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Abstract Thoracic spinal cord injury (SCI) profoundly impairs motor and sensory functions, significantly reducing life quality without currently available effective treatments for neuroprotection or full functional regeneration. This study investigated the neurotrophic and synaptic recovery potential of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) treatments in ovariectomized rats subjected to thoracic SCI. Employing a multidisciplinary approach, we evaluated the effects of these hormones upon gene expression of classical neurotrophins (NGF, BDNF, and NT3) as well as indicative markers of synaptic function (Nlgn1, Nxn1, SNAP25, SYP, and syntaxin-1), together with morphological assessments of myelin sheath integrity (Klüver-Barrera staining and MBP immunoreactivity) and synaptogenic proteins (PSD95, SYP) by immunohystochemistry (IHC) , and also on the neuromotor functional recovery of hindlimbs in the lesioned animals. Results demonstrated that chronic administration of GnRH and GH induced notable upregulation in the expression of several neurotrophic and synaptogenic activity genes. Additionally, the treatment showed a significant impact on the restoration of functional synaptic markers and myelin integrity. Intriguingly, while individual GnRH application induced certain recovery benefits, the combined treatment with GH appeared to inhibit neuromotor recovery, suggesting a complex interplay in hormonal regulation post-SCI. GnRH and GH are bioactive and participate in modulating neurotrophic responses and synaptic restoration under neural damage conditions, offering insights into novel therapeutic approaches for SCI. However, the intricate effects of combined hormonal treatment accentuate the necessity for further investigation that conduce to optimal and novel therapeutic strategies for patients with spinal cord lesions.

Background: X-linked hypophosphatemic rickets (XLHR) is the most frequent form of inherited rickets. In children, stunted growth and disproportionately short stature are frequently the early signs of XLHR. Objective: To review different opinions in the review of literature about the use of growth hormone in the treatment of XLHR. Methods: This review article followed a systematic literature review approach, there are no exclusion criteria. Main Findings: Growth retardation may continue even after receiving appropriate conventional treatment (phosphate supplements and active analogs of vitamin D) in XLHR, even if it is initiated early in childhood. Recently, regardless of a well-controlled disease, treatment with recombinant human growth hormone (rhGH) was suggested as an effective way of supporting growth in children with XLHR exhibiting a lack of growth. It is necessary to follow until reaching adult height to assess the long-term effects of rhGH treatment on the ultimate height. Conclusion: The addition of rhGH to optimal medical treatment might represent a promising option in the significant portion of affected patients with XLHR and growth failure. Follow-up is needed until the final height is reached to evaluate the long-term benefit of rhGH treatment on final height. Further studies will be necessary to determine the most efficient treatment protocol concerning doses, duration, and age of initiation or rhGH in short children with XLHR. However, further studies would be needed to study the addition of rhGH to optimal medical treatment in short children with XLHR.

ABSTRACT Objectives Individuals with congenital isolated growth hormone deficiency (IGHD) in Northeastern Brazil have a normal lifespan with a prolonged healthspan. We hypothesize that their increased healthspan is accompanied by a reduced cognitive decline during aging. We have recently shown that these individuals have a similar total cognitive function and better attention and executive function than controls. These data were obtained using a Portuguese version of the Literacy Independent Cognitive Assessment (LICA) instrument, whose translation to facilitate cognitive research in Portuguese-speaking countries is described here. Subjects and methods In the first stage, a psychologist and a psychiatrist translated the LICA instrument from English into Portuguese, and an English teacher proofread the translation. The second stage included its synthesis and cultural adaptation, carried out by Brazilian authors, and changes in some words and images. The third stage involved an evaluation round with two referees (independent psychologists). The fourth stage involved a back translation of the instrument, which demonstrated > 95% agreement with the original version. The fifth stage included a study to verify the understanding of the questionnaire by responders. In the sixth stage, an endocrinologist and a psychiatrist approved the final Portuguese version of the instrument, which was then administered to 15 individuals with IGHD and 15 controls older than 50 years. Results The LICA instrument was applied 59 times (5 times in the pilot study, 24 in the variability studies, and 30 in the experimental step). The interobserver and intraobserver variabilities were 99% and 96%, respectively. Cronbach’s alpha was 0.76, indicating good reliability. The mean (± standard deviation) duration of the application was 39 ± 8.6 and 48.5 ± 5.8 minutes in literate and illiterate individuals, respectively. Conclusion The Portuguese version of the LICA instrument was valuable for the cognitive assessment of individuals with Itabaianinha syndrome.

Abstract Background Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). Methods The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. Results Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. Conclusions The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.

Abstract The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: − 0.031, 95% credibility interval [CrI]: − 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: − 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: − 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: − 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: − 0.15, 95% CrI: − 1.1, 0.66) than somatrogon (MD: − 0.055, 95% CrI: − 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: − 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment. Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

Key Clinical Message Our case highlights the importance of recognizing acromegaly as a potential risk factor for venous thromboembolism (VTE). Despite a thorough thrombophilia workup yielding unremarkable results, further research is warranted to elucidate the underlying mechanisms linking acromegaly and thrombophilia. This understanding will aid in improving risk assessment and management strategies for patients with acromegaly. Abstract Acromegaly, a rare disorder characterized by excessive growth hormone secretion, is associated with various comorbidities including hypertension, diabetes mellitus, and obstructive sleep apnea. While previous studies have identified abnormalities in hemostatic factors in acromegaly patients, the association between acromegaly and venous thromboembolism (VTE) remains poorly understood. We present the case of a 36‐year‐old male with a history of acromegaly who presented with acute dyspnea, chest pain, and cough. Despite a prior trans‐sphenoidal hypophysectomy, his acromegaly symptoms persisted. Upon evaluation, he was found to have bilateral pulmonary embolism. Thorough thrombophilia workup was unremarkable, suggesting acromegaly as a potential risk factor for VTE.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by various clinical features linked to hypothalamic/pituitary gland abnormalities. Growth hormone deficiency is a prominent feature of PWS that results in poor linear growth and delayed development. This review discusses the evaluation and effects of growth hormone therapy (GHT) in PWS. Heterogeneity in growth hormone secretion patterns based on genotype and the potential for personalized GHT were explored. The benefits of GHT, including improvements in motor and cognitive development, growth, and body composition, are discussed in detail. Safety considerations for GHT initiation and response to GHT in adults with PWS are discussed, along with ongoing debates regarding the efficacy and safety. Although controversies persist, an evolving understanding of the long-term effects and safety of GHT underscores the need for comprehensive research in this field.

Objective To evaluate the application of airway anatomical indices in magnetic resonance imaging (MRI) to predict difficult airways in patients with growth hormone pituitary adenoma. Methods This is a retrospective analysis for patients with pituitary adenoma excision under general anesthesia at Beijing Tiantan Hospital, Capital Medical University, from December 2018 to December 2022. Patients with growth hormone pituitary adenoma (GH group, n=81) and patients with nonfunctioning pituitary adenoma (NF group, n=81) were included. Linear distance between upper lip and uvula (ULUD), tongue thickness on the plane of cervical vertebra 2/3 (TTC2/3), linear distance of supraglottic airway cervical vertebra 2/3(SADC2/3) and linear distance between underlip and posterior pharyngeal wall (ULPD) were measured in the median sagittal plane of head MRI. The data in the two groups were compared. Results ULUD, TTC2/3, and ULPD in the GH group were significantly longer than those in the NF group (P＜0.05). SADC2/3 was not significantly different (P＞0.05). GH was confirmed to be correlated with TTC2/3 and ULPD. Conclusions ULUD, TTC2/3, ULPD found by head MRI and GH can be used as predictors of difficult airway in patients with growth hormone pituitary adenoma.

Background and purpose: Fatty liver disease and overcoming it is a health concern. This study aimed to investigate the effect of a period of high-intensity interval training (HIIT) and somatotropin injection on hepatocyte apoptosis markers and atherogenic index in mice with fatty liver disease. Materials and methods: In this basic experimental study, 21 male mice were randomly divided into three groups (n=7): control (C), exercise (HIIT), Exercise + somatotropin (H-GH). The HITT was performed for eight weeks/ five sessions a week. The speed was 25 meters per minute at the beginning which increased to 70 meters per minute at the end of week eight. The somatropin dosage was 1 mg/kg. Markers, including CK-18, paraoxonase, insulin resistance, ALT/AST ratio, and LDL/HDL were measured. Statistical analysis was carried out using One-way ANOVA and post hoc Tukey test. Results: CK18 values significantly decreased only in the HIIT group (P=0.01). Paraoxonase levels in both HIIT (P=0.00) and H-GH (P=0.01) groups significantly increased compared to the control group. Between groups changes of HOMA-IR index significantly reduced in the HIIT group (P=0.05) and slightly increased in the H-GH group but was not significant (P=0.36). The ratio of ALT/AST in both HIIT (P=0.02) and H-GH (P=0.03) groups significantly reduced. LDL/HDL ratio showed significant decrease only in the HIIT group (P=0.01). Conclusion: High-intensity interval training produced a more effective response in improving the markers of none alcoholic fatty liver disease than GH. Injection of growth hormone alone can have negative consequences on some indicators of the disease.

Abstract Background The global delay in women’s reproductive age has raised concerns about age-related infertility. The decline in oocyte quality is a limiting factor of female fertility, yet there are currently no strategies to preserve oocyte quality in aged women. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aged oocytes. Methods For the in vivo experiments, the aged mice (8-month-old) were intraperitoneally injected with GH daily for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aged mice were treated with GH during oocyte maturation. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to assess oocyte quality, aneuploidy and developmental potential characteristics. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aged oocytes. Results In this study, we demonstrated that GH supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, we discovered that GH supplementation reduced aneuploidy in aged oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the MAPK3/1 pathway may be involved in the reduction in aneuploidy of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 may also act as a mediator in how GH regulates MAPK3/1. Conclusions In conclusion, our research reveals that GH supplementation protects oocytes against aging-related aneuploidy and enhances the quality of aged oocytes, which has clinical significance for aged women undergoing assisted reproduction technology. Graphical Abstract

ABSTRACT Objective: This research aimed to evaluate retrospectively the effect of anastrozole on height gain and sex hormone levels in pubertal boys receiving growth hormone (GH). Materials and methods: Pubertal boys who received both GH and anastrozole (GH+A) were one-to-one matched with boys who received only GH (GH-Only) for chronological and bone age, pubertal stage and height before the GH initiation, treatment duration and midparental height. Anthropometric measurements throughout treatment and adult heights were compared between the groups. Sex hormone levels were evaluated longitudinally in the GH+A group. Results: Forty-eight cases (24 in each group) were included. There was no statistical difference in adult height between the GH+A and GH-Only (p = 0.071). However, when the analysis was limited to those receiving anastrozole for at least 2 years, mean adult height was higher in the GH+A than in the GH-Only group (173.1 ± 6.2/169.8 ± 5.6 cm, p = 0.044). Despite similar growth rates between the two groups, bone age advancement was slower in the GH+A than in the GH-Only in a mean anastrozole treatment period of 1.59 years (1.37 ± 0.80/1.81 ± 0.98 years, p = 0.001). The greatest increase for FSH, LH, total and free testosterone and decrease for estradiol levels were observed in the third month after anastrozole was started, albeit remaining within the normal ranges according to the actual pubertal stages. Conclusions: Using anastrozole with GH for at least 2 years decelerates the bone age advancement resulting in adult height gain with no abnormality in sex hormone levels. These results suggest anastrozole can be used as an additional treatment to GH for further height gain in pubertal boys.

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Key Clinical Message In patients presenting with aortic ectasia and myxomatous valve diseases at young ages, possible underlying acromegaly should be in mind. Abstract Acromegaly is a chronic systemic disease mainly caused by the benign pituitary adenoma secreting growth hormone (GH) in excess. Acromegaly is associated with various complications such as cardiovascular diseases. In this regard, timely diagnosis, and management of these patients could be life‐saving. Herein, a case of aneurysmal dilation of the sinus of Valsalva with severe aortic and mitral regurgitation in a patient with undiagnosed acromegaly is presented.

