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Excessive growth hormone (GH) has been shown to promote joint degeneration in both preclinical and clinical studies. Little is known about the effect of disrupted GH or GH receptor (GHR) on joint health. The goal of this study is to investigate joint pathology in mice with either germline (GHR-/-) or adult inducible (iGHR-/-) GHR deficiency. Knee joints from male and female GHR-/- and WT mice at 24 months of age were processed for histological analysis. Also, knee joints from male and female iGHR-/- and WT mice at 22 months of age were scanned by micro-CT (μCT) for subchondral bone changes and characterized via histology for cartilage degeneration. Joint sections were also stained for the chondrocyte hypertrophy marker, COLX, and the cartilage degeneration marker, ADAMTS-5, using immunohistochemistry. Compared to WT mice, GHR-/- mice had remarkably smooth articular joint surfaces and an even distribution of proteoglycan with no signs of degeneration. Quantitatively, GHR-/- mice had lower OARSI and Mankin scores compared to WT controls. By contrast, iGHR-/- mice were only moderately protected from developing aging-associated OA. iGHR-/- mice had a significantly lower Mankin score compared to WT. However, Mankin scores were not significantly different between iGHR-/- and WT when males and females were analyzed separately. OARSI scores did not differ significantly between WT and iGHR-/- in either individual or combined sex analyses. Both GHR-/- and iGHR-/- mice had fewer COLX+ hypertrophic chondrocytes compared to WT, while no significant difference was observed in ADAMTS-5 staining. Compared to WT, a significantly lower trabecular thickness in the subchondral bone was observed in the iGHR-/- male mice but not in the female mice. However, there were no significant differences between WT and iGHR-/- mice in the bone volume to total tissue volume (BV/TV), bone mineral density (BMD), and trabecular number in either sex. This study identified that both germline and adult-induced GHR deficiency protected mice from developing aging-associated OA with more effective protection in GHR-/- mice.

Aim Methods Results Conclusion This study evaluated feeding problems and gastrointestinal symptoms in children with Silver‐Russell syndrome (SRS), which is a rare epigenetic disorder. It also compared the symptoms experienced during different feeding methods, including percutaneous endoscopic gastrostomy (PEG).The national expert team for children with SRS at Queen Silvia Children's Hospital, Gothenburg, studied 46 referrals (63% male) who were born with SRS in Sweden from 1984 to 2018. Patient data were extracted from the Paediatric National Growth Hormone Registry.The medical records covered a median of 68% of the time of the patients' childhood, with a median follow‐up of 9 years. Their symptoms were most prevalent during infancy and decreased when they were toddlers. Feeding problems and gastrointestinal symptoms were reported in 91% of the 46 patients, with vomiting in 57% and constipation in 46%. There were 19 children who relied on enteral feeding for their nutrition and 13 of those received PEG. Their body mass index (BMI) increased significantly 2 years after PEG started (p = 0.005).Feeding problems and gastrointestinal symptoms were very common in children with SRS, but partly disappeared during childhood. Providing treatment, such as PEG, normalised the BMIs of children with SRS and reduced their symptoms. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system. [ABSTRACT FROM AUTHOR]

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is a rare disorder. The signs and symptoms of ectopic acromegaly are indistinguishable from acromegaly due to a somatotroph adenoma. A 35-yearold female presented with secondary amenorrhea for 10 years, intermittent headache, and reduced vision in both eyes for 4 years, which worsened over 4 months before presentation. Additionally, she was diagnosed with uncontrolled diabetes mellitus. On examination, she had coarse facial features, a fleshy nose, and acral enlargement. She had diminished visual acuity (left>right) and bitemporal hemianopia on perimetry. Biochemical investigations revealed elevated IGF-1 [588 ng/ml, reference range (RR) 100--242], markedly elevated basal growth hormone (>80 ng/ml; RR, 0.12--9.88), and hyperprolactinemia in the tumoral range (832 ng/ml; RR, 5--25). MRI sella demonstrated a 22x30x34mm sellar-suprasellar mass with T2 hypointensity. Chest imaging revealed a 75x87x106mm left lung mass, which was found to be a welldifferentiated neuroendocrine tumor (NET) on biopsy. Plasma GHRH levels were elevated [38,088 ng/l; RR, <250--300], and a diagnosis of ectopic acromegaly secondary to lung neuroendocrine tumor was considered. During workup, the patient developed in-hospital pituitary apoplexy, which improved with medical management. After a left pneumonectomy, her clinical features of acromegaly improved, her diabetes underwent remission, and there was a marked reduction in plasma GHRH and pituitary size. Histopathology was suggestive of a neuroendocrine tumor, with immunohistochemistry positive for GHRH and negative for prolactin. Her final diagnosis was ectopic acromegaly due to GHRH secreting a lung NET with pituitary somatotroph and lactotroph pituitary hyperplasia and apoplexy in the hyperplastic pituitary. [ABSTRACT FROM AUTHOR]

