty-two subjects with a genetically confirmed diagnosis of PWS were included in this study at the University of California, Irvine. Blood samples for baseline thyroxine stimulating hormone (TSH) and free thyroxine (fT4) levels were obtained in the morning after an overnight fast for 8-12 h. Statistical analyses were performed with SPSS (SPSS Inc., 21.0). Mean values were analyzed by one-way ANOVA, and student's t-test and statistical significance were set at p < 0.05. The subjects included 26 males and 26 females with an age range of 3-38 years. There were 29 subjects with chromosome 15q11-q13 deletions and 23 with UPD; 28 were GH treated currently or in the past, and 24 never received GH. There was no significant difference in age or body mass index (BMI) (kg/m2) between GH-treated versus non-GH-treated groups. BMI was higher in the deletion group compared to the UPD group (p = 0.05). We identified two individuals who were clinically diagnosed and treated for hypothyroidism, one of whom was on GH supplements. We identified two additional individuals with subclinical hypothyroidism who were not on GH treatment, giving a frequency of 7.6% (4/52) in this cohort of patients. We did not find significant differences in thyroid function (TSH) in the deletion versus UPD groups. We found significant differences in thyroid function, however, between GH-treated and non-GH-treated groups. The mean TSH was lower (2.25 ± 1.17 uIU/M, range 0.03-4.92 uIU/M versus 2.80 ± 1.44 uIU/M, range 0.55-5.33 uIU/M respectively, p = 0.046), and the free T4 levels were significantly higher (1.13 ± 0.70 and 1.03 ± 0.11 ng/dL, respectively, p = 0.05) in the GH-treated individuals compared to non-GH-treated individuals. In this cohort of subjects with PWS, we identified two previously diagnosed individuals with hypothyroidism and two individuals with subclinical hypothyroidism (4/52, 7.6%), three of whom were not receiving GH treatment. We did not find any significant differences in thyroid function between molecular subtypes; however, we found that euthyroid status (lower TSH levels and higher free T4 levels) was significantly higher in individuals who were treated with GH compared to the untreated group. We recommend that individuals with PWS should be screened regularly for thyroid deficiency and start treatment early with GH in view of the potentially lower incidence of thyroid deficiency.

Carotid Intima-Media Thickness and Cardiometabolic Profile in Turner Syndrome: A Cross-Sectional Study.

Turner syndrome (TS), one of the most common chromosomal abnormalities in females, often results in adult cardiovascular and metabolic complications. Information on pediatric age is scarce. This study aimed to compare the presence of cardiometabolic risk factors in children with TS and healthy controls. This is a cross-sectional study comparing patients with TS to age-matched healthy controls, regarding cardiometabolic risk factors includinglipid profile, fasting glucose, insulin resistance, body composition, body mass index, blood pressure, and carotid intima-media thickness (cIMT). We included nine TS patients and ninecontrols with a median age of 13 years (9-14 years). Three TS patients and three controls were prepubertal. All TS patients received growth hormone treatment (GHT), median treatment of six years (3-10 years); four patients underwent treatment with estradiol. No statistically significant differences were detected between TS patients and controls regarding body mass index (BMI), cholesterol levels, and insulin resistance. cIMT indexed to body surface area showed no significant differences between TS patients and controls (0.37 vs 0.35 mm/m2, respectively, p=0.605). TS patients had lower body fat levels (7.2% vs 34.9%, p=0.004). On the other hand, TS patients had higher levels of systolic (z-score 1.04 vs -0.08, p=0.001) and diastolic (z-score 1.08 vs 0.33, p=0.031) blood pressure (BP) and aspartate (AST) and alanine (ALT) aminotransferase levels (26 vs 20 U/L, p=0.008 and 19 vs 14 U/L, p=0.004, respectively). Patients with TS, all submitted to GHT, had lower body fat levels compared with controls, despite similar BMI. Although we found no differences in cIMT between the two groups, young girls with TS had higher BP and transaminase levels. Early anthropometric, cardiovascular, and analytical monitoring of patients with TS is essential to detect abnormalities and prevent further complications.