Introduction Hypertrophy is the process of increasing the mass of a tissue. In this article, we focused on the impact of the mechanisms of muscle hypertrophy, its effect on the human body, correlation with the course of diseases and tolerance of treatment. We considered the benefits of having well-developed, and also touched on the problems of underdeveloped muscle mass. Results The main factors causing hypertrophy are resistance exercise training, mechanotransduction, metabolic pathways, ribosomal biogenesis, gene expression and the impact of hormones. The beneficial effect of high concentrations of testosterone and growth hormone, also IGF1, on skeletal muscle hypertrophy has been proven. On the other side, the studies have shown that high concentrations of glucocorticoids, such as cortisol are associated with reduced muscle mass. There are many positive aspects of a well-developed muscle mass such as an impact on the prognosis in patients with cancers and sometimes reduces mortality among them. The problems of low muscle mass and sarcopenia are also mentioned. Low muscle mass can affect the poor prognosis of diseases such as cancer, hepatic cirrhosis and COVID-19. Postoperative complications are more common in patients with low muscle mass. One way to prevent this process may be to introduce resistance exercise training in patients struggling with problems of muscular atrophy. Conclusion Skeletal muscles have multiple functions in the human body. In addition to movement, they play a role in molecular processes like hormonal regulation. In addition, they can, when well developed, positively influence healing processes and the course of disease.

Background: Growth hormone (GH), Insulin-like growth factor 1 (IGF-1), and exercise play a crucial role in female reproductive function. At the perimenopausal age, there is a decrease in GH, estrogen, and testosterone levels. In previous studies, the impact of physical activity on serum IGF-1 levels in geriatric was inconsistent and needed further investigation. Objective: The purpose of this study was to look into the effect of GH and exercise on serum IGF-1 levels in perimenopausal Wistar rats. Methods: It is an experimental study with a randomized posttest-only control group design using 24 perimenopausal Wistar rats aged 14 months as the sample. The control rats (C) were given 0.1 ml of distilled water subcutaneously every day for 30 days. Treatment group 1 (T1) rats swam for 30 minutes at a time five times per week. Meanwhile, rats of T2 were given 0.016 IU/0.1ml GH daily injection subcutaneously only for 30 days and T3 were given combination both of GH injection in same dose and swam for 30 minutes at a time 5 times a week for 30 days Data analysis used One-Way ANOVA. Results: The finding revealed that the mean serum IGF-1 levels in the T3 (588.50 84.04 ng/mL) were significantly higher than the control (242.03 ± 46.08 ng/mL), T1 (334.23 ± 75.90 ng/mL) and T2 (428.69 ± 95.10 ng/mL). Conclusion: Our study shows that GH administration and exercise combination increases levels of IGF-1 serum higher than only administrated GH or exercise.

Purpose: to determine the relationship between the functional state of the pituitary-thyroid system and the growth hormone/insulin-like growth factor type 1 (GH/IGF-1) system in adolescents with type 1 diabetes mellitus (DM1) during puberty Material & Methods: 165 children (85 girls (51,5%) and 80 boys (48,5%) aged 8 to 18 years old who have DM1 and are in the endocrinology department of the State Institution "Institute for Children and Adolescents Health Care at the National Academy of Medical Sciences of Ukraine" (SI "ICAHC NAMS"). The criterion for inclusion in the study was the duration of DM1 for more than one year (from 1 to 16 years). The level of thyrotropin (TSH), free fractions of thyroxin (fT4) and triiodothyronine (fT3), GH and IGF-1 was determined and the ratio (fT3/fT4 and TSH/fT4) was calculated. Study participants were divided into groups depending on the level of sexual development (T1-T4) at the time of the study, assessed by the Marshall & Tanner scale (Marshall & Tanner, 1969; Marshall & Tanner, 1970); functional state of the pituitary-thyroid system: (euthyroidism (TSH/fТ4 0,29 c.u.) (Turchina et al., 2016). Results: it was found that among adolescents with DM1, almost every child has signs of thyroid dysfunction. An increase in the fT3 level and the fT3/fT4 ratio were more often diagnosed. The frequency of increase in the level of TSH and the ratio of TSH/fT4 fluctuated widely and depended on the sexual development of the child. More often, signs of SGH were determined during early puberty (23,5%), which probably exceeded those in prepubertal (16%, Pφ

Introduction : Turner syndrome (TS) is one of the most common genetic disorders affecting approximatley 1 in 2,000-25000 live-born girls. TS is the result of complete oraz partial monosomy of the C chromosome. About half have monosomy X (45,X) and 5-10% have duplication (isochromosome) of the long arm of one X (46,X,i(Xq)). Most of the rest have mosaicism.(1) The aim of the study: The purpose of this review paper is to present the observations regarding this disease, including epidemiology, diagnosis and detailed examination of the individual needs of the patient affected by the disease. Matrials and methods: This review was based on available data collected in the PubMed database and Google Scholar web serach engine, using key words: Turner’s syndrome, diagnosis of Turner Syndrome, sex chromosome aneuploidies Summary: The article draws attention to the complexity of Turner syndrome, the variety of symptoms and the progress in the diagnosis and therapy of this disease. Early diagnosis, specialist care and modern therapeutic methods have a positive impact on the quality of life of TS patients. Future studies of molecular mechanisms and therapeutic efficacy may improve the care of patients affected by this rare disease.

Abstract Background Prader–Willi syndrome (PWS) is a rare and multisystemic genetic disorder that is characterized by severe hypotonia, hyperphagia, short stature, and global developmental delay. Although early recombinant human growth hormone (rhGH) treatment has been proven to rescue some symptoms and bring additional benefits to PWS patients, studies in patients under 2 years old are scarce. Thus, this study aims to investigate the effectiveness and safety of rhGH treatment for young children. Methods A total of 96 genetically confirmed Chinese PWS infants or toddlers (47 males) followed between 2013 and 2022 were retrospectively analyzed. Sixty-five infants (early treatment group) started rhGH treatment during their first year, and 31 toddlers (later treatment group) started at the age of 1–2 years. Auxological parameters, carbohydrate metabolism parameters, thyroid function, liver function, insulin-like growth factor-1 (IGF-1), and radiographs were acquired before the initiation of the treatment and every 3–6 months thereafter. Height/length, weight, and weight for height were expressed as standard deviation scores (SDSs) according to WHO child growth standards. Results The mean SDS of length/height in the early treatment group was significantly higher than that in the later treatment group throughout the observation period (all P

Moyamoya disease is a progressive rare type of cerebrovascular disease marked by stenosis and occlusion of the distal internal carotid arteries and circle of Willis branches, leading to the development of a collateral network of blood vessels at the base of the brain. For Moyamoya angiopathy, endocrinopathies may be risk factors, sequelae, or just coincidental findings. So, it is worth checking and regularly monitoring for these endocrinopathies in patients with Moyamoya angiopathy, aiming for early diagnosis and appropriate treatment.

