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Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.

Acromegaly is a rare systemic syndrome induced by the overproduction of growth hormone (GH) and insulin-like growth factor type one (IGF1). It is responsible for changes in the skeletal and soft tissue systems and it almost always occurs because of a pituitary adenoma. Amongst the skin complications related to acromegaly, cutis verticis gyrate (CVG) is occasionally found. It is a skin condition characterized by excessive growth of the skin of the scalp, resulting in furrows and folds. Only a few cases of this uncommon association have been reported in the literature. The present clinical case illustrates typical CVG associated with acromegaly. Imaging revealed a pituitary macroadenoma lesion and hormonal evaluation revealed elevated IGF1 and hypopituitarism. The patient underwent a transsphenoidal resection of the pituitary adenoma and the histopathological examination confirmed the diagnosis. The diagnosis of CVG is clinical, so radiologic assessments are generally not necessary. The management of acromegaly associated with CVG depends on controlling the serum levels of GH and IGF1. In some cases, specific injections or surgery can be used to minimize CVG.

Prior studies have shown that interrupting the growth hormone/insulin‐like growth factor‐I (GH/IGF‐I) signaling axis extends laboratory mouse lifespan, but confounding effects of additional gene or hormone deficiencies that exist in commonly used models of GH/IGF‐I interruption obscure the specific effect of GH on longevity. We address this issue by using mice with a specific knockout of the GH gene and show that both males and females on a mixed genetic background display extended lifespans resulting from GH deficiency. Our physiological assessment of these mice revealed that in addition to weighing significantly less and displaying significantly greater body fat (as a percentage of body weight), GH deficient mice display significant impairments in glucose metabolism and preferential fat utilization. These data provide strong evidence that GH deficiency is directly responsible for the altered nutrient utilization and extended lifespan that is commonly observed in mouse models of GH/IGF‐I interruption. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) exhibits various essential physiological functions, which are exerted by its binding to growth hormone receptor (GHR). Ethanol has been demonstrated to have an impact on GH’s biological activity. Nevertheless, mechanism underlying the regulation of the biological activity of GH by ethanol have yet to be fully elucidated.This study utilized an indirect immunofluorescence assay to identify GHR expression in mouse hepatocytes. Western blot was used to determine the impact of ethanol on GH-induced intracellular signalling. Indirect immunofluorescence and colocalization experiments were used to determine the effect of ethanol on GH-GHR’s nuclear localization and endocytosis.GHR was primarily localized in the cell membrane and cytoplasm. The phosphorylation levels of JAK2 and STAT1/3/5 were markedly lowered after treatment with ethanol. On this basis, we further explored the mechanism underlying the regulation of GH biological activity by ethanol from the perspective of cell internalization. We found that the nuclear translocation of GH-GHR was inhibited when treated with ethanol. In addition, the results of colocalization analyses revealed that ethanol inhibited GHR-mediated nuclear translocation may mainly by inhibiting caveolin-dependent endocytosis.Our study showed that ethanol inhibits GH signaling ability in a time-dependent manner. Ethanol could inhibit the nuclear localization of GH-GHR, which may be linked to the inhibition of the interaction between GHR and caveolin. The combined effect of these factors downregulated the GH-GHR signal. This study laid a foundation for further exploring the mechanism that the effects of ethanol on GH biological activity. [ABSTRACT FROM AUTHOR]

Childhood-onset craniopharyngiomas, though rare, are intracranial malformations that can cause obesity by disrupting the hypothalamus, a condition that often persists even after tumor resection. This severe obesity increases the risk of diabetes and fatty liver disease in childhood. Concurrently, panhypopituitarism, including growth hormone (GH) deficiency, may develop. Notably, some individuals with GH deficiency may exhibit a normal growth rate, making GH therapy unnecessary for growth purposes. However, in these cases, GH therapy may still be beneficial in preventing the progression of nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. Although weight management is traditionally considered the gold standard for preventing liver cirrhosis, its effectiveness can be limited by hypothalamic dysfunction and the difficulty of achieving successful weight control. Our case study highlights a patient with normal growth despite GH deficiency, who did not receive GH replacement therapy and continued to struggle with hypothalamic obesity. Despite effective body weight control, the patient developed hepatopulmonary syndrome, indicating that relying solely on weight management may not be sufficient to prevent liver complications. This case underscores the importance of addressing GH deficiency even when growth is normal. Our findings suggest that GH replacement therapy could be beneficial for preventing liver cirrhosis in such cases. [ABSTRACT FROM AUTHOR]

