Search Results (55)

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

Background/Objectives: Hyperprolinemia is a rare autosomal recessive disorder with two distinct types: I (HPI) and II (HPII). The clinical presentation varies widely, with some individuals remaining asymptomatic and others exhibiting neurological, renal, or auditory defects and seizures. However, it has never been associated with hypoglycemia. The present case report describes a 5-year and 6/12-month-old boy with HPII, with an episode of severe hypoglycemia and Pituitary Stalk Interruption Syndrome (PSIS) with isolated growth hormone (GH) deficiency (GHD). Results: The boy was presented to the Department of Pediatric Endocrinology for routine thyroid function assessment due to hypothyroidism. He was diagnosed with HPII at the age of 2 years old during an investigation for seizure episodes. Clinically, the boy exhibited attention deficit hyperactivity disorder (ADHD) and a reduction in growth velocity (1.6 cm/year). Hematological and biochemical analyses were within the reference range. Hormone profiling revealed lower-than-expected insulin-like growth factor-1 (IGF-1) concentrations, prompting a GH stimulation test, which, in turn, revealed GHD. Brain magnetic resonance imaging (MRI) showed features consistent with PSIS. Noteworthy is the occurrence of severe hypoglycemia during an episode of gastroenteritis, leading to hospitalization, eventually attributed to GHD. Following the exogenous administration of recombinant human GH, the boy exhibited increased growth velocity, with no adverse events over the follow-up period. Conclusions: Hyperprolinemia is a rare condition; in this context, the occurrence of severe hypoglycemia accompanied by a low growth velocity poses a challenge for the clinical pediatrician. Furthermore, the coexistence of hyperprolinemia and PSIS has never been reported in the literature thus far. Full article

Background/Objectives: Growth hormone deficiency (GHD) is a rare endocrine disorder characterized by inadequate secretion of growth hormone, which affects growth, cellular processes, and physiological functions. In addition to growth impairment, GHD is associated with a range of otorhinolaryngological (ENT) symptoms, such as sensorineural hearing loss, dizziness, and voice alterations. These symptoms may be underrecognized due to a lack of routine ENT evaluations in GHD management. Methods: This systematic review, conducted in accordance with PRISMA guidelines, assessed the prevalence of ENT symptoms in patients with GHD by analyzing studies from the PubMed, Embase, and Scopus databases. Results: Based on the analysis of eleven studies that met the inclusion criteria, more than half of patients with GHD experience ENT symptoms (61.4%). Symptom variability appeared to correlate with treatment access, age of onset, and the presence of comorbidities. The study underscores the importance of routine ENT assessments as part of the multidisciplinary management of patients with GHD. Conclusions: Early detection and management of ENT symptoms may significantly improve quality of life, reduce social and educational challenges, and support long-term health outcomes. Further research is needed to clarify the role of recombinant human growth hormone therapy in mitigating ENT manifestations in this patient population. Full article

Recombinant human growth hormone (rhGH) is utilized in pediatric patients with short stature for a variety of indications, including those in which the primary growth defect is not related to growth hormone deficiency (GHD). However, due to the instability of the hormone in the gastrointestinal tract and its short half-life, an alternative route of administration is being sought, which may be the skin. One strategy to extend the half-life of proteins involves the use of biodegradable polymeric matrices for transdermal drug delivery systems. While hydrogels are recognized for their high stability, the transport of proteins through the skin may be hindered. To address this, the use of active carriers is being investigated to enhance the efficiency of protein permeation through the skin. In this study, an effort was made to optimize the concentration of phosphitin (PV) as a carrier for somatotropin (STH). PV is a protein that possesses a distinctive cation chelating capability and amphiphilic character. As the concentration of PV increased, the rate of its emulsifying activity increased concomitantly. Methylcellulose (MC) was used as the hydrogel matrix. The study investigated three distinct concentrations of PV to ascertain the most optimal concentration to enhance STH availability. Following the formulation of hydrogel compositions containing STH and PV, the permeation process through porcine skin was examined using Franz’s chambers. The findings revealed that the incorporation of PV significantly impacted both the penetration time of STH and the extent of STH penetration. Subsequently, an extensive evaluation of the physicochemical parameters of the formulations, encompassing pH, rheological, and textural properties, was conducted to assess their suitability for skin application. This evaluation aimed to ensure not only adequate persistence time of the formulation on the skin surface but also formulation stability and persistence of the active substance (STH). Full article

Background: Growth hormone deficiency (GHD) is one of the primary endocrine-related causes of short stature in pediatric patients; while neonatal GHD symptoms are well-documented in populations with known genetic and/or organic causes, their exact prevalences in pediatric patients categorized as having idiopathic GHD remains unclear. Materials and Methods: We retrospectively analyzed the medical records of patients with idiopathic GHD followed at the Pediatric Endocrinology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS starting from January 2010. We analyzed information from 190 patients with idiopathic GHD and examined the prevalences of the most common neonatal signs and symptoms of neonatal GHD. We also included an age- and sex-matched control group that consisted of patients without a confirmed diagnosis of GH deficiency to assess significant differences in the frequencies of neonatal symptoms between the two cohorts. Results: Regarding neonatal GHD symptoms, the prevalence was the highest for hypoglycemia (n = 53, 27.9%), which was managed through the intravenous administration of glucose in 21 out of 53 cases. Prolonged jaundice that lasted more than 5 days was observed in 37 patients (19.5%) and required phototherapy in 20 out of 37 patients, while exchange transfusion was not performed in any patient. Hyperglycemia and feeding difficulties (n = 17, 8.9%) were less frequent, while the other symptoms were relatively rare. Compared with the control group, the prevalence of hypoglycemia was significantly higher in the GHD patient group (p-value = 0.000016). Conclusions: In our cohort of pediatric patients with idiopathic GHD, the prevalences of neonatal signs and symptoms of GHD was low, except for neonatal hypoglycemia observed in 27.9% of the analyzed patients. Although these are not specific signs of idiopathic GHD, it is beneficial to investigate this information in the medical history during the clinical assessment of the child. Full article

Background: Among the potential indications for growth hormone (GH) therapy is the presence of mutations in the SHOX (short stature homeobox-containing) gene, located in the telomeric pseudotautosomal region (PAR1) on the short arm of both sex chromosomes. Despite general recommendations supporting GH therapy in these cases, there is a lack of comprehensive evidence specifically evaluating its efficacy and safety in this subgroup of pediatric patients. Aim: The objective of this scoping review was to evaluate the efficacy and safety of growth hormone therapy in patients with SHOX gene variants, providing a narrative synthesis of the included studies. Materials and Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. We summarized information extracted from 22 articles identified by our search strategy. Currently, only one randomized clinical trial has analyzed the efficacy profile of GH in patients with SHOX mutations. Results: Growth hormone is a valuable therapeutic aid for these patients. However, its prescription in children with SHOX gene mutations should consider the specific characteristics of each patient, similar to the approach taken for patients with idiopathic growth hormone deficiency (GHD). Conclusion: Growth hormone therapy in patients with SHOX gene alterations appears to be both safe and effective. However, longitudinal prospective studies and targeted clinical trials are necessary to confirm these findings. Despite this, GH remains one of the preferred hormonal therapies for patients with short stature and confirmed SHOX gene mutations. 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

Background/Objectives: the aim of the current cross-sectional study is to explore and compare the emotional and behavioural conditions of children and adolescents with short stature (i.e., familial short stature and constitutional delay of growth), idiopathic growth hormone deficiency (GHD), and normal height. Methods: Twenty-nine participants (15 males, 14 females; mean age ± standard deviation (SD) = 11.2 ± 1.96 years) with short stature (height standard deviation score (SDS): −2.10 ± 0.57), 10 age-matched participants (4 males, 6 females; mean age ± SD = 10.9 ± 2.35 years) with growth hormone deficiency (GHD; height SDS: −2.44 ± 0.29), and 36 age-matched participants (19 males, 17 females; mean age ± SD = 11.3 ± 1.93 years) with normal stature (height SDS: 0.56 ± 0.78) were admitted to this study. Psychological distress was evaluated using the Depression Anxiety and Stress Scale (DASS-21), and emotional and behavioural problems using the Child Behaviour Checklist for Children (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Results: Participants with GHD exhibited higher levels of the “withdrawn/depressed subscale” score of CBCL (H = 7.794, df = 2, p = 0.020), compared to their peers with normal height, while no significant differences were observed between participants with short stature and those with normal stature. Normal-statured participants reported higher levels of the “conduct problems” subscale score (H = 10.421, df = 2, p = 0.005) and the “rule-breaking behaviour” subscale score of CBCL (H = 10.358, df = 2, p = 0.006) compared to both short-statured groups. No significant differences among the three subgroups were found in the DASS-21 and SDQ scores questionnaires, suggesting the lack of short stature-dependent effects on psychological distress and emotional and behavioural adjustment. Conclusions: Although participants with GHD exhibited higher levels of the “withdrawn/depressed subscale” score of CBCL (H = 7.794, df = 2, p = 0.020) compared to their peers with normal height, participants with short stature did not experience the same problems. Although short-statured participants had lower levels of “conduct problems” and “rule-breaking behaviours” scores than their normal-statured peers, the psychological distress and emotional and behavioural adjustment were not affected by short stature, being comparable to those recorded in normal-statured participants. 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

Background: Adult growth hormone deficiency (GHD) has been recognized since the late 1980s. The clinical manifestations of adult GHD are often nonspecific, and diagnosis relies on GH stimulation tests, which are intricate, costly, time-consuming, and may carry the risk of adverse effects. Diagnosis is further complicated by factors like age, sex, and BMI, which affect GH response during testing. Therefore, GH replacement therapy remains challenging, requiring careful individualized evaluation of risks and benefits. The aim of this review is to provide an update on diagnosing and treating adult GHD, addressing current limitations and challenges based on recent studies. Methods: We conducted a comprehensive review of the literature regarding the diagnosis and management of adult GHD by searching PubMed and EMBASE. Only articles in English were included, and searches were conducted up to August 2024. Results: A review of guidelines and literature up to 2024 highlights the significant heterogeneity in the data and reveals various protocols for managing GHD, covering both diagnostic and therapeutic approaches. Conclusions: Despite diagnostic and treatment advances, managing adult GHD remains challenging due to variable presentation and the need for personalized GH therapy. Future efforts should aim to improve and standardize diagnostic and treatment protocols. Full article

Background: We report a rare case highlighting the progression of liver disease in a male patient with idiopathic childhood-onset growth hormone (GH) deficiency. Case presentation: The patient was diagnosed with hypopituitarism at six years old and was treated with thyroxine therapy and GH for his short stature, with testosterone added at the age of 15. GH therapy was discontinued when the patient was 18 years old, but thyroid and testosterone treatments continued. The patient had been taking medication for hyperlipidemia until the age of 30 and was noted to have impaired glucose tolerance at the age of 40, but HbA1c levels remained normal. At the age of 47, esophageal varices were incidentally discovered via endoscopy, revealing liver cirrhosis. Laboratory tests showed liver dysfunction and abnormal lipid levels, and hepatitis viral markers were absent. The patient had no history of drinking alcohol or smoking, and no family history of diabetes. Results: Ultimately, this case demonstrates that metabolic dysfunction-associated steatotic liver disease (MASLD/metabolic dysfunction-associated steatohepatitis (MASH)) is under-recognized in GH deficiency cases and can progress to liver cirrhosis. Conclusions: Therefore, careful evaluation of MASLD/MASH in childhood-onset GH deficiency is necessary, and GH replacement therapy should continue into adulthood, if possible. Full article

The aim of this review article is to highlight the consequences of COGHD after the end of linear growth on bone mass and body composition and the opposing beneficial effects of continuing GH replacement in the transition period and young adults. The role of growth hormone in the period of late adolescence and young adulthood is well established, mainly in achieving peak bone mass and a favorable body composition, characterized by muscle mass increase and fat mass reduction. Patients with childhood onset growth hormone deficiency (COGHD), after reaching the adult height, have a reduced bone mineral density and muscle mass with increased fat mass compared to healthy controls. Inadequate body composition is a predictor for cardiovascular risk, while low bone mass in early youth hallmarks the risk of osteoporosis and bone fractures in later life. Cessation of growth hormone replacement (GHr) after completion of growth will lead to delayed peak bone mass and unbalanced body composition with increased abdominal fat deposits. According to numerous clinical studies monitoring the effects of GH treatment on the physical and psychological status of patients with persistent GHD after completion of growth, we suggest continuing this treatment between 16 and 25 years of age. It is advised that GHr in the transition period be administered in intermediate doses between those for the pediatric population and those for the adult population. Usual daily GHr doses are between 0.3 and 0.5 mg but need to be individually optimized, with the aim of maintaining IGF-I in the age-specific normal range. Full article

Background/Objectives: Obesity can be associated with impaired growth hormone (GH) secretion, with possible negative repercussions on bone health. We aimed to investigate the relationships between GH secretory capacity, evaluated with GHRH + arginine stimulation test, and bone parameters, assessed with a dual-energy X-ray absorptiometer, in a population of adult female patients affected by overweight and obesity. Methods: We assessed 276 women affected by overweight or obesity referred to the High-Specialization Center for the Care of Obesity, Umberto I Polyclinic, between 2014 and 2019 with signs or symptoms of growth hormone deficiency (GHD). Results: A total of 97 patients were diagnosed with GHD, and 179 patients with normal GH secretion were considered our control group. GHD patients showed a significantly reduced trabecular bone score (TBS) (p = 0.01). Bone quality parameters corrected for body mass index (BMI) had a positive and significant linear correlation with stimulated GH secretory capacity. Conclusions: In conclusion, bone quality, evaluated by TBS and hip structural analysis, correlates with GH-stimulated secretory capacity. GHD may act as an additive factor in the alteration of bone microarchitecture in patients affected by obesity, who are already at a higher risk of fractures. 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