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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.

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Aim Methods Results Conclusion To evaluate the indications, population characteristics and latency between short stature diagnosis to treatment with recombinant growth hormone (GH) therapy in a large cohort of children in Israel.We performed a retrospective medical chart review of all children treated with GH for conditions associated with short stature in three central districts in Israel from 1 January 2010 to 31 December 2021. Data extracted from the medical files included demographics, time to diagnosis, treatment indications and GH therapy duration.The study group comprised 5148 children aged 1 day to 17 years. A total of 64.1% were diagnosed with idiopathic short stature (ISS), 31.1% with GH deficiency (GHD) and 2.5% with small‐for‐gestational age (SGA). Males were treated more than females (58.9% vs. 41.1%). The mean age at first documentation of short stature was 6.9 ± 3.5 years. GH therapy was initiated at a mean age of 9.8 ± 3.3 years. A total of 51.2% were of high socio‐economic status (SES); 78.2% were non‐ultraorthodox Jews, 13%, ultraorthodox Jews, and 8.8% were Arabs.Meticulous growth follow‐up from early childhood for all children, specifically females, those of low SES, and minorities is important to provide appropriate referral, treatment and final adult height outcomes. [ABSTRACT FROM AUTHOR]

Microorganisms and plants can produce indole-3-acetic acid (IAA) by mechanisms that either involve tryptophan or do not involve tryptophan. The control of Zone of inhibition (ZOI) ranged from 1.2 cm to 1.0 cm. A promising antagonistic isolate, Streptomyces sp. VSMKU1027, exhibited robust antagonistic activity against two significant soil-borne phytopathogenic fungi, namely Rhizoctonia solani and Fusarium oxysporum, outperforming the control. The morphology of both R. solani and F. oxysporum, including their sclerotium and spores, became condensed and indistinct, and mycelial disintegration was observed due to the action of VSMKU1027, in contrast to the control. The isolate significantly produced antimicrobial traits and hydrolytic enzymes except hydrogen cyanide and cellulase. Furthermore, the promising isolate VSMKU1027 was identified as Streptomyces sp. based on its morphological, physiological, and biochemical characteristics. In comparison to the control, the isolate VSMKU1027 demonstrated increased synthesis of IAA and the hydrolytic enzyme protease with the corresponding substrates. The production of IAA was optimized on the sixth day, at 35°C and pH 6.5. The highest generation of IAA was recorded, with an ISP2 and 0.4% concentration of L-tryptophan. [ABSTRACT FROM AUTHOR]

Globally, African marigold (MG) derived essential oils (EOs) have attained an immense economic pertinence in the flavor, fragrance, food, medicinal, and floricultural industries, which necessitate boosting its production on a commercial scale. Therefore, we aimed to assess varying levels (0, 50, 100, 150, and 200 mg L-1) of exogenously applied melatonin (MT) as a growth hormone to trigger growth, flower yield, and EOs of MG. The MT was applied as a foliar spray after thirty days of transplantation of MG plants and repeated thrice at fifteen-day intervals. The results depicted that exogenous MT (150 mg L-1) recorded the maximum plant height and leaves number along with fresh and dry weights of leaves and roots. The same treatment exhibited 66%, 64%, and 18% higher flower fresh and dry weights and flower yield respectively, than the control. Additionally, MT remained effective in reducing days taken to bud emergence and flowering, while flower retention duration increased by 11 days. Following the trend of vegetative growth traits, foliar-applied MT (150 mg L-1) remained unmatched in terms of physiological attributes (transpiration rate, stomatal conductance, chlorophyll a, and b contents) of MG. Moreover, for EOs extracted from fresh and dry flowers and leaves, this treatment remained effective by producing 77%, 73%, 53%, and 85% higher content, respectively than the control. Finally, the chemical profiling analyses detected eighty-seven chemical constituents (Caryophyllene oxide was the most dominant compound, and cis-Z-alpha-Bisabolene epoxide followed it) in MG flowers. In terms of the retention time of different chemical compounds in MG flowers, Calarene epoxide had the highest retention time of 19.75 minutes among major compounds. Based on these results, 150 mg L-1 dose of MT may be recommended to growers for boosting MG growth, floral yield and EOs content sustainably. [ABSTRACT FROM AUTHOR]