Objective: Hepatopulmonary syndrome (HPS) is a rare complication of metabolic associated fatty liver disease (MAFLD) occurring subsequent to hypopituitarism, often developing after resection of hypothalamic or pituitary tumors. The aim of this study is to report an illustrative case of an HPS patient who was successfully treated with growth hormone replacement therapy, without liver transplantation which is conventionally regarded as the only treatment option. Additionally, we conducted a comprehensive review of published case reports of HPS in the pediatric population. Methods: We systematically searched literature databases to identify case reports and case series of HPS associated with hypopituitarism diagnosed in childhood. The search included MEDLINE/PubMed, Scopus, Embase, and Google Scholar from 1990 to 2023. The review process adhered to the PRISMA checklist for comprehensive reporting and methodological transparency. Results: An 18-year-old female, who had been followed up for MAFLD after craniopharyngioma resection, presented with cyanosis and progressive dyspnea. She was diagnosed with severe degree of HPS. The patient began treatment with recombinant human growth hormone, leading to a significant improvement in respiratory symptoms within 3 months, and normalization of lung shunt ratio after 6 months of therapy. In our systematic review, nine patients from nine studies across six countries were identified. The median age at diagnosis of hypopituitarism was 10.5 years (range 1–16 years), and HPS was diagnosed at a median interval of 7 years later (range 0–26 years). Half of the patients had not received growth hormone therapy after being diagnosed with hypopituitarism, which subsequently led to the diagnosis of HPS. Three patients underwent liver transplantation, but non-alcoholic steatohepatitis recurred in all cases. Six patients were successfully treated with growth hormone replacement therapy without undergoing liver transplantation. Conclusions: HPS can occur in pediatric patients with MAFLD who have undergone resection of the tumor in the hypothalamus or pituitary gland. Our findings suggest that growth hormone replacement therapy can be a possible alternative to liver transplantation for HPS patients. However, further investigations need to be performed to validate the efficacy of growth hormone treatment in different causes of HPS cases. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), a chronic joint disease characterized by primary or secondary degeneration of articular cartilage and bone dysplasia, is associated with various risk factors and is the leading cause of musculoskeletal pain and disability, severely impacting the quality of life. Growth hormone (GH), secreted by the anterior pituitary gland, is essential in mediating the growth and development of bone and cartilage. Reportedly, osteoarthritis increases, and the growth hormone decreases with age. A negative correlation between GH and OA suggests that GH may be related to the occurrence and development of OA. Considering that abnormal growth hormone levels can lead to many diseases related to bone growth, we focus on the relationship between GH and OA. In this review, we will explain the effects of GH on the growth and deficiency of bone and cartilage based on the local pathological changes of osteoarthritis. In addition, the potential feasibility of treating OA with GH will be further explored and summarized. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Growth hormone deficiency (GHD) causes growth disturbances during childhood. The most recommended treatment of GHD is the administration of recombinant human growth hormone (rhGH). Recent studies have proved that well-nourished GHD children respond better to rhGH therapy compared to undernourished individuals. The aim of this study was to analyze nutritional status along with height velocity in GHD children during the first two years of rhGH therapy, and to estimate the optimal BMI z-score range in which these children achieve the best growth results. Methods: This retrospective analysis included 80 prepubertal idiopathic GHD children treated with rhGH. Anthropometric data were obtained from medical records made at an initial visit and then follow-up visits after 12 and 24 months of treatment. The body mass index (BMI) was calculated and standardized into z-score, basing on Cole's LMS method. Then, the BMI z-score was analyzed in relation to the parameters of growth response. Results: The higher the BMI z-score at treatment entry, the greater the increase in height during the first twelve months of rhGH therapy. BMI z-score ≥0 noted at the beginning of each year of the treatment are associated with significantly better growth increments throughout the first and the second years of the therapy. Conclusion: Prepubertal idiopathic GHD children with BMI z-score below 0 would probably benefit from the improvement of their nutritional status prior to the rhGH treatment beginning. It seems that increasing BMI z-score to obtain values between 0 and 1 would be optimal for the growth process. [ABSTRACT FROM AUTHOR]

Context Rare patients with short stature and growth hormone (GH) resistance have dominant-negative variants in the GH receptor. We describe a patient with GH resistance due to elevated levels of GH binding protein and demonstrate the potential for a precision medicine intervention. Objective To determine whether high-dose GH can overcome GH resistance in this specific patient resulting in normal insulin-like growth factor (IGF)-1 levels and improved growth rates. Methods Single patient trial of ascending doses of GH followed by a dose stable phase: total 12 months of treatment. The patient has a heterozygous variant in the GH receptor resulting in elevated levels of GH binding protein manifesting as GH resistance and severe short stature. Daily subcutaneous GH was administered, starting at 50 µg/kg/day and escalating to 250 µg/kg/day until goal IGF-1 achieved. The subject continued on 250 µg/kg/day for a total treatment duration of 12 months. The primary outcome measure was the dose of GH required to achieve an IGF-1 level above the midpoint of the normal range. Secondary endpoints included height velocity and the change in height SDS during the first year of treatment. Results A dose of GH of 250 µg/kg/day achieved the target IGF-1 level. The patient's annualized height velocity was 8.7 cm/year, an increase of 3.4 cm/year from baseline, resulting in a 0.81 SD gain in height. Conclusion A precision medicine approach of extremely high dose GH was able to overcome GH resistance in a patient with a dominant-negative variant in the GH receptor resulting in elevated GH binding protein levels. [ABSTRACT FROM AUTHOR]

Context Patients with Turner syndrome (TS) often present with short stature and ovarian insufficiency. The optimal method of pubertal induction to maximize adult height (AH) is unknown. Objective To identify variables related to pubertal induction that are associated with growth and AH. Methods This retrospective cohort analysis of patients attending a specialized TS clinic at a quaternary children's hospital included patients with TS (n = 107) who attended the clinic between 2015 and 2021. Among them, 51 received estradiol for pubertal induction. Main outcome measures were changes in height SD score (ΔHeightSDS) during pubertal induction and AH. Age at pubertal induction, bone age delay, mid-parental height (MPH), growth hormone treatment, and karyotype were assessed as predictors of AH and ΔHeightSDS. Associations between karyotype and comorbidities were also assessed. Results AH was predicted by MPH (0.8 cm/cm, P =.0001) and bone age delay (−1.84 cm/year, P =.006). ΔHeightSDS was predicted by growth hormone dose (0.09 SDS/mg/m2/week; P =.017), bone age delay (−1.37 SDS/year; P =.003), and age at pubertal induction (0.44 SDS/year; P =.001). There was an interaction between bone age delay and pubertal induction age (P =.013), with the combination of younger age at pubertal induction and a less-delayed bone age associated with a lower ΔHeightSDS. Karyotype did not influence AH or ΔHeightSDS but did affect rates of other comorbidities. Conclusion Decisions around timing of pubertal induction in patients with TS should be tailored to the individual. The current approach to estrogen supplementation needs to be refined in order to facilitate pubertal induction in a physiological manner without compromising height. [ABSTRACT FROM AUTHOR]

