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Frontiers in Endocrinology 2023To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH)....
OBJECTIVE
To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.
METHODS
National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height, AH, and age at PO and at AH were evaluated.
RESULTS
At GH start, height was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height at PO ranged from 13 years/-0.42 for GH to 15.2 years/-1.47 for GH. At AH, GH group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain, 1.55) compared to GH group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH group (17.3 years; 153.7 cm: -2.28 SDS; total gain, 0.53), and the most delayed was the GH group, (18.5 years; 156.5 cm; -1.82 SDS; total gain, 0.98).
CONCLUSION
For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
Topics: Female; Adolescent; Humans; Adult; Child, Preschool; Child; Human Growth Hormone; Growth Hormone; Turner Syndrome; Sweden; Body Height; Puberty; Estradiol
PubMed: 37529614
DOI: 10.3389/fendo.2023.1197897 -
Frontiers in Endocrinology 2024The liver plays pivotal roles in nutrient metabolism, and correct hepatic adaptations are required in maternal nutrient metabolism during pregnancy. In this review,... (Review)
Review
The liver plays pivotal roles in nutrient metabolism, and correct hepatic adaptations are required in maternal nutrient metabolism during pregnancy. In this review, hepatic nutrient metabolism, including glucose metabolism, lipid and cholesterol metabolism, and protein and amino acid metabolism, is first addressed. In addition, recent progress on maternal hepatic adaptations in nutrient metabolism during pregnancy is discussed. Finally, the factors that regulate hepatic nutrient metabolism during pregnancy are highlighted, and the factors include follicle-stimulating hormone, estrogen, progesterone, insulin-like growth factor 1, prostaglandins fibroblast growth factor 21, serotonin, growth hormone, adrenocorticotropic hormone, prolactin, thyroid stimulating hormone, melatonin, adrenal hormone, leptin, glucagon-like peptide-1, insulin glucagon and thyroid hormone. Our vision is that more attention should be paid to liver nutrient metabolism during pregnancy, which will be helpful for utilizing nutrient appropriately and efficiently, and avoiding liver diseases during pregnancy.
Topics: Pregnancy; Female; Humans; Liver; Insulin; Growth Hormone; Glucagon; Nutrients
PubMed: 38572473
DOI: 10.3389/fendo.2024.1295677 -
Best Practice & Research. Clinical... Dec 2023Growth hormone (GH) deficiency (GHD) is one of the most prevalent deficiencies in patients with hypopituitarism and several cohort studies have demonstrated an increased... (Meta-Analysis)
Meta-Analysis Review
Growth hormone (GH) deficiency (GHD) is one of the most prevalent deficiencies in patients with hypopituitarism and several cohort studies have demonstrated an increased mortality risk in hypopituitary patients with a presumed GHD. The cause of the excess mortality is most likely multifactorial, including the etiology of the hypopituitarism, non-physiological replacement therapies (mostly glucocorticoid), tumor treatment and its side effects as well as untreated GHD. Several years later, other cohort studies that investigated life expectancy in patients with hypopituitarism on GH replacement therapy (GHRT) that showed a normalized mortality. By comparison of the distribution of characteristics of interest between cohorts, we discuss the existing literature to answer the following question: does growth hormone replacement really improve mortality rates in adult patients with hypopituitarism and GHD? We also conducted a meta-analysis of these studies. Since the literature suffers from selection and time bias (improvement of tumor management and other pituitary hormone replacement therapies), there is no high-quality evidence that replacement therapy for GHD really improves mortality. However, the available data does suggest that GHRT plays a significant part in the normalization of the mortality in patients with hypopituitarism.
Topics: Adult; Humans; Hypopituitarism; Dwarfism, Pituitary; Human Growth Hormone; Growth Hormone; Pituitary Neoplasms; Hormone Replacement Therapy
PubMed: 37914564
DOI: 10.1016/j.beem.2023.101835 -
Frontiers in Immunology 2023Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and...
INTRODUCTION
Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming.
METHODS
Here we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy.
RESULTS
We demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae.
CONCLUSIONS
Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases.
Topics: Humans; Growth Hormone; Macrophages; Glycolysis; Homeostasis; Mitochondria
PubMed: 37475858
DOI: 10.3389/fimmu.2023.1200259 -
The Pan African Medical Journal 2023Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1)....
Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). This is a retrospective study of patients who were hospitalized in the Endocrinology Department of the Mohammed V Military Academic Hospital in Rabat over a period of 14 years (2008 to 2022), reporting on their clinical, paraclinical and evolutionary profiles and comparing the results with the data in the literature. Nineteen patients were included in our study. The mean age was 42.7 ± 11.6 years, with a male predominance. The clinical manifestations were dominated by a dysmorphic syndrome present in 97.4% of cases, followed by complications related to acromegaly in 88.9% of cases. The diagnosis was made when GH and IGF-1 values were elevated in 88.9% and 93.8% of cases, respectively; with a mean GH value of 25.1 μg/L. Magnetic resonance imaging (MRI) was used to diagnose the location of pituitary adenoma in all cases, 78.9% of which were macroadenomas and 21.1% microadenomas. The majority of patients (78.9%) had recourse to transsphenoidal surgery. Medical treatment was carried out in 89.5% of cases. Postoperative radiotherapy was performed in 33% of cases. Disease control was achieved in 30.1% of cases. This study shows the complex management of acromegaly. Disease control is a necessary condition in order to avoid complications, but is often difficult to obtain.
Topics: Humans; Male; Adult; Middle Aged; Female; Acromegaly; Insulin-Like Growth Factor I; Retrospective Studies; Treatment Outcome; Human Growth Hormone; Pituitary Neoplasms
PubMed: 38465009
DOI: 10.11604/pamj.2023.46.116.41952 -
Frontiers in Endocrinology 2023Hormones and mechanical loading co-regulate bone throughout the lifespan. In this review, we posit that times of increased hormonal influence on bone provide... (Review)
Review
Hormones and mechanical loading co-regulate bone throughout the lifespan. In this review, we posit that times of increased hormonal influence on bone provide opportunities for exercise to optimize bone strength and prevent fragility. Examples include endogenous secretion of growth hormones and sex steroids that modulate adolescent growth and exogenous administration of osteoanabolic drugs like teriparatide, which increase bone stiffness, or its resistance to external forces. We review evidence that after bone stiffness is increased due to hormonal stimuli, mechanoadaptive processes follow. Specifically, exercise provides the mechanical stimulus necessary to offset adaptive bone resorption or promote adaptive bone formation. The collective effects of both decreased bone resorption and increased bone formation optimize bone strength during youth and preserve it later in life. These theoretical constructs provide physiologic foundations for promoting exercise throughout life.
Topics: Adolescent; Humans; Bone Density; Bone and Bones; Bone Resorption; Osteogenesis; Growth Hormone
PubMed: 37790607
DOI: 10.3389/fendo.2023.1219454 -
Clinical Endocrinology Oct 2023Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim...
OBJECTIVE
Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim of the study was to evaluate T2 MRI signal intensity and its relation with pasireotide therapeutic effectiveness in real-life clinical practice.
DESIGN, PATIENTS AND MEASUREMENTS
Retrospective multicentre study including acromegaly patients treated with pasireotide. Adenoma T2-weighted MRI signal at diagnosis was qualitatively classified as iso-hyperintense or hypointense. Insulin-like growth factor (IGF-I), growth hormone (GH) and tumour volume reduction were assessed after 6 and 12 months of treatment and its effectiveness evaluated according to baseline MRI signal. Hormonal response was considered 'complete' when normalization of IGF-I levels was achieved. Significant tumour shrinkage was defined as a volume reduction of ≥25% from baseline.
RESULTS
Eighty-one patients were included (48% women, 50 ± 1.5 years); 93% had previously received somatostatin receptor ligands (SRLs) treatment. MRI signal was hypointense in 25 (31%) and hyperintense in 56 (69%) cases. At 12 months of follow-up, 42/73 cases (58%) showed normalization of IGF-I and 37% both GH and IGF-I. MRI signal intensity was not associated with hormonal control. 19/51 cases (37%) presented a significant tumour volume shrinkage, 16 (41%) from the hyperintense group and 3 (25%) from the hypointense.
CONCLUSIONS
T2-signal hyperintensity was more frequently observed in pasireotide treated patients. Almost 60% of SRLs resistant patients showed a complete normalization of IGF-I after 1 year of pasireotide treatment, regardless of the MRI signal. There was also no difference in the percentage tumour shrinkage over basal residual volume between the two groups.
Topics: Humans; Female; Male; Acromegaly; Insulin-Like Growth Factor I; Adenoma; Human Growth Hormone; Magnetic Resonance Imaging; Treatment Outcome; Octreotide
PubMed: 37421211
DOI: 10.1111/cen.14946 -
Growth Hormone & IGF Research :... Feb 2024GATA2 is a key transcription factor involved in the differentiation and determination of thyrotrophs and gonadotrophs in pituitary and hematopoietic development....
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.
Topics: Mice; Animals; Growth Hormone; STAT5 Transcription Factor; Janus Kinases; Signal Transduction; STAT Transcription Factors; Human Growth Hormone; Milk Proteins
PubMed: 38281404
DOI: 10.1016/j.ghir.2024.101572 -
Frontiers in Endocrinology 2023To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing fertilization (IVF).
METHODS
Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.
RESULTS
Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol ( < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG ( < 0.05).
CONCLUSION
For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk PROSPERO (CRD42023421739).
Topics: Pregnancy; Female; Humans; Growth Hormone; Gonadotropin-Releasing Hormone; Ovarian Reserve; Gonadotropins; Fertilization in Vitro; Infertility, Female; Human Growth Hormone; Ovarian Diseases; Estradiol
PubMed: 38027219
DOI: 10.3389/fendo.2023.1215755 -
Endocrine Practice : Official Journal... Nov 2023Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene... (Review)
Review
OBJECTIVE
Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene variants. The underlying cause of the defective physiology is decreased BGH binding affinity to both growth hormone binding proteins and growth hormone receptors (GHRs). GHR cannot dimerize when it is in a quiescent state because BGH cannot activate it. Nondimerized GHR is unable to activate intracytoplasmic signaling pathway molecules such as Janus kinase 2 and signal transducer and activator of transcription, which initiate insulin-like growth factor-1 (IGF-1) transcription. IGF-1 cannot therefore be synthesized and IGF-1 levels in the circulation decrease. In contrast to children with growth hormone insensitivity, children with short stature due to BGH, known as Kowarski syndrome, exhibit an outstanding linear growth response to recombinant growth hormone therapy. For a number of reasons, differential diagnosis presents some difficulties. Similar diseases caused by genetic abnormalities that cause short stature range in severity from minor to severe clinical spectrum. Furthermore, some patients with Kowarski syndrome have previously been diagnosed with familial short stature, constitutional delayed puberty, and idiopathic short stature. This paper aims to review the particular clinical and laboratory findings of BGH.
METHODS
This study collected clinical and laboratory data from KS cases reported in the literature.
RESULTS
This review reports that KS cases have lower SDSs for height and IGF-1 compared to growth hormone deficiency.
CONCLUSION
The diversity of genetic defects underlying Kowarski syndrome (KS) will provide new insights into growth hormone insensitivity. As the availability of genetic analysis, including functional investigations expands, researchers will identify new underlying genetic pathways.
Topics: Child; Humans; Growth Hormone; Insulin-Like Growth Factor I; Dwarfism, Pituitary; Human Growth Hormone
PubMed: 37657628
DOI: 10.1016/j.eprac.2023.08.013