The effect of gastrostomy tube feeding on growth in children with chronic kidney disease and on dialysis.

Gastrostomy tube (GT) feeding is used to promote nutrition and growth in children with chronic kidney disease (CKD). We explored the relationship between gastrostomy feeding and growth parameters in children with CKD, looking specifically at the nutritional composition of feeds. Children with CKD stages 3-5 or on dialysis in a tertiary children's kidney unit were studied. Data on anthropometry, biochemistry, and nutritional composition of feeds were collected from the time of GT insertion for 3years or until transplantation. Forty children (18 female) were included. Nineteen children were on peritoneal dialysis, 8 on hemodialysis, and 13 had CKD stages 3-5. The median (interquartile range [IQR]) age at GT insertion was 1.26 (0.61-3.58) years, with 31 (77.5%) under 5years of age. The median duration of gastrostomy feeding was 5.32 (3.05-6.31) years. None received growth hormone treatment. Children showed a significant increase in weight standard deviation score (SDS) (p = 0.0005), weight-for-height SDS (p = 0.0007) and body mass index (BMI) SDS (p < 0.0001). None of the children developed obesity. Although not statistically significant, the median height-SDS increased into the normal range (from -2.29 to -1.85). Weight-SDS positively correlated with the percentage of energy requirements from feeds (p = 0.02), and the BMI-SDS correlated with the percentage of total energy intake as fat (p < 0.001). GT feeding improves weight-SDS and BMI-SDS without leading to obesity. GT feeding improved height-SDS but this did not reach statistical significance, suggesting that factors in addition to nutritional optimization need to be considered for statural growth.

Ambulatory blood pressure monitorisation in children with recombinant growth hormone treatment.

It is safe to use recombinant growth hormone in children. Studies have shown it to be effective and safe, except for a few side effects in the short and long term after treatment. The present study investigated the presence of hypertension in pediatric patients receiving growth hormone treatment using 24 h ambulatory blood pressure monitoring (ABPM). This study is a single-center, retrospective study. Eighty-four patients aged 5-16 years who received growth hormone treatment for at least 3months, who underwent 24 h ABPM were analyzed. They were compared with 67 patients who had no risk factors for hypertension. In the study, 84 rhGH-treated patients (45.2 % male, 54.8 % female) and 67 healthy control groups (49.3 % male, 50.7 % female) were analyzed. The mean age of the patient group was 10.83±2.85 years and the mean age of the healthy control group was 13.1±2.93 years. The diagnostic classification of the patients receiving treatment was as follows: 66.6 % (n=56) partial growth hormone deficiency, 22.6 % (n=19) growth hormone deficiency, 7.1 % (n=6) bioactive growth hormone, 2.3 % (n=2) idiopathic short stature, 1.1 % (n=1) low birth weight for gestational age (SGA). Body mass index was significantly lower in the treated group (p=0.013). The duration of treatment was 6.04±4.9months. Daytime diastolic blood pressure was significantly lower in the treated group (p=0.001). There was no correlation between BMI and ABPM parameters in the treatment group and the control group. The present study shows that growth hormone treatment is safe in terms of high blood pressure.

Growth hormone treatment in pediatrics: What can we improve?