Purpose: to study the level of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1) in patients with type 1 diabetes mellitus (DM1) at the stages of puberty. Material & Methods: 165 children (85 girls (51.5%) and 80 boys (48.5%), aged 8 to 18 years old, suffering from DM1 and staying in the endocrinology department of the State Institution "Institute of Health for Children and Adolescents”) of the National Academy of Medical Sciences of Ukraine" (State Institution "IOZGP NAMS"). The criterion for inclusion in the study was the duration of T1DM for more than one year (from 1 to 16 years). The level of GH and IGF-1 was determined in 165 children 8-18 years old (85 girls and 80 boys) with DM1, taking into account gender, the level of sexual development at the time of the survey, the duration of DM1 and the level of glycemic control. Study participants were divided into groups depending on the level of sexual development (T1-T4) at the time of the study, assessed by the Marshall & Tanner scale (Marshall, & Tanner, 1969; Marshall, & Tanner, 1970); duration of DM1 (10 years); level of glycemic control (optimal (HbA1c9.0%) according to ISPAD 2018 recommendations (DiMeglio, et al., 2018) Results: in adolescents with DM1, a physiological type of activation of the GH/IGF-1 system was established with an increase in its activity during the period of puberty proper. Sexual characteristics were determined in the levels of GH and IGF-1 at the stages of puberty. Girls had higher levels of IGF-1 than boys, especially during prepuberty. During prepuberty and puberty proper, GH values were higher in boys, and in late puberty, in girls. It has been established that in girls and boys with an increase in the duration of diabetes, there is an increase in the level of GH and a decrease in IGF-1. The nature of the state of GH/IGF-1 in patients with different experience of DM1 is affected by the level of sexual development at the time of the examination and the sex of adolescents. In boys aged 14-18 years (the period of proper and late puberty), with an increase in the duration of the disease, an increase in the level of GH (pk-w

Co-regulated genes of the Imprinted Gene Network are involved in the control of growth and body size, and imprinted gene dysfunction underlies human paediatric disorders involving the endocrine system. Imprinted genes are highly expressed in the pituitary gland, among them, Dlk1, a paternally expressed gene whose membrane-bound and secreted protein products can regulate proliferation and differentiation of multiple stem cell populations. Dosage of circulating DLK1 has been previously implicated in the control of growth through unknown molecular mechanisms. Here we generate a series of mouse genetic models to modify levels of Dlk1 expression in the pituitary gland and demonstrate that the dosage of DLK1 modulates the process of stem cell commitment with lifelong impact on pituitary gland size. We establish that stem cells are a critical source of DLK1, where embryonic disruption alters proliferation in the anterior pituitary, leading to long-lasting consequences on growth hormone secretion later in life.

Objective:Acromegaly is a chronic disease that causes high concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). GH and IGF-1 levels have important effects on bone homeostasis, bone turnover, and bone remodeling. The results of studies investigating the relationship between acromegaly and bone mineral density (BMD) are controversial. The aim of the current study was to evaluate BMD in newly diagnosed acromegaly patients and to determine the relationship between GH and IGF-1 levels with BMD.Materials and Methods:This cross-sectional study was conducted on 36 newly diagnosed acromegaly patients without a history of hypogonadism, whose BMD values can be obtained from the records of University of Health Sciences Turkey, Dışkapı Yıldırım Beyazıt Training and Research Hospital. The relationship between GH and IGF-1 levels and BMD measured from the femur and lumbar regions was examined separately.Results:The mean age of the patients was 46.2±12.5 years. Median IGF-1 and BH levels were 551 ng/mL and 8.2 ng/mL, respectively. While 58.3% of the patients had osteopenia, no osteoporosis was found in any patient. A positive correlation was found between the BMD value measured from the femoral neck and IGF-1 (r=0.484, p=0.036) and GH (r=0.595, p=0.007) levels. There was no significant correlation between BMD measurements evaluated from lumbar vertebrae and GH and IGF-1 levels.Conclusion:It was found that the increase in GH and IGF-1 levels in newly diagnosed eugonadal acromegaly patients increased BMD measured from the femur. There was no significant relationship between BMD measured from the lumbar region and GH and IGF-1 levels.

Aim: In this study, the effect of intermittent fasting on growth hormone (GH) and ghrelin was examined in rats that fed on a standard diet without any application that may cause the values to decrease or increase in order to see the net effect of intermittent fasting. Materials and Methods: 12 Wistar albino male rats were divided into the 1st group as Control (standard diet 2.8% crude fat. 23.1% crude protein. 5% crude fiber. 7.1% crude ash and 12.8% moisture) and the 2nd group as the intermittent fasting together with the diet group (with a 24-hour break from the non-consecutive diet for 2 days a week and all food restricted except water). Results: As a result of the analysis, it was found that the growth hormone in the intermittent fasting together with the standard diet group tended to increase compared to the control group, and while this value difference was not statistically significant, the ghrelin level was found to be statistically lower than the control group. Conclusion: As a result, it was found that intermittent fasting tends to increase the level of growth hormone, and to have a decreasing effect on ghrelin level, and it was concluded that it can be considered among the methods to be used to treat obesity and prevent its occurrence.

Introduction. In the cases of neurosurgery failure in acromegaly treatment, drug therapy with somatostatin analogues (SSA) octreotide or lanreotide is indicated. The effectiveness of SSA is limited by the presence of resistance, there is an opinion that in some cases it can be overcome by replacing one drug with another.Aim. Own experience analysis of transferring acromegaly patients from therapy with long-acting octreotide to lanreotide autogel 120 mg.Materials and methods. The case histories of acromegaly patients who were recommended to replace long-acting octreotide therapy with lanreotide therapy 120 mg were analyzed. GH and insulin-like growth factor-1 (IGF-1) dynamics was evaluated at least 6 months after the replacement of the drug. The target value for GH was considered to be less than 2.5 micrograms/l, for IGF-1 – an excess of no more than 30% of the upper normal limit.Results. 24 patients were transferred to lanreotide therapy 120 mg. Of the 19 patients with insufficient reduction of GH and IGF-1 on prolonged-acting octreotide therapy at a dose of 40 mg every 28 days (OCT40) the prescription of lanreotide 120 mg every 28 days (LAN120) led to the target values of both GH and IGF-1 in 4 (21%) cases. These patients had no more than a twofold excess of IGF-1, and the level of GH was less than 2.5 mcg/l on the background of OCT 40 therapy. In 6 (32%) patients, IGF-1 levels normalized or decreased, but GH remained outside the target values. In 9 (47%) cases, the replacement of the SSA did not lead to a significant positive dynamics in the levels of GH and IGF-1. The effects of lanreotide therapy 120 mg in another five patients initially treated with octreotide 20 mg are also described.Conclusions. Replacement of OCT4 with LAN120 may be effective in some patients with acromegaly. A slight increase in the level of IGF-1 together with the target values of GH before replacing the SSA may be the predictor of success.

