Recombinant Human Growth Hormone Therapy Research Articles

Ciliopathies are responsible for short stature and insulin resistance: A systematic review of this clinical association regarding SOFT syndrome.

SOFT syndrome (Short stature-Onychodysplasia-Facial dysmorphism-hypoTrichosis) is a rare primordial dwarfism syndrome caused by biallelic variants in POC1A encoding a centriolar protein. To refine the phenotypic spectrum of SOFT syndrome, recently shown to include metabolic features, we conducted a systematic review of all published cases (19 studies, including 42 patients). The SOFT tetrad affected only 24 patients (57%), while all cases presented with short stature from birth (median height: -5.5SDS([-8.5]-[-2.8])/adult height: 132.5cm(103.5-148)), which was most often disproportionate (90.5%), with relative macrocephaly. Bone involvement resulted in short hands and feet (100%), brachydactyly (92.5%), metaphyseal (92%) or epiphyseal (84%) anomalies, and/or sacrum/pelvis hypoplasia (58%). Serum IGF-I was increased (median IGF-I level: + 2 SDS ([-0.5]-[+ 3])). Recombinant human growth hormone (rhGH) therapy was stopped for absence/poor growth response (7/9 patients, 78%) and/or hyperglycemia (4/9 patients, 45%). Among 11 patients evaluated, 10 (91%) presented with central distribution of fat (73%), clinical (64%) and/or biological insulin resistance (IR) (100%, median HOMA-IR: 18), dyslipidemia (80%), and hepatic steatosis (100%). Glucose tolerance abnormalities affected 58% of patients aged over 10years. Patients harbored biallelic missense (52.4%) or truncating (45.2%) POC1A variants. Biallelic null variants, affecting 36% of patients, were less frequently associated with the SOFT tetrad (33% vs 70% respectively, p = 0.027) as compared to other variants, without difference in the prevalence of metabolic abnormalities. POC1A should be sequenced in children with short stature, altered glucose/insulin homeostasis and/or centripetal fat distribution. In patients with SOFT syndrome, rhGH treatment is not indicated, and IR-related complications should be regularly screened and monitored.PROSPERO registration: CRD42023460876.

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

This study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment. 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. 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. 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.

Bioethical, medical, and social problems in children with growth hormone deficiency

Background. Medical and practical advancements have brought about new possibilities for providing healthcare to people, but with it comes new bioethical challenges. In many pediatric medical institutions, consultations on pediatric ethics have become common practice. However, the bioethical problems related to short children have not been studied enough yet. The purpose of this study is to identify and analyze bioethical, medical, and social issues in children with growth hormone deficiency (GHD), which can potentially hinder timely diagnosis and adherence to replacement therapy. Materials and methods. The identification of bioethical, medical, and social problems was conducted at the Odesa Regional Children’s Hospital between 2012 and 2020. The study involved a cohort of 94 children with GHD and short stature (SDS 3.4 ± 0.1), aged 7.2 ± 0.4 years, as well as their parents (124 individuals). The study was based on a questionnaire survey, history taking, interviews, objective examination of patients, and analysis of medical records. Results. The study found evidence of violations of the Hippocratic principle of help and assistance (“do good”) in the form of delayed or incorrect diagnosis in 10.6 % of cases and incomplete adherence to local protocols for managing sick children in 6.4 % of cases. Violations of the Hippocratic principle of non-harm (“first, do no harm”) were evidenced by adverse events (16.0 %) and serious adverse events (3.2 %) during replacement therapy. Children with GHD were subject to violations of social justice, such as neglect (8.5 %), socio-economic problems in the family (12.8 %), and external environmental restrictions (9.6 %). Violations of the personal autonomy of children with GНD inclu­ded physical and psychological abuse in the family (29.8 and 38.3 % of cases, respectively), stigmatization (25.5 %), school bullying (27.2 %), medical neglect (5.3 %), medical paternalism (6.4 %), and overprotection (10.6 %). Conclusions. In the management of children with GHD, various bioethical, medical, and social issues have come to light. Low adherence to recombinant human growth hormone therapy can be considered an independent bioethical problem associated with medical paternalism and medical neglect.

Exploring the cardiovascular effects of recombinant human growth hormone therapy: a prospective study on endothelin-1 and asymmetric dimethyl arginine in adults with growth hormone deficiency

Exploring the cardiovascular effects of recombinant human growth hormone therapy: a prospective study on endothelin-1 and asymmetric dimethyl arginine in adults with growth hormone deficiency

Growth hormone in pediatric chronic kidney disease: more than just height.

