-
Scientific Reports Apr 2024The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal... (Meta-Analysis)
Meta-Analysis
The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.
Topics: Child; Humans; Growth Hormone; Network Meta-Analysis; Human Growth Hormone; Dwarfism, Pituitary; Growth Disorders; Hormone Replacement Therapy
PubMed: 38580693
DOI: 10.1038/s41598-024-58616-4 -
Zhongguo Dang Dai Er Ke Za Zhi =... Dec 2023The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in...
The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
Topics: Child; Humans; Growth Hormone; Insulin-Like Growth Factor I; Insulin-Like Peptides; Insulin-Like Growth Factor Binding Protein 3; Human Growth Hormone; Dwarfism, Pituitary
PubMed: 38112135
DOI: 10.7499/j.issn.1008-8830.2308076 -
Clinical Endocrinology May 2024Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript...
OBJECTIVES
Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised.
METHODS
Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α = .05 level.
RESULTS
Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p < .001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p = .056), even across pGH groups (p = .06). Both boys and girls had a similar distribution of imaging abnormalities.
CONCLUSION
Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance.
Topics: Female; Humans; Child; Male; Retrospective Studies; Hypopituitarism; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone; Sex Distribution
PubMed: 38463009
DOI: 10.1111/cen.15047 -
Hormone Research in Paediatrics 2024Growth hormone deficiency (GHD) may be associated with subtle cardiovascular abnormalities, reversible upon starting GH treatment. Data on vascular morphology and...
INTRODUCTION
Growth hormone deficiency (GHD) may be associated with subtle cardiovascular abnormalities, reversible upon starting GH treatment. Data on vascular morphology and function in GHD children are scanty and inconclusive. The aim of our study was to evaluate the effects of GHD and GH treatment on endothelial function and intima-media thickness (IMT) in children and adolescents.
METHODS
We enrolled 24 children with GHD (10.85 ± 2.71 years) and 24 age-, sex-, and BMI-matched controls. We evaluated anthropometry, lipid profile, asymmetric dimethylarginine (ADMA), brachial flow-mediated dilatation (FMD), and IMT of common (cIMT) and internal (iIMT) carotid artery at study entry in all subjects and after 12 months of treatment in GHD children.
RESULTS
At baseline GHD, children had higher total cholesterol (163.17 ± 18.66 vs. 149.83 ± 20.68 mg/dL, p = 0.03), LDL cholesterol (91.18 ± 20.41 vs. 77.08 ± 19.73 mg/dL, p = 0.019), atherogenic index (AI) (2.94 ± 0.71 vs. 2.56 ± 0.4, p = 0.028), and ADMA (215.87 ± 109.15 vs. 164.10 ± 49.15 ng/mL, p < 0.001), compared to controls. GHD patients also exhibited increased higher waist-to-height ratio (WHtR) compared to controls (0.48 ± 0.05 vs. 0.45 ± 0.02 cm, p = 0.03). GH therapy resulted in a decrease in WHtR (0.44 ± 0.03 cm, p = 0.001), total (151.60 ± 15.23 mg/dL, p = 0.001) and LDL cholesterol (69.94 ± 14.40 mg/dL, p < 0.0001), AI (2.28 ± 0.35, p = 0.001), and ADMA (148.47 ± 102.43 ng/mL, p < 0.0001). GHD showed lower baseline FMD than controls (8.75 ± 2.44 vs. 11.85 ± 5.98%, p = 0.001), which improved after 1-year GH treatment (10.60 ± 1.69%, p = 0.001). Baseline cIMT and iIMT were comparable between the two groups, but slightly reduced in GHD patients after treatment.
CONCLUSION
GHD children may exhibit endothelial dysfunction in addition to other early atherosclerotic markers like visceral adiposity, and altered lipids, which can be restored by GH treatment.
Topics: Adolescent; Child; Humans; Atherosclerosis; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol, LDL; Dwarfism, Pituitary; Human Growth Hormone
PubMed: 37290420
DOI: 10.1159/000531473 -
Frontiers in Endocrinology 2024Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are...
Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (=0.50; <0.001) and patients with GHD (=0.39; =0.08), a negative correlation was found in the NGRD group (=-0.23; <0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (=-0.45; <0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (=-0.51; <0.001 and =-0.59; <0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.
Topics: Adult; Humans; Growth Hormone; Acromegaly; Insulin-Like Peptides; Insulin-Like Growth Factor I; Retrospective Studies; Human Growth Hormone; Dwarfism, Pituitary; General Practice; Albumins
PubMed: 38596224
DOI: 10.3389/fendo.2024.1381083 -
Growth Hormone & IGF Research :... Feb 2024Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility...
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.
Topics: Humans; Female; Young Adult; Adult; Hypopituitarism; Growth Hormone; Dwarfism, Pituitary; Human Growth Hormone; Infertility; Insulin
PubMed: 38280246
DOI: 10.1016/j.ghir.2024.101571 -
Annals of Pediatric Endocrinology &... Apr 2024Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to...
PURPOSE
Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to determine if pituitary volume (PV) can distinguish patients with growth hormone (GH) deficiency from those with idiopathic short stature (ISS), (2) to validate an association between PV and severity of GH deficiency, and (3) to compare PV between good and poor response groups in children with GH deficiency or ISS after 1 year of treatment.
METHODS
Data were collected from the medical records of 152 children with GH deficiency or ISS who underwent GH stimulation test, sella MRI, and GH treatment for at least 1 year. Estimated PVs were calculated using the formula of an ellipsoid. We compared the PVs in patients with GH deficiency with those of patients with ISS. In addition, we assessed the association between PV and severity of GH deficiency, and we assessed growth response after treatment.
RESULTS
No difference was observed in PV between patients with GH deficiency and those with ISS. The severity of the GH deficiency seemed to be associated with PV (P=0.082), and the height of the pituitary gland was associated with severity of GH deficiency (P<0.005). The PV in the good response group was less than that of the poor response group in patients with GH deficiency (P<0.005), and PV showed no association with responsiveness to GH treatment in patients with ISS (P=0.073).
CONCLUSION
The measurement of PV cannot be used for differential diagnosis between GH deficiency and ISS. In patients with GH deficiency, PV tended to be smaller as the severity of GH deficiency increased, but the difference was not significant. PV may be a good response predictor for GH treatment. Further studies, including a radiomics-based approach, will be helpful in elucidating the clinical implications of pituitary morphology in patients with short stature.
PubMed: 37946439
DOI: 10.6065/apem.2346052.026 -
Frontiers in Endocrinology 2023Non-compliance to recombinant human growth hormone (rhGH) treatment is universally recognized as a key detrimental factor to achieve the expected clinical outcomes in... (Observational Study)
Observational Study
The adult growth hormone multicentric retrospective observational study: a 24-month Italian experience of adherence monitoring via Easypod™ of recombinant growth hormone treatment in adult GH deficiency.
INTRODUCTION
Non-compliance to recombinant human growth hormone (rhGH) treatment is universally recognized as a key detrimental factor to achieve the expected clinical outcomes in adult GH deficiency (aGHD). The Easypod™ electronic device allows objective measurement of adherence. Adherence to treatment has been reported to be related with IGF-1 levels and consequently with clinical satisfactory results. The aim of this multicentric, observational, retrospective, 24- month study, is to objectively assess aGHD patients' compliance to rhGH, using the Easypod™ device. Additionally, the study aims to compare the biochemical responses of adherent vs non-adherent patients.
METHODS
Forty-three patients (28 females and 15 males) affected by aGHD and equipped with Easypod™ from 3 Italian centers were included in the study. Adherence to treatment was defined as the proportion of injections correctly administered during the observational period, out of the expected total number of injections. All patients were evaluated for IGF-1, glucose, insulin, HOMA and QUICKI index, total/LDL/HDL cholesterol and triglycerides.
RESULTS
Mean adherence rate was consistently under 85% across the 2-year observation period (73% at year 2). A trend toward significant difference in adherence was shown when comparing female and male patients (respectively 76% and 61%) after a 2-year period. Among the anamnestic features, the prescribed frequency of administration of rhGH and the number of administered therapies appeared to be the most relevant adherence-influencing factors. A strong direct correlation between IGF-1 z-score and adherence to rhGH therapy was detected in the whole population.
DISCUSSION
Compliance to rhGH therapy is still a major issue in aGHD treatment. Adherence relates to therapy efficacy in aGHD. The use of Easypod™ could be beneficial for physicians to better manage aGHD patients and to achieve improved better biochemical and clinical responses.
Topics: Humans; Male; Adult; Female; Human Growth Hormone; Growth Hormone; Insulin-Like Growth Factor I; Retrospective Studies; Dwarfism, Pituitary; Pituitary Hormones, Anterior; Recombinant Proteins; Cholesterol, LDL; Medication Adherence
PubMed: 38027149
DOI: 10.3389/fendo.2023.1298775 -
Frontiers in Endocrinology 2024It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH...
Clinical and laboratory characteristics but not response to treatment can distinguish children with definite growth hormone deficiency from short stature unresponsive to stimulation tests.
INTRODUCTION
It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Only children with a monogenic cause of GHD or an identifiable combined hormonal deficiency or anatomical anomaly in the hypothalamic-pituitary axis should be considered definite GHD (dGHD). The remaining patients can be defined as a separate group of patients, "short stature unresponsive to stimulation tests" (SUS). The aim of this proof-of-concept study, was to assess whether SUS patients treated with rhGH exhibit any differences compared to GHD patients undergoing the same treatment.
METHODS
Retrospective analysis on 153 consecutive patients with short stature and pathological response to two GH stimulation tests. Patients with dGHD were defined as those with a clear genetic or anatomical hypothalamic-pituitary anomaly, as well as those with combined pituitary hormone deficiencies and those with a known insult to the hypothalamic-pituitary axis (i.e. total brain irradiation) (n=38, 25%); those without any of the previous anomalies were defined as SUS (n=115, 75%).
RESULTS
At diagnosis, dGHD and SUS populations did not differ significantly in sex (F 32% vs 28%, p=0.68), age (11.9 vs 12.1, p=0.45), height SDS at diagnosis (-2.2 vs. -2.0, p=0.35) and prevalence of short stature (height <-2 SDS) (56% vs 51%, p=0.45). IGF-1 SDS were significantly lower in dGHD (-2.0 vs -1.3, p<0.01). After 1 year of treatment, the prevalence of short stature was significantly reduced in both groups (31% in dGHD vs. 21% in SUS, p<0.01) without any significant differences between groups (p=0.19), while the increase in IGF-1 SDS for bone age was greater in the dGHD category (+1.9 vs. +1.5, p<0.01), with no further difference in IGF-1 SDS between groups. At the last available follow-up, 59 patients had reached the near adult height (NAH) and underwent retesting for GHD. No differences in NAH were found (-0.3 vs. -0.4 SDS, 0% vs. 4% of short stature). The prevalence of pathological retesting was higher in dGHD (60% vs. 10%, p<0.01) as well as of overweight and obesity (67% vs. 26%).
CONCLUSION
Stimulation tests and the equivalent benefit from rhGH therapy, cannot distinguish between dGHD and SUS populations. In addition, lower IGF-1 concentrations at baseline and their higher increase during treatment in dGHD patients, and the lack of pathological retesting upon reaching NAH in SUS patients, are facts that suggest that deficient GH secretion may not be the cause of short stature in the SUS studied population.
Topics: Child; Adult; Humans; Insulin-Like Growth Factor I; Retrospective Studies; Dwarfism, Pituitary; Human Growth Hormone; Growth Hormone
PubMed: 38495788
DOI: 10.3389/fendo.2024.1288497 -
Journal of Pediatric Endocrinology &... Apr 2024This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects...
OBJECTIVES
This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects of the children's condition on parents themselves within the first year of human growth hormone (hGH) treatment and (2) to predict based on main and interaction effects of children's HRQOL and increase in height.
METHODS
A total of 110 parents of children aged 4-18 years, diagnosed with idiopathic growth hormone deficiency, small for gestational age, or idiopathic short stature, were recruited from 11 participating German pediatric endocrinologists and asked to fill out the short stature-specific Quality of Life in Short Stature Youth (QoLISSY) Questionnaire before hGH treatment was initiated and one year later.
RESULTS
Negative effects of the children's short stature on the parents decrease over time, independent of diagnosis and treatment status. Furthermore, treatment status and height increase moderated the links between children's improved HRQOL as perceived by their parents and decreased caregiving burden.
CONCLUSIONS
Based on the children's improved HRQOL and the parent's decrease in caregiving burden, patient-reported outcomes that consider parental and child's perspectives should be considered when deciding on hGH treatment for children.
Topics: Child; Adolescent; Humans; Quality of Life; Prospective Studies; Body Height; Dwarfism, Pituitary; Surveys and Questionnaires; Parents; Human Growth Hormone
PubMed: 38421314
DOI: 10.1515/jpem-2023-0420