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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]

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]

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]

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]

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]

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]

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]

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]

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]

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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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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.

We recommend acromegaly to be ruled in all patients with characteristic changes in appearance (A3). In all patients without characteristic changes in appearance, we recommend to rule out acromegaly, if several clinical signs suspicious for acromegaly are present (B3). We recommend acromegaly to be ruled out in all patients with pituitary adenoma (B3). We recommend to rule out acromegaly in all patients with prolactin-secreting adenomas (C4). For laboratory confirmation of acromegaly, we recommend to measure serum insulin-like growth factor-1 (IGF-1, somatomedin C) level (A3). In patients without obvious clinical signs of acromegaly and/or with a moderate increase in IGF-1 levels (IGF-1 index less than 1.3), we recommend to assess the response of somatotropic hormone (GH) to hyperglycemia (GH during an oral glucose tolerance test) (B3). In all patients with biochemically confirmed acromegaly, magnetic resonance imaging of the pituitary gland with intravenous contrast is recommended to assess pituitary adenoma size, location and growth pattern (A3). We recommend to measure blood glucose and glycated hemoglobin in all patients with confirmed acromegaly (B3). We recommend to measure serum prolactin levels in all patients with acromegaly (B3).In all patients with acromegaly and pituitary adenoma, transnasal transsphenoidal adenomectomy is recommended as first-line treatment if the patient’s consent is given and there are no contraindications (A1). For all patients with acromegaly for whom neurosurgical treatment is indicated, surgical intervention is recommended in medical centers, specializing in pituitary diseases, by neurosurgeons who perform at least 50 such operations per year (A3). We recommend that morphological and immunohistochemical examination of the removed pituitary adenoma is performed in all patients with acromegaly (A3). We do not recommend routine medical therapy for acromegaly before surgery as a mean to reduce tumor size (B2).For patients with acromegaly in whom neurosurgical treatment is not indicated or ineffective or while patient awaiting for the effect of radiation therapy, we recommend medical therapy (A1). Long-acting first-generation somatostatin analogues are recommended as first-line drug therapy for acromegaly. In case of partial/complete resistance to or intolerance to somatostatin analogs, pegvisomant is recommended as a second-line medical therapy for acromegaly (A1). We recommend starting pegvisomant from a single dose of 40–80 mg per day subcutaneously, then continue injections at a starting dose of 10 or 15 mg per day with IGF-1 monitoring after 4–6 weeks and dose adjustment if necessary (B2). In patients with acromegaly and a moderate increase in IGF-1 levels, we recommend to initiate cabergoline as medical monotherapy or, if somatostatin analogs are ineffective, in combination with them (B2).In patients with acromegaly, if the disease remains active after surgical treatment, if drug treatment is unavailable, intolerable or ineffective, and repeated neurosurgical intervention is inappropriate, it is we recommend radiation therapy (A1). A multidisciplinary approach is recommended in the management of acromegaly complications (C3).

Background/Objective: Collision tumors composed of craniopharyngiomas and pituitary adenomas are extremely rare. We report a collision tumor formed by a papillary craniopharyngioma and a growth hormone-secreting pituitary adenoma, which is the first report of such a tumor, to the best of our knowledge. Case Report: A 49-year-old man presented with 2 months of headaches and blurry vision. An exam demonstrated frontal bossing, enlarged jaw and hands, macroglossia, and bitemporal hemianopsia, and magnetic resonance imaging (MRI) showed a 4.1 cm sellar/suprasellar mass with mass effect on the optic chiasm. The tumor was resected twice via a craniotomy, the second time due to interval growth, with the pathology after both surgeries showing a papillary craniopharyngioma. IGF-1 was 517 ng/mL (68-225) and growth hormone suppression test was positive. Repeat MRI showed residual tumor with ongoing mass effect on the optic chiasm and radiation therapy was initiated. MRI showed interval growth of the mass and IGF-1 rose to 700 ng/mL after which the patient underwent a transsphenoidal resection of the tumor; the pathology showed a residual papillary craniopharyngioma and a PIT1 lineage adenoma with most cells expressing growth hormone. After developing numerous complications, the patient passed away. Discussion: Collision tumors of the sella are often associated with an aggressive clinical course, as they often go undiagnosed preoperatively, thus reducing the likelihood of total resection and leading to higher rates of craniopharyngioma recurrence. Conclusion: A pituitary mass with an aggressive clinical course should prompt a high index of suspicion for a sellar collision tumor, though prognosis remains poor.

Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be found in extra-pituitary tissues including placenta. Furthermore, GH, PRL, and their receptors structurally belong to the cytokine family of proteins, and indeed they have remarkable pleiotropic effects. In this review, we analyzed the biological roles of GH/PRL from an evolutionary perspective. We have recognized that the biological significance of GH/PRL can be summarized as follows: cytokines (metabokines) that regulate the shift of nutrients and even of whole bodies to live in the most appropriate environment(s) for conducting growth and reproduction. In this sense, the common keyword of the two metabokines is “shift” for environmental adaptation. Considering that these metabokines flexibly changed their biological roles, GH/PRL may have played important roles during vertebrate evolution.