Introduction: Congenital hypopituitarism (CH) is characterized by the deficiency of pituitary hormones. Among CH patients, 85% lack a molecular diagnosis. Whole Exome Sequencing (WES) identified a homozygous variant (c.865G>A, p.Val289Ile) in the CDH2 gene, responsible for N-Cadherin production, crucial for cell-cell adhesion. Predicted to be likely pathogenic, the variant was found in a patient deficient in GH, TSH, ACTH, and LH/FSH. Its impact on cell adhesion was confirmed in L1 fibroblast cell lines. Objective: Create a cdh2 knockdown in zebrafish for investigating its role in pituitary development through growth hormone and transcription factors expression. Methods: Utilized pET28B-RfxCas13d-His plasmid for Cas13 mRNA production via in vitro transcription, guiding Cas13 to cdh2 with three RNAs. Injected the complex into single-cell embryos for analysis up to 96 hpf. Assessed gene expression of cdh2, prop1, pit1, and gh1 using RT-qPCR. Evaluated cdh2 protein expression through the western blot technique. Results: Knockdown animals displayed developmental delay. The cdh2 expression decreased by 75% within 24 hours, rebounded by 48 hours, and reached wild-type levels by 96 hpf. gh1 expression decreased at 48h but increased by 96 hpf, aligning with WT. No significant differences in prop1 and pit1 expression were observed. Conclusion: Our findings underscore cdh2's role in pituitary development and hormonal regulation, offering insights for developmental biology research. [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]

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength. Transitioning from pediatric to adult care presents challenges, including accurately identifying candidates for continued GH therapy, reevaluating persistent GHD, and preventing treatment discontinuation. Assessing readiness for transition and self-management skills is crucial. This Policy and Practice Review provides a comprehensive overview of current policies, regulations, and guidelines pertinent to managing GHD transition in Belgium. We integrate perspectives from national academic and nonacademic clinical stakeholders in pediatric and adult endocrine care to provide an updated policy framework. This framework underscores the importance of sustained GH therapy during transition, particularly for individuals with persistent GHD, with the goal of optimizing practices and improving outcomes during this critical period. [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]

Objective: To investigate the efficacy of the dopamine agonist cabergoline in uncontrolled acromegaly despite long-acting somatostatin analog (SSA). Methods: Thirty-five patients with acromegaly who were followed up in the department of endocrinology and metabolism of our university were analyzed. Thirty-five patients with acromegaly who did not respond adequately to postoperative SSA and in whom cabergoline was added to the treatment were analyzed. Patients were retrospectively evaluated in terms of age, gender, insulin-like growth factor-1 (IGF-1) values before and after cabergoline, disease duration, treatment dose, adenoma size, growth hormone level, and prolactin staining on pathologic examination. Results: Seventeen (48.6%) patients were female. The median age was 46.0 (41-53) years, and the median disease age was 10 (3-43) years. Twenty-eight (80.0%) were macroadenomas, 7 (20.0%) were microadenomas, and prolactin staining was observed in 10 (27.8%) cases. The IGF-1 level was 443 (346-628) ng/mL before cabergoline treatment and 27.4% decrease in IGF-1 was observed after treatment (p<0.001). There was no correlation between IGF-1 decrease and cabergoline dose. The change in IGF-1 was not correlated with tumor size and age but was correlated with pre-cabergoline IGF-1 level (r=0.364, p=0.03). 8 (22.9%) patients went into remission with cabergoline treatment. There was no difference in age, gender, tumor size, or pre-treatment IGF-1 levels between those who went into remission with cabergoline treatment and those who did not. When these 8 patients were analyzed, it was observed that cabergoline treatment was continued throughout the follow-up period; remission was maintained in one patient by discontinuing SSA treatment, in three patients by decreasing the SSA dose, in two patients without treatment change, and in two patients by changing the SSA preparation. Conclusion: Cabergoline is used in the treatment of acromegaly due to its antiproliferative and proapoptotic effects on pituitary adenoma cells. The efficacy of cabergoline added to SSA treatment is controversial in the literature. In our study, remission was achieved in 22.9% and IGF-1 reduction was observed in 27.4% with cabergoline treatment in patients with inadequate response to SSA treatment. Cabergoline added to SSA is an effective treatment in terms of IGF-1 control. This effect may continue in the long-term. [ABSTRACT FROM AUTHOR]

Objective: This study is aimed at identifying the most common drugs associated with the risk of intracranial pressure increase (IPI) based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: OpenVigil 2.1 was used to query the FAERS database and data from the first quarter of 2004 to the third quarter of 2022 were retrieved. Pharmacovigilance tools were employed for the quantitative detection of signals, where a signal represents a drug‐induced adverse event, including the reporting odds ratio (ROR > 1 with 95% confidence interval, the reports number ≥ 2) and proportional reporting ratio (PRR > 2, χ2 ≥ 4). Results: Among the 12,060,031 adverse event reports, there were 3113 cases in which drugs were the primary suspect cause of IPI. Drug‐induced intracranial pressure increase (DIPI) was more often observed in young females. The Top 5 drugs with the highest ROR and PRR were minocycline, doxycycline, acetazolamide, somatropin recombinant, and cytarabine. Conclusion: Potential risks of DIPI should be closely monitored in clinical practice. Our study is consistent with clinical observations, which call for further research to establish the basis of these drugs and IPI. [ABSTRACT FROM AUTHOR]