Abstract Background Unregulated use of a variety of drugs and supplements by bodybuilders and athletes is common and can lead to severe adverse complications. Only a small proportion of acute pancreatitis cases are drug induced, and case reports are essential for identifying potential drug-related risks for pancreatitis. Here we present the first case report published of acute pancreatitis linked to recreational use of anabolic–androgenic steroids, subcutaneous growth hormone, and clenbuterol in a previously healthy male after excluding all other causes of pancreatitis. Case presentation A 31-year-old Arab male bodybuilder presented with acute abdominal pain associated with nausea and sharp pain radiating to the back. The patient was not using tobacco or alcohol but was using multiple drugs related to bodybuilding, including anabolic–androgenic steroids, subcutaneous growth hormone, clenbuterol, and multiple vitamin supplements. Laboratory studies revealed a normal white blood cell count, elevated C-reactive protein, minimally elevated aspartate aminotransferase and total bilirubin with normal remaining liver tests, and elevated amylase and lipase. The patient had no hypertriglyceridemia or hypercalcemia, and had had no recent infections, abdominal procedures, trauma, or scorpion exposure. Imaging and laboratory investigations were negative for biliary disease and IgG4 disease. Abdominal computed tomography revealed hepatomegaly and diffuse thickening and edema of the body and tail of the pancreas with peripancreatic fat stranding. An abdominal ultrasound showed slight hepatomegaly with no evidence of cholelithiasis. Genetic testing for hereditary pancreatitis-related mutations was negative. A diagnosis of drug-induced acute pancreatitis was made, and he was treated with aggressive intravenous hydration and pain management. The patient has avoided further use of these drugs and supplements and had no further episodes of pancreatitis during 1 year of follow-up. Conclusions This case describes a patient with drug-induced acute pancreatitis after the intake of anabolic–androgenic steroids, subcutaneous growth hormone, and clenbuterol, where all other common causes of acute pancreatitis were excluded. Clinicians should be alert to the possibility of drug-induced acute pancreatitis occurring in bodybuilders and athletes using similar drug combinations.

Osteoporosis is a serious implication of Turner syndrome (TS). Common methods for the treatment of TS are growth hormone (GHT) and estrogen replacement therapy (ERT). We examined the relationship between the treatment of TS and bone mineral density (BMD) of the lumbar spine. The purpose of our study was to show the currency of BMD states among patients with TS for treatment with GHT and ERT. We searched databases for studies published from inception to April 2023. The articles were related to TS, osteoporosis, ERT, GHT, BMD and treatment patients with TS. We applied the selection criteria: lumbar spine values at L1–L4; dual-energy X-ray absorptiometry (DXA); treatment which was applied: one group of articles: ERT and two group of articles: GHT; results performed as means ± SD. In total, 79 articles were analyzed, of which 20 studies were included and 5 were considered for meta-analysis. The total number of women in the articles selected was 71. Based on the results of the meta-analysis, the effect of ERT on BMD demonstrated a significant increase in BMD (the standardized mean difference in the random model was 0.593 g/cm2, 95% CI: 0.0705 to 1.116; p = 0.026), which showed that treatment with estrogen particularly increases bone mass during treatment, which contributes to reducing the risk of fractures. The effect of GHT on BMD demonstrated a non-significant decrease in BMD in patients with TS. The results for growth hormone show that this therapy does not improve bone density. However, our review emphasizes the beneficial effect of supplementing growth hormone (GH) on the clinical presentation of TS.

Moyamoya disease is a rare, progressive cerebrovascular disease marked by stenosis and occlusion of the distal internal carotid arteries and branches of the circle of Willis, leading to creation of a collateral network of blood vessels at the base of the brain. It has been found to be a significant cause of childhood stroke. We would like to present two cases of moyamoya angiopathy with a growth hormone deficiency, in 13-year-old and 10-year-old brothers in Iraq. Hypothalamic-pituitary dysfunction may complicate Moyamoya angiopathy, which is attributed to chronic cerebrovascular insufficiency. Therefore, it is worth checking and regularly monitoring for this problem, especially in growing children and adolescents, to achieve normal growth and development.

Obesity is a public health problem that increasingly becomes widespread and causes various complications. Food addiction is a hedonic eating behavior characterized by overconsumption of palatable foods (i.e., foods involve a high amount of salt, sugar and fat). Disturbances in the growth hormone signaling pathway were shown to be associated with increased food intake and adiposity. The study aimed to determine the growth hormone (GH), growth hormone receptor (GHR), insulin, and insulin-like growth factor 1 (IGF-1) serum levels in individuals with obesity and food addiction. The present study involved 30 adults with obesity (23 females and 7 males) and 10 healthy adults (5 females and 5 males). 18 obese adults were diagnosed with food addiction, whereas only 2 individuals with food addiction were in the control group. GH, GHR, IGF-1 and insulin values were analyzed with ELISA kits. It was revealed that the obese subjects had significantly lower serum IGF-1 levels compared to healthy individuals (144.55±22.69 ng/ml vs 338.70±61.90 ng/ml, P < 0.001)). No significant differences in the GH, GHR and insulin levels between obese and control groups were detected (P > 0.05). No significant differences between the group with food addiction and the group without food addiction in terms of gender, age, weight, BMI, GH, GHR, insulin and IGF-1 levels were observed. Our study demonstrates that normal IGF-1 levels may be protective for the development of obesity. The serum levels of GH, GHR, insulin, IGF-1 are not associated with food addiction and, therefore, can not be used as novel markers of food addiction.