In dairy cattle, oxidative stress is a predominant problem associated with diseases and reproductive health issues. This study aimed to detect the variation in the antioxidant biomarkers by adding different concentrations of β-hydroxybutyric acid (BHBA) and sought to elucidate its effects on the gene expression levels of growth hormone (GH) and antioxidant biomarkers in bovine hepatocytes.

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis. Materials and methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15–1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis. [ABSTRACT FROM AUTHOR]

DNA damage‐induced senescence is initially sustained by p53. Senescent cells produce a senescence‐associated secretory phenotype (SASP) that impacts the aging microenvironment, often promoting cell transformation. Employing normal non‐tumorous human colon cells (hNCC) derived from surgical biopsies and three‐dimensional human intestinal organoids, we show that local non‐pituitary growth hormone (npGH) induced in senescent cells is a SASP component acting to suppress p53. npGH autocrine/paracrine suppression of p53 results in senescence evasion and cell‐cycle reentry, as evidenced by increased Ki67 and BrdU incorporation. Post‐senescent cells exhibit activated epithelial‐to‐mesenchymal transition (EMT), and increased cell motility. Nu/J mice harboring GH‐secreting HCT116 xenografts with resultant high GH levels and injected intrasplenic with post‐senescent hNCC developed fourfold more metastases than did mice harboring control xenografts, suggesting that paracrine npGH enables post‐senescent cell transformation. By contrast, senescent cells with suppressed npGH exhibit downregulated Ki67 and decreased soft agar colony formation. Mechanisms underlying these observations include npGH induction by the SASP chemokine CXCL1, which attracts immune effectors to eliminate senescent cells; GH, in turn, suppresses CXCL1, likely by inhibiting phospho‐NFκB, resulting in SASP cytokine downregulation. Consistent with these findings, GH‐receptor knockout mice exhibited increased colon phospho‐NFκB and CXCL1, while GH excess decreased colon CXCL1. The results elucidate mechanisms for local hormonal regulation of microenvironmental changes in DNA‐damaged non‐tumorous epithelial cells and portray a heretofore unappreciated GH action favoring age‐associated epithelial cell transformation. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Melanoma, a severe type of skin cancer, often becomes resistant to chemotherapy, making it difficult to treat. This research investigates a novel mechanism by which growth hormone (GH) contributes to chemotherapy resistance. We examined small particles, called exosomes, which are released from melanoma cells treated with GH and found to carry proteins that increase drug resistance and cancer cell movement. The effects were more pronounced when GH was combined with the chemotherapy drug, doxorubicin. We also found that blocking the GH action with a drug called pegvisomant reduced the expression of these exosomal proteins, ultimately making the cancer cells more responsive to chemotherapy and less likely to migrate. Our findings provide new insights into how GH action promotes melanoma chemoresistance via exosomes, suggesting that targeting/inhibiting GH action could improve melanoma treatment. Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to the resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and the GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to the recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin, and MMP2, enhancing drug resistance and migration in the recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights into the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment. [ABSTRACT FROM AUTHOR]

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level (p = 0.166), basal GH level (p = 0.001), and nadir GH level (p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission. [ABSTRACT FROM AUTHOR]

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations. [ABSTRACT FROM AUTHOR]

Since the use of antibiotics as growth promoters in animal feed has been restricted or banned in several countries, finding suitable alternatives is crucial for maintaining animal health. In this study, a novel formate acidifier named sodium diformate (NaDF) was synthesized, and the effects on growth performance and the prevention effects against Salmonella enterica serovar Pullorum infections in chickens were assessed. In broilers, NaDF supplementation improved growth performance, as evidenced by increased body weights and reduced feed conversion ratios. At 38 days of age, NaDF supplementation increased the levels of growth-hormone and ghrelin in the serum, lowered pH values in the gut, improved duodenal morphology, as shown by increased villus length/crypt depth ratios. NaDF also modulated the abundance of beneficial and harmful bacteria without changing the general microbiota diversity and short-chain fatty acids levels, which would be beneficial for maintaining gut homeostasis during its use. NaDF exhibited a broad spectrum of antibacterial activity in vitro. Supplementation with NaDF effectively decreased S. Pullorum colonization in the cecum, liver and spleen in chickens, and mitigated pathological changes in the tissues. Therefore, as a novel acidifier, NaDF can improve chicken growth performance by increasing growth-related hormones levels while maintaining the diversity of gut microbiota, and also resist intestinal bacterial infection. These results provided evidences for the application of NaDF as an effective and safe animal feed in poultry farming. [ABSTRACT FROM AUTHOR]