The risk of predation is an important driver that tailors life histories in various ways. Using an evolutionary model based on hormonal control, we study how different predation regimes affect adaptive risk‐taking and growth in fish populations. Growth, metabolism and foraging in the modelled fish are regulated by three simplified hormone functions: growth hormone, orexin, and thyroid hormone. A dynamic state‐dependent optimization model finds optimal hormone profiles for adaptive growth strategies in juvenile fish. We consider a gradient from species where behaviour and metabolic activity have large consequences for risk (typically benthic and camouflaged species), to the opposite endpoint where behaviour may modify predation risk to a smaller degree (as in the pelagic). Along this gradient, the model predicts changes in the pace of life from slow to fast, enacted by up‐regulation of the three hormone functions which in turn increase foraging and metabolism and change the priorities of energy reserves versus growth. Under all types of predation risk investigated, growth is faster when food availability is higher. Energy reserves are maintained primarily during periods of poor food availability and are used to accelerate growth during periods when food availability is high. The thyroid hormone function is up‐regulated predominantly when food availability is high and has an important role in trade‐offs balancing energetic gain and survival. At the individual time scale, the hormone system improves organismic flexibility and robustness. Over the phylogenetic time scale, hormone system adaptations have also restricted the phenotypic plasticity of individuals. [ABSTRACT FROM AUTHOR]

Objectives: Double pituitary adenoma is a rare entity that can pose a significant challenge. The incidence of double or multiple pituitary adenomas is ∼1% in autopsy cases and 0.4–1.3% in surgical series. Its definition varies, including 'double adenomas' in the literature in contrast to 'multiple adenomas', which is more specific and suitable. While some authors require separating topographically unique tumours, others have used a looser definition of separate immunohistochemistry. Case presentation: We presented the case of a 26-year-old patient with recurrent carpal tunnel syndrome symptoms, with double pituitary adenomas secreting growth hormone (GH) and thyroid-stimulating hormone (TSH). To date, 89 patients have been reported in the literature with symptomatic carpal tunnel syndrome, but only five had GH-TSH secretion. Conclusions: Double adenoma resection is of great importance for ensuring successful biochemical treatment. To ensure a successful operation, a careful preoperative 3T MRI examination is of great importance. [ABSTRACT FROM AUTHOR]

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2–0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed. Conclusion: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments. What is Known: • Recombinant human growth hormone (rhGH) has been used to increase adult height in children with idiopathic short stature (ISS), and its safety profile is comparable to other indications for growth hormone treatment. • The use of long-acting rhGH in children with ISS is still an area of uncertainty. What is New: • This 2-year real-world study provides new evidence that PEGylated rhGH (PEG-rhGH) is more effective than daily rhGH in promoting catch-up growth in children with ISS. • PEG-rhGH also demonstrated superior treatment adherence compared to daily rhGH in children with ISS. • The safety profiles of PEG-rhGH and daily rhGH were found to be similar. [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]