Abstract Growth hormone treatment for children with Prader Willi syndrome (PWS) has shown proven benefits not only in increasing final height but also with positive effects on body composition and motor development. In a recent letter to the editor, Hoybye and colleagues recommend growth hormone treatment for adults with PWS based exclusively on the genetic diagnosis and without regard for growth hormone secretory status. We question whether the benefits of growth hormone treatment in PWS adults, mainly improvement in body composition, are significant enough to justify the as yet unkown consequences of long-term treatment in an adult population. Morbidity and mortality in PWS are mainly due to complications of obesity, and growth hormone treatment does not result in a decrease in BMI or waist circumference. Increases in insulin-like factor-1 as a result of growth hormone treatment over the course of several decades in PWS adults raises concern over possible increase risk of cancer. Compliance with daily injections is likely to be poor. We suggest that efforts to provide appropriate dietary and exercise regimens may be more beneficial and cost-effective than advocating for growth hormone treatment for adults with PWS.

The objectives of the study were to evaluate the effect of ethanolic extract of P. indica Less leaf (EPI) on serum growth hormone (GH), milk yield, body weight gain of dams, and dam’s organ weight in lactating rats. A total of 25 lactating rats with six pups were randomized and distributed to one of five treatments (control (RO water), standard (domperidone 2,5 mg/kg BW/day), EPI 250 (250 mg/kg BW of EPI), EPI 500 (500 mg/kg BW of EPI), and EPI 750 (750 mg/kg BW of EPI)). The treatment was administered daily starting from the 2nd until the 15th day of lactation. On the 16th day serum growth hormone level, body and organ weight of rats were measured. Serum GH levels in the EPI 750 group (1963.25 ± 360.91 pg/µL) increased significantly compared to the domperidone (409.46 ± 28.80 pg/µL) and the control group (723.40 ± 95.78 pg/µL, p0.05). There was significant body weight gain in the EPI 750 group compared with the domperidone group. There was no significant difference in organ weight gain in each group. The study revealed that ethanolic extract of P. indica Less leaf can increase serum growth hormone in lactating rats.

Complex relationships between growth hormone (GH) signaling and mammalian aging continue to attract attention of many investigators. Recent results include evidence that the impact of GH on genome maintenance (DNA damage and repair) is drastically different in normal as compared to cancer cells, consistent with GH promoting aging and cancer progression. Impact of GH on DNA methylation was studied as a possible mechanism linking actions of GH during early life to the trajec-tory of aging. Animals with reduced or enhanced GH signaling and novel animals with adipocyte-specific deletion of GH receptors were used to elucidate the effects of GH on white and brown adipose tissue, including the impact of this hormone on lipolysis, fibrosis, and thermogenesis. Effects of GH on adipose tissue related to lipid and energy metabolism emerge as mechanistic links between GH, healthspan, and lifespan. Treatment of healthy men with a combination of GH, dehydroepi-androsterone, and metformin was reported to restore thymus function and reduce epigenetic age. Studies of human subjects with deficiency of GH or GH receptors and studies of mice with the same endocrine syndromes identified several pheno-typic changes related (positively or negatively) to the previously reported predisposition to healthy aging. Results of these and other recent studies advance present understanding of the mechanisms by which GH influences aging and longevity and of the trade-offs involved.

Prader-Willi syndrome (PWS) is a genetic disorder described by multifaceted clinical features with implications on the endocrine system, metabolism, and behavior. Some symptoms of PWS syndrome can be confused with the relative clinical aspects of hypothyroidism, such as lethargy, muscular hypotonia, and poor sucking ability. In this review, we would like to enlighten the importance of checking thyroid function in PWS patients at birth, at least annually, in those on growth hormone (GH) treatment, in any child of PWS with growth failure, and in those in whom there is an insufficient response to GH therapy, to ensure that any aberrant thyroid function is not overlooked and adequately treated.

Purpose: Recombinant human growth hormone (rhGH) has been used to treat short stature and rhGH-related syndromes. However, there are concerns that rhGH-treatment may cause precocious puberty. We investigated the effects of rhGH-treatment on the puberty onset, sexual maturation, androgen production, and hypothalamic gene expression in prepubertal male rats. Materials and Methods: Sprague-Dawley male rats were injected subcutaneously daily with 1 or 2 IU/kg/d rhGH or 0.1 mL saline from postnatal day (PND) 21 to 30. At PND 31 bodyweight, reproductive organs weight, preputial separation, testis histology, circulating testosterone, and expression of testicular steroidogenic pathway genes and hypothalamic Kiss1 were examined. Results: By day 4 of injection bodyweights of rhGH groups were significantly higher than those of controls. rhGH 2 IU group showed earlier preputial separation compared to the control group. At PND 31, the weights of testes, epididymides, seminal vesicles, prostates, and preputial glands of the 2 IU-rhGH group were significantly higher than control group. Serum testosterone levels of the 2 IU-rhGH group were significantly higher than control group. Testicular steroidogenic pathway gene Hsd17b3 and Nr5a1 mRNA and cell counts and areas of Leydig cells in rhGH groups were significantly higher than control group, suggesting functional differentiation of Leydig cells. Hypothalamic Kiss1 mRNA levels of the 1 IU-rhGH group were significantly lower than control group, suggesting negative feedback of Kiss1 by elevated testosterone. Conclusions: Prepubertal rhGH-treatment in male rats may induce early onset of puberty, sexual maturation, elevation of testosterone, and spermatogenesis, and accompanies downregulation of hypothalamic KISS1.

Acromegaly is a chronic endocrinopathy with pathologically increased levels of growth hormone (GH) and insulin-like growth factor-1 due to a pituitary adenoma that produces GH. One of the partially irreversible complications of acromegaly is arthropathy associated with severe morbidity in these patients. Joint complaints, such as pain, stiffness, or functional limitations, often occur with typical radiological abnormalities at an early age. We present a case of a 24-year-old acromegalic male patient with non-traumatic spontaneous right rectus femoris muscle rupture and an accompanying intramuscular haematoma.

Background and Aim: Obesity is a clinical condition that affects the growth-related hormonal system, especially in adolescents. High-Intensity Intermittent Training (HIIT) might reduce such destructive effects. Methods & Materials: In this quasi-experimental research, among adolescent boys [age: 13-18 years, height: 154±8 cm, Body Mass Index (BMI): 27.05±1.4 kg/m²], 30 volunteer subjects were selected. The study participants were divided into 3 groups of short-term and long-term periodic exercises as well as controls. The short-term exercise group performed 9 bouts of 30 seconds with 150-second breaks between sessions; the long-term exercise group performed 4 bouts of 150 seconds with 240-second breaks between sessions 3 times a week for 8 weeks. Body composition and blood samples were obtained 48 hours before and after conducting the training protocol to measure the desired parameters. The changes of each index were analyzed by repeated-measures Analysis of Variance (ANOVA) at the significant level of P0.05). Conclusion: Short- and long-term HIIT have the potential to improve the growth hormone status and body composition of overweight adolescents.

Abstract Prader-Willi syndrome (PWS) is a complex, multi-system, neurodevelopmental disorder characterised by neonatal muscular hypotonia, short stature, high risk of obesity, hypogonadism, intellectual disabilities, distinct behavioural/psychiatric problems and abnormal body composition with increased body fat and a deficit of lean body mass. Growth hormone (GH) deficiency and other hormone deficiencies are common due to hypothalamic dysfunction. In children with PWS GH treatment has been widely demonstrated to improve body composition, normalise height and improve psychomotor development. In adults with PWS, GH’s main effects are to maintain normal body structure and metabolism. The positive effects of GH treatment on body composition, physical fitness and beneficial effects on cardiovascular risk markers, behaviour and quality of life in adults with PWS are also well established from several studies. GH treatment is approved for treatment of children with PWS in many countries, but until recently not as a treatment in young adults in the transition period or for adults in general. In this commentary we want to draw attention to the uneven global use of GH treatment, specifically in adults with PWS, and advocate for GH treatment to be approved internationally, not just for children, but also for adults with PWS and based only on the diagnosis of genetically confirmed PWS.

Interactions between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the immune system are complex, bidirectional, but not fully explained. Current reviews based on numerous studies have indicated that chronic inflammation could suppress the GH/IGF-1 axis via several mechanisms such as relative GH and/or IGF-1 insufficiency, peripheral resistance to GH and/or IGF-1 resulting from down-regulation of GH and IGF-1 receptors, disruption in the GH/IGF-1 signalling pathways, dysregulation of IGF binding proteins (IGFBPs), reduced IGF bioavailability, and modified gene regulation due to changes in the microRNA system. It is well-known that relationships between the immune system and the GH/IGF-1 axis are mutual and GH as well as IGF-1 could modulate inflammatory response and the activity of systemic inflammation. Available data indicate that the GH/IGF-1 axis exerts both pro-inflammatory and anti-inflammatory effects. Pro-inflammatory cytokines such as interleukin-6 (IL-6), tumour necrosis factor- (TNF-), and interleukin-1(IL-) are some of the most significant factors, besides malnutrition, chronic stress, and prolonged use of glucocorticoids, which impair the activity of the GH/IGF-1 axis, and consequently lead to growth retardation in children suffering from childhood-onset chronic inflammatory diseases. In this review, we discuss the mechanisms underlying the impact of chronic inflammation on the GH/IGF-1 axis and growth processes during childhood and adolescence, based on a number of experimental and human studies.

ABSTRACT Objectives: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves “short long-lived people”, rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices. Material and methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain). Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions. Conclusions: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

The growth hormone (GH), although most well known for regulating linear growth, has a great number of another important biological functions like controlling physiological processes related to the cardiovascular, hepatobiliary, renal, gastrointestinal, and reproductive systems. Despite intensive studies during the past decade, the exact molecular mechanisms of Jak activation have largely remained controversial. It is evident that much more detailed structural information regarding Jaks and the Jakcytokine-receptor complex is needed to enhance our understanding of the mechanism of Jak activation. A substantial number of key class I cytokine receptors utilize Janus kinase 2 (JAK2) for signalling. The growth hormone (GH) and erythropoietin (EPO) receptors were the first of these to be discussed, and later the prolactin, interleukins 3, 5 and 6, (GM-CSF), interferon-γ (IFNγ), thrombopoietin (TPO) and leptin receptors were found to recruit this ubiquitous tyrosine kinase. Therefore, the growth hormone activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. The spectrum of physiological processes regulated by JAK2 is therefore vast, ranging from postnatal growth, reproduction and lactation through the regulation of metabolism and body composition, bone formation. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK–STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2 , also able to trigger the mitogen-activated protein kinase (MAPK) pathways. Also, the exact mechanism and functional relevance of autophosphorylation at different sites in Jaks is not known but will be an interesting area for future research. Another important topic for future studies is to define the mechanisms of crosstalk between Jaks and other pathways. Therefore, this review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling.

Aim.To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly. Materials and methods.A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery. Results.Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%). Conclusion.The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.

Objective: The aim of this study was to evaluate physician attitudes and practices in the management of adult growth hormone deficiency (GHD) following pituitary surgery. Materials and Methods: An online questionnaire survey was sent to a sample group of physicians. Results: A total of 131 respondents provided usable responses. More than three quarters were senior physicians, with most practicing in tertiary care centers (73%). Four-fifths of the respondents see at least 1 to 5 patients with GHD following pituitary surgery per year. Seventy-four percent acknowledge the benefit in principle of growth hormone replacement therapy (GHRT) for patients with GHD after pituitary surgery. Most respondents (84%) would only consider GHRT for symptomatic patients. However, 16% stated that patients with GHD after pituitary surgery generally suffer from the side effects of GHRT. Forty-four percent said that the serum insulin-like growth factor-1 (IGF-1) level is the best screening test for assessing GHD after pituitary surgery but 57% of the respondents would use IGF-I levels, and 29% the insulin tolerance test (ITT), in patients with a documented deficiency in three pituitary axes. The main barriers to long-term GHRT use were that it requires injections (67%), and is costly with limited supply (61%). Other reasons not to use GHRT include an absence of GHD symptoms and apparent GHT ineffectiveness (44%), physician lack of familiarity with the medication (40%), and lack of adherence to available guidelines (38%). Conclusion: This survey addressed physician attitudes and practices in recognizing and treating GHD in adult’s post-pituitary surgery. Regional guidelines must be developed to help address/tackle these issues and assist physicians in understanding and treating this condition.