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy.

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

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. To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. 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. 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%). 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.

Considerations on the improvement of height benefit in children with central precocious puberty

With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.

Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency.

Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1year in adolescent males with GHD. Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II). Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9-13.7) and 12.8 (12.0-14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8-0.9) and 1.0 (0.9-1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4-10.1) cm/year [1.5 (0.8-5.0) SD score] and 8.7 (7.5-9.9) cm/year [1.1 (0.3-3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal. When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

The Interplay between Muscular Grip Strength and Bone Mineral Density with Consideration of Metabolic and Endocrine Parameters in Individuals with Turner Syndrome.

Patients with Turner syndrome (TS) often face skeletal and muscular challenges, including reduced bone mineral density (BMD) and muscle weakness. This comprehensive study sheds light on the complex interplay between muscle strength, BMD, and metabolic and endocrine parameters in TS and healthy subjects. A cross-sectional study involving 42 TS patients and 70 healthy women was conducted. All patients had their BMD determined in the L1-L4 lumbar spine section and in the whole skeleton as well as the parameters of body fat mass (BF), and visceral fat mass (VF) were also determined. The maximum gripping force was measured with a hydraulic manual dynamometer. In addition, a number of blood hormonal and metabolic parameters were determined. In the TS group, hand grip strength correlated positively with triglyceride levels but not with BMD. Healthy individuals had a positive link between hand grip strength and BMD, while patients with TS did not show a significant association between the two. A trend suggested that longer recombinant human growth hormone (rhGH) therapy might improve BMD in the L1-L4 region. Multiple linear regression analysis revealed that muscle strength assessment may be a potential exponent of reduced BMD, and also used clinically in young adult women but not in individuals with TS. The relationship between BMD variables and hand grip might differ between the two groups, potentially indicating distinct musculoskeletal characteristics in TS patients. Longer rhGH therapy in TS patients may have a positive effect on BMD in the L1-L4 region. Understanding the intricate relationships between these factors is important for optimizing clinical management strategies and improving the quality of life for TS patients.

Early psychomotor development and growth hormone therapy in children with Prader-Willi syndrome: a review.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of imprinted gene expression on the paternal chromosome 15q11-q13. PWS is characterized by varying degrees of early psychomotor developmental deficits, primarily in cognition, language, and motor development. This review summarizes the early mental cognitive development, language development, and motor development in patients with PWS, compares the correlation of genotype with phenotype, and provides an update regarding the effects and concerns related to potential main side effects of treatment with recombinant human growth hormone on early psycho-cognitive and motor function development along with the linear growth and body composition of children with PWS.Conclusion: Early psychomotor development is strongly correlated with the prognosis of patients with PWS; moreover, current studies support that the initiation of interventions at an early age can exert significant beneficial effects on enhancing the cognitive and linguistic development of patients with PWS and allow them to "catch up" with motor development. What is Known: • Prader-Willi syndrome is a rare genetic disorder characterized by multisystem damage, andchildren with Prader-Willi syndrome are typically characterized by early developmental delays, specifically in the areas of cognitive and motor development. •Recombinant human growth hormone therapy is the only medical treatment approved for Prader-Willi syndrome. What is New: •Extensive presentation of psycho-cognitive and motor development features and genotype-phenotype correlation in children with Prader-Willi syndrome. • The effects of growth hormone on early psychomotor development in children with Prader-Willi syndrome were thoroughly reviewed, including their short- and long-term outcomes and any associated adverse effects.

Magnetic resonance imaging of knees: a novel approach to predict recombinant human growth hormone therapy response in short-stature children in late puberty.

There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty. In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later. Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV1-3 mon from 9.38 to 6.08 to 4.56cm/year, GV4-6 mon from 6.75 to 4.92 to 3.25cm/year, and height gain from 4.03 to 2.75 to 1.95cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01). The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty.

Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

Cross-sectional and retrospective cohort study. We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. Level III.

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.

Development of a Minimum Dataset for the Monitoring of Recombinant Human Growth Hormone Therapy in Children with Growth Hormone Deficiency: A GloBE-Reg Initiative

Introduction: Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods: This study was undertaken by the growth hormone (GH) scientific study group in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives, and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with growth hormone deficiency (GHD) was compiled. Each member was asked to determine the: (1) importance of the data field and (2) ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided Results: A total of 246 items were compiled and 27 were removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GHD on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months, and 9 every 12 months. Conclusion: In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the MDS requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting GH.

Chinese patients with 3M syndrome: clinical manifestations and two novel pathogenic variants.

Background: 3M syndrome is a rare autosomal recessive disease, characterized by intrauterine and postnatal growth retardation, facial dysmorphism, large head circumference, and skeletal changes, has rarely been reported in the Chinese population. Methods: We describe the clinical manifestations and gene variants in four sporadic cases of 3M syndrome in Chinese individuals from different families. Results: All cases had significant growth retardation, relative macrocephaly, and typical facial features. Exome sequencing revealed that two patients with 3M syndrome had homozygous variants of the CUL7 gene: one novel pathogenic variant and one previously reported pathogenic variant; the other two patients were heterozygous for variants in OBSL1, one of which had not been reported previously. Clinical evaluation indicated that these Chinese patients with 3M syndrome shared similar recognizable features with those reported in patients of other ethnic backgrounds, but not all patients with 3M syndrome in this study had normal development milestones. Two patients underwent recombinant human growth hormone (rhGH) therapy and showed accelerated growth in the first 2years; however, the growth rate slowed in the third year in one case. There were no obvious adverse reactions during rhGH treatment. Conclusion: We report one novel CUL7 and one novel OBSL1 mutation in patients with 3M syndrome. Children with short stature, specific facial features, and physical symptoms should be referred for genetic testing to obtain precise diagnosis and appropriate treatment. The effects of rhGH treatment on adult height requires long-term observation and study in a large sample.

Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature

ObjectiveTo evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth. DesignFour DMD patients on Deflzacort 0.6–0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6–18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD). ResultsGrowth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3–7.8 cm/year over a period of 6–18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment. ConclusionsrhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.

The Impact of Growth Hormone Therapy on Sleep-Related Health Outcomes in Children with Prader-Willi Syndrome: A Review and Clinical Analysis.

This literature review of growth hormone (GH) therapy and sleep-related health outcomes in children diagnosed with Prader-Willi syndrome (PWS) assembles evidence for the consequences of sleep deprivation and poor sleep quality: difficulty concentrating and learning at school, behavioral problems, diminished quality of life, and growth impairment. Sleep-disordered breathing (SDB) is another factor that impacts a child's well-being. We searched the electronic databases Medline PubMed Advanced Search Builder, Scopus, and Web of Science using MeSH terms and text words to retrieve articles on GH deficiency, recombinant human growth hormone (rhGH) therapy, sleep quality, SDB, and PWS in children. The censor date was April 2023. The initial search yielded 351 articles, 23 of which were analyzed for this review. The study findings suggest that while GH may have a role in regulating sleep, the relationship between GH treatment and sleep in patients with PWS is complex and influenced by GH dosage, patient age, and type and severity of respiratory disorders, among other factors. GH therapy can improve lung function, linear growth, and body composition in children with PWS; however, it can also trigger or worsen obstructive sleep apnea or hypoventilation in some. Long-term GH therapy may contribute to adenotonsillar hypertrophy and exacerbate sleep apnea in children with PWS. Finally, GH therapy can improve sleep quality in some patients but it can also cause or worsen SDB in others, leading to diminished sleep quality and overall quality of life. The current evidence suggests that the initial risk of worsening SDB may improve with long-term therapy. In conclusion, rhGH is the standard for managing patients with PWS. Nonetheless, its impact on respiratory function during sleep needs to be thoroughly evaluated. Polysomnography is advisable to assess the need for adenotonsillectomy before initiating rhGH therapy. Close monitoring of sleep disorders in patients with PWS receiving GH therapy is essential to ensure effective and safe treatment.

Effect of Growth Hormone Therapy on Pubertal Timing: Systematic Review and Meta-Analysis

Introduction: Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing. Methods: Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children. Results: Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = −0.46 years; 95% CI, −0.90 to −0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284). Conclusions: Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.

Real life long-term efficacy and safety of rhGH therapy in children with SHOX deficiency.

This Italian survey aims to evaluate real-life long-term efficacy and safety of rhGH therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3, T4) and at near-final height (nFH) (T5), when available. 117 SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33years (74% prepubertal), 99 completed the 1st year of treatment, and 46 reached nFH. During rhGH therapy, growth velocity (GV) SDS and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14±0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (β -0.31, p = 0.030) and the GV during the first year of rhGH treatment (β 0.45, p = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype.

Regression from stage 3 to stage 2 type 1 diabetes mellitus after discontinuing growth hormone therapy.

Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH. Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement. Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment. The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment.