Search Results (29)

Background: SET domain-containing 5 (SETD5) is a member of the protein lysine-methyltransferase family. SETD5 gene mutations cause disorders of the epigenetic machinery which determinate phenotypic overlap characterized by several abnormalities. SEDT5 gene variants have been described in patients with KBG and Cornelia de Lange (CdL) syndromes. Case description: A female patient with severe short stature and intellectual disability had been followed since she was 9 years old. Several causes of short stature were ruled out. At the age of 12 years, her height was 114 cm (−5.22 SDS), weight 19 kg (−5.88 SDS), BMI 14.6 kg/m² (−2.26 SDS), and was Tanner stage 1. The target height for the proband was 151.65 cm (−1.80 SDS). The bone age (BA) was delayed by 3 years compared to chronological age. The growth rate was persistently deficient (<<2 SDS). Physical examination revealed dysmorphic features. Genetic analysis documented a de novo SETD5 gene mutation (c.890_891delTT), responsible for phenotypes in the context of an overlap syndrome between the phenotype of MDR23, CdL and KBG syndromes. Recombinant growth hormone therapy (rhGH) was started at the age of 12 years. After both one year (+3.16 SDS) and two years (+2.9 SDS), the growth rate significantly increased compared with the pre-therapy period. Conclusion: This is the first case of a patient with overlap syndrome due to SETD5 mutation treated with rhGH. The review of the scientific literature highlighted the clinical and molecular features of SETD5 gene mutation and the use of rhGH therapy in patients suffering from CdL and KBG syndromes. Full article

It is hypothesized that growth hormone deficiency (GHD) is associated with increased oxidative stress (OS), contributing to elevated cardiovascular risk. This preliminary study evaluates changes in OS markers and cardiovascular biomarkers in 15 adult patients with severe GHD undergoing 12 months of recombinant human growth hormone (rhGH) therapy. IGF-1 concentrations increased significantly following 6 and 12 months of therapy (p = 0.0003 and p = 0.0001, respectively). These changes were accompanied by a significant decrease in endothelin-1 (ET-1) levels at 12 months (p = 0.007), as well as reductions in asymmetric dimethylarginine (ADMA) levels at both 6 and 12 months (p = 0.01 for each timepoint). Total oxidative capacity (TOC) decreased significantly after 6 months of therapy (p = 0.02), followed by a significant increase at 12 months (p = 0.04), whereas total antioxidant capacity (TAC) showed a significant increase at 12 months (p = 0.02). Tissue fat % showed significant reductions at 6 months (p = 0.006), suggesting early improvements in body composition. Correlation analyses indicated negative associations between IGF-1 and TOC (p < 0.006; R = −0.73), and positive associations with TAC (p < 0.001; R = 0.83). These findings suggest that rhGH therapy in adult patients with severe GHD reduces OS and cardiovascular risk through the modulation of biomarkers and improved body composition. This study explores the role of rhGH therapy in reducing cardiovascular risks in GHD, emphasizing the importance of individualized treatment approaches. Full article

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article

Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency. Full article

Background/Objectives: Recombinant growth hormone (rhGH) treatment plays an important role in the transition phase in those subjects diagnosed as having persistent growth hormone deficiency (GHD). We aimed to identify the main predictors of persistent GHD in a large cohort of subjects with childhood-onset GHD who underwent retesting and their correlation with height gain and mid-parental height (MPH). Methods: Anthropometric data, such as growth rate; bone age (BA); IGF-1 SDS at the start, at 1 year, and at the end of rhGH therapy; GH peak at diagnosis and at retesting; brain Magnetic Resonance Imaging (MRI) at diagnosis; and height gain upon reaching final height (FH) and compared to MPH, were obtained from medical records of GHD patients. Results: Persistent GHD was detected in 37 out of 91 (40.7%) GHD subjects. In univariate analysis, persistent GHD was associated with growth rate at 1 year (p = 0.0117) and with the first test GH peak (p = 0.0290). In the regression analysis, persistent GHD was positively associated with growth rate at 1 year (p = 0.0294) and negatively with female gender (p = 0.0424). Height gain was positively associated with growth rate (p = 0.0010) and with age at onset (p = 0.0021), while an inverse association with BA at baseline (p = 0.0002) and IGF-1 SDS (p = 0.0321) was found. Conclusions: Our study confirmed that the most important predictor of persistent GHD is the growth rate in the first year of therapy. Furthermore, growth rate in the first year, female gender, and lower BA at diagnosis are predictors of rhGH efficacy both in terms of height gain and target height achievement. Full article

Before 1985, growth hormone (GH) was extracted from human pituitaries, and its therapeutic use was limited to children with severe GH deficiency (GHD). The availability of an unlimited amount of recombinant GH (rhGH) allowed for investigating the efficacy of its therapeutic use in a number of conditions other than GHD. Nowadays, patients with Turner syndrome, SHOX deficiency, Noonan syndrome, Prader–Willi syndrome, idiopathic short stature, chronic kidney disease, and children born small for gestational age can be treated with rhGH in order to improve adult height. In patients with Prader–Willi syndrome, rhGH therapy also improves body composition and cognitive function. Large post-marketing multinational studies in a large number of pediatric patients demonstrated a good safety profile for rhGH. Recently, long-acting formulations of rhGH have been approved and licensed for GHD, and clinical trials are ongoing for other conditions. In this paper, we review the rhGH therapy in children with conditions other than GHD. Full article

Recombinant human growth hormone therapy (rhGH) has been widely accepted as the safe treatment for short stature in children with such genetic syndromes as Prader–Willi syndrome and Turner or Noonan syndrome. Some patients with short stature and rare genetic syndromes are treated with rhGH as growth hormone-deficient individuals or as children born small for their gestational age. After years of experience with this therapy in syndromic short stature, it has been proved that there are some aspects of long-term rhGH treatment beyond growth promotion, which can justify rhGH use in these individuals. This paper summarizes the data of a literature review of the effects of rhGH treatment beyond growth promotion in selected genetic syndromes. We chose three of the most common syndromes, Prader–Willi, Turner, and Noonan, in which rhGH treatment is indicated, and three rarer syndromes, Silver–Russel, Kabuki, and Duchenne muscular dystrophy, in which rhGH treatment is not widely indicated. Many studies have shown a significant impact of rhGH therapy on body composition, resting energy expenditure, insulin sensitivity, muscle tonus, motor function, and mental and behavioral development. Growth promotion is undoubtedly the primary benefit of rhGH therapy; nevertheless, especially with genetic syndromes, the additional effects should also be considered as important indications for this treatment. Full article

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

Short stature affects approximately 2.5% of children. Some of them, when diagnosed with growth hormone deficiency (GHD), benefit from recombinant human growth hormone (rhGH) therapy; in others, this treatment is controversial. We aimed to present the clinical characteristics of Polish short stature children in the context of current GHD diagnostic standards, as obtaining more data gives a broader foundation for the potential modifications of diagnostic and therapeutic recommendations. This retrospective analysis was based on a cohort of 277 short stature children divided into two subgroups depending on their peak growth hormone (GH) cutoff level, set at 10 ng/mL: 138 had growth hormone deficiency (GHD) and 137 had normal growth hormone secretion (GHN). These subgroups were then compared based on the extracted clinical data. In the obtained result, no significant differences between the GHD and GHN subgroups were found in any of the variables, including the following: gender distribution, birth weight, bone age delay, height SDS, IGF-1 SDS, vitamin D levels, celiac disease indices, prevalence of hypothyroidism or anemia. As our results point to major clinical similarities between the GHD and GHN children, it seems that distinguishing patients with normal GH secretion from those with deficient GH secretion based on a 10 ng/mL cutoff value might not be clinically relevant. Full article

The present review focuses on growth hormone (GH) deficiency in pediatric and adult patients following surgery for hypothalamic-pituitary tumors, with a special emphasis on hormone replacement therapy with recombinant human growth hormone (rhGH). The symptoms and metabolic changes associated with GH deficiency are reviewed, and the potential risks and therapeutic outcomes of rhGH treatment in these patients are discussed. This review emphasizes the importance of rhGH in the normalization of growth in children and the improvement of quality of life (QoL) and metabolic health in adults. Aspects related to efficacy, safety, dosage, duration of treatment, and QoL in this population are analyzed. The need for regular follow-up and dose adjustment to maintain the optimal IGF-I levels in these patients is emphasized, as is the importance of individualized assessment and collaboration with a specialized multidisciplinary medical team to make the appropriate therapeutic decisions. Furthermore, continuous follow-up are necessary to optimize the clinical outcomes in this patient population. Full article

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients. Full article

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

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. Full article

Objectives: Löwe syndrome (the oculocerebrorenal syndrome of Löwe, OCRL, OMIM #309000, ORPHA: 534) is a very rare multisystem X-linked disorder characterized by ocular, kidney and nervous system anomalies. Case presentation: We present the first Bulgarian genetically confirmed patient with OCRL. The patient had facial dysmorphism, cryptorchidism, congenital cataracts, nystagmus, delayed physical and mental development, and poor nutritional status. He had severe rickets, metabolic acidosis, hypokalaemia, hypophosphataemia, and low IGF-1 levels at the age of three, in addition to his developmental delay. The molecular-genetic analysis reported a pathogenic variant c.1124A>G, p.H375R in the OCRL gene. This variant was inherited from the mother, who was a carrier. Following the diagnosis of OCRL, treatment with potassium citrate, phosphate, and calcitriol was initiated, along with an increase in caloric intake. Following general physical and biochemical improvement, therapy with rhGH started 4 years ago, and current results are presented. Conclusions: The patient with Löwe syndrome who was presented with a 6-year follow-up demonstrates the complexity of rare disease cases and the value of multidisciplinary care together with growth hormone treatment for better results in these patients. Full article

Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal (<85%). Adherence data were available for 8915 patients before and 7606 patients during COVID-19. A high SI (mean ≥68) and a high proportion of required school closure (≥88%) resulted in an increase in the proportion of optimal adherence during COVID-19 versus pre-COVID-19 (p < 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH. Full article