Growth disorders are one of the common complications of chronic kidney disease (CKD) in children, adversely affecting both the quality of life and survival time of CKD patients. Recombinant human growth hormone (rhGH) is an effective treatment for growth disorders in children with CKD. This article reviews the mechanisms underlying growth disorders in children with CKD, the therapeutic effects, safety, and precautions of rhGH, and long-term management of diagnosis and treatment of this disorder.
Humans ; Human Growth Hormone/adverse effects* ; Child ; Recombinant Proteins/adverse effects* ; Renal Insufficiency, Chronic/complications* ; Growth Disorders/etiology*

OBJECTIVES: To compare serum insulin-like growth factor 1 (IGF-1) and peak growth hormone (GH) levels between girls with isolated premature thelarche (IPT) and central precocious puberty (CPP), to construct a prediction model for progression from IPT to CPP, and to assess its diagnostic value. METHODS: Girls diagnosed with IPT (n=111) between January 2022 and August 2023 at the China-Japan Friendship Hospital and the Xinjiang Production and Construction Corps Hospital were retrospectively included. According to follow-up outcomes, participants were categorized into a CPP group (35 cases) and an IPT group (36 cases). A clinical prediction model for progression to CPP was constructed by multivariable logistic regression, and the contributions of IGF-1 and peak GH were evaluated. Restricted cubic spline analysis was used to assess the dose-response relationships of IGF-1 and peak GH with CPP. Decision curve analysis was applied to evaluate clinical utility. RESULTS: IGF-1 and peak GH were higher in the CPP group than in the IPT group (P<0.05). Compared with model 1 (without IGF-1 and peak GH), model 2 (with IGF-1 and peak GH) showed significantly higher area under the curve, integrated discrimination improvement, and net reclassification improvement (all P<0.05). Model 2 (χ 2=6.054, P=0.889) also demonstrated better goodness-of-fit than model 1 (χ 2=7.717, P=0.634). Nonlinear dose-response relationships were observed for peak GH and IGF-1 with CPP (P for overall trend <0.05; P for nonlinearity <0.05). Decision curve analysis indicated that combined prediction using IGF-1 and peak GH provided greater net benefit than either biomarker alone. CONCLUSIONS Peak GH and IGF-1 are closely associated with progression from IPT to CPP in girls. A clinical prediction model incorporating peak GH and IGF-1 can improve prediction of progression to CPP and yield higher net benefit.
Humans ; Female ; Puberty, Precocious/etiology* ; Insulin-Like Growth Factor I/analysis* ; Child ; Retrospective Studies ; Human Growth Hormone/blood* ; Predictive Value of Tests ; Child, Preschool ; Logistic Models

The oral glucose growth hormone suppression test is commonly used in the clinical diagnosis of acromegaly, but its results can be influenced by a variety of factors. This case report discusses a patient with a pituitary tumor and concurrent liver cirrhosis, highlighting the complexities in interpreting test results under such conditions. The patient, a 54-year-old male, presented with blurred vision as his primary complaint. Notably, the physical examination revealed no changes in facial features, no enlargement of hands or feet, and no other symptoms typically associated with acromegaly, which might otherwise suggest excessive growth hormone activity. Magnetic Resonance Imaging (MRI) of the pituitary gland indicated that the gland was within normal size parameters, but a small low-intensity lesion mea-suring approximately 3 mm×2 mm identified. This finding was consistent with a pituitary microadenoma. The patient's fasting growth hormone levels were significantly elevated at 8.470 μg/L, compared with the normal range of less than 2.47 μg/L. Conversely, fasting insulin-like growth factor-1 (IGF-1) levels were notably low, recorded at 41 and 52 μg/L, whereas the normal range for a person of his age was between 87 and 234 μg/L. Other pituitary hormones, including those regulating the thyroid, adrenal cortex, and sex hormones, were found to be within normal ranges. Despite this, during the glucose growth hormone suppression test, an abnormal elevation of growth hormone was observed. To investigate further, the patient was administered branched-chain amino acids, and the suppression test was repeated. However, the abnormal elevation of growth hormone persisted, indicating a failure to normalize the response. Given the patient's lack of clinical signs typically associated with elevated growth hormone secretion, the history of liver cirrhosis became a significant consideration. The disparity between elevated growth hormone levels and reduced IGF-1 levels suggested that the pituitary lesion was a non-functional adenoma rather than a source of excess hormone production. Consequently, it was concluded that the abnormal response of growth hormone to the glucose suppression test was likely related to the patient's liver cirrhosis. In addition to chronic liver disease, various other conditions could influence the results of the oral glucose tolerance growth hormone suppression test. According to the literature, factors such as puberty, diabetes, anorexia nervosa, and protein malnutrition could also affect test outcomes. These conditions could cause similar abnormalities in growth hormone dynamics, complicating the diagnosis. Therefore, clinicians must be vigilant and consider these potential influences when interpreting test results.For an accurate diagnosis of acromegaly, it is essential to combine clinical symptoms, detailed medical history, and imaging studies. The presence of conditions like liver cirrhosis should prompt careful interpretation of the test results, ensuring that other contributing factors are not overlooked. This comprehensive approach is crucial to avoid misdiagnosis and to ensure that appropriate treatment strategies are implemented based on a thorough understanding of the patient's overall health status.
Humans ; Male ; Middle Aged ; Pituitary Neoplasms/blood* ; Liver Cirrhosis/blood* ; Adenoma/blood* ; Human Growth Hormone/blood* ; Insulin-Like Growth Factor I/metabolism* ; Acromegaly/etiology* ; Magnetic Resonance Imaging