Introduction: Human growth hormone (hGH) therapy in children can be administered by subcutaneous injection using either a manual non-connected device, which is a portable injection pen loaded with a pre-filled cartridge, or an electronic connected device. The electronic device is connected to a platform where adherence data is recorded and available for health care professionals (HCPs) and patient support programs. Real-world data used in the clinic, includes regular monitoring of adherence data which are shared with families during patients' visits and aim to determine the root causes of poor adherence. This study aimed to identify whether there are differences in growth during the first four years of treatment depending on the device, i.e. non-connected versus connected devices. Methods: This retrospective study reports treatment of either GH deficiency or short stature secondary to birth size small for gestational age (SGA) in 174 pediatric patients attending Miguel Servet Hospital, Zaragoza, Spain. hGH treatment was administered with manual non-connected devices in 87 patients and 87 patients used connected devices. Height was followed for 4 years after start of hGH therapy. Results: In total, 57% of subjects had GHD and 43% were SGA. Height standard deviation score (HSDS) at treatment start was higher (p<0.001) in the non-connected device group compared to the connected device group. Change of HSDS in the connected device group was significantly higher in the second (+0.13), third (+0.20) and fourth (+0.23) year of treatment compared to the non-connected group after adjustment for age and HSDS at treatment start, sex, indication, dose and Tanner stages during treatment, and timing of measurements. Discussion: These results support the use of the connected device for hGH treatment of pediatric growth disorders. [ABSTRACT FROM AUTHOR]

Smart technologies and connected health are providing opportunities for improved healthcare for chronic conditions. Acceptance by healthcare professionals (HCPs) and patients is crucial for successful implementation. Evidence-based standards, technological infrastructure and regulatory processes are needed to integrate digital tools into clinical practice. Personal health records provide continuity and aid decision-making, while machine-learning algorithms may help in optimizing therapies and improving outcomes. Digital healthcare can negate geographical barriers, enabling patients in remote areas to access specialist endocrine expertise. We review available and developing digital tools to manage care for patients requiring growth hormone (GH) therapy for growth failure conditions. GH is most often administered via daily injections over several years; continuous adherence is necessary but may become insufficient. Future development and integration of electronic platforms for GH therapy requires involvement of all stakeholders in design-thinking approaches and human-factor testing. Growzen Connect is an innovative digital ecosystem designed to increase the management and monitoring of GH therapy, comprising the easypod device and connected mobile apps. It provides a real-time overview of a patient's therapy, including adherence and growth response, which aids decision-making by HCPs and empowers patients to engage in their therapy journey. Incorporating prediction models for adherence and growth in the ecosystem helps patients build treatment habits and allows issues to be addressed in a timely fashion. A connected ecosystem for GH therapy can enhance outcomes and empower patients, fostering a collaborative and patient-centered approach that is more proactive, beyond the traditional clinic-based approach. [ABSTRACT FROM AUTHOR]

This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

In humans' and experimental animals' components of the somatotropic axis, such as growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations, decrease with advancing age. Although there is evidence regarding IGF-1, the effect of age on GH in mares, as well as the relationships between both parameters, have not yet been elucidated. On the other hand, although GH and IGF-1 are related to follicular development, it is unknown if they could be correlated with the circulating concentrations of ovarian steroids in mares, as occurs in other species. The hypothesis of this study was that both GH and IGF-1 could experience physiological changes with advancing age also in mares, and that both GH/IGF-1 could be correlated with oestradiol-17β (E 2) and progesterone (P 4), as recorded for other species. Hence, the objective of this study was to evaluate the concentrations of GH, IGF-1, E 2 , and P 4 in mares, according to the different ages. Blood samples were drawn from 56 healthy cyclic Spanish Purebred mares belonging to four different age groups: 6–9 years, 10–13 years, 14–16 years and >16 years. Mares aged 6–9 years and 10–13 years showed higher GH concentrations (P < 0.05) than mares of 14–16 and >16 years; and mares aged 14–16 showed higher GH concentrations (P < 0.05) than >16 years (P < 0.05). Mares aged >16 years showed lower IGF-1 concentrations (P < 0.05) than mares of 6–9, 10–13 and 14–16 years (P < 0.05). The concentrations of E 2 and P 4 showed no significant differences among different age groups. Both GH and IGF-1 were not correlated with each other or with E 2 and P 4. The concentrations of E 2 and P4 did not change with age. Advancing age leads to a decrease in the activity of the somatotropic axis in physiological cyclic mares, represented by a significant GH reduction, which, however, was ascribed for IGF-1 exclusively to mares over 16 years of age, without alterations in steroid hormone patterns. • Age-related changes on GH, IGF-1, oestradiol-17β, and progesterone concentrations in mares were evaluated. • Mares aged 6–9 years and 10–13 years showed higher GH than mares of 14–16 and >16 years. • Mares aged 14–16 showed higher GH concentrations than >16 years. • Mares aged >16 years showed lower IGF-1 concentrations compared to all three age groups. • No correlations between GH, IGF-1, and ovarian steroids were observed. • Advancing age leads to a significant GH reduction which was ascribed for IGF-1 exclusively to mares >16 years [ABSTRACT FROM AUTHOR]

Acromegalic cardiomyopathy is a significant cardiovascular complication associated with acromegaly, caused by excessive growth hormone production from a pituitary adenoma. Early diagnosis can be challenging due to its insidious nature. This case underscores the critical significance of timely medical intervention, illustrating favorable outcomes resulting from prompt therapeutic measures. [ABSTRACT FROM AUTHOR]

The endocrine system is an essential regulator of the osmoregulatory organs that enable euryhaline fishes to maintain hydromineral balance in a broad range of environmental salinities. Because branchial ionocytes are the primary site for the active exchange of Na+, Cl−, and Ca2+ with the external environment, their functional regulation is inextricably linked with adaptive responses to changes in salinity. Here, we review the molecular-level processes that connect osmoregulatory hormones with branchial ion transport. We focus on how factors such as prolactin, growth hormone, cortisol, and insulin-like growth-factors operate through their cognate receptors to direct the expression of specific ion transporters/channels, Na+/K+-ATPases, tight-junction proteins, and aquaporins in ion-absorptive (freshwater-type) and ion-secretory (seawater-type) ionocytes. While these connections have historically been deduced in teleost models, more recently, increased attention has been given to understanding the nature of these connections in basal lineages. We conclude our review by proposing areas for future investigation that aim to fill gaps in the collective understanding of how hormonal signaling underlies ionocyte-based processes. [ABSTRACT FROM AUTHOR]

Somatrogon‐ghla is a long‐acting, recombinant human growth hormone approved for the treatment of pediatric patients with growth hormone deficiency. Forty‐nine healthy, adult males were enrolled in a randomized, crossover study to compare somatrogon exposure after subcutaneous doses administered using a frozen vial presentation or a prefilled, multiple dose pen. Somatrogon, insulin‐like growth factor‐I, and IGF‐1 binding protein‐3 concentrations were collected for up to 240 hours post dose to assess pharmacokinetic and pharmacodynamic responses. There was a 2‐week washout between administration of the doses. Seven participants did not complete the study due to withdrawal of consent (n = 2) or loss to follow‐up. Two treatment‐emergent adverse events, headaches, were judged by the investigator as possibly related to study drug administration. Both were mild. Injection site reactions were observed in 6/48 participants after administration with the pen and 12/46 after administration using the vial. Drug and biomarker concentrations were assessed using validated assays and noncompartmental methods were used to determine pharmacokinetic and pharmacodynamic parameters. Bioequivalence was demonstrated for somatrogon area under the concentration‐time curve, but not for the peak somatrogon concentration, where the lower limit of the 90% confidence interval for the ratio of pen/vial was 74.2%, which is less than the lower limit, 80.0%, dictated by bioequivalence criteria. The IGF‐1 responses were largely within bioequivalence limits. It was concluded that the 2 formulations are comparable. [ABSTRACT FROM AUTHOR]

Purpose: Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels. Methods: This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis. Results: Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046). Conclusion: The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is the most common genetic syndrome with obesity and results from loss of expression of paternally inherited genes on chromosome 15q11‐q13 by a variety of mechanisms which include large deletions (70%–75%), maternal uniparental disomy (UPD) (20%–30%), and imprinting defects (2%–5%) or balanced translocations. Individuals often have a characteristic behavior disorder with mild intellectual disability, infantile hypotonia associated with poor sucking, short stature, and obesity. PWS is characterized by hypothalamic–pituitary axis dysfunction with growth hormone (GH) deficiency, hypogonadism, and several other hormonal deficiencies resulting in short stature, centrally driven excessive appetite (hyperphagia), central obesity, cryptorchidism, and decreased lean body mass. In this study, we determined and sought differences in the incidence of thyroid abnormalities among the common genetic subtypes in a cohort of 52 subjects with PWS because there was limited literature available. We also sought the effects of growth hormone (GH) treatment on the thyroid profile. Fifty‐two subjects with a genetically confirmed diagnosis of PWS were included in this study at the University of California, Irvine. Blood samples for baseline thyroxine stimulating hormone (TSH) and free thyroxine (fT4) levels were obtained in the morning after an overnight fast for 8–12 h. Statistical analyses were performed with SPSS (SPSS Inc., 21.0). Mean values were analyzed by one‐way ANOVA, and student's t‐test and statistical significance were set at p < 0.05. The subjects included 26 males and 26 females with an age range of 3–38 years. There were 29 subjects with chromosome 15q11‐q13 deletions and 23 with UPD; 28 were GH treated currently or in the past, and 24 never received GH. There was no significant difference in age or body mass index (BMI) (kg/m2) between GH‐treated versus non‐GH‐treated groups. BMI was higher in the deletion group compared to the UPD group (p = 0.05). We identified two individuals who were clinically diagnosed and treated for hypothyroidism, one of whom was on GH supplements. We identified two additional individuals with subclinical hypothyroidism who were not on GH treatment, giving a frequency of 7.6% (4/52) in this cohort of patients. We did not find significant differences in thyroid function (TSH) in the deletion versus UPD groups. We found significant differences in thyroid function, however, between GH‐treated and non‐GH‐treated groups. The mean TSH was lower (2.25 ± 1.17 uIU/M, range 0.03–4.92 uIU/M versus 2.80 ± 1.44 uIU/M, range 0.55–5.33 uIU/M respectively, p = 0.046), and the free T4 levels were significantly higher (1.13 ± 0.70 and 1.03 ± 0.11 ng/dL, respectively, p = 0.05) in the GH‐treated individuals compared to non‐GH‐treated individuals. In this cohort of subjects with PWS, we identified two previously diagnosed individuals with hypothyroidism and two individuals with subclinical hypothyroidism (4/52, 7.6%), three of whom were not receiving GH treatment. We did not find any significant differences in thyroid function between molecular subtypes; however, we found that euthyroid status (lower TSH levels and higher free T4 levels) was significantly higher in individuals who were treated with GH compared to the untreated group. We recommend that individuals with PWS should be screened regularly for thyroid deficiency and start treatment early with GH in view of the potentially lower incidence of thyroid deficiency. [ABSTRACT FROM AUTHOR]

Background: This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM), and influencing cardiorespiratory fitness (VO2max) in Vit-D-deficient middle-aged healthy men. Methods: Participants (n = 28) were quasi-randomly assigned to one of two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) during participation in a 12-week supervised RT program. Results: During the intervention, serum Vit-D concentrations increased 2.6-fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. Conclusions: In conclusion, in healthy Vit-D-insufficient middle-aged men engaged in resistance training, Vit-D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM, or decreases in fat mass and fat percentage, and does not affect cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

The increased availability of recombinant human GH (rhGH), albeit at a relatively high cost, has increased a demand for treatment of children and adolescents of normal height to increase their adult stature. There are no scientific reports on the efficacy and safety of rhGH therapy in this condition; therefore, the authors comment on the possible causes and consequences based on their personal opinion and experience. As in gigantism, when GH action and end-organ are normal, enough GH is expected to result in increased growth velocity. Short-term adverse effects related to rhGH therapy for approved indications of short stature in children have been very rare. Data on long-term adverse effects are still scarce. A small increase in height might be statistically significant but not functionally or socially relevant. Considering that an increase in height represents more a desire than a need, physicians should emphasize the normality and qualities of these children, discuss with families the alternatives, such as counseling, and refrain from supporting the concept that taller is better. [ABSTRACT FROM AUTHOR]

