Growth Hormone & Igf Research最新文献

Prader-Willi syndrome (PWS) is a rare genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioral challenges, cognitive dysfunction, and hormone deficiencies. Hypogonadism is common but knowledge on potential side effects of testosterone replacement is limited, in particular, the long-term effects on behavior and PSA.

Patients and methods

Retrospective case studies of seven men, median age 46 years, with genetically verified PWS, testosterone treated hypogonadism and available PSA values were included. Long-term follow-up of PSA was accessible in four patients. Medical records were reviewed for adverse effects.

Results

Five men were treated with intramuscular testosterone undecanoate, two had no hypogonadism. Median PSA was 0.68 μg/L (0.23–1.3), median testosterone 15 nmol/L. After a median time of 17 years of testosterone replacement median PSA was 0.75 μg/L (range 0.46–1.4). Testosterone replacement was well tolerated, and no major behavioral changes were reported. Five were treated with growth hormone for >20 years.

Conclusion

Levels of PSA were low. Long-term treatment with testosterone was working well and did not result in any clinically meaningful increase in PSA. Our results indicate that testosterone replacement is neither associated with serious adverse events regarding changes in behavior or effect on PSA. However, larger studies are needed to confirm our results.

Childhood growth hormone deficiency (GHD) is a rare disorder associated with significant burden on both patients and caregivers. Although previous reports have detailed aspects of the burden experienced by patients and their caregivers, there is a paucity of first-hand information on the patient and caregiver journeys from their respective voices. To address this need, an advisory board meeting was conducted on September 30, 2022, with 4 pediatric patients with GHD and their caregivers to discuss their experiences prior to GHD diagnosis, during the diagnostic process, and during ongoing treatment with recombinant growth hormone. Feedback from patients and caregivers was reviewed by pediatric endocrinologists, who provided their own perspectives on the patient and caregiver journeys based on the information reported. Despite the small sample size, important insights were obtained: patients and caregivers reported remarkable growth benefits achieved with treatment, which provided strong motivation to remain adherent to daily injection regimens. Patient and caregiver accounts reflected wide variability between families in time from suspicion to diagnosis and in treatment challenges faced, ranging from practical issues such as handling and administration of medication to broader concerns about treatment access and continuity, as well as key knowledge gaps among patients, caregivers, and clinicians. Recommendations are provided to enhance the patient and caregiver journeys, including increasing development and availability of educational materials, providing opportunities for patient advocacy by clinicians and health care providers, and encouraging institutional improvements to ensure that patients continue to receive uninterrupted treatment during their critical period of growth.

Objective

Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.

Design

A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library. Inclusion criteria: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.

Results

The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.

Conclusion

Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.

Objective

Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients.

Design

A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively.

Results

Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06–5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7.

Conclusion

IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

Purpose

Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group.

Methods

We included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency.

Results

Twenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency.

Conclusion

The rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.

Objective

Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.

Design

An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients.

Results/conclusions

Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.

Objective

GATA2 is a key transcription factor involved in the differentiation and determination of thyrotrophs and gonadotrophs in pituitary and hematopoietic development. However, studies on the upstream ligands of the GATA2 signal transduction pathway have been limited. To identify upstream ligands, we examined growth hormone (GH) as a plausible stimulator.

Design

We evaluated GH-induced GATA2 expression in murine TtT/GF thyrotrophic pituitary tumor cells and its direct impact on the GHR/JAK/STAT5 pathway using a combination of a reporter assay, real-time quantitative polymerase chain reaction, and western blotting.

Results

GATA2 expression increased with activated STAT5B in a dose-dependent manner and was inhibited by a STAT5 specific inhibitor. Moreover, we found functional STAT5B binding site consensus sequences at −359 bp in the GATA2 promoter region.

Conclusion

These findings suggest that GH directly stimulates GATA2 via the GHR/JAK/STAT pathway and participates in various developmental phenomena mediated by GATA2.

Objective

To evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth.

Design

Four DMD patients on Deflzacort 0.6–0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6–18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD).

Results

Growth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3–7.8 cm/year over a period of 6–18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment.

Conclusions

rhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.

The role of the insulin-like growth factor (IGF) system has attracted close attention. The activity of IGF binding proteins (IGFBPs) within the ovary has not been fully elucidated to date. These proteins bind to IGF with an equal, or greater, affinity than to the IGF1 receptor, thus being in the main position to regulate IGF signalling, in addition to extending the half-life of IGFs within the bloodstream and promoting IGF storage in specific tissue niches. IGF1 has an important part in cell proliferation, differentiation and apoptosis. Considering the importance of IGFs in oocyte maturation, this review sought to elucidate aspects including: IGF production mechanisms; constituent members of their family and their respective functions; the role that these factors play during folliculogenesis, together with their functions during oocyte maturation and apoptosis, and their performance during luteal development. This review also explores the role of IGFs in biotechnological applications, focusing specifically on animal genetic gain.

Objective

The precise and accurate quantification of human growth hormone (GH) in plasma/ serum is crucial for the diagnosis and treatment of diseases like GH deficiency or acromegaly. However, the ligand-binding assays (LBAs) currently used for routine testing show considerable methodological variability. Here, we present a complementary, combined top-down and bottom-up LC-MS-based method to quantify (intact) GH in plasma and serum, which concurrently provides a basis for a MS-based analysis of GH in doping controls.

Design

Extraction of GH from plasma/ serum was accomplished by protein precipitation, followed by an immunocapture step using protein A-coupled magnetic beads and a polyclonal anti-GH antibody. The intact protein was subsequently analyzed top-down on a 2D-LC-HRMS/MS system. In addition, sample extracts were digested with trypsin and analyzed for signal peptides corresponding to ‘total’, 22 kDa and 20 kDa GH (bottom-up). Both assays were validated according to current guidelines and compared to the GH isoform differential immunoassay used in routine doping control analysis. GH concentrations in serum samples of healthy adults, patients with acromegaly, and in samples obtained after administration of recombinant GH were analyzed as proof-of-principle.

Results

The intact monomeric 22 kDa isoform of GH was selectively quantified in a representative working range of 0.5 to 10 ng/ml by top-down LC-HRMS/MS. Subsequent bottom-up analysis provided additional data on ‘total’ and 20 kDa GH. Top-down and bottom-up assay results for the 22 kDa isoform correlated well with the corresponding immunoassay results (R² > 0.95). For a possible application of the method in an anti-doping context, the ratio between 22 kDa and ‘total’ GH was evaluated, indicating differences between the various donor groups, but only with limited significance.

Conclusion

The top-down and bottom-up LC-HRMS/MS method developed here presents a valuable tool for the quantification of GH in plasma/ serum complementary to established LBAs used at present in clinical measurements. Albeit the examination of the GH isoform proportions by the LC-MS method does not yet allow for the assessment of GH abuse, the obtained findings provide an important basis to enable LC-MS-based GH analysis of doping control samples in the future.