ABSTRACT Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of gene expression in the 15q11.2-q13 paternal chromosome. Patients with PWS develop hypothalamic dysfunction that can lead to various endocrine changes such as: obesity, growth hormone deficiency, hypogonadism, hypothyroidism, adrenal insufficiency and low bone mineral density. In addition, individuals with PWS have increased risk of developing type 2 diabetes mellitus. This review summarizes and updates the current knowledge about the prevention, diagnosis and treatment of endocrine manifestations associated with Prader Willi syndrome, especially diagnosis of growth hormone deficiency, management and monitoring of adverse effects; diagnosis of central adrenal insufficiency and management in stressful situations; screening for central hypothyroidism; research and treatment of hypogonadism; prevention and treatment of disorders of glucose metabolism. Careful attention to the endocrine aspects of PWS contributes significantly to the health of these individuals. Arch Endocrinol Metab. 2020;64(3):223-34

Aim:The Amelogenesis Imperfecta (AI) term includes numerous inherited congenital enamel defects indicating clinical and genetic heterogeneity. The aim of the present study was to emphasize the importance of the potential prediction of AI via biochemical parameters.Materials and Methods:In total, 50 children were assessed in the study. The subjects included 13 syndromic AI, 22 isolated AI and 15 healthy children with a mean-age of 12.01±3.79 years old. The bone alkaline Phosphatase (BALP) and growth hormone (GH) blood levels of the children were evaluated. All data were statistically analysed by the SPSS 15.0 programme, one-way ANOVA and chi-square tests.Results:72.7% of syndromic AI and 47.6% of isolated AI group children have higher than normal BALP levels; 33% of syndromic AI and 28% of isolated AI group children have lower than normal blood GH levels. Subjects with AI have statistically significant abnormal blood BALP and GH levels and the presence of an Additional syndrome other than AI did not affect the results.Conclusion:Pediatricians may have a key role in early AI diagnosis via the evaluation of abnormal BALP and GH levels in blood tests and may help in providing comprehensive dental treatment in terms of prevention, prognosis and restoration of teeth in children with AI.

Abstract Background In children with Prader-Willi syndrome (PWS), the benefits of growth hormone treatment are well established. Several one-year studies have shown that growth hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects. This study investigated the effects on body composition in adult patients with PWS during 3 years of growth hormone therapy in a dose of 0.33 mg/m2/day. Methods Open-label, prospective study in 43 young adults with PWS with a median (IQR) age of 19.0 (17.5 to 20.7) years. Fat mass percentage SDS and lean body mass SDS were measured annually by DXA. Results Estimated mean (95% CI) fat mass percentage SDS decreased during the three-year study from 2.1 (1.9 to 2.3) SDS at start to 1.9 (1.8 to 2.1) SDS, p = 0.012, while lean body mass SDS remained stable at − 2.1 (− 2.4 to − 1.8) SDS at start to − 1.9 (− 2.3 to − 1.6) after 3 years, p = 0.15. Fasting glucose and insulin remained similar during the three-year study, glucose being 4.6 (4.4 to 4.8) mmol/l at start and 4.6 (4.5 to 4.7) mmol/l after 3 years of growth hormone, p = 0.93 and insulin being 59.5 (42.2 to 81.5) pmol/l and 55.0 (42.4 to 69.2) pmol/l, resp., p = 0.54. There were no growth hormone-related adverse events during the study. Conclusions Three years of growth hormone treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term growth hormone treatment. Trial registration EudraCT, EudraCT number 2011-001313-14 . Registered 17 October 2012.

Background: By studying the types of hormones, the role of genetic and hormonal and chemical agents in schizophrenia can be found. The aim of this study was to determine the effectiveness of Growth Hormone based on ELISA method on the Treatment of Schizophrenic Patients. Methods: This study was a semi-experimental study with pretest-posttest with control group. The study population consisted of all schizophrenic patients admitted to Bostan psychiatric hospital in Ahvaz. A sample of 60 patients was selected using the available method and divided into two experimental and control groups. Results: In this study, there was significant difference between the level of growth hormone in pre and post-treatment patients. Therefore, more studies are recommended on this hormone (P

Introduction: Turner's syndrome (TS) is the most common sex chromosome disorder in women, with an incidence of 1 in 2,500 female births. TS is characterized by distinctive features of short stature, streak gonads, increased risk of heart and renal defects and specific cognitive and psychosocial phenotype. Materials and Methods: We conducted a study in the department of endocrinology, GGH, Kurnool, for one year. 27 cases presented with short stature and primary amenorrhea, recurrent otitis media, were diagnosed as TS after detailed workup. We started growth hormone therapy for some patients with short stature. Gonadectomy was conducted for TS patients with Y component, and they were asked for regular follow-up. Results: Out of 27 cases, 12 were found to be turner mosaic, 15 were classical cases of TS. Conclusion: TS can be diagnosed with a high degree of clinical suspicion and confirmed by karyotyping. TS if identified earlier, growth can be achieved to the maximum potential. Early identification and proper management can improve the outcome and decrease the complications associated with TS.

ABSTRACT In addition to auxiological, clinical and metabolic features measurements of growth hormone (GH) and insulin-like growth factor I (IGF-I) complement our tools in diagnosis and follow-up of GH-related disorders. While comparably robust during the pre-analytical phase, measurement and interpretation of concentrations of both hormones can be challenging due to analytical issues and biological confounders. Assay methods differ in terms of antibody specificity, interference from binding proteins, reference preparations and sensitivity. GH assays have different specificity towards different GH-isoforms (e.g. 20 kDa GH, placental GH) and interference from the GH antagonist Pegvisomant. The efficacy to prevent binding protein interference is most important in IGF-I assays. Methodological differences between assays require that reference intervals and diagnostic cut-offs are assay-specific. Among biological variables, pubertal development and age are most relevant for IGF-I, making detailed reference intervals mandatory for interpretation. GH has pulsatile secretion and short half-life. Its concentration is modified by acute factors such as stress, exercise and sleep, but also by intake of oral estrogens and anthropometric factors (e.g. BMI). Other GH dependent biomarkers such as free IGF-I, IGF binding protein 3 (IGFBP 3) and acid labile subunit (ALS) have been proposed. Their concentrations largely mirror the information obtained through measurement of IGF-I, but their measurement can be helpful in particular situations. In this review, we describe the evolution of analytical methods to measure biomarkers of GH action, the impact of the methodological changes on laboratory results and the need to include biological variables in their interpretation. Arch Endocrinol Metab. 2019;63(6):618-29

ABSTRACT The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17

ABSTRACT Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports. Athletic performance depends on muscle strength and the energy required to power muscle function. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that in muscle GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. In recreational athletes, GH improves anaerobic capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH appears likely to selectively benefit sprint events and not physical performance that depends on strength and endurance. Arch Endocrinol Metab. 2019;63(6):576-81