Introduction: The glucagon stimulation test (GST) is widely used to assess growth hormone (GH) and cortisol secretion, nevertheless the precise mechanisms underpinning these hormonal responses remain unclear. We have endeavoured to explore the relationship between glucose and insulin fluctuations during GST and their impact on GH and cortisol secretion. Subjects and methods: We retrospectively studied 139 subjects (mean age 35.5 ± 15.1 years, BMI 26.6 ± 6.61 kg/m²), including 62 individuals with a history of pituitary disease (27 with an intact adrenal axis) and 77 healthy controls. Standard dose intramuscular GST was performed in all subjects. Results: Once BMI and age were excluded from multivariate model, the nadir of glucose concentration during GST was the sole variable associated with maximal GH secretion (DGH, p<0.0003), while neither glucose/insulin peak, nor Dglucose/Dinsulin concentrations contributed to DGH. 100% pass rate for GH secretion above 3 ng/ml or 1.07 ng/ml cut-offs was observed for glucose concentrations at, or below 60 mg/dl (3.33 mmol/l) (for Controls), or 62 mg/dl (3.44 mmol/l) (for Controls and patients with an intact adrenocortical axis). Such low glucose concentrations were obtained, however, only in about 30% of studied individuals. Conversely, cortisol secretion did not correlate with glucose or insulin fluctuations, suggesting alternative regulatory mechanisms. Conclusions: This study reveals that glucose nadir below 3.33 mmol/l is the only biochemical biovariable linked with optimal GH secretion during GST, whereas mechanisms responsible for cortisol secretion remain unclear. We emphasize the importance of glucose monitoring during GST to validate GH stimulation and support clinical decisions in GH deficiency management. [ABSTRACT FROM AUTHOR]

The study examines the complex relationship between growth hormone (GH) and thyroid hormones in hypo and hyperthyroid conditions in premature male rats, concentrating on the physiological impacts of hormonal alterations and genetic effects. It was done in an animal housing facility at the University of Mosul Faculty of Veterinary Medicine. A study of 50 male rats, 30 days old and weighing 160 ± 5g, was conducted over 21 days. The first control group (G1) received normal saline subcutaneously. The second group (G2) induced by growth hormone deficiency via sodium diethyldithiocarbamate (SDDT) subcutaneously, the third group (G3) were given a growth hormone drug (Norditropin) subcutaneously, while fourth group (G4) induced hypothyroidism by Propylthiouracil (PTU) orally, and the fifth group (G5) induced hyperthyroidism by (Levothyroxine) orally. This experiment showed that thyroid stimulating hormone (TSH) has a high significance value at p>0.05 in G4 and G2 compared to G1. However, Triiodothyronine (T3) and Thyroxin (T4) are significant in G3 and G5. Regarding Reverse Triiodothyronine (rT3) in G3 and G4 display highest level in contrast to the other groups. Thyroid- binding globulin (TBG) and Thyroid peroxidase antibodies (TPO) were greatest in G4, whereas growth hormone (GH) and IGF-1 were highest in G2 and G5. The gene expression results showed that GH and IGF-1are up-regulated in comparison to the rest of the groups by using a modified conventional PCR with the formula. In conclusion, one hormonal agent system may significantly affect other hormonal activities, stressing the need for a complete endocrine approach. [ABSTRACT FROM AUTHOR]

Introduction: Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA). Methods: The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children. Results: We identified 25 different heterozygous ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was −2.6 SDS (−3.2 to −2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncating ACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (−2.8 SDS and −2.1 SDS, respectively, p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9–1.4). In pubertal children, height SDS remained relatively stable. Conclusion: The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment. [ABSTRACT FROM AUTHOR]

Objective: Mixed gonadal dysgenesis (MGD) is an uncommon chromosomal Disorder of Sexual Development (DSD). There is insufficient information regarding clinical findings and growth patterns. This study aimed to provide more information about mixed gonadal dysgenesis, which has not yet been sufficiently defined. Materials and Methods: Data from 10 patients diagnosed with mixed gonadal dysgenesis were retrospectively reviewed. Clinical presentations, complaints at admission, imaging, genetic results, and treatments received by the patients were examined. Gonadal status and the gender of the patients were reared and evaluated by a multidisciplinary council decision. If received, growth hormone treatment doses and height gains were examined. Results: The patients’ ages at admission range from 6 months to 17.5 years. The median height SDS of the patients was −0.75 (2.73), the mean body weight SDS was −0.49 (±1.46), and the mean body mass index (BMI) SDS was 0.26 (±0.97). The complaints at admission varied, including ambiguous genitalia, short stature, and absence of menstruation. Some patients are completely in the female phenotype, while some are inadequately virilized male phenotype. External Masculinization Score (EMS) ranges from 1 to 6.5. The decision to raise 6 patients as female and 4 patients as male was made by a multidisciplinary council. Growth hormone treatment was administered to patients raised as female and diagnosed with short stature. The height SDS gain in treated patients was 0.42 (±0.49). Conclusion: Due to its rarity and varied clinical presentation, our knowledge about mixed gonadal dysgenesis is limited. Therefore, early diagnosis and individualized treatment plans are crucial for this patient group. [ABSTRACT FROM AUTHOR]

Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of insomnia and sleep quality in a cohort of patients with a low risk of OSAS before and after therapies for acromegaly. A total of 27 naïve acromegalic patients (mean age 55.15 ± 10.53 years) were submitted to a psychometric sleep evaluation and compared to a matched control group of 24 Non-Functioning Pituitary micro-Adenoma patients (mean age 51.08 ± 11.02 years). A psychometric sleep evaluation was carried out 4 years later, after achieving acromegaly control in all patients. The role of different therapies for acromegaly (somatostatin analogues, pegvisomant, or adenomectomy) was evaluated. At the initial evaluation, most untreated acromegalic patients had a higher rate of impaired sleep quality and clinical insomnia than NFPA patients (p = 0.001 ES = 1.381, p = 0.001 ES = 1.654, respectively). Patients treated with somatostatin analogues or pituitary adenomectomy had an improvement in insomnia parameters (p = 0.046 ES = 0.777, p = 0.038 ES = 0.913, respectively). Conversely, in patients treated with pegvisomant, sleep quality and insomnia worsened (p = 0.028 ES = 1.002, p = 0.009 ES = 1.398, respectively). In summary, therapies for acromegaly seem to have divergent effects on perceived sleep disorders. Concerning sleep, somatostatin analogues and adenomectomy seem to have favorable effects on the psychometric parameters of sleep. [ABSTRACT FROM AUTHOR]