High neonatal growth hormone (GH) secretion has been described in several species. However, the neuroendocrine mechanisms behind this surge remain unknown. Thus, the pattern of postnatal GH secretion was investigated in mice and rats. Blood GH levels were very high on postnatal day (P)1 and progressively decreased until near zero by P17 in C57BL/6 mice without sex differences. This pattern was similar to that observed in rats, except that female rats showed higher GH levels on P1 than males. In comparison, follicle-stimulating hormone exhibited higher secretion in females during the first 3 weeks of life. Hypothalamic Sst mRNA and somatostatin neuroendocrine terminals in the median eminence were higher in P20/P21 mice than in newborns. Knockout mice for GH-releasing hormone (GHRH) receptor showed no GH surge, whereas knockdown mice for the Sst gene displayed increased neonatal GH peak. Leptin deficiency caused only minor effects on early-life GH secretion. GH receptor ablation in neurons or the entire body did not affect neonatal GH secretion, but the subsequent reduction in blood GH levels was attenuated or prevented by these genetic manipulations, respectively. This phenotype was also observed in knockout mice for the insulin-like growth factor-1 (IGF-1) receptor in GHRH neurons. Moreover, glucose-induced hyperglycemia overstimulated GH secretion in neonatal mice. In conclusion, GH surge in the first days of life is not regulated by negative feedback loops. However, neonatal GH secretion requires GHRH receptor, and is modulated by somatostatin and blood glucose levels, suggesting that this surge is controlled by hypothalamic-pituitary communication. [ABSTRACT FROM AUTHOR]

Background Serum insulin-like growth factor 1 (IGF-1) is an important biochemical tool to diagnose and monitor growth hormone (GH)-related disorders. However, ethnicity-specific Indian data, following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage–specific normative data for IGF-1 in healthy Indian children and adolescents. Methods A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. Results We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, earlier peak, and higher IGF-1 values. The reference interval (2.5th to 97.5th percentile) was broader during peripubertal ages, indicating a higher physiological variability. Conclusion This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents. [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]

Thermal bleaching, or the loss of symbiotic algae that provide most energetic resources for the coral host, is an increasing threat to reefs worldwide and is projected to worsen with climate change. While bleaching is a well-recognized threat, the impact on the process of reproduction in bleaching survivors is not well resolved, despite being central to coral resilience. Montipora capitata can survive bleaching while completing a full gametogenic cycle, offering an ideal system to study gametogenic resilience and physiological tradeoffs. We experimentally bleached fragments of M. capitata colonies and followed their gametogenesis and physiological responses for 10 months (six time points). All bleached colonies produced gametes at the same time as controls, suggesting that reproductive processes were energetically prioritized. However, proteomic analysis revealed tradeoffs and delays in activating key physiological processes earlier in gametogenesis in areas such as skeletal growth and reproductive hormone synthesis. Tradeoffs during the gametogenic cycle, likely a direct response to thermal bleaching, resulted in smaller oocytes from bleached colonies, potentially indicating decreased transfer of parental resources to gametes. While gametogenesis is likely to continue in this species, it is unknown how the fecundity, synchrony of spawning, viability and success of future offspring may be impacted by future bleaching events. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) has a short half‐life and declines abruptly following somatotropinoma surgery, enabling its prompt measurement as an indicator of surgical success. This study assesses the predictive value of early postoperative GH levels for 3‐month and >1‐year remission of acromegaly. We conducted a retrospective search in our database of patients who had undergone transsphenoidal surgery of GH‐secreting pituitary adenoma from January 2011 to June 2022. Only the patients who underwent the first pituitary surgery and had GH measurements on the fifth postoperative day were included. The 3‐month and >1‐year remission of acromegaly was defined as achieving the GH nadir of <0.4 μg/L during an oral glucose tolerance test and maintaining normal insulin‐like growth factor 1 levels at the initial follow‐up visit 3 months after surgery and throughout at least the first year postoperation. We included 63 patients in the analysis, with a median follow‐up of 51.8 (13–155) months. The 3‐month remission was achieved in 42 (66.7%) patients, and >1‐year remission without additional therapy in 38 (60.3%) patients. Those who achieved >1‐year remission had significantly lower fifth‐day postoperative GH levels (0.59 [0.09–8.92] vs. 2.63 [0.25–24.64] μg/L, p <.001). Receiver‐operating characteristic analysis revealed a significant value of fifth‐day postoperative GH levels regarding the prediction of 3‐month (area under the curve [AUC], 0.834; p <.0001) and >1‐year (AUC, 0.783; p <.0001) acromegaly remission. The GH threshold of ≤1.57 μg/L yielded a sensitivity of 90.5% and a specificity of 71.4% at 3 months and 89.5% sensitivity and 60% specificity at the >1‐year remission, respectively. Notably, all patients with fifth‐day postoperative GH levels ≤0.23 μg/L exhibited remission of acromegaly throughout the follow‐up period. Early postoperative GH measurement could be a reliable predictor of both 3‐month and >1‐year remission of acromegaly. [ABSTRACT FROM AUTHOR]

