The growzen™ buddy smartphone app to improve adherence in patients receiving recombinant human growth hormone therapy: a retrospective observational study in Argentina.

Introduction: This study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment. Methods: The adherence data, invitation dates with a link to the app, app activation dates, and height measurements entered were extracted from the growzen™ digital health ecosystem. Patients with 12 months of adherence data, aged ≥2 years at treatment start, and aged <19 years were selected both before and after app implementation. Mean adherence was classified as optimal (≥85%) versus suboptimal (<85%). Adherence before and after implementation and the pre-post effect on adherence were assessed. Results: Data for 830 patients were available. Prior to app implementation, the proportion of patients with optimal adherence was 68% (n = 348/515). Following the app implementation, out of 315 patients, 302 (96%) received an invitation with a link to the app, 225 (71%) activated their account, and 127 (40%) entered height data in the first year. There was a significant early increase in the proportion of patients with optimal adherence following implementation: 82% (n = 258/315), p < 0.001. After implementation, the proportion of patients with optimal adherence included 80% (n = 78/98) of those with an active account who did not enter height measurements and 89% (n = 113/127) of those who did. There was a significant and positive pre-post app effect on adherence (p < 0.01) in patients with an active account. Discussion: Our results show that using the growzen™ buddy app has a rapid and positive impact on adherence to r-hGH treatment, and patients who were more engaged with the app demonstrated better adherence.

Long-acting growth hormone in the management of GHD in France.

Approximately 10,000 children in France with growth hormone deficiency (GHD) are being administered daily recombinant human growth hormone (rhGH). Although this treatment has long proved efficient for restoring children's growth and metabolism, daily injections of rhGH have a few limitations, such as difficulties in terms of adherence to treatment, which may compromise growth during childhood but also metabolism in adulthood. In addition to the disease burden and besides the adherence hurdles, the obligations related to daily injection have a negative impact on the quality of life of patients and their families. The hypothesis that injections administered at intervals of 1 week, or even 1 month, could improve compliance, reduce treatment discontinuations, and optimize quality of life and therapeutic effectiveness has led to the emergence of new long-acting growth hormone (LAGH). Recent access to LAGHs (somatrogon MA) on the European and French market will likely be followed by a high demand from the families concerned and may raise questions on their effectiveness, safety, and practical use. Numerous practical and practice-related points are needed to guide prescribing physicians while many concerns are still left unresolved (treatment effectiveness or ineffectiveness endpoints, long-term effectiveness, etc.). These issues can only be addressed in the future by compiling registries and conducting long-term real-world studies.

Primary response in GHD children treatment as a predictor for long-term therapy effectiveness therapy effectiveness.

INTRODUCTION: Short stature in growth hormone deficiency (GHD) can be treated with recombinant human growth hormone (rhGH), which is proven to be both safe and effective. However, a considerable number of patients does not achieve satisfying therapy outcomes. AIM OF THE STUDY: To evaluate the predictive effect of height increase in the first year of rhGH treatment on long-term therapy outcomes. MATERIAL AND METHODS: 165 short-stature children (mean age 10.72 ±3.33 years; 63% males), diagnosed with GHD, treated with rhGH for at least one year (mean follow-up 4.32 ±1.80 years), divided into 2 groups according to the change in height standard deviation score (SDS) after the first year of rhGH treatment: good responders (GR) and poor responders (PR). Then, in one-year intervals, patient's chronological age, bone age, height, weight, insulin-like growth factor level, and rhGH dose were all assessed. RESULTS: In the GR group, mean height velocity SDS up to five years of observation was 1.19 ±0.41/year and in the PR group 0.59 ±0.38/year. The differences were statistically significant (p < 0.05). CONCLUSIONS: The primary response to the rhGH treatment in GHD children seems to be a good predictor for long-term therapy outcomes.

A case report: Alport syndrome and growth hormone deficiency associated with a new COL4A4 mutation.

Background: Alport syndrome (AS) is a rare progressive hereditary kidney disease that is clinically principally associated with hematuria, proteinuria, and progressive renal dysfunction. This condition not only impairs renal function but also potentially affects auditory and ocular health, significantly impacting the patient's quality of life. Case Description: This article reports a young girl with AS, combined with dwarfism attributable to growth hormone (GH) deficiency, diagnosed at Wenzhou People's Hospital in 2019. The clinical data and diagnostic steps were retrospectively analyzed. Genetic testing showed that she carried a new mutation in the COL4A4 gene, c.2317_2318delAG (p.R773Gfs*14), classified as "pathogenic" under the criteria of the American College of Medical Genetics and Genomics (ACMG), confirming her AS diagnosis. Significantly, the patient's height was more than two standard deviations (SDs) below the average for children of her race, sex, and age. The peak GH level post-stimulation was below 5 ng/mL, coupled with a growth rate of less than 5 cm/year, leading to the diagnosis of GH deficiency. Consequently, recombinant human GH (rhGH) therapy was initiated. Conclusions: After a year of rhGH treatment, we observed a notable increase in her height, without any adverse effects like elevated intracranial pressure, hypothyroidism, or worsening kidney function.

Clinical profiles and molecular genetic analyses of 98 Chinese children with short statures.

Background: Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration. Methods: The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures. Results: The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome. Conclusion: WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.

Gonadal Failure in a Male With 3-M Syndrome.

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

INTRODUCTION: Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation. These considerations are further complicated by the varying timing and dosages of treatment with growth hormone and sex hormones. METHODS: We conducted a cross-sectional study comparing 44 individuals with TS with 52 age-matched control subjects. Growth hormone treatment in the study group was administered for varying lengths of time, depending on clinical response. We collected anthropometric, metabolic, endocrine and body composition data. Statistical analyses included logistic regression. RESULTS: Baseline characteristics, including age, BMI and height, were comparable between the TS and control groups. Hormonally, individuals with TS showed lower levels of testosterone, DHEA-S, and cortisol, as well as elevated FSH. Lipid profiles indicated an atherogenic profile, and the body composition analysis showed increased visceral adipose tissue in those with TS. Other metabolic abnormalities were common in individuals with TS too, including hypertension and impaired fasting glucose levels. The risk of MetS components was assessed in subgroups according to karyotypes: monosomy 45X0 vs. other mosaic karyotypes. Logistic regression analysis showed a significant association between increased visceral adipose tissue in subjects with TS. Those with metabolic complications tended to have less muscle strength compared to those without these complications in both the study and control groups. CONCLUSIONS: This study highlights the unique metabolic and cardiovascular risk profile of individuals with TS, characterized by atherogenic lipids, higher levels of visceral adipose tissue and increased metabolic abnormalities. These findings underscore the importance of monitoring metabolic health in individuals with TS, regardless of age, BMI or karyotype, and suggest the potential benefits of lifestyle modification, building more muscle strength, and weight control strategies. Further research is needed to better understand and address the metabolic challenges faced by women with TS.

Optimal final adult height achieved by low-dose recombinant human growth hormone therapy.

Background: Thailand has been administering the recombinant human growth hormone (rhGH) treatment for >20 years. Due to limited resources being available, efforts have been directed toward utilizing rhGH at the lowest feasible dose. However, there is currently a lack of evidence in terms of the efficacy and outcomes. Objective: To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. Methods: Data of 40 patients were retrospectively reviewed. The clinical characteristics, auxological data, and results of biochemical and endocrine investigations before and during rhGH treatment were evaluated. In addition, GH retesting was performed in 24 patients using the insulin tolerance test. Results: Twenty patients (50%) had complete growth hormone deficiency (GHD), defined as peak stimulated GH level <5 ng/mL, and the remaining patients had partial GHD. Most patients were male (n = 25, 62.5%). The mean age at which rhGH was initiated was 8.9 years. Patients with partial GHD received a higher dose of rhGH than those with complete GHD (30.9 µg/kg/d vs. 26.2 µg/kg/d, P = 0.02). Patients with complete and partial GHD reached FAH at height standard deviation scores (SDSs) of -0.65 and -1.47, respectively. The factors associated with obtaining a good clinical response in terms of height gain included peak-stimulated GH level, age of puberty, and age of discontinuing rhGH. After completing the rhGH treatment, 13 of the 24 patients showed normal GH secretion. Patients with multiple pituitary hormone deficiency (MPHD) were likely to have persistent GHD through adulthood (n = 8, 88.9%). Conclusion: This study has demonstrated that the use of low-dose rhGH could result in healthy populations achieving optimal FAHs. Patients with MPHD might not require retesting as they were likely to have persistent GHD. The results obtained in this research highlight the benefits of the treatment. This treatment can be applied in resource-limited countries.

[Safety considerations for the clinical application of recombinant human growth hormone]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ ä¸´åºŠåº”ç”¨çš„å®‰å ¨æ€§æ€è€ƒ.

Recombinant human growth hormone (rhGH) is an effective therapeutic drug for improving short stature. Currently, rhGH can be used for various causes of short stature, including growth hormone deficiency, and the expansion of its clinical application has raised concerns about its safety. Based on existing evidence, when rhGH is used in a standardized manner for physiological replacement therapy, its safety profile is favorable. In clinical practice, attention should be focused on short-term safety during rhGH treatment, with the combination of literature evidence and clinical experience. There is still no definitive conclusion on the long-term safety due to insufficient duration of rhGH treatment. This paper reviews the possible adverse events that may occur during rhGH treatment and their risk control measures, aiming to help clinical physicians understand the overall safety of rhGH treatment and improve its clinical standardization.

[Management of transition growth hormone deficiency]. / è¿‡æ¸¡æœŸç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡çš„ç®¡ç†.

With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in clinical practice. The inadequate diagnosis and treatment of TGHD have been a major clinical concern, leading to the development of relevant guidelines and consensus internationally. This article summarizes the evaluation, diagnosis, treatment, and clinical challenges of TGHD based on these guidelines, consensus, and existing clinical studies, aiming to optimize and further improve the clinical diagnosis, treatment, and management of TGHD.

The efficacy of therapeutic interventions on paediatric burn patients' height, weight, body composition, and muscle strength: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. METHODS: A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn. RESULTS: Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% ( ± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support. CONCLUSIONS: Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers.

An overview of growth hormone therapy in pediatric cases documented in the Kabi International Growth Study (Pfizer International Growth Database).

The Kabi International Growth Study (KIGS) was first established in 1987 and is the largest pharmaco-epidemiological study of recombinant human growth hormone (rhGH). KIGS is aimed at evaluating long-term safety and treatment outcomes in pediatric subjects who received Genotropin rhGH therapy (Pfizer, New York, NY, USA) as prescribed by physicians in real-world clinical practice settings. KIGS data have been used to answer multiple research questions related to growth, growth prediction, and growth hormone treatment, leading to the publication of 129 peer-reviewed manuscripts and 24 biannual reports, outcomes from 10 expert meetings, and 3 books. The KIGS has shown that rhGH is safe and increases both the short-term height gain and adult height in patients with GH deficiency (GHD) and multiple other non-GHD conditions associated with short stature.

[Pharmacological therapies for height improvement in pubertal children with short stature]. / 青春期矮身材儿童身高改善的药物治疗.

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

Evaluating the effect of recombinant human growth hormone treatment on sleep-related breathing disorders in toddlers with Prader-Willi syndrome: a one-year retrospective cohort study.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy is beneficial for children with Prader-Willi syndrome (PWS) in improving short stature and metabolism, but the effect of early rhGH treatment on respiratory and sleep parameters for PWS children under three years old remains elusive. Thus, this study aimed to investigate the impact of rhGH treatment on sleep-related breathing disorders (SRBDs) for toddlers with PWS. METHODS: A total of 17 age-matched PWS patients receiving rhGH treatment (rhGH group) and 17 control individuals not receiving rhGH treatment (non-rhGH group) were recruited for this study between October 2018 and January 2023. Data related to polysomnography-polygraphy (PSG) and serum levels of insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) were collected. RESULTS: The mean age in the rhGH group was 20.76 ± 9.22 months, which was comparable to that of the non-rhGH group (25.23 ± 13.81 months). The demographic and anthropometric parameters were similar across the two groups after 52 weeks of treatment. Administration of rhGH to toddlers did not exert adverse effects on the obstructive apnea-hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), mean percutaneous oxygen saturation (SpO2), lowest SpO2, duration when SpO2 is lower than 90%, or proportion of the patients with SpO2 lower than 90%. Furthermore, the increased IGF-1 z-score and IGFBP-3 level did not worsen SRBDs. CONCLUSION: Treatment with rhGH for 52 weeks on young toddlers with PWS showed no deleterious effects on SRBDs. This shed more light on the importance of initiating rhGH therapy early in PWS patients.

Molecular diagnosis is an important indicator for response to growth hormone therapy in children with short stature.

BACKGROUND: Significant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment. METHODS: A total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined. RESULTS: Pathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH. CONCLUSIONS: This study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.

Effects of different therapy regimens to increase final adult height in males at advanced bone age with idiopathic short stature.

BACKGROUND: This retrospective study explored the effect on adult height of a combination of recombinant human growth hormone (rhGH) and aromatase inhibitors (AIs), or rhGH and a gonadotropin-releasing hormone analog (GnRHa), and compared their effects with rhGH alone in males at advanced bone age with idiopathic short stature (ISS). METHODS: In this retrospective study, rhGH or rhGH combined with GnRHa or rhGH combined with AI therapy was given to males with advanced bone age (13-15 years) and diagnosed with ISS. The patients were followed to assess their adult height. RESULTS: (1) A total of 68 patients were reviewed; 22 males were treated with rhGH for 24.9 ± 4.47 months, 22 males were treated with GnRHa + rhGH for 34.1 ± 3.36 months, and 24 males were treated with AI + RHGH for 22.7 ± 2.49 months. (2) Before treatment, the HtSDS-CA for the three groups were -1.04 ± 0.95, -1.23 ± 1.06, and -0.85 ± 0.98, respectively, and the HtSDS-BA were -2.14 ± 0.29, -2.14 ± 0.21, and-2.26 ± 0.31, respectively. The target heights for each group were 169.7 ± 4.0 cm, 169.7 ± 3.9 cm, and 169.1 ± 3.9 cm, respectively. The predicted adult heights were 161.7 ± 3.35 cm, 162.3 ± 1.75 cm, and 161.6 ± 2.89 cm, respectively. (3) After treatment, the HtSDS-CA for the rhGH group increased by 1.30 ± 0.58, and the HtSDS-BA increased by 2.00 ± 0.27. For the GnRHa + rhGH group, the HtSDS-CA and HtSDS-BA increased by1.42 ± 0.73and 2.74 ± 0.28, respectively. The AI + RHGH group increased by1.39 ± 0.64 and 2.76 ± 0.31, respectively. (4) There was no significant difference between the adult height (170.9 ± 0.7 cm) and target height for the rhGH group (P > 0.05), but the adult heights for the GnRHa + rhGH and AI + RHGH groups (173.2 ± 1.5 cm and 173.5 ± 1.0 cm, respectively, P > 0.05) were higher than the target height (P < 0.05). (5) Compared with the predicted adult height, the adult heights for the three groups improved significantly (P < 0.05). (6) No severe adverse reactions during the treatment occurred in any of the children. However, the total incidence of side effects in the three groups was significant (χ2 = 20.433, P = 0.00). CONCLUSION: Different therapeutic approaches have been investigated to improve the final adult height of males at advanced bone ages with ISS, and the optimal strategy remains controversial. In children at advanced bone ages with ISS, clinicians should carefully consider the advantages and disadvantages prior to treatment.

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency.

BACKGROUND: With the improvement of economy and living standards, the attention paid to short stature in children has been increasingly highlighted. Numerous causes can lead to short stature in children, among which growth hormone deficiency (GHD) is a significant factor. AIM: To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in the treatment of GHD in children. METHODS: We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018. Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week, forming the high-dose group. Meanwhile, 21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week, establishing the low-dose Group. The total treatment period was 2 years, during which we monitored the patients' height, annual growth velocity (GV), height standard deviation score (HtSDS), chronological age (CA), bone age (BA), and serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) before treatment and at 6 mo, 1 year, and 2 years after treatment initiation. We also monitored thyroid function, fasting plasma glucose, fasting insulin, and other side effects. Furthermore, we calculated the homeostatic model assessment for insulin resistance. RESULTS: After 1 year of treatment, the GV, HtSDS, IGF-1, BA, and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels (P < 0.05). Moreover, when comparing GV, HtSDS, IGF-1, BA, and IGFBP-3 between the two groups, there were no statistically significant differences either before or after the treatment (P > 0.05). During the treatment intervals of 0-1.0 years and 1.0-2.0 years, both patient groups experienced a slowdown in GV and a decline in HtSDS improvement (P < 0.05). CONCLUSION: The use of PEG-rhGH in treating GHD patients was confirmed to be effective, with similar outcomes observed in both the high-dose group and low-dose groups, and no significant differences in the main side effects.

Longitudinal unraveling: The impact of recombinant human growth hormone on spontaneous brain activity in children with short stature-A resting-state fMRI study.

Recombinant human growth hormone (rhGH) is an approved method to improve the growth and ameliorate behavioral issues in children with short stature. However, the data concerning the effects of rhGH treatment on spontaneous brain activity remains unclear. This study included 35 children with short stature, categorized into two groups: the treated group (n = 14) and the untreated group (n = 21). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessments at baseline and at the end of a one-year follow-up. The rs-fMRI based amplitude of low frequency fluctuation (ALFF) analysis method was employed to assess spontaneous brain activity. Interaction effects between rhGH and time on ALFF were detected using a mixed-effects analysis. Additionally, Stepwise regression analysis was conducted to investigate the associations between ALFF values and significant clinical indicators. The treated group exhibited significant improvements in height, weight, insulin-like growth factor-1 (IGF-1) levels, insulin-like growth factor binding protein 3 (IGFBP-3) levels, and processing speed index (PSI) when reevaluated from baseline. The interaction effect of rhGH × time was evident in the right putamen (RPUT), where the ALFF value showed a significant increase following rhGH treatment, while also demonstrating a notable positive correlation with height. Moreover, The main effect of time was manifested as a significant decrease in the ALFF value of the left dorsolateral superior frontal gyrus (LSFG) within the untreated group during the follow-up period, concurrently displaying a positive correlation with age. In conclusion, rhGH treatment not only has a positive effect on the growth, cognition, and behavior of children with short stature, but also improves and normalizes spontaneous brain activity.

Evaluation of Clinical Characteristics and Growth Hormone Response in a Rare Skeletal Dysplasia: Pycnodysostosis.

Introduction Pycnodysostosis is a rare osteosclerotic skeletal dysplasia; its clinical features include short stature, characteristic facial features, increased bone fragility, and acro-osteolysis of the distal phalanx. Lack of clear guidelines for treatment and follow-up in rare diseases such as pycnodysostosis with growth hormone (GH) deficiency poses a difficulty for the clinician. This study aims to identify clinical, radiological, and endocrine findings of patients with pycnodysostosis focusing on the first year of recombinant human growth hormone (rhGH) treatment response. The eminence of this study is that it presents clinical experience with rhGH, providing an approach for future similar cases. Methods Three girls and two boys from three different families diagnosed with pycnodysostosis via clinical, radiological, and genetic evaluation followed up in the pediatric endocrinology clinic between 2022 and 2023 were enrolled in this study. Clinical findings, anthropometric measurements (weight, height, body mass index [BMI]), and laboratory, radiological, and genetic examinations were evaluated retrospectively. Participants were evaluated for GH deficiency using L-DOPA and clonidine tests if growth rate was below -2 standard deviation score (SDS) for gender and age after one-year follow-up. Results Complaints on admission were short stature (80%) and recurrent bone fractures (20%). Characteristic facial features and brachydactyly were seen in all the patients. Median height SDS on admission was -3.0 (range: -1.9 to -3.8). Median height SDS on last clinic visit was -3.2 (range: -1.7 to -4.2) at a median age of 8 years (range: 3.5-14 years). BMI was normal in four patients, while one was overweight. Bone mineral densitometry z-score was high, and two patients had bone fractures following minor trauma, while one had recurrent fractures. Two siblings (first and second cases) and the third case were diagnosed with GH deficiency, and anterior pituitary hormones were normal otherwise. One had partial empty sella in hypophyseal magnetic resonance imaging. rhGH (33 mcg/kg/day, subcutaneously) was started. Growth rate of the first, second, and third cases increased from 3.3, 3.1, 3.9 to 5, 4.3, 7.2 cm/year, respectively. Prior to rhGH, two had adenoid hypertrophy which was stable following rhGH. Growth rate follow-up of the fourth case continues, while the fifth case, the only participant who has reached adult height, has normal height according to age and gender normative. Conclusion Although rare, pycnodysostosis should not be overlooked in a patient with characteristic facial features, disproportionate short stature, and recurrent fractures. GH deficiency should be evaluated early if growth rate is declining. rhGH may restore growth rate and the possibility of catch-up in growth in patients with pycnodysostosis and GH deficiency. Hence, after first year of rhGH, growth rate of patients with pycnodysostosis is lower when compared to other etiologies of GH deficiency.

PLGA and PEG based porous microparticles as vehicles for pulmonary somatropin delivery.

Breakthrough advances in protein therapeutics and sustained release systems continue to fuel innovation in novel, non-invasive polymeric platforms for delivery of biologicals. Despite the bench potential and proof-of-concept work, market analysis still shows biologicals to be predominantly injections. Characterized by insufficient secretion of growth hormone by the pituitary gland, growth hormone deficiency (GHD) is a rare disorder. Currently, chronic somatropin (r-hGH) replacement therapy is only available as subcutaneous injections administered several times a week. We aim to prepare large, porous, biodegradable and aerodynamically light microparticles as tunable carriers for pulmonary r-hGH delivery. We developed a range of microparticles using PLGA 5050 1Awith sizes between 5 µm and 13 µm, densities lower than 0.4 g/cc and aerodynamic diameters lower than 6 µm. Polyethylene glycol's multitude of advantages - plasticizing PLGA, improving the biocompatibility of the system and preventing protein burst release - have been extensively studied, making it our excipient (pore-former) of choice. Drug loading was characterized at pH 4.0 (acidic), 5.3 (pI) and pH 7.2 (neutral) and was a result of an interplay of electrostatic and hydrophobic interactions between the polymer and somatropin. Considering the physicochemical interactions, we observed some pH dependent protein unfolding characterized by reduction in intrinsic fluorescence of the Tryptophan 86 residue at 331 nm. The secondary ⍺-helix structure characterized by 2 negative minima at 209 nm and 222 nm in the circular dichroism spectra, was intact at all pH values. R-hGH was released over a period of seven days, and the release profile was a function of the microparticle porosity.