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

Background/Objectives: Develop a clinical and genetic characterization, in a group of small-for-gestational-age (SGA) patients who did not experience catch-up growth Methods: In an ambispective cohort study with (SGA) patients. These patients received one treatment with growth hormone (GH) over 14 years. This study analyzes their response to treatment and conducts a genetic analysis in order to identify cases with specific phenotypic and auxological characteristics, defined as presenting two or more dysmorphic traits and/or a stature below −3 SDS (standard deviation score). Whole-exome sequencing (WES) was performed on selected patients. Results: Forty-four SGA patients were examined, with an average age of 6.4 (2.49) years and an initial size of −3.3 SDS. The pubertal growth was 24.1 (5.2) cm in boys and 14.7 (4.3) cm in girls. WES in 11 SGA patients revealed conclusive genetic variants in eight, including two pathogenic ACAN variants, one 15q26.2-q26.3 deletion, and four variants of uncertain significance in other genes. Conclusions: Treatment with GH in SGA patients was shown to be effective, with a similar response in the group with positive genetic results and in the group who did not undergo a genetic study. Genetic testing based on auxological and clinical criteria proved highly cost-effective. [ABSTRACT FROM AUTHOR]

Turner syndrome is one of the most frequent chromosomal disorders and has an increased associated morbidity. The clinical picture of Turner syndrome reveals itself gradually, not every patient exhibits the full clinical picture, but gonadal dysgenesis and short stature are invariably present. We describe the long-term outcomes in a cohort of 41 patients with Turner syndrome followed at the Regional Center for Medical Genetics Bihor. A retrospective study was performed using the medical records; epidemiological, clinical, laboratory, cytogenetic, and imaging data were analyzed. The frequency of congenital heart abnormalities and intellectual disability was increased in the study group, necessitating a more effective screening technique in our country, to identify all the cases with TS. Early diagnosis and hormonal treatment are critical for a patient's favorable prognosis in stature, bone metabolism, cardiovascular system, and quality of life. Patients with TS have higher rates of related morbidity, especially skeletal, kidney, ophthalmological, and dermatological and a multidisciplinary team is essential for the management of TS cases. [ABSTRACT FROM AUTHOR]

Objective: It was previously shown that the levels of several biomarkers increase due to acromegaly disease-related inflammation, and some markers are parallel to the disease's activity. The current study compared the possible relationship of growth differentiation factor-15 (GDF-15) with acromegaly disease activity in healthy subjects. Methods: This case-control study was conducted in a single center. It included 40 acromegaly patients (25 active/15 controlled) (47.7 ± 9.4 years, 20 female/20 male) and 24 healthy individuals (49.9 ± 10.1 years, 13 female/11 male) with age-sex-body mass index similar to the patient group. Demographic data, metabolic and hormonal parameters, and GDF-15 levels of the study population were studied. Results: The median GDF-15 levels were significantly higher in patients with acromegaly compared to healthy subjects (HS) (280.4 (Q1-Q3: 197.0-553.2) vs. 213.3 (Q1-Q3: 179.9-297.2) ng/L, P = .01). Serum GDF-15 levels of active and controlled acromegaly patients were comparable (P = .39). Interestingly, compared to HS, GDF-15 levels were significantly higher in controlled disease (P = .013), whereas GDF-15 levels tended to be higher in active disease but did not reach statistical significance (P = .06). Growth differentiation factor-15 levels were positively correlated with fasting plasma glucose (r = 0.304, P = .01) and HbA1c (r = 0.292, P = .02). When evaluated across the entire cohort, GDF-15 levels were found to be higher in diabetic patients compared to non-diabetic individuals (P = .04). Conclusion: Plasma GDF-15 levels were increased in the patients with acromegaly compared to healthy subjects. This increment may be due to accompanying diseases such as diabetes rather than a disease-specific effect. [ABSTRACT FROM AUTHOR]

Context: Meditation and related relaxation techniques are good means of alleviating stress and maintaining good health. Osho dynamic meditation decreases several psychopathological variables such as anxious‐depressive syndrome, aggressive behaviors, and depression which is practiced in Nepal and all over the world. Various studies have shown alteration in different hormone levels due to meditation by strengthening adaptive mechanisms. Aim: The aim of this study was to evaluate the effect of Osho meditation on serum hormonal levels in pre‐ and postmeditation participants. Methods: A pre–post study was conducted among 70 healthy volunteers (42 male and 28 female) where various types of Osho dynamic meditation techniques were incorporated together to understand their combined effects on serum hormone levels in participants attending the 7 days meditation camp. Serum hormones such as cortisol, estrogen, progesterone, free triiodothyronine (fT3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH), testosterone, and growth hormone were measured by chemiluminescence immunoassay. Results: Out of 70 participants, 68 participants (97%) had subjective opinion of Osho dynamic meditation being effective in alleviating stress, depression, and anger. Also, there was a significant decline in body weight and body mass index in both male and female populations after a strict vegetarian diet and meditation. Likewise, a significant rise in the level of estrogen (p < 0.001), progesterone (p < 0.001), growth hormone (p < 0.001), testosterone (p = 0.002), and fT3 (p = 0.049) in postmeditation male participants indicates the importance of Osho dynamic meditation on elevating sex hormones such as estrogen, progesterone, testosterone as well as fT3, and growth hormones among Osho meditation practicing participants. Conclusion: Our findings suggest significant changes in the hormonal levels and improvement in stress and depression in participants undergoing Osho meditation. [ABSTRACT FROM AUTHOR]