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

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

Approximately 30%--40% of growth hormone--secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial--mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNASexpressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

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

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

The TCP gene family encodes plant transcription factors crucial for regulating growth and development. While TCP genes have been identified in various species, they have not been studied in Phoebe bournei (Hemsl.). This study identified 29 TCP genes in the P. bournei genome, categorizing them into Class I (PCF) and Class II (CYC/TB1 and CIN). We conducted analyses on the PbTCP gene at both the protein level (physicochemical properties) and the gene sequence level (subcellular localization, chromosomal distribution, phylogenetic relationships, conserved motifs, and gene structure). Most P. bournei TCP genes are localized in the nucleus, except PbTCP9 in the mitochondria and PbTCP8 in both the chloroplast and nucleus. Chromosomal mapping showed 29 TCP genes unevenly distributed across 10 chromosomes, except chromosome 8 and 9. We also analyzed the promoter cis-regulatory elements, which are mainly involved in plant growth and development and hormone responses. Notably, most PbTCP transcription factors respond highly to light. Further analysis revealed three subfamily genes expressed in five P. bournei tissues: leaves, root bark, root xylem, stem xylem, and stem bark, with predominant PCF genes. Using qRT-PCR, we examined six representative genes—PbTCP16, PbTCP23, PbTCP7, PbTCP29, PbTCP14, and PbTCP15—under stress conditions such as high temperature, drought, light exposure, and dark. PbTCP14 and PbTCP15 showed significantly higher expression under heat, drought, light and dark stress. We hypothesize that TCP transcription factors play a key role in growth under varying light conditions, possibly mediated by auxin hormones. This work provides insights into the TCP gene family's functional characteristics and stress resistance regulation in P. bournei. [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]

There are five subtypes of somatostatin receptors (SST1‐5), which are expressed in several types of solid neoplasms, neuroendocrine tumors, and pituitary adenomas. Most commonly, SST2 and SST5, are of interest regarding diagnostic, treatment, and prognostic purposes. In this article the basic biological characteristics of SST are briefly reviewed, and focus given to the immunohistochemical evaluation of SST2 and SST5 in growth hormone (GH)‐secreting pituitary tumors, and their quantification as predictors of response to treatment with somatostatin receptor ligands (SRL), the mainstay of the pharmacological therapy available for these tumors. Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Case: Physeal stability in slipped capital femoral epiphysis (SCFE) depends on integrity of the hypertrophic zone. This in turn is affected by imbalance between circulating growth hormones and gonadal hormones. This case describes the occurrence of SCFE in a Māori (indigenous New Zealander) transgender girl, undergoing gender-affirming therapy with a gonadal-releasing hormone analog (GnRHa). Conclusion: Surgeons and clinicians alike should be aware that GnRHa in gender-affirming therapy may confer an additional risk factor, lowering the threshold required for SCFE to occur. Counseling patients about potentially increased risk, and need for timely presentation could be warranted, particularly in high-risk individuals. [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]

As an endocrine disruptor chemical, pesticide exposure may affect the regulation of growth hormones such as insulin-like growth factor-1 (IGF-1). A few current studies to date have noted that long-term pesticide exposure disrupted IGF-1, a potential risk of stunting in children. This study aims to evaluate studies to date of the effect of pesticide exposure on stunting incidence. This systematic review and meta-analysis adhered to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. The PubMed and EBSCO databases were searched for relevant articles without publication restrictions. This review aimed to include reviews, randomized controlled trials (RCT), and cohort, case-control, and cross-sectional studies, which provide actual exposure types of pesticides with stunting measurement by heightage z score. A screening, extraction, and synthesis were conducted, leading to a consensus for reaching mutual agreement. The analysis was performed using Microsoft Excel 2017 for the screening and extraction, Revman version 5.4 software for the meta-analysis, and OpenMEE software for the meta-regression. Of the 13 studies subjected to the qualitative analysis, 6 were eligible for inclusion in the meta-analysis: 2 reviews, 2 RCTs, 2 cohorts, 2 case-control, and 5 cross-sectional studies. Exposure to organophosphate and pyrethroid pesticides was not associated with stunting (P=0.78; odds ratio [OR], 1.11; 95% confidence interval [CI], 0.65-1.88). Heterogeneity existed for 79% of the meta-analysis (P=0.000; z=-5.37; 95% CI, -0.034 to -0.016), and the meta-regression identified age as the causative covariate. Pesticide exposure, regardless of type, is not associated with stunting in children. [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]

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]

Purpose: Adherence to growth hormone treatment is known to affect growth outcomes. Both device preference and ease of use have been shown to affect treatment adherence. In this study, we assessed device preference and ease of use with two long-acting growth hormones, somapacitan (Sogroya®, Novo Nordisk A/S) and somatrogon (Ngenla®, Pfizer). Patients and Methods: In a randomized, crossover study conducted between September 20 and November 2, 2023, we recruited 33 adolescents with a growth-related disorder, and 37 caregivers, at six locations in the United States. Each participant was trained in the use of both devices and asked to perform a simulated injection. Device training time, preparation and injection time, and injection completeness were recorded. Participants also completed the Device Handling and Preference Questionnaire (DHPAQ) to indicate their device preference and ease of use opinions. Following conclusion of the "standard" visit, 10 adolescents and 10 caregivers were randomly selected to participate in a sub-study to validate the relevance, comprehensiveness, and comprehension of the DHPAQ. Results: The majority of participants (84.3%; 95% confidence interval [CI]: 74;92) preferred the somapacitan device to the somatrogon device (p <  0.0001). Almost all (98.6%; 95% CI: 92;100) participants answered that the somapacitan device was easy or very easy to use, while three-quarters (74.3%; 95% CI: 62;84) answered the same for the somatrogon device. Average training and injection times were lower for the somapacitan device than for the somatrogon device. Also, more patients successfully completed the injection with the somapacitan device than with the somatrogon device (97.1% vs 92.9%). Cognitive debriefing interviews indicated the DHPAQ was relevant, comprehensive, and fully comprehended. Conclusion: The somapacitan device was preferred to the somatrogon device by a majority of participants. More participants considered the somapacitan device to be easy or very easy to use than the somatrogon device. Plain Language Summary: • Children who grow slower in height than their peers often need growth hormone replacement treatment to reach normal height. This treatment involves daily or weekly injections for several years. Injecting treatment regularly is important for it to work properly, but the schedule can be difficult to adhere to. • From previous research, we know injection devices can influence adherence to treatment. Researchers in this study aimed to compare two different pen injectors (once-weekly medicines called somapacitan and somatrogon) to see which one patients and caregivers prefer and find easier to use. • This USA-based study included 33 adolescents with growth problems who injected themselves, and 37 caregivers of younger patients. During one visit, they were trained in how to use each device, observed giving a practice injection, and asked to fill in a questionnaire with their experience. Half of the participants did this with the somapacitan pen injector first and the somatrogon one second, while the other half followed the opposite order. • The researchers found that 84.3% of participants preferred the somapacitan pen‑injector, while 12.9% preferred the somatrogon pen-injector, and this difference was statistically significant. Almost all (98.6%) participants found the somapacitan pen‑injector easy or very easy to use, while three-quarters (74.3%) answered the same for somatrogon. On average, the participants learned to use the somapacitan device faster and more correctly than the somatrogon device. • In conclusion, given the device preference and ease of use, patients may be more likely to adhere to treatment with somapacitan compared with those receiving somatrogon. [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]

Animal husbandry as a branch of agriculture plays a vital role in providing the world's growing population with food products of animal origin: meat, milk, eggs, wool. At the same time, the need for them only increases every year. In this regard, deeper and more extensive knowledge is required about the hormonal processes that regulate metabolism in cells, tissues and the body as a whole, which will allow for a more complete realization of the genetic potential of animals. To solve this problem, it is necessary to apply new effective biotechnological methods of regulating the productive functions of both the brood stock and fattened young stock. One of these methods is the assessment and correction of the hormonal status of farm animals to improve their productive and reproductive qualities. This is explained by the fact that the level of hormones affects many important indicators, such as growth and development, productivity, product quality, fertility and health, characterizing their physiological state and adaptive abilities. Thus, the hormones testosterone, somatotropin (growth hormone), adrenocorticotropic hormone (ACTH) affect productive qualities (weight growth, slaughter indicators), quality characteristics of meat and conversion of feed into products, which is important for fattened cattle. Lactotropic hormone, oxytocin and prolactin play a key role in the lactation process, increasing the volume and changing the quality characteristics of milk. It has been proven that the use of exogenous hormones in animals improves a number of quantitative and qualitative characteristics of livestock products. However, today there are gaps in understanding the role, application and consequences of hormone use in animal husbandry, which makes further research promising. In this review, we have conducted a comprehensive analysis of available domestic and foreign literature sources using the following databases: Pubmed, Elsevier, Google Academy, Russian Scientific Citation Index (elibrary) and others on the mechanism of action of hormones, their level, affecting meat and milk productivity.

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]

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]

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: 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]