ObjectivesTo analyze the age at which treatment with growth hormone (GH) is started in the different indications approved in our country, as well as to assess the response to it and detect points of improvement. Material and methodsA descriptive, observational and retrospective study of pediatric patients receiving GH treatment in December 2020 and monitored in the pediatric Endocrinology Unit of a tertiary care hospital. ResultsA total of 111 patients (52 females) were included in the study. The mean age at the start of treatment was 6.6 years old, being delayed in all diagnostic groups with respect to what is approved for each indication. The indication for which they most frequently received treatment was GH deficiency (n = 60, 54%). In this diagnostic group, there is a predominance of males (39 boys vs 21 girls, and a significantly greater increase in height z score (greater height SDS) is observed in those with early start of treatment compared to those who start late (greaterheight SDS 0.93 vs 0.6; P < .05).All diagnostic groups presented a greater height SDS and height velocity. No adverse effects were observed in any patient. ConclusionGH treatment is effective and safe for the approved indications. The age of initiation of treatment is a point to improve in all indications, especially in SGA patients. For this, good coordination between primary care pediatricians and pediatric endocrinologists is essential, as well as specific training to identify early signs of different pathologies.

성장호르몬 치료를 받고 있는 아동에게 수직점프운동 적용이 신장, 다리길이, 체질량지수에 미치는 효과

This study aims to examine additional growth promoting effect of Vertical jump training in children with Growth hormone deficiency (GHD) during Growth hormone (GH) therapy. In this study, 22 children participated ,and all of them were diagnosed with GHD and receiving GH treatment. They randomly assigned to the experiential group (n=11) and the control group (n=11). The experimental group received Vertical jump training sessions along with GH therapy secretion, and the control group were given GH therapy only. GH therapy was provided for both groups once a day, 6times a week for 12 weeks. The participants in the experimental group were instructed to perform three different vertical jump sessions (4 weeks per session). After 12 weeks of the intervention exercise program, the average value of height and body mass index (BMI) of all participants were measured to examine the significant difference between the two groups. First, the vertical jump exercise group showed a significant increase in the height compared to the control group(p<0.05). Second, the vertical jump exercise group showed a significant increase in the leg length compared to the control group(p<0.05). Third, there was no significant difference in body mass index between the two groups(p>0.05). The findings of this study suggest that vertical jump performance in children being treated with growth hormone therapy may improve additional height growth. Therefore, vertical jump training as a component of the growth hormone therapy plan may play an important role to stimulate growth in children when used with GH secretion.

Tratamiento con hormona de crecimiento en pediatría, ¿qué podemos mejorar?

ObjectivesTo analyze the age at which treatment with growth hormone (GH) is started in the different indications approved in our country, as well as to assess the response to it and detect points of improvement. Material and methodsA descriptive, observational and retrospective study of pediatric patients receiving GH treatment in December 2020 and monitored in the Pediatric Endocrinology Unit of a tertiary care hospital. ResultsA total of 111 patients (52 females) were included in the study. The mean age at the start of treatment was 6.6 years old, being delayed in all diagnostic groups with respect to what is approved for each indication. The indication for which they most frequently received treatment was GH deficiency (n=60, 54%). In this diagnostic group, there is a predominance of males (39 boys vs 21 girls, and a significantly greater increase in height z score (greater height SDS) is observed in those with early start of treatment compared to those who start late (greater height SDS 0.93 vs 0.6; p<0.05).All diagnostic groups presented a greater height SDS and height velocity. No adverse effects were observed in any patient. ConclusionGH treatment is effective and safe for the approved indications. The age of initiation of treatment is a point to improve in all indications, especially in small for gestational age patients. For this, good coordination between primary care pediatricians and pediatric endocrinologists is essential, as well as specific training to identify early signs of different pathologies.

Body proportions in patients with Turner syndrome on growth hormone treatment.

: In this cross-sectional study, we aimed to evaluate auxological measurements and detailed body proportions of recombinant human growth hormone (GH)-treated patients with Turner syndrome (TS) and compare them with a group of healthy females. We evaluated 42 patients with TS who received GH treatment and 20 healthy controls. Anthropometric measurements were taken and target height, body mass index (BMI), arm span-height difference, extremity-to-trunk ratio, and Manouvrier's skelic index were calculated. : The median (min-max) age of the patients at the time of evaluation was 13.6 (4.3-20.7) years, and the control group was 12.9 (3.8-23.7) years. Height, sitting height, and arm span of TS patients were significantly lower than those of the control group. Sitting height/height ratio (SHR) was in normal ranges in both groups and BMI was significantly higher in TS patients when compared to the control group. According to Manouvrier's skelic index, TS patients had shorter legs than the control group (p = 0.001). The extremity-trunk ratio was significantly decreased in TS patients compared to healthy controls (p < 0.001). There was no significant difference between the karyotype groups in terms of these indexes. TS patients had short stature, increased BMI and waist circumference, normal head circumference, and decreased extremity-trunk ratio. Sitting height and leg length were short; however, the SHR standard deviation score (SDS) was in the normal range. Despite being treated with GH, TS patients had disproportionate short stature. The disproportion in TS patients was similar to short-stature homeobox-containing gene (SHOX) deficiency, which is considered to be SHOX haploinsufficiency in the etiopathogenesis of short stature.

Height outcomes in Korean children with idiopathic short stature receiving growth hormone treatment.

ObjectivesGrowth hormone (GH) therapy’s capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment.MethodsWe retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis.ResultsWe included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2–3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device.ConclusionISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS.

Digital health for emotional and self-management support of caregivers of children receiving growth hormone treatment: a feasibility study protocol

BackgroundCaregivers of children undergoing growth hormone treatment often face stress and stigma. In this regard, family-centered approaches are increasingly considered, wherein caregivers’ mental wellbeing is taken into account to optimize children’s health-related outcomes and behaviors (e.g., treatment adherence). Here, mindfulness and parenting-based programs have been developed to support the mental wellbeing of caregivers and, in turn, promote richer interactions with the children. Nevertheless, this type of program can face drawbacks, such as the scheduling and availability of family members. Recent digital health (DH) solutions (e.g., mobile apps) are showing promising advantages as self-management support tools for improving wellbeing and behaviors related to the treatments. Although, further evidence is necessary in the field of Growth Hormone Treatment (GHt). Accordingly, this study aims to examine the usability of a mobile DH solution and the feasibility of a DH intervention designed to promote emotional and mental wellbeing of caregivers of children undergoing GHt.MethodsThis is a prospective mixed-methods (qualitative-quantitative) exploratory study composed of two sub-studies, including caregivers of children undergoing GHt. Sub-study one (SS1; n = 10) focuses on the usability of the DH solution (detecting potential barriers and facilitators) and an ad hoc semi-structured interview will be administered to the caregivers after using the DH solution for one month. Sub-study two (SS2; n = 55) aims to evaluate the feasibility of the DH intervention on caregivers’ perceived distress, positive affectivity, mental wellbeing, self-efficacy, together with the children’s quality of life and treatment adherence. All these parameters will be assessed via quantitative methods before and after 3-months of the DH intervention. Usability and engagement will also be assessed during and at the end of the study.ResultsIt is expected that significant amounts of data will be captured with regards of the feasibility of the DH solution.DiscussionThe manuscript provides a complete protocol for a study that will include qualitative and quantitative information about, on one hand, the user-friendliness of the DH solution, and on the other, the effects on caregivers’ emotional, as well as, behavioral parameters in terms of the usability and engagement to the DH solution. The findings will contribute to the evidence planning process for the future adoption of digital health solutions for caregiver support and better health-related outcomes.Trial registration ClinicalTrials.gov, ID: NCT04812665.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency.

Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Evaluation of the growth response to growth hormone therapy in short children with normal growth hormone secretion

Introduction The availability of biosynthetic growth hormone (GH) ensures that children who are deficient can have replacement therapy, but it has also created the opportunity to treat children who are short but do not have a deficiency. The target height of children with short stature who have normal GH secretion, idiopathic short stature (ISS), without treatment, fails to reach their midparental potential. GH therapy for these children has resulted in variable height outcomes. While some children reached or exceeded genetic target height, others did not have a favorable response. Aim The aim of this study was to report the outcome of the children with ISS who had initial height standard deviation score (HtSDS) (Z score) less than −2, with normal stimulated GH levels (&gt;10 μg/l), after treatment with biosynthetic GH for at least 1 year. Patients and methods This retrospective study included 20 children with ISS, with initial HTSDS less than −2, normal stimulated GH levels (&gt;10 μg/l), who were treated with rhGH (0.04 mg/kg/day) for at least 1 year. None had any other systemic or endocrine disorder. All had normal complete blood count, liver, and renal functions. Results Twenty children (15 males and five females) with ISS, aged between 4.3 and 13.8 years (mean=9.88±2.62 years), who had mean peak GH=15.58±6.95 μg, were studied. All received GH treatment (average GH dose was 0.04 mg/kg/day) for a mean duration=2.49±1.61 years. The mean midparental HtSDS (MPHSDS) was −1.23±0.57. Their bone age did not differ significantly compared with their chronological age (the mean difference=−0.13±0.67 years). The mean HSDS before treatment was −2.34±0.41 and after 1 year of GH treatment was −1.83±0.48. This gave a gain of an average of 0.5 SD. At the last visit (after a mean of 2.5 years), the HtSDS −1.57±0.55 SD with a gain of 0.77±0.14 SD versus before treatment. The difference between children HtSDS compared with their MPHSDS was −1.08 SD before treatment that was changed to −0.3 SD at the last visit. The increment in HSDS was positively correlated with the duration of rhGH therapy (r=0.82, P=0.01) and negatively correlated with age at the start of treatment (r=−0.54, P=0.01). Conclusion Growth hormone therapy that benefits short children with normal growth hormone secretion achieves near-normal HSDS and approaches MPHSDS.

Growth charts in FGFR2- and FGFR3-related faciocraniosynostoses

ObjectiveFaciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating Fibroblast Growth Factor Receptor (FGFR) 1–3 mutations. Gain-of-function FGFR3 mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with FGFR-related faciocraniosynostoses may present extra-cranial growth anomalies. Study designWe retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for FGFR-related FCS between 2000 and 2021 at the Craniofacial Unit of Necker – Enfants Malades University Hospital in Paris, France. ResultsWe showed that FGFR-related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1–3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight. ConclusionsPatients with FGFR-related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in FGFR-related faciocraniosynostoses and support the hypothesis that all conditions with activating FGFR mutations affect both membranous ossification and long bones.

Digital Health Platform for Emotional and Self-Management Support of Caregivers of Children Receiving Growth Hormone Treatment.

In recent years there has been growing research on the combination of evidence-based behavioral change techniques with mobile-based recommender systems. In this paper, we have focused on understanding the psychological burdens experienced by caregivers of children undergoing growth hormone treatment (GHt) and the perceived barriers to and drivers of the adoption of a digital health solution. This is a mixed-methods formative research study looking into technical acceptance aspects of using digital health for the emotional support of parents of children undergoing GHt. After one month using the ADHERA CARING platform (Adhera Health, Inc., Palo Alto, CA), individual semi-structured interviews were conducted. ADHERA CARING provides tailored emotional and self-management support to caregivers of children undergoing GHt to improve adherence to treatment through positive education, personalized motivational messages, and emotional support. A preliminary thematic analysis and categorization were carried out, based on the Behavioral Intervention Technology (BIT) model. The majority of participants were female. All caregivers positively valued having the tool, especially at the beginning of treatment. Information provided in the educational module was useful and improved self-efficacy. Motivational messages contributed to commitment and reinforced the educational content, thus promoting continuity of treatment and potentially improving treatment efficacy. Most participants (n=10, 80%) accessed all educational units and completed all the 27 quiz questions. Regarding the motivational messages, the overall average rating was 4.55 out of 5.00. ADHERA CARING has the potential to help caregivers to understand the treatment journey. Nevertheless, users have identified that some types of educational content are more valuable at specific stages of the treatment journey, which suggests that personalization of educational content is required to adapt to different stages of the patient journey.

Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF-1 levels, while improving height in patients small for gestational age A long-term observational study.

ObjectiveIn children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long‐term (10 years) effect of GH to SGA‐children on IR and safety during treatment.DesignThis was a multicenter observational study. Patients: SGA‐children who received GH treatment in Spain (stratified by Tanner‐stage and age at GH onset [two groups: ≤6 years old or >6 years old]). Measurements: The analysed variables (yearly measures) included auxologic, metabolic (insulin‐like growth factor‐1 (IGF‐1), height velocity [HV], weight and homeostatic model assessment‐IR [HOMA‐IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005–2007).ResultsA total of 389 SGA children (369 Tanner‐I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF‐1 (standard deviation score [SDS]) and HOMA‐IR values tended to increase until the sixth year of GH‐treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: −3.0; tenth year: −1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39).ConclusionsHOMA‐IR values increased significantly in SGA‐children during the first year of GH‐treatment, remained stable and were within normal ranges in all cases. Our 10‐year data suggests that long‐term GH treatment does not promote IR and is well‐tolerated, safe and effective.

Sleep disordered breathing in patients with Prader willi syndrome: Impact of underlying genetic mechanism

IntroductionSleep-disordered breathing (SDB) is common in children with PWS. In the current study, we aimed to evaluate the severity of SDB in patients with PWS using polysomnography (PSG), and assess the effect of the underlying genetic mechanism on PSG parameters. MethodsChildren with PWS, referred to our sleep laboratory between March 2016 and January 2020 were enrolled. PSG parameters, demographic data, body mass index (BMI), and symptoms related to SDB were recorded. The effect of non-invasive ventilation strategies and the outcome of therapy on PSG parameters were evaluated. ResultsIn our study, 64.5% of the patients had severe sleep apnea syndrome (total apnea hypopnea index (AHI) ≥10 events/hour). 22.6% had significantly high (>5 events/hour) central sleep apnea. Patients with a deletion had significantly lower initial and mean SaO2, longer sleep time SaO2 under 90%, oxygen desaturation % and total AHI when compared to those with uniparental disomy. PSG parameters were similar between patients who did or didn't receive growth hormone treatment. ConclusionThe majority of the PWS patients had severe sleep apnea syndrome characterized mainly by hypopneas which were accompanied by central apneas. There was a more severe impact on oxygen parameters and total AHI in patients with deletions.

Effects of Childhood Multidisciplinary Care and Growth Hormone Treatment on Health Problems in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about the effects of childhood GHMDc on health outcomes in adulthood. We retrospectively collected clinical data of 109 adults with PWS. Thirty-nine had received GHMDc during childhood and adolescence (GHMDc+ group) and sixty-three had never received growth hormone treatment (GHt) nor multidisciplinary care (GHMDc− group). Our systematic screening revealed fewer undetected health problems in the GHMDc+ group (10%) than in the GHMDc− group (84%). All health problems revealed in the GHMDc+ group had developed between the last visit to the paediatric and the first visit to the adult clinic and/or did not require treatment. Mean BMI and the prevalence of diabetes mellitus type 2 were significantly lower in the GHMDc+ group compared to the GHMDc− group. As all patients who received GHt were treated in a multidisciplinary setting, it is unknown which effects are the result of GHt and which are the result of multidisciplinary care. However, our data clearly show that the combination of both has beneficial effects. Therefore, we recommend continuing GHMDc after patients with PWS have reached adult age.

Incidental Pituitary Cysts in Children: Does Growth Hormone Treatment Affect Cyst Size?

ObjectiveTo evaluate the response of incidentally discovered pituitary cysts to growth hormone (GH) treatment. MethodsA retrospective chart review was performed of children with pituitary cysts on magnetic resonance imaging (MRI) over a 5-year period. Records and images were reviewed, and the results were analyzed using descriptive statistics. Children with pituitary cysts who received GH treatment were compared with those without. ResultsWe identified 109 children with pituitary cysts, 24 were treated with GH therapy. The average age was 8.5 ± 5.1 years. Children whose initial MRI scan was to evaluate growth hormone deficiency were more commonly male and non-Hispanic White compared with those with scans for other indications (male, 18 of 24 vs 35 of 85, P = .003; White, 23 of 24 vs 58 of 85, P = .004). Among patients who received GH treatment, 12 had follow-up MRI. Six had no change in cyst size and 6 had a decrease in cyst size. We observed no difference in the likelihood of cyst growth between those who received GH and those who did not (0 of 12 cysts with GH vs 1 of 15 cysts without GH showed growth at follow-up). No patient had neurologic deficits attributable to the pituitary cyst at any time. ConclusionIn a single-institution, retrospective study, we find no evidence of growth in pituitary cysts in response to GH therapy.

Late Endocrine Effects After HSCT in Children With Nonmalignant Diseases; A Single Center Cohort Analysis

Endocrine complications are amongst the most frequent late effects after pediatric hematopoietic stem cell transplantation (HSCT) for malignant diseases. Little is known about the prevalence and risk factors of endocrine complications in children transplanted for nonmalignant diseases. This retrospective study included 134 males and 63 females transplanted for a non-malignant disease between 1997 and 2018 with at least 2 years of follow up. Endocrine late effects and growth were evaluated. Gonadal dysfunction was defined as transient or permanent elevation of gonadotropins or hypogonadotropic hypogonadism.Median age at HSCT was 5.7 years (IQR 2.8-11.3) and median follow-up was 6.2 years (IQR 3.0-10.4). Underlying diseases were inborn errors of immunity (n=74), hemoglobinopathies (n=66) and bone marrow failure (n=57). The majority of patients had received busulfan-based conditioning (46%) or treosulfan-based conditioning (34%).Gonadal dysfunction occurred in 24/44 (post)pubertal female patients (55%) and was permanent in 19/44 (43%). 22/44 received hormonal substitution, which could be discontinued in 7. In females who received busulfan-based conditioning 16/17 (94%) developed gonadal dysfunction compared to 5/15 (33%) patients with treosulfan-based conditioning; the odds ratio for permanent gonadal dysfunction was 18.7 (3.61-135, p=0.001).Gonadal dysfunction occurred in 28/66 (post)pubertal male patients (42%) and was permanent in 23/66 (35%). 6/66 received hormonal substitution, which could be discontinued in 1. Gonadal dysfunction was more common in males (post)pubertal at HSCT, 14/21 (67%), compared to those prepubertal at HSCT, 14/45 (31%), p=0.014. 3/15 treated with a treosulfan-based regimen (20%) developed gonadal dysfunction, all transient, versus 19/39 with a busulfan-based regimen (49%), with 2 transient.29/187 patients developed hypothyroidism (16%), 7 patients received thyroxine treatment (4%). All patients with persistent primary hypothyroidism (n=6) had positive TPO-antibodies.17 patients received growth hormone treatment and were excluded from analysis. In patients without growth hormone treatment near adult height (NAH) was -1.2 SDS (median, IQR -2.0- -0.3) below mean parental height (MPH) in males and -0.4 SDS (median, IQR -1.6-0.3) in females. NAH below -2 SDS was seen in 13/43 males (30%) and 2/36 females (6%). The majority of these patients already had a height below -2 SDS before HSCT (73%).In conclusion, this study on late endocrine effects after HSCT in children with nonmalignant diseases indicates frequent gonadal dysfunction, present in 55% of females and 42% of males. In this cohort, risk of gonadal dysfunction in females was higher after busulfan-based conditioning than treosulfan-based conditioning. Careful long-term endocrine follow-up is indicated.