Dataset Information

Metabolic Effects of Recombinant Human Growth Hormone Replacement Therapy on Juvenile Patients after Craniopharyngioma Resection

ABSTRACT: Objective: To investigate the effect of short-term recombinant human growth hormone (rhGH) replacement therapy on metabolic parameters in juvenile patients following craniopharyngioma (CP) resection. Methods. This retrospective study included 42 cases of juvenile patients that had undergone CP resection in the Department of Endocrinology at the Peking Union Medical College Hospital, from April 2013 to August 2020. According to whether they received growth hormone replacement therapy, the patients were divided into either the growth hormone replacement therapy (GHRT) group (30 cases) or the control group (12 cases). Changes in body mass index (BMI), BMI z-score, transaminase activity, fasting blood glucose (FBG) levels, blood lipid profile, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated after one year of GHRT treatment. Results. The average age of the GHRT group was 13.00 (8.00–14.00) years old and these patients had undergone a CP operation an average of 2.00 (1.62–3.15) years earlier. Prior to receiving GHRT treatment, they received appropriate doses of adrenocortical hormone and thyroid hormone replacement therapy. After one year of GHRT treatment, the average BMI z-score decreased from 1.60 ± 1.76 to 1.13 ± 1.73 (P=0.005). Alanine aminotransferase (ALT) activity decreased from 26.50 (17.00∼98.00) U/L to 18.00 (13.00∼26.48) U/L (P ≤ 0.001), and similar changes were observed with regard to aspartate aminotransferase (AST) and glutamyl transferase (GGT) activity in the GHRT treatment group. The average total cholesterol (TC) decreased from 4.67 (4.10–6.14) mmol/L to 4.32 ± 0.85 mmol/L (P=0.002), and low-density lipoprotein (LDL) levels decreased from 3.05 ± 0.95 mmol/L to 2.56 ± 0.65 mmol/L (P=0.001) in the GHRT treatment group. The average blood urea nitrogen level decreased from 4.53 ± 1.09 mmol/L to 3.92 ± 0.82 mmol/L (P=0.016) and the average serum creatinine (SCr) level decreased from 55.59 ± 12.54 µmol/L to 51.15 ± 10.51 µmol/L (P=0.005) in the GHRT treatment group. The average hsCRP level decreased from 3.23 (1.79∼4.34) mg/L to 0.92 (0.42∼1.21) mg/L in the GHRT treatment group. In the control group, the average ALT activity increased from 26.58 ± 8.75 U/L to 42.58 ± 24.59 U/L (P=0.039), GGT activity increased from 19.0 (13.25–29.25) U/L to 25.00 (14.75–34.75) U/L (P=0.026), and LDL levels increased from 2.27 ± 0.76 mmol/L to 3.43 ± 1.28 mmol/L (P=0.04). Conclusion. GHRT treatment improves the metabolic parameters of juvenile patients that have undergone craniopharyngioma resection by reducing BMI z-scores, low-density lipoprotein, and hsCRP levels and improving liver function.

SUBMITTER: Li S

PROVIDER: S-EPMC9279072 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. OBJECTIVES:To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. SEARCH METHODS:We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 15 May 2013.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 15 March 2012. SELECTION CRITERIA:Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). DATA COLLECTION AND ANALYSIS:Two authors independently screened papers, extracted trial details and assessed their risk of bias. MAIN RESULTS:Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. There is moderate improvement in one parameter of pulmonary function tests, functional vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. AUTHORS' CONCLUSIONS:Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients.