Objective Spermatozoa are susceptible to oxidative radicals when antioxidant defenses are inadequate. The extent to which oxidative radicals contribute to sperm damage in patients with acromegaly remains unclear. This study aimed to investigate and elucidate this relationship. Methods The overall status of oxidants and antioxidants in both seminal plasma and serum of patients with acromegaly compared to a control group of healthy individuals was investigated. In addition, sperm parameters, including important measures such as growth hormone and insulin-like growth factor-1 concentrations. Results Twenty-two patients with acromegaly with controlled disease and 14 healthy controls were included. The total oxidant status was significantly higher in the semen samples of the patients with acromegaly. A negative correlation was found between sperm total oxidant status and total sperm count and sperm concentration. Similarly, a negative correlation was found between the total sperm count and the sperm oxidative stress index. In individuals diagnosed with acromegaly, there was a statistically significant increase in sperm growth hormone levels. Conversely, the level of insulin-like growth factor 1 was significantly increased in the sperm of the control group, which consisted of healthy individuals. The correlation analysis revealed a significant relationship between venous total oxidant status and growth hormone levels in semen. Conclusion The elevated levels of reactive oxygen radicals in individuals with acromegaly suggest a possible link between oxidative stress and its effects on semen quality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to understand the effect of time to remission of acromegaly on survival in people living with acromegaly. Design, Patients and Measurement: This cross‐sectional study used data from the UK Acromegaly Register. We considered remission of acromegaly growth hormone controlled at ≤2 μg/L following the diagnosis of acromegaly. We used the accelerated failure time model to assess the effect of time to remission on survival in acromegaly. Results: The study population comprises 3569 individuals with acromegaly, with a median age of diagnosis of 47.3 (36.5–57.8) years, 48% females and a majority white population (61%). The number of individuals with the first remission of acromegaly was 2472, and the median time to first remission was 1.92 (0.70–6.58) years. In this study, time to first remission in acromegaly was found to have a significant effect on survival (p <.001); for every 1‐year increase in time to first remission, there was a median 1% reduction in survival in acromegaly. In an analysis adjusted for covariates, the survival rate was 52% higher (p <.001) in those who underwent surgery as compared to those who did not have surgery, 18% higher (p =.01) in those who received treatment with somatostatin analogues (SMA) as compared to those with dopamine agonists and 21% lower (p <.001) in those who received conventional radiotherapy as compared to those who did not receive radiotherapy. Conclusion: In conclusion, this population‐based study conducted in patients with acromegaly revealed that faster remission time, surgical intervention and treatment with SMA are linked to improved survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow‐up exist. However, not all recommendations are strictly evidence‐based. To evaluate consensus on the treatment and follow‐up of patients with acromegaly in the Nordic countries. Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow‐up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert‐type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert‐type scale. Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first‐generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first‐generation SSA and pegvisomant as second‐ or third‐line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence‐based data. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine if genetically modified porcine kidneys used for xenotransplantation had sufficient tissue integrity to support long-term function in a human recipient. Background: Kidney transplantation remains the best available treatment for patients with end-stage kidney disease. However, a shortage of available donor human kidneys prevents many patients from achieving the benefits of transplantation. Xenotransplantation is a potential solution to this shortage. Recent pre-clinical human studies have demonstrated kidneys from genetically modified pig donors can be transplanted without hyperacute rejection and are capable of providing creatinine and other solute clearance. It is unknown whether the porcine kidneys would tolerate the relatively higher resting blood pressure in an adult human recipient compared with the pig donor or non-human primate (NHP) recipients used in translational studies. Furthermore, previous experience in NHPs raised concerns about the tissue integrity of the porcine ureter and post-xenotransplant growth of the porcine kidney. Methods: Kidneys recovered from porcine donors with 10 gene edits were transplanted into decedent brain-dead recipients who were not eligible for organ donation. Decedents underwent bilateral native nephrectomy before transplant and were followed for 3 to 7 days. Standard induction and maintenance immunosuppression was used as previously reported. Vital signs, including blood pressure, were recorded frequently. Kidney xenografts were assessed daily, serially biopsied, and were measured at implantation and study completion. Results: Three decedents underwent successful xenotransplantation. Subcapsular hematomas developed, requiring incision of the xenograft capsules to prevent Page kidney. Blood pressures were maintained in a physiologic range for adult humans (median arterial pressures (MAP) 108.5 mm Hg (Interquartile Range (IQR): 97-114 mm Hg), 74 mm Hg (IQR: 71-78 mm Hg), and 95 mm Hg (IQR: 88-99 mm Hg, respectively) and no bleeding complications or aneurysm formation was observed. Serial biopsies were taken from the xenografts without apparent loss of tissue integrity despite the lack of a capsule. Ureteroneocystotomies remained intact without evidence of urine leak. Xenograft growth was observed, but plateaued, in 1 decedent with increased volume of the left and right xenografts by 25% and 26%, respectively, and in the context of human growth hormone levels consistently less < 0.1 ng/ml and insulin-like growth factor 1 levels ranging from 34-50 ng/ml. Conclusions: The findings of this study suggest kidneys from 10-gene edited porcine donors have sufficient tissue integrity to tolerate xenotransplantation into a living human recipient. There was no evidence of anastomotic complications, and the xenografts tolerated needle biopsy without issue. Xenograft growth occurred but plateaued by the study end; further observation and investigation will be required to confirm this finding and elucidate underlying mechanisms. [ABSTRACT FROM AUTHOR]

It is unclear exactly how bariatric surgery affects the body’s metabolic and physiological functions. The purpose of the study was to assess the activity of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in obese individuals before and six months after laparoscopic sleeve gastrectomy. Materials and methods. This study included 52 patients with a body mass index (BMI) ranging from 35 to 56 kg/m² who qualified for laparoscopic sleeve gastrectomy and had completed data at the 6-month postoperative follow-up. All patients were clinically examined by a team of surgeons and a physician before operation. The serum levels of GH and IGF-1 were assessed pre- and post-operatively. Results. The study included 52 patients with obesity who were undergoing laparoscopic gastric sleeve surgery. Their mean age was 32.04 ± 6.90 years. More than half of the patients, 27 (51.9 %), were aged 19 to 32 years, 32 (61.5 %) patients were females, and 38 (73.1 %) had a BMI of 35–49.9 kg/m² . There was a significant increase in the serum GH after the sleeve gastrectomy compared to the pre-operative level (0.95 ± 0.30 vs 0.62 ± 0.40 ng/ml, p = 0.0001). IGF-1 also significantly increased after the surgery: 117.13 ± 32.40 vs 102.63 ± 33.90 ng/ml (p = 0.0001). Concerning BMI, there was no significant difference in the GH mean for patients with a BMI of 35–49.9 and 50–56 kg/m² pre- and post-operatively: 0.6 vs 0.8 (p = 0.07) and 0.9 vs 1 (p = 0.5), respectively. On the other hand, IGF-1 exhibited a significant difference before and after surgery: 107.7 vs 88.9 ng/ml (p = 0.02) and 123.2 vs 100.7 (p = 0.03). Conclusions. This study concludes that sleeve gastrectomy significantly increases the serum level of both GH and IGF-1 and, consequently, their effects on disturbed lipid and protein metabolism in morbidly obese patients [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: In childhood, growth hormone (GH) deficiency (GHD) diagnosis is based on auxological assessment and biochemical provocative tests, whose reliability remains disputed. Recently, several papers have been published on standardising the duration of some tests. The aim of our study was to analyse the possible length reduction of the L‐DOPA provocative test. Methods: We retrospectively investigated the response of GH to L‐DOPA in 256 children, analysing 267 tests (some patients were retested over time for the persistence of severe auxopathy). We studied the same data considering GH peak threshold both at 8 ng/mL (Italian GHD cut‐off) and at 10 ng/mL (international cut‐off). Based on stimulation tests, patients were divided into two groups: GHD and no‐GHD short children. We described the results in the whole population and then clustering for gender and pubertal stage. We termed as index the test stopped at 90 min. Results: The GH peak after L‐DOPA mostly occurred at 60 min. The sensitivity of the index test was the highest, while the specificity was slightly higher using the 8 ng/mL threshold (specificity = 0.68; 95% CI 0.60–0.76) then using the 10 ng/mL threshold (specificity = 0.56; 95% CI 0.47–0.65) at 90 min. The two ROC curves showed moderate performance of the test at 90 min. While the negative predictive value was 100% in both tests, the positive predictive value was slightly better with 10 ng/mL cut‐off. Considering the two groups established by GHD definition and placing a GH threshold at 10 ng/mL, stopping L‐DOPA test time at 90 min would have changed the test result and subsequentially patient's classification in 3/267 of the analysed tests (1.1%), while with the Italian GH threshold value at 8 ng/mL in 7/267 of the tests (2.6%). Conclusions: Our research shows that omitting 120‐min time reduces L‐DOPA test specificity, especially with GHD cut‐off at 10 ng/mL. [ABSTRACT FROM AUTHOR]

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.

Purpose Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement. Methods We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS. Results At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST). Conclusions The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.

Background. It is unclear exactly how bariatric surgery affects the body’s metabolic and physiological functions. The purpose of the study was to assess the activity of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in obese individuals before and six months after laparoscopic sleeve gastrectomy. Materials and methods. This study included 52 patients with a body mass index (BMI) ranging from 35 to 56 kg/m2 who qualified for laparoscopic sleeve gastrectomy and had completed data at the 6-month postoperative follow-up. All patients were clinically examined by a team of surgeons and a physician before operation. The serum levels of GH and IGF-1 were assessed pre- and post-operatively. Results. The study included 52 patients with obesity who were undergoing laparoscopic gastric sleeve surgery. Their mean age was 32.04 ± 6.90 years. More than half of the patients, 27 (51.9 %), were aged 19 to 32 years, 32 (61.5 %) patients were females, and 38 (73.1 %) had a BMI of 35–49.9 kg/m2. There was a significant increase in the serum GH after the sleeve gastrectomy compared to the pre-operative level (0.95 ± 0.30 vs 0.62 ± 0.40 ng/ml, p = 0.0001). IGF-1 also significantly increased after the surgery: 117.13 ± 32.40 vs 102.63 ± 33.90 ng/ml (p = 0.0001). Concerning BMI, there was no significant difference in the GH mean for patients with a BMI of 35–49.9 and 50–56 kg/m2 pre- and post-operatively: 0.6 vs 0.8 (p = 0.07) and 0.9 vs 1 (p = 0.5), respectively. On the other hand, IGF-1 exhibited a significant difference before and after surgery: 107.7 vs 88.9 ng/ml (p = 0.02) and 123.2 vs 100.7 (p = 0.03). Conclusions. This study concludes that sleeve gastrectomy significantly increases the serum level of both GH and IGF-1 and, consequently, their effects on disturbed lipid and protein metabolism in morbidly obese patients.

The study examines the complex relationship between growth hormone (GH) and thyroid hormones in hypo and hyperthyroid conditions in premature male rats, concentrating on the physiological impacts of hormonal alterations and genetic effects. It was done in an animal housing facility at the University of Mosul Faculty of Veterinary Medicine. A study of 50 male rats, 30 days old and weighing 160 ± 5g, was conducted over 21 days. The first control group (G1) received normal saline subcutaneously. The second group (G2) induced by growth hormone deficiency via sodium diethyldithiocarbamate (SDDT) subcutaneously, the third group (G3) were given a growth hormone drug (Norditropin) subcutaneously, while fourth group (G4) induced hypothyroidism by Propylthiouracil (PTU) orally, and the fifth group (G5) induced hyperthyroidism by (Levothyroxine) orally. This experiment showed that thyroid stimulating hormone (TSH) has a high significance value at p>0.05 in G4 and G2 compared to G1. However, Triiodothyronine (T3) and Thyroxin (T4) are significant in G3 and G5. Regarding Reverse Triiodothyronine (rT3) in G3 and G4 display highest level in contrast to the other groups. Thyroid-binding globulin (TBG) and Thyroid peroxidase antibodies (TPO) were greatest in G4, whereas growth hormone (GH) and IGF-1 were highest in G2 and G5. The gene expression results showed that GH and IGF-1are up-regulated in comparison to the rest of the groups by using a modified conventional PCR with the formula. In conclusion, one hormonal agent system may significantly affect other hormonal activities, stressing the need for a complete endocrine approach.

Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of insomnia and sleep quality in a cohort of patients with a low risk of OSAS before and after therapies for acromegaly. A total of 27 naïve acromegalic patients (mean age 55.15 ± 10.53 years) were submitted to a psychometric sleep evaluation and compared to a matched control group of 24 Non-Functioning Pituitary micro-Adenoma patients (mean age 51.08 ± 11.02 years). A psychometric sleep evaluation was carried out 4 years later, after achieving acromegaly control in all patients. The role of different therapies for acromegaly (somatostatin analogues, pegvisomant, or adenomectomy) was evaluated. At the initial evaluation, most untreated acromegalic patients had a higher rate of impaired sleep quality and clinical insomnia than NFPA patients (p = 0.001 ES = 1.381, p = 0.001 ES = 1.654, respectively). Patients treated with somatostatin analogues or pituitary adenomectomy had an improvement in insomnia parameters (p = 0.046 ES = 0.777, p = 0.038 ES = 0.913, respectively). Conversely, in patients treated with pegvisomant, sleep quality and insomnia worsened (p = 0.028 ES = 1.002, p = 0.009 ES = 1.398, respectively). In summary, therapies for acromegaly seem to have divergent effects on perceived sleep disorders. Concerning sleep, somatostatin analogues and adenomectomy seem to have favorable effects on the psychometric parameters of sleep.

INTRODUCTION: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. METHODS: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence). RESULTS: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and “others“ (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 μg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased. DISCUSSION AND CONCLUSION: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Background/Objective: We present an adolescent male with Noonan syndrome (NS) and celiac disease (CD) who attained normal adult height with growth hormone (GH) treatment and gluten-free diet (GFD). Case Report: A 15 ½ year old healthy male presented with short stature and delayed puberty. His mother and maternal grandmother were short with heights 142.2 cm and 147.3 cm, respectively. Examination showed bilateral epicanthal folds and down slanting eyes like his mother, fifth finger clinodactyly, height 147.5 cm (

Recombinant human growth hormone (rhGH) and GH receptor antagonists (GHAs) are used clinically to treat a range of disorders associated with GH deficiency or hypersecretion, respectively. However, these biotherapeutics can be difficult and expensive to manufacture with multiple challenges from recombinant protein generation through to the development of long-acting formulations required to improve the circulating half-life of the drug. In this review, we summarize methodologies and approaches used for making and purifying recombinant GH and GHA proteins, and strategies to improve pharmacokinetic and pharmacodynamic properties, including PEGylation and fusion proteins. Therapeutics that are in clinical use or are currently under development are also discussed.

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Background: GHRH is produced in the hypothalamus and affects various tissues beyond the pituitary, including the lungs.GHRH antagonists exert anti-inflammatory properties in several experimental models of disease, but their role inprotecting the endothelial barrier during inflammation is less understood. This study investigates the effects ofGHRHAnt on LPS-induced endothelial dysfunction. Methods: BPAEC and HMVEC-L cells were exposed to LPS to induce endothelial injury. GHRHAnt was administered eitherpre- or post-LPS treatment. Western blot analysis was used to evaluate protein expression levels. Paracellularpermeability was assessed utilizing FITC-dextran assay to evaluate endothelial barrier function. Results: GHRHAnt post-treatment significantly reduced LPS-induced MLC2 phosphorylation and cofilin activation inBPAECs. Furthermore, pretreatment with GHRHAnt enhanced barrier function and ameliorated LPS-inducedhyperpermeability in both human and bovine endothelial cells. Conclusions: GHRHAnt treatment mitigates LPS-induced endothelial barrier dysfunction. These findings suggest that GHRHAntcould serve as potential therapeutic agents towards endothelial dysfunction-related illness (e.g. sepsis). [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA). Methods: A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion. Results: Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores. Conclusions: In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to analyze the effect of a four-week moderate-intensity exercise regimen on increasing growth hormone (GH) levels in individuals with obesity. Materials and methods. A total of 25 female individuals aged 20-25 years, with a body mass index (BMI) of 27.50-37.00 kg/m², were involved in the study and randomly divided into two groups, namely the control group (CON; n = 12) and the moderate-intensity exercise group (MIE; n = 13). The moderate-intensity exercise regimen (treadmill exercise for 30 minutes at 60-70% of HRmax, and resistance exercise for 30 minutes at 60-70% of 1RM) was conducted 3 times per week for a period of 4 weeks. Blood samples from participants were collected pre- and post-exercise sessions, and GH levels were analyzed using the Enzyme-Linked Immunosorbent Assay method. Data analysis techniques used the paired sample t-test with a significance level of 5 %. Results. The paired sample t-test results of GH levels between the pre-exercise and post-exercise sessions in the CON group showed a change from (1291.79 ± 383.76 to 1151.53 ± 484.80 pg/mL; p = 0.694), while the MIE group demonstrated the following dynamics of change — from (1161.79 ± 133.72 to 2103.83 ± 357.09 pg/mL; p = 0.006). Conclusions. The main findings of this study revealed that after implementing a four-week moderate-intensity exercise intervention, a significant increase in GH levels was observed in obese females.