Background: Growth hormone-secreting pituitary neuroendocrine tumors can be pathologically classified into densely granulated (DGGH) and sparsely granulated types (SGGH). SGGH is more aggressive and associated with a poorer prognosis. While epigenetic regulation is vital in tumorigenesis and progression, the role of N6-methyladenosine (m6A) in aggressive behavior has yet to be elucidated. Methods: We performed m6A-sequencing on tumor samples from 8 DGGH and 8 SGGH patients, complemented by a suite of assays including ELISA, immuno-histochemistry, -blotting and -fluorescence, qPCR, MeRIP, RIP, and RNA stability experiments, aiming to delineate the influence of m6A on tumor behavior. We further assessed the therapeutic potential of targeted drugs using cell cultures, organoid models, and animal studies. Results: We discovered a significant reduction of m6A levels in SGGH compared to DGGH, with an elevated expression of fat mass and obesity-associated protein (FTO), an m6A demethylase, in SGGH subtype. Series of in vivo and in vitro experiments demonstrated that FTO inhibition in tumor cells robustly diminishes hypoxia resistance, attenuates growth hormone secretion, and augments responsiveness to octreotide. Mechanically, FTO-mediated m6A demethylation destabilizes desmoplakin (DSP) mRNA, mediated by the m6A reader FMR1, leading to prohibited desmosome integrity and enhanced tumor hypoxia tolerance. Targeting the FTO-DSP-SSTR2 axis curtailed growth hormone secretion, therefor sensitizing tumors to octreotide therapy. Conclusion: Our study reveals the critical role of FTO in the aggressive growth hormone-secreting pituitary neuroendocrine tumors subtype and suggests FTO may represent a new therapeutic target for refractory/persistent SGGH. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acromegaly-induced prolonged exposure to growth hormone and insulin-like growth factor 1 may have significant cardiovascular effects. The purpose of this study was to assess the relationship between hemodynamic parameters measured via impedance cardiography (ICG) and parameters of systolic left ventricular function measured via echocardiography in patients with acromegaly. Methods: The observational cohort study included 33 patients with newly diagnosed acromegaly, with a mean age of 47 years and without significant comorbidities. Correlation analysis (Spearman's rank correlation coefficient R) was performed on parameters obtained by ICG and left ventricular systolic function parameters obtained by echocardiography. ICG assessment included indices of (1) cardiac function as a pump: stroke volume index (SI), cardiac index (CI), Heather index (HI), velocity index (VI), and acceleration index (ACI); (2) afterload: systemic vascular resistance index (SVRI) and total arterial compliance index (TACI); and (3) thoracic fluid content (TFC). Echocardiographic examinations evaluated left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Results: A lower LVEF was associated with a lower SI (R = 0.38; p = 0.03) and a higher SVRI (R = −0.35; p = 0.046), whereas lower GLS was associated with lower SI (R = 0.43; p = 0.02), CI (R = 0.62; p < 0.001), VI (R = 0.59; p < 0.001), ACI (R = 0.38; p = 0.048), HI (R = 0.59; p < 0.001), and TACI (R = 0.50; p = 0.006) and a higher SVRI (R = −0.59; p < 0.001). No significant correlation was observed between either LVEF or GLS and TFC. Conclusions: In patients with acromegaly, poorer echocardiographic parameters of left ventricular systolic function are associated with impaired function of the heart as a pump and higher afterload as assessed via ICG. [ABSTRACT FROM AUTHOR]

Background: Acromegaly is a rare endocrine condition caused by excessive growth hormone (GH) production. Hypogonadotropic hypogonadism (HH) affects 30%–50% of acromegaly patients. Objectives: This study examined the frequency of HH in men with acromegaly and the effects of neurosurgical treatment during the follow-up period. Materials and Methods: A retrospective analysis of medical records from January 2015 to December 2022 was conducted. Data included clinical history, laboratory results, and pituitary MRI findings. Statistical analysis was performed using Statistica 13.3. Results: Patients were divided into two groups: a cross-sectional sample (preoperative n = 62; postoperative n = 60) and a longitudinal sample (n = 53). In the longitudinal sample, preoperative HH was diagnosed in 41 males (77.36%). Post-surgery, HH prevalence decreased to 58.49% (n = 31), with a significant increase in postoperative testosterone levels (9.1 vs. 12.1 nmol/L; p < 0.001), particularly in patients with preoperative HH (7.2 vs. 10.2 nmol/L; p < 0.001). Among 41 patients with HH, 12 (29.27%) showed recovery. Testosterone levels were lower in patients with macroadenomas (7.2 nmol/L vs. 11.05 nmol/L; p < 0.001). Patients with HH had higher baseline levels of GH and insulin-like growth factor 1 (IGF-1) (GH: 3.37 ng/mL; IGF-1: 551 ng/mL vs. GH: 1.36 ng/mL; IGF-1: 355 ng/mL). Luteinizing hormone (LH) levels above 3.3 mIU/mL and follicle-stimulating hormone (FSH) levels above 4.4 mIU/mL predicted hypogonadism remission (Area under the curve (AUC): 0.838 and 0.792, respectively). Conclusions: Younger patients with macroadenoma and hyperprolactinemia are more likely to have preoperative hypogonadism. Neurosurgical treatment can normalize LH, FSH, and total testosterone in approximately 30% of these patients. [ABSTRACT FROM AUTHOR]

Introduction: We assessed metabolic and hormonal responses to high-load resistance exercise under varying normobaric hypoxia conditions with a saturation clamp. Methods: Employing a counterbalanced, crossover test design, ten well-trained men participated in three exercise trials with normoxic or hypoxic gas mixtures to maintain arterial oxygen saturation at --90% and 80% [moderate (MH) and severe (SH) hypoxia, respectively]. The resistance exercise regimen comprised five sets of 10 repetitions of barbell back squats at 70% of one repetition maximum, with 1- min rest between sets. Metabolic and hormonal responses were measured before normoxia or hypoxia exposures (Pre 1), 15 min after the exposures (Pre 2), and at 0-, 15-, and 30-min post-exercises (T0, T15, and T30, respectively). Results: Compared to Pre 2, blood lactate concentrations and growth hormone values were elevated at T0, T15, and T30 (p ≤ 0.001), while testosterone values increased at T0 in all conditions (p ≤ 0.009). Epinephrine values increased significantly from Pre 2 to T0 in SH only (p < 0.001). SH had significantly higher blood lactate concentrations (p = 0.023), growth hormone (p = 0.050), and epinephrine (p = 0.020) values at T30 compared to NM. Cortisol values were elevated above Pre 2 at T15 in MH and SH, while lower testosterone values were noted at T0 and T15 for SH compared to NM and MH (all p ≤ 0.05). Discussion: Severe simulated hypoxia, achieved through a saturation clamp during barbell back squats, may enhance metabolic and hormonal responses, particularly 30 min post-session. Nevertheless, the acute effects of hypoxia exposure seem to be overridden by the impact of high-load resistance exercise. [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]