Project description:UnlabelledReplacement of growth hormone (GH) in patients suffering from GH deficiency (GHD) offers clinical benefits on body composition, exercise capacity, and skeletal integrity. However, GH replacement therapy (GHRT) is also associated with insulin resistance, but the mechanisms are incompletely understood. We demonstrate that in GH-deficient mice (growth hormone-releasing hormone receptor (Ghrhr)(lit/lit)), insulin resistance after GHRT involves the upregulation of the extracellular matrix (ECM) and the downregulation of microRNA miR-29a in skeletal muscle. Based on RNA deep sequencing of skeletal muscle from GH-treated Ghrhr(lit/lit) mice, we identified several upregulated genes as predicted miR-29a targets that are negative regulators of insulin signaling or profibrotic/proinflammatory components of the ECM. Using gain- and loss-of-function studies, five of these genes were confirmed as endogenous targets of miR-29a in human myotubes (PTEN, COL3A1, FSTL1, SERPINH1, SPARC). In addition, in human myotubes, IGF1, but not GH, downregulated miR-29a expression and upregulated COL3A1. These results were confirmed in a group of GH-deficient patients after 4 months of GHRT. Serum IGF1 increased, skeletal muscle miR-29a decreased, and miR-29a targets were upregulated in patients with a reduced insulin response (homeostatic model assessment of insulin resistance (HOMA-IR)) after GHRT. We conclude that miR-29a could contribute to the metabolic response of muscle tissue to GHRT by regulating ECM components and PTEN. miR-29a and its targets might be valuable biomarkers for muscle metabolism following GH replacement.Key messagesGHRT most significantly affects the ECM cluster in skeletal muscle from mice. GHRT downregulates miR-29a and upregulates miR-29a targets in skeletal muscle from mice. PTEN, COL3A1, FSTL1, SERPINH1, and SPARC are endogenous miR-29a targets in human myotubes. IGF1 decreases miR-29a levels in human myotubes. miR-29a and its targets are regulated during GHRT in skeletal muscle from humans.

Project description:Muscle mass and strength reduce during ageing with a steeper decline in women around the age of 50, which suggests that the menopausal transition is one of the mechanisms for age-induced neuromuscular deteriorations. At the moment, there is no clear explanation for the decline in muscle properties although both physical exercise and maintaining near premenopausal estrogen levels by hormonal replacement have been helpful in their preservation. However, the molecular consequences of both treatments in skeletal muscle are mostly unknown. The goal of this genome-wide study was to investigate the transcriptional networks through which power training (PT) comprising of jumping activities and estrogen containing hormone replacement therapy (HRT) may aid in the prevention of functional limitation ensued from insufficient muscle mass and physical performance after menopause. We used m. vastus lateralis samples obtained from postmenopausal women participating in a yearlong randomized double-blinded placebo-controlled trial with PT and HRT interventions. Muscle samples were available from eight PT, ten HRT and nine control women. Women in the PT group participated in a progressive PT program comprising mostly of jumping exercises for lower limbs with additional resistance exercises for the upper body. HRT intervention was double-blinded. All participants used either estradiol/noretisterone acetate preparation or placebo. Using statistical threshold p-value <0.05 and |fold change| >1.2 we identified 665 genes being differentially expressed among the studied 50-57-yr-old postmenopausal women. We used the hierarchical clustering method with extensive enrichment analysis in order to reveal enrichment of known GO or KEGG functional categories among co-regulated gene-clusters. In the enrichment analysis false discovery rate was set to be less than 15%. Transcription of “response to contraction”-, “insulin signaling”- and “adipocytokine signaling”-genes were upregulated by PT. Both PT and HRT were similarly effective on transcriptional regulation of glycolytic energy metabolism and calcium signaling. The HRT specifically affected “mitochondrion”-genes. In addition, we identified functional categories, such as “muscle development”, which were changed during the trial in all study groups. Our study revealed transcriptional changes in several functional categories in thigh muscle tissue of early postmenopausal women. The results emphasize that during the first years of the postmenopausal period, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle mass and performance. More specifically, our findings indicate that PT and HRT may function through improving energy metabolism, improving the response to contraction, preserving functionality of mitochondria and reducing reorganization of muscle tissue. Therefore these treatments are recommended for preservation of adequate muscle mass and function. 54 samples, which formed 3 study groups with 2 timepoints, i.e., 8 power training subjects, 10 hormone replacement subjects and 9 controls. 6 control subjects had replicated samples resulting in a total of 60 hybridizations.

Dataset Information

Metabolic Effects of Recombinant Human Growth Hormone Replacement Therapy on Juvenile Patients after Craniopharyngioma Resection

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets