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Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls (p < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue.
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In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.
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Hormona de Crecimiento Humana , Factor I del Crecimiento Similar a la Insulina , Humanos , Masculino , Niño , Femenino , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adolescente , Preescolar , Trastornos del Crecimiento/diagnóstico , EstaturaRESUMEN
Background: Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. Methods: The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother's Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons-of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Results: Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts (p < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value (p < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. Conclusions: A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children-omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.
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Introduction: Sirtuin 1 (SIRT1) is known to be involved in sensing cellular energy levels and regulating energy metabolism. This study aimed to evaluate fasting serum SIRT1 levels in healthy children, and to analyse the influence of age, sex, puberty, body weight, height, and diet on its concentration. Methods: 47 healthy children aged 4-14 with weight and height within normal range and no chronic disease were included into the study. Fasting serum SIRT1 concentrations were estimated by Enzyme Linked Immunosorbent Assay (ELISA). Results: Results showed that serum SIRT1 concentrations in healthy children did not differ with respect to sex, age, height, weight and puberty. Whereas, it appeared that a higher frequency of fruits, vegetables and dairy products consumption was associated with an increase in serum SIRT1 levels. Discussion: Studying SIRT1 in the context of children's health may have implications for a broader understanding of growth processes, pubertal development, metabolic disorders and nutrition.
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Pubertad , Sirtuina 1 , Niño , Humanos , Índice de Masa Corporal , Peso Corporal , Ayuno , Pubertad/fisiología , Preescolar , AdolescenteRESUMEN
INTRODUCTION: Children born small for gestational age (SGA) are predisposed to obesity, insulin resistance (IR), and lipid disorders. The HOMA-IR index is commonly used to assess IR (IRIHOMA), calculated from fasting glucose and insulin. However, sometimes, during the oral glucose tolerance test (OGTT), elevated and prolonged postprandial insulin secretion is observed despite normal fasting insulin levels. IRIBelfiore is an IR index that analyses glucose and insulin levels during OGTT according to the method proposed by Belfiore. THE AIM OF THE STUDY: was to assess the frequency of IR based on IRIHOMA and IRIBelfiore results in SGA children aged 6-8 years, after catch-up phenomenon, to determine the usefulness of IRIBelfiore in diagnosis of IR and in predicting future metabolic complications. MATERIAL AND METHODS: In 129 SGA normal-height children, aged 6-8 years, height, weight, waist circumference, blood pressure, as well as lipids, IGF-1, cortisol, C-peptide, leptin, adiponectin, and resistin concentrations were measured. The glucose and insulin concentrations were evaluated at 0, 60, and 120 minutes of OGTT. RESULTS: IRIHOMA was normal in all children, while elevated IRIBelfiore was found in 22.5% of them. Children with IR diagnosed by IRIBelfiore were taller, had higher blood pressure, higher leptin, and lower HDL-cholesterol concentrations. CONCLUSIONS: It seems worth recommending IRIBelfiore derived from OGTT as a valuable diagnostic tool for identifying IR in SGA prepubertal children. Abnormal IRIBelfiore is related to higher blood pressure and lower HDL-cholesterol concentration in this group.
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Resistencia a la Insulina , Niño , Humanos , Glucemia/metabolismo , Colesterol , Retardo del Crecimiento Fetal , Edad Gestacional , Incidencia , Insulina , Resistencia a la Insulina/fisiología , LeptinaRESUMEN
The regulation of growth processes in children depends on the synthesis of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Insulin-like growth factor 1, which is mainly secreted in the liver in response to GH, is the main peripheral mediator of GH action. Newly discovered factors regulating GH secretion and its effects are being studied recently. One of them is sirtuin 1 (SIRT1). This NAD+-dependent deacetylase, by modulating the JAK2/STAT pathway, is involved in the transduction of the GH signal in hepatocytes, leading to the synthesis of IGF-1. In addition, it participates in the regulation of the synthesis of GHRH in the hypothalamus and GH in the somatotropic cells. SIRT1 is suggested to be involved in growth plate chondrogenesis and longitudinal bone growth as it has a positive effect on the epiphyseal growth plate. SIRT1 is also implicated in various cellular processes, including metabolism, cell cycle regulation, apoptosis, oxidative stress response, and DNA repair. Thus, its expression varies depending on the different metabolic states. During malnutrition, SIRT1 blocks GH signal transduction in hepatocytes to reduce the IGF-1 secretion and prevent hypoglycemia (i.e., it causes transient GH resistance). In this review, we focused on the influence of SIRT1 on GH signal transduction and the implications that may arise for growth processes in children.
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Hormona de Crecimiento Humana , Factor I del Crecimiento Similar a la Insulina , Niño , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Transducción de Señal/fisiología , Sirtuina 1/metabolismoRESUMEN
Cushing's disease (CD) is an extremely rare diagnosis in children. In this report, we present the case of an almost 16-year-old, short and thin boy with CD, the first symptoms of which were spinal pain and vertebral fractures as a result of osteoporosis. In light of his growth retardation and short stature, the boy underwent diagnostics, which excluded growth hormone (GH) deficiency, hypothyroidism and celiac disease. Finally, based on cortisol profile results, dexamethasone suppression tests and bilateral sampling during catheterization of the inferior petrosal sinuses, CD was diagnosed.
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The aim of the study was to investigate the effects of seasonal variability of insolation, the implementation of new recommendations for vitamin D supplementation (2018), and the SARS-CoV-2 pandemic lockdown (2020) on 25(OH)D concentrations in children from central Poland. The retrospective analysis of variability of 25(OH)D concentrations during the last 8 years was performed in a group of 1440 children with short stature, aged 3.0-18.0 years. Significant differences in 25(OH)D concentrations were found between the periods from mid-2014 to mid-2018, from mid-2018 to mid-2020, and from mid-2020 to mid-2022 (medians: 22.9, 26.0, and 29.9 ng/mL, respectively). Time series models created on the grounds of data from 6 years of the pre-pandemic period and used for prediction for the pandemic period explained over 80% of the seasonal variability of 25(OH)D concentrations, with overprediction for the first year of the pandemic and underprediction for the second year. A significant increase in 25(OH)D concentrations was observed both after the introduction of new vitamin D supplementation guidelines and during the SARS-CoV-2 pandemic; however, the scale of vitamin D deficiency and insufficiency was still too high. Time series models are useful in analyzing the impact of health policy interventions and pandemic restrictions on the seasonal variability of vitamin D concentrations.
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COVID-19 , Vitamina D , Niño , Humanos , Pandemias , Polonia/epidemiología , Estudios Retrospectivos , COVID-19/epidemiología , SARS-CoV-2 , Control de Enfermedades Transmisibles , Vitaminas , Suplementos DietéticosRESUMEN
Not required for Clinical Vignette.
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BACKGROUND: A diagnosis of "idiopathic short stature" (ISS) in a child means that the cause of the disease has not been established, although there are certainly some unknown factors that contributed to its occurrence. Ghrelin and leptin are important in controlling food intake; ghrelin is also a growth hormone (GH) stimulator. Both enterohormones are produced in the stomach and their secretion may be affected by a Helicobacter pylori (H. pylori) infection. METHODS: Our study included a group of 61 children (53 prepubertal and 8 peripubertal) with ISS, without any gastrointestinal tract symptoms but in whom the histopathological evaluation of stomach tissue was made during gastroscopy to diagnose H. pylori infection. In each child, fasting ghrelin, leptin and IGF-1 concentrations, and GH levels in two stimulation tests were assessed. RESULTS: H. pylori infection was confirmed in 24.6% of the children. Ghrelin and IGF-1 concentrations were significantly lower in H. pylori-positive than H. pylori-negative children (this was more noticeable in prepubertal subgroups), however there was not a discrepancy in regards to GH concentrations in stimulation tests, leptin levels or the nutritional state between groups. CONCLUSIONS: Short children, infected by H. pylori seem to have lower ghrelin and IGF-1 concentrations than children without infection, this may be the reason for a worse growth rate in this subgroup.
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CONTEXT: The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. OBJECTIVE: This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. METHODS: Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥â 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. RESULTS: The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. CONCLUSION: Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Adulto , Femenino , Niño , Humanos , Masculino , Hormona de Crecimiento Humana/efectos adversos , Hormona del Crecimiento , Trastornos del Crecimiento/tratamiento farmacológico , Estatura , Proteínas Recombinantes/efectos adversosRESUMEN
Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases.
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Hipotiroidismo Congénito , Complicaciones del Embarazo , Anciano , Peso al Nacer , Niño , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Prevalencia , TirotropinaRESUMEN
Introduction: Growth hormone (GH) and thyroid hormones are important for children growing. In some obese children a slightly elevated TSH concentration is observed. This may be an adaptive mechanism: stimulation of pro-TRH biosynthesis in the hypothalamus in response to elevated leptin. The increased TSH may also reflect the necessity of maintaining the resting energy expenditure or may be a result of inappropriate, low FT4 concentration. Thus, we evaluated serum TSH and FT4 concentrations in idiopathic short stature (ISS) children (non GH-deficient) and examined the effect of children's nutritional status and levels of selected adipocytokines on thyroid function, searching for the presence of various forms of subclinical hypothyroidism, which may be the cause of the slow growth rate. Methods: The study group included 115 children (50 girls and 65 boys) with ISS, aged (mean ± SD) 10.4 ± 3.34 years. In each child, lipids, TSH, FT4, IGF-1, maxGH during the stimulation tests, leptin, adiponectin and resistin concentrations were determined. Based on BMI SDS, 3 subgroups: slim (n=26), obese (n=21) and normal weight (n=68) were distinguished. Results: There was no correlation between leptin level and TSH, FT4 levels. The levels of leptin, total cholesterol and LDL-cholesterol in obese short children were significantly higher than in children from other subgroups. In turn, the levels of adiponectin, resistin, TSH and FT4 did not differ between subgroups. In 7% of children, an elevated TSH level was found (but less than 10 mIU/L), with a similar frequency across subgroups. The higher the leptin, the lower maxGH in clonidine stimulation test was recorded. Conclusions: It seems that in obese children with idiopathic short stature leptin does not increase TSH secretion. This may be related to a disruption of the effect of leptin on TSH production and could indicate wide ranging disturbances of hypothalamic signals, and consequently be the cause of inappropriate GH secretion.
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Hormona de Crecimiento Humana , Hipertiroidismo , Leptina , Obesidad Infantil , Tirotropina , Adiponectina , Adolescente , Estatura , Niño , Colesterol , Femenino , Hormona del Crecimiento , Humanos , Masculino , Obesidad Infantil/complicaciones , Resistina , Tirotropina/sangreRESUMEN
CONTEXT: Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). OBJECTIVE: We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. METHODS: In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. RESULTS: HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: -0.24, 0.89). The lower bound of the 2-sided 95% CI was higher than the prespecified noninferiority margin (-1.8 cm/year), demonstrating noninferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height standard deviation score at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon: 78.9%, somatropin: 79.1%). CONCLUSION: The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles. (ClinicalTrials.gov no. NCT02968004).
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Estatura , Niño , Preescolar , Enanismo Hipofisario/tratamiento farmacológico , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/efectos adversos , Humanos , Masculino , Proteínas Recombinantes/efectos adversosRESUMEN
INTRODUCTION: Prader-Willi syndrome (PWS) is a genetically determined disease that manifests itself in a number of abnormalities resulting, among others, from dysfunction of the hypothalamic-pituitary system. Only integrated, multidisciplinary care gives patients the chance to significantly improve the quality of life and achieve a life expectancy that does not differ from the general population. AIM: The aim of the study was to summarize the available literature on the management of patients suffering from PWS. CONCLUSIONS: More and more reports based on clinical trials conducted around the world indicate the undeniable benefits of rhGH therapy in patients with PWS in childhood and after the end of growth period. They consist in improving the body composition, improving the lipid profile, increasing bone mineral density and improving the mental state and patients' quality of life.
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Hormona de Crecimiento Humana , Síndrome de Prader-Willi , Adulto , Composición Corporal , Niño , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Síndrome de Prader-Willi/tratamiento farmacológico , Calidad de Vida , Proteínas Recombinantes/uso terapéuticoRESUMEN
INTRODUCTION: There is a discussion about growth hormone therapy in idiopathic short stature (ISS) children. To diagnose ISS, it is necessary to exclude other diseases; gastrointestinal tract diseases (GIDs) are among them. However, GID symptoms may be scarce. The aim of the study was to evaluate the frequency of unexpected oligosymptomatic GIDs in ISS and assess their influence on auxological parameters and insulin-like growth factor I (IGF-I) concentration. MATERIAL AND METHODS: The analysis included 101 children with ISS and 95 controls. All patients were tested for celiac disease (CD), inflammatory bowel disease (IBD), lactose malabsorption (LM), cystic fibrosis (CF), Helicobacter pylori (HP) and Ascaris sp. (Asc) infections, as well as Candida albicans (Calb) colonization, by applying simple blood and stool tests and gastrofiberoscopy. RESULTS: In 75.2% of short children, one or more than one GIDs listed above were diagnosed, with the highest frequency of: Calb (46.5%), LM (33.7%), HP (24.7%) and/or Asc (21.8%). The incidence of GIDs was significantly higher than in the control group. The GID frequency increases with the age of children. In most ISS children, the IGF-I SDS was below -1.0 and it was the lowest in children with HP (p < 0.05). CONCLUSIONS: High frequency of unexpected oligosymptomatic GIDs in children diagnosed with ISS indicates the need to search for gastrointestinal (GI) causes in each case of short stature in children. The pathomechanisms responsible for short stature in these cases may vary, although it seems that reduced production of IGF-I plays an important role.
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Short stature is characteristic for Turner syndrome (TS) patients, and particular karyotype abnormalities of the X chromosome may be associated with different responsiveness to recombinant human GH (rhGH) therapy. The aim of the study was to analyze the effect of different types of TS karyotype abnormalities on the response to rhGH therapy. A total of 57 prepubertal patients with TS treated with rhGH with a 3 year follow-up were enrolled in the study and categorized according to their karyotype as X monosomy (n = 35), isochromosome (n = 11), marker chromosome (n = 5), or X-mosaicism (n = 6). Height and height velocity (HV) were evaluated annually. In the first year, all groups responded well to the therapy. In the second year, HV deteriorated significantly in X-monosomy and isochromosome in comparison to the remaining two groups (p = 0.0007). After 3 years of therapy, all patients improved the score in comparison to their target height, but better outcomes were achieved in patients with marker chromosome and X-mosaicism (p = 0.0072). X-monosomy or isochromosome determined a poorer response during the second and third year of rhGH therapy. The results of the study indicate that the effects of rhGH therapy in patients with TS may depend on the type of TS karyotype causing the syndrome.
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In this review we described the interactions between ghrelin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in children and adults with growth hormone deficiency (GHD). A possible involvement of these interactions in the pathogenesis of unexplained cases of GHD was suggested. Current research provides more and more details to the knowledge on the circadian rhythm of ghrelin. We gathered reports on the decreasing effect of Helicobacter pylori-related chronic gastritis on the number of ghrelin immunopositive cells and the consequent decrease in ghrelin serum concentration. The gastrointestinal tract microflora modification of the ghrelin action, by the mechanism of molecular mimicry, was also stressed. Moreover, the mutual relationships between ghrelin and the TSH-FT4/FT3 axis in growth and metabolic processes are described. It is to be recalled that FT4 and FT3 exert a permissive impact on IGF-1 action and, in turn, GH, in reaction mediated by IGF-1, enhances the monodeiodination of FT4 to FT3. Finally, we discussed the latest attempts to use the GH secretagogue receptor (GHS-R) analogues for possible diagnostic and therapeutic purposes.
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Ghrelina/metabolismo , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/metabolismo , Animales , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptores de Ghrelina/metabolismoRESUMEN
Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.