OBJECTIVE: To explore the clinical features and genetic etiology in a child with Hereditary hemorrhagic telangiectasia (HHT) complicated by growth hormone deficiency. METHODS: A child presented at Yantai Yuhuangding Hospital in October 2014 for "short stature for over 4 years" was selected as the study subject. Peripheral venous blood samples were collected from the child and his parents for genomic DNA extraction and whole-exome sequencing (WES). The pathogenicity of the candidate variants was assessed by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2025-003). RESULTS: The patient, a 4-year-and-2-month-old male, presented with short stature and recurrent epistaxis since early childhood. Initial diagnosis of GHD was made via growth hormone stimulation testing. During follow-up, telangiectatic macules and polycythemia gradually appeared. WES revealed that he has harbored a heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene, which was absent in both parents and classified as likely pathogenic based on ACMG guidelines. Sanger sequencing confirmed the candidate variant to be de novo. CONCLUSION Patients with HHT combined with GHD may exhibit clinical features such as short stature, telangiectasia, and arteriovenous malformations. The heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene probably underlay the pathogenesis of the disease in the proband. Above finding has expanded the mutational spectrum of the ENG gene.
Humans ; Telangiectasia, Hereditary Hemorrhagic/complications* ; Male ; Child, Preschool ; Phenotype ; Endoglin/genetics* ; Mutation ; Human Growth Hormone/deficiency* ; Exome Sequencing

OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Child ; Humans ; Human Growth Hormone/therapeutic use* ; Growth Disorders/therapy*

Idiopathic short stature (ISS) is a term that encompasses a group of short stature disorders with unknown etiology. The genetic factors associated with ISS are complex, and the known genetic mechanisms include alterations in hormones, hormone receptors, or related pathways, defects in fundamental cellular processes (such as intracellular signaling pathways and transcriptional regulation), issues with extracellular matrix or paracrine signaling, as well as genetic variations in the genes encoding these proteins. Recombinant human growth hormone (rhGH) therapy is currently an effective clinical method for improving height in children with ISS. However, the efficacy of rhGH treatment on ISS varies among children with different genetic mechanisms. This paper analyzes and elucidates the genetic mechanisms of ISS and the effects of rhGH on ISS based on existing clinical research, aiming to enhance the understanding of ISS and provide references for improving the height of these children.
Humans ; Human Growth Hormone/therapeutic use* ; Growth Disorders/genetics* ; Child ; Body Height/genetics*

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
Child ; Female ; Humans ; Pregnancy ; Body Height ; Human Growth Hormone/therapeutic use* ; Hyperplasia ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Prospective Studies ; Pituitary Gland/pathology* ; Recombinant Proteins/therapeutic use*

OBJECTIVES: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. METHODS: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. RESULTS: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). CONCLUSIONS The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
Child ; Humans ; Human Growth Hormone/pharmacology* ; Insulin-Like Growth Factor I/pharmacology* ; Fibroblast Growth Factor-23 ; Prospective Studies ; Growth Disorders ; Phosphates/pharmacology* ; Body Height

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.
Child ; Humans ; Growth Hormone/metabolism* ; Insulin-Like Growth Factor I/metabolism* ; Insulin-Like Peptides ; Insulin-Like Growth Factor Binding Protein 3 ; Human Growth Hormone/metabolism* ; Dwarfism, Pituitary/diagnosis*