Salinity is a crucial environmental factor that influences the growth, reproduction, and physiological responses of fish species. Understanding how different salinities affect Liza ramada is essential for selecting optimal conditions for aquaculture. This study aimed to assess the effects of salinity on the growth, osmoregulation, stress response, and maturation of L. ramada in captivity. In this investigation, blood levels of hormones related to growth, adaptation, and stress response were measured, along with glucose levels in L. ramada broodstock raised in the waters of varying salinities. Results indicated that prolactin and growth hormone levels were higher in freshwater and lower in saline conditions. Additionally, these hormone levels increased during gonad maturation across all salinities. In contrast, thyroxine concentrations exhibited a pattern similar to cortisol, with significantly higher levels in saline water compared to freshwater. Mature fish also displayed elevated hormone levels. Glucose concentrations in the fish raised in different salinities followed a similar trend to cortisol levels. Furthermore, triiodothyronine hormone levels varied slightly during maturation and across different salinities. The L. ramada stock in freshwater demonstrated superior growth rates in both length and weight, alongside higher condition factor and survival rates. However, broodstock grown in freshwater had a lower food conversion ratio. In saline environments, L. ramada exhibited increased sexual activity, with a higher frequency of mature gonad stages and elevated values of the gonadosomatic index (GSI) and hepatosomatic index (HSI). In light of these findings, we conclude that freshwater is conducive to the growth of L. ramada, while saline water is essential for achieving sexual maturity. [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]

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]

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

Objectives: In this study, the effects of sex and birth type on growth performance, withers height (WH), radiographic measurements and selected hormone profiles in Gurcu goat kids were investigated. Methods: Twenty kids (single female = 5, single male = 5, twin female = 5, twin male = 5) were included in the study. Body weight (BW), WH, radiographic measurements (humerus length [HL], radius length [RL], proximal humerus epiphyseal plate width [HEP] and distal ulna epiphyseal plate width [UEP]) and biochemical analysis (for serum calcitonin, free triiodothyronine [FT3], free thyroxine [FT4], growth hormone [GH] and insulin‐like growth factor‐I [IGF‐I]) were performed at 1, 3, 5, 7, 9 and 12 months of age. Results: BW was significantly higher in males starting from the seventh month compared to females (p < 0.05). HL was higher in males at seventh (p = 0.009) and ninth (p = 0.033) months, whereas RL was lower in twins at the third month (p = 0.021). UEP was wider in males at seventh (p = 0.008) and ninth (p = 0.036) months. Closure of HEP was observed in 65% of kids by the 12th month. Calcitonin was lower in twins at third (p = 0.045) and fifth (p = 0.006) months, with changes observed due to group and time effects (p < 0.05), whereas other hormones only changed with time (p < 0.05). Positive correlations were observed between BW, WH, HL, RL and IGF‐I. There was a negative correlation between BW, WH, HL, RL, IGF‐I and HEP, UEP, calcitonin, FT3, FT4, GH. Conclusion: Sex and birth type in Gurcu goat kids may have an impact on growth performance, radiographic measurements and certain hormonal profiles. [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]

Pituitary adenomas are a type of of the most frequent intracranial tumors. These tumors can extend outside the sella, but very rarely originate ectopically to the sellar region. A 71-year-old patient presented to our institution, with prior clinical history of noncontrolled arterial hypertension and new-onset high-intensity pulsatile headache. Upon suspicion of a hypertensive emergency with probable brain compromise, a nonenhanced computed tomography of the head was performed. A mass within the sphenoid sinus was found. Endocrinological workup demonstrated a significant elevation of the growth hormone. As an incidental finding, a brain aneurysm was evidenced, which was treated endovascularly prior to the mass treatment. Subsequently, the patient successfully underwent a gross total resection through an endonasal transsphenoidal approach. Histopathological results were consistent with a pituitary ectopic adenoma. A postoperative improvement in levels of somatomedin C was documented postoperatively. [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]

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications. Patients with acromegaly are commonly affected by diabetes mellitus, which occurs as a complication of growth hormone hypersecretion. This Review discusses the pathophysiology of diabetes mellitus in acromegaly and explores management options in these patients. Key points: Diabetes mellitus is a common complication of acromegaly, occurring in approximately 30% of patients. Diabetes mellitus has an important effect on outcomes in acromegaly; patients with acromegaly and associated diabetes mellitus have 60% higher overall mortality and a twofold higher cardiovascular mortality than those without diabetes mellitus. Measures aimed at preventing diabetes mellitus and optimizing its treatment are of crucial importance for reducing cardiovascular risks and possibly improving long-term outcomes in patients with acromegaly. In managing patients with acromegaly and associated diabetes mellitus, a multimodal personalized approach is needed to achieve biochemical, tumour, symptom and metabolic control, ultimately preventing comorbidities. Data on management of acromegaly-related diabetes mellitus are limited; treatment options with a favourable effect on acromegaly-related complications are preferred. [ABSTRACT FROM AUTHOR]

An incision wound is a wound caused by being sliced. Two ingredients that play a key role in the wound-healing process are glucomannan and acemannan, which are rich in polysaccharides and growth hormones. Growth hormones stimulate fibroblast activity and proliferation. The present study involved 35 Sprague Dawley male rats, aged 2-3 months old and weighing 200-300 grams. The study comprised seven groups including, negative control group (G1), positive control (aquades, G2), betadine 10% (G3), gel base (0.5 mg, G4), gel base + sodium metabisulfite 0.2 gr (G5), gel base + Aloe vera 5% (G6), and gel base + Aloe vera 5% + sodium metabisulfite 0.2 gr (G7). Each group had five replications. Initially, a 4-cm incision was made on the dorsal skin of each rat. The study lasted 15 days with observations made on days 3, 7, and 15. After the observation period, the rats were anesthetized and then terminated to collect skin tissues for microscopic examination. The tissue samples were then stained immunohistochemically to assess fibroblast growth factor (FGF) expressions. The results showed that the highest FGF expression was observed in the 5% Aloe vera + 2% metabisulfite group (G7), while the lowest FGF expression was in the negative control group (G1). It is concluded that Aloe vera L. extract gel at 5% + 2% metabisulfite (G7) significantly enhances the expression of FGF. [ABSTRACT FROM AUTHOR]

Herbaceous peony (Paeonia lactiflora Pall) is resistant to drought but not waterlogging. The main production areas of peony are prone to waterlogging, seriously affecting the growth and development of herbaceous peony. Polyamines have been observed to significantly enhance the ability of plants to defend and repair adverse damage and affect the synthesis and accumulation of the endogenous growth hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). In this study, two herbaceous peony varieties ('Lihong', 'Qihualushuang') with different waterlogging tolerances were selected for artificial simulated waterlogging treatment to observe their morphological indexes and to determine their endogenous polyamine and hormone contents. Simultaneously, transcriptome sequencing and bioinformatics analysis were performed, focusing on screening differentially expressed genes in the polyamine metabolism pathway. The results showed that flood-tolerant varieties of herbaceous peony respond to waterlogging stress by continuously synthesizing spermidine (Spd) and spermine (Spm) through putrescine (Put) to counteract adversity. In the waterlogging-intolerant varieties, the expression of polyamine oxidase-related genes was annotated; their response to waterlogging stress was the simultaneous degradation of Spm and Spd to Put in the process of synthesis, and a decrease in the accumulation of Spm and Spd led to the early appearance of the symptoms of damage. In addition, polyamines influence key hormones that respond to plant adversity (IAA; ABA). The objective of this work was to initially analyze the mechanism of the polyamine signaling pathway in response to flooding in herbaceous peonies for further in-depth research on the mechanism of flooding tolerance in herbaceous peony, screen flood-tolerant varieties, and promote of their use. [ABSTRACT FROM AUTHOR]

Context Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown. Objective We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment. Methods Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children. Results Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio. Conclusion The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients. [ABSTRACT FROM AUTHOR]

Introduction Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. Source of data Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. Areas of agreement Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. Areas of controversy The management of secondary chronic SCI is challenging, with unpredictable outcomes. Growing points Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. Areas timely for developing research Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date. [ABSTRACT FROM AUTHOR]

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]

Introduction: Pregnancy results in significant changes in drug pharmacokinetics (PK). While previous studies have elucidated the impact of pregnancy-related hormones (PRH) on mRNA or protein expression and activity of major hepatic metabolizing enzymes, their effect on hepatic drug transporters remains largely unexplored. Therefore, we investigated the effect of a cocktail of PRH on the mRNA expression and activity of hepatic transporters. Methods: Plated human hepatocytes (PHH) from 3 premenopausal donors were incubated, in triplicate, for 72 h, with vehicle (DMSO < 0.01%), rifampin (10 μM; positive control) or a cocktail of PRH consisting of estrone, estradiol, estriol, estetrol, progesterone, cortisol, testosterone, oxytocin, and placental growth hormone. The PRH concentrations replicated 0.1×, 1×, or 10× of the plasma concentrations of these hormones observed during each of the three trimesters of pregnancy. After treatment, mRNA expression (quantified by qPCR) of hepatic influx and efflux transporters as well as the activity of influx transporters was quantified (uptake of a selective substrate ± corresponding transporter inhibitor). The data were expressed relative to that in the control (vehicle) group. Significance was evaluated by ANOVA (followed by Dunn'smultiple comparisons) or unpaired t-test when the withinlot data were analyzed, or repeated measures ANOVA (followed by Dunn's multiple comparisons) or paired t-test when data from all 3 lots were analyzed (p < 0.05). Results and Discussion: In general, a) PRH cocktails significantly induced transporter mRNA expression in the following order OAT2 ≈ NTCP ≈ OCT1 > OATP2B1 and repressed mRNA expression in the following order OATP1B3 > OATP1B1; b) these changes translated into significant induction of OAT2 (T1-T3) and NTCP (T2-T3, in only two lots) activity at the 1× PRH concentration. Compared with the influx transporters, the induction of mRNA expression of efflux transporters was modest, with mRNA expression of MRP2 and BSEP being induced the most. Conclusion: Once these data are verified through in vivo probe drug PK studies in pregnancy, they can be populated into physiologically based pharmacokinetic (PBPK) models to predict, for all trimesters of pregnancy, transporter-mediated clearance of any drug that is a substrate of the affected transporters. [ABSTRACT FROM AUTHOR]

Context Several endocrine abnormalities were reported in children with Prader–Willi syndrome (PWS), including hypothyroidism. Growth hormone (GH) treatment may impact the thyroid hormone axis by direct inhibition of T4 or TSH secretion or by increased peripheral conversion of free T4 (FT4) to T3. Objective The objective of this study is to evaluate thyroid function during GH treatment in a large group of children with PWS. Methods Serum FT4, T3, and TSH are measured in a 2-year randomized controlled GH trial (RCT) and 10-year longitudinal GH study (GH treatment with 1.0 mg/m²/day [∼0.035 mg/kg/day]). Results Forty-nine children with PWS were included in the 2-year RCT (median [interquartile range, IQR] age: GH group 7.44 [5.47-11.80] years, control group 6.04 [4.56-7.39] years). During the first 6 months, median (IQR) FT4 standard deviation score (SDS) decreased in the GH group from −0.84 (−1.07 to −0.62) to −1.32 (−1.57 to −1.08) (P <.001) and T3 SDS increased from 0.31 (−0.01-0.63) to 0.56 (0.32-0.79) (P =.08), while in the control group, FT4 and T3 SDS remained unchanged. In our 10-year GH study, 240 children with PWS (median [IQR] age: 1.27 (0.54-4.17) years] were included. Between 2 and 10 years, median (IQR) FT4 SDS remained unchanged, being −0.87 (−0.98 to −0.77) after 2 years and −0.88 (−1.03 to −0.74) after 10 years (P =.13). TSH SDS decreased from −0.35 (−0.50 to −0.21) after 2 years to −0.68 (−0.84 to −0.53) after 10 years (P <.001). Conclusions Our findings suggest that GH treatment decreases FT4 levels, due to increased peripheral conversion of FT4 to T3 in the first months of treatment, but thereafter, FT4 and T3 normalize and remain stable during long-term GH treatment in almost all children and adolescents with PWS. [ABSTRACT FROM AUTHOR]

Dysregulation of growth hormone (GH) signaling consistently leads to increased lifespan in laboratory rodents, yet the precise mechanisms driving this extension remain unclear. Understanding the molecular underpinnings of the beneficial effects associated with GH deficiency could unveil novel therapeutic targets for promoting healthy aging and longevity. In our pursuit of identifying metabolites implicated in aging, we conducted an unbiased lipidomic analysis of serum samples from growth hormone‐releasing hormone knockout (GHRH‐KO) female mice and their littermate controls. Employing a targeted lipidomic approach, we specifically investigated ceramide levels in GHRH‐KO mice, a well‐established model of enhanced longevity. While younger GHRH‐KO mice did not exhibit notable differences in serum lipids, older counterparts demonstrated significant reductions in over one‐third of the evaluated lipids. In employing the same analysis in liver tissue, GHRH‐KO mice showed pronounced downregulation of numerous ceramides and hexosylceramides, which have been shown to elicit many of the tissue defects that accompany aging (e.g., insulin resistance, oxidative stress, and cell death). Additionally, gene expression analysis in the liver tissue of adult GHRH‐KO mice identified substantial decreases in several ceramide synthesis genes, indicating that these alterations are, at least in part, attributed to GHRH‐KO‐induced transcriptional changes. These findings provide the first evidence of disrupted ceramide metabolism in a long‐lived mammal. This study sheds light on the intricate connections between GH deficiency, ceramide levels, and the molecular mechanisms influencing lifespan extension. [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]

Thyrotroph pituitary adenomas have been reported to be a rare cause of 'thyroid storms', causing myriad metabolic and autonomic disturbances. In this case, we describe the second reported case in literature of a 'GH storm' in an infarcted somatotroph adenoma. We describe a residual invasive somatotroph macroadenoma that underwent infarction, producing a dramatic elevation in serum GH levels. While infarction of adenomas may in some cases lead to remission, the patient went on to require re-surgery and re-radiation due to growth of the residual viable tumour. 'GH storms' are rare but interesting events that may occur in somatotroph adenomas. Infarction or apoplexy must be considered when managing residual adenomas. [ABSTRACT FROM AUTHOR]

The objective was to assess the potential differential effects of human versus mouse growth hormone in vivo, given that human unlike mouse growth hormone can bind prolactin as well as the growth hormone receptor. To this end, a transgenic CD-1 mouse expressing human but not mouse growth hormone was generated, and the phenotypes of male mice fed with a regular chow or high-fat diet were assessed. Pancreas and epididymal white adipose tissue gene expression and/or related function were targeted as the pancreas responds to both prolactin and growth hormone receptor signaling, and catabolic effects like lipolytic activity are more directly attributable to growth hormone and growth hormone receptor signaling. The resulting human growth hormone-expressing mice are smaller than wildtype CD-1 mice, despite higher body fat and larger adipocytes, but both mouse types grow at the same rate with similar bone densities. Unlike wild-type mice, there was no significant delay in glucose clearance in human growth hormone-expressing mice when assessed at 8 versus 24 weeks on a high-fat diet. However, both mouse types showed signs of hepatic steatosis that correlated with elevated prolactin but not growth hormone RNA levels. The larger adipocytes in human growth hormone-expressing mice were associated with modified leptin (higher) and adiponectin (lower) RNA levels. Thus, while limited to observations in the male, the human growth hormone-expressing mice exhibit signs of growth hormone insufficiency and adipocyte dysfunction as well as an initial resistance to the negative effects of high-fat diet on glucose clearance. [ABSTRACT FROM AUTHOR]

Purpose: Sweat glands and cutaneous vessels possess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors. Here, we assessed if exercise increases GH and IGF-1 in skin interstitial fluid, and whether baseline and exercise-induced increases in GH and IGF-1 concentrations in skin interstitial fluid/blood are associated with heat loss responses of sweating and cutaneous vasodilation. Methods: Sixteen young adults (7 women) performed a 50-min moderate-intensity exercise bout (50% VO2peak) during which skin dialysate and blood samples were collected. In a sub-study (n = 7, 4 women), we administered varying concentrations of GH (0.025–4000 ng/mL) and IGF-1 (0.000256–100 µg/mL) into skin interstitial fluid via intradermal microdialysis. Sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC) were measured continuously for both studies. Results: Exercise increased sweating and CVC (both P < 0.001), paralleled by increases of serum GH and skin dialysate GH and IGF-1 (all P ≤ 0.041) without changes in serum IGF-1. Sweating was positively correlated with baseline dialysate and serum GH levels, as well as exercise-induced increases in serum GH and IGF-1 (all P ≤ 0.044). Increases in CVC were not correlated with any GH and IGF-1 variables. Exogenous administration of GH and IGF-1 did not modulate resting sweat rate and CVC. Conclusion: (1) Exercise increases GH and IGF-1 levels in the skin interstitial fluid, (2) exercise-induced sweating is associated with baseline GH in skin interstitial fluid and blood, as well as exercise-induced increases in blood GH and IGF-1, and (3) cutaneous vasodilation during exercise is not associated with GH and IGF-1 in skin interstitial fluid and blood. [ABSTRACT FROM AUTHOR]

Background: Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end‐stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch‐up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health‐related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3–5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events. Conclusions: rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer‐term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations. [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]

Simple Summary: In commercial hatcheries, chicken embryos are incubated in complete darkness. However, in a natural environment, chicken embryos receive light stimulation during the incubation process as hens need to leave the nest to feed or turn the eggs. Therefore, providing light during incubation is closer to the natural growth environment of chicken embryos, which may have a positive effect on their growth and development. This study investigated the effects of providing different wavelengths of light during incubation on the behaviour, growth, immunity, and stress responses of post-hatch chicks. The results indicated that providing white light during incubation may enhance the growth performance of post-hatch chicks and potentially improve their ability to cope with environmental changes. This study aims to determine the effects of light exposure during incubation on the growth and development of post-hatch chicks and to provide a basis for the development of effective lighting strategies during the incubation period. Manipulation of light during incubation may have an effect on post-hatch chicks through the role of prenatal stage. The effects of providing different wavelengths of light (white, blue, and green lights, dark as control) during incubation on the growth performance, organ development, immune response, stress related hormones, digestive enzymes and behaviour of post-hatch chicks were investigated for 1–42 days. A total of 60 chicks per light treatment in three batches were used in this study. The results showed that the percentage of chicks accessing to feed and water resources appeared not to be affected by incubation light. Chicks hatched under white light were found to have a growth advantage (p < 0.05). The weight of organs (except thymus), IgA, IgY, IgM and heterophil to lymphocyte (H/L) ratio for post-hatch chicks were not affected by incubation light (p > 0.05). Thymus weight was reduced in chicks incubated under blue light compared to dark incubation (p < 0.05). The jejunum amylase and ileum lipase activities were significantly affected by the light treatments (p < 0.01). All light incubation chicks had stable plasma corticosterone levels and may have better ability to cope with environmental changes. Hence, white light photoperiod incubation may have potential to improve post-hatch chicks' growth performance and environmental adaptability. [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. [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]

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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.

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica 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.)