Search Results (72)

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article

Background/Objectives: Hyperprolinemia is a rare autosomal recessive disorder with two distinct types: I (HPI) and II (HPII). The clinical presentation varies widely, with some individuals remaining asymptomatic and others exhibiting neurological, renal, or auditory defects and seizures. However, it has never been associated with hypoglycemia. The present case report describes a 5-year and 6/12-month-old boy with HPII, with an episode of severe hypoglycemia and Pituitary Stalk Interruption Syndrome (PSIS) with isolated growth hormone (GH) deficiency (GHD). Results: The boy was presented to the Department of Pediatric Endocrinology for routine thyroid function assessment due to hypothyroidism. He was diagnosed with HPII at the age of 2 years old during an investigation for seizure episodes. Clinically, the boy exhibited attention deficit hyperactivity disorder (ADHD) and a reduction in growth velocity (1.6 cm/year). Hematological and biochemical analyses were within the reference range. Hormone profiling revealed lower-than-expected insulin-like growth factor-1 (IGF-1) concentrations, prompting a GH stimulation test, which, in turn, revealed GHD. Brain magnetic resonance imaging (MRI) showed features consistent with PSIS. Noteworthy is the occurrence of severe hypoglycemia during an episode of gastroenteritis, leading to hospitalization, eventually attributed to GHD. Following the exogenous administration of recombinant human GH, the boy exhibited increased growth velocity, with no adverse events over the follow-up period. Conclusions: Hyperprolinemia is a rare condition; in this context, the occurrence of severe hypoglycemia accompanied by a low growth velocity poses a challenge for the clinical pediatrician. Furthermore, the coexistence of hyperprolinemia and PSIS has never been reported in the literature thus far. Full article

Background: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by mutations in the CYP27B1 gene, leading to a deficiency in active vitamin D (1,25-dihydroxyvitamin D). This study examines the genotypic and phenotypic characteristics of VDDR1A in Vietnamese children. Patients and Methods: A retrospective analysis was conducted on 19 Vietnamese children diagnosed with VDDR1A. Clinical, radiological, biochemical, and molecular data were collected. Rickets Severity Scores (RSSs), biochemical parameters, and height standard deviation scores (HtSDSs) were used to assess the severity of the condition. Results: The study included 19 children from 17 families (ten males and nine females). The median age of rickets diagnosis was 19.2 months, while with VDDR1A, the median time of diagnosis was 7.5 months. Common symptoms among the children included thickened wrists and ankles (19/19), genu varum or genu valgum (18/19), failure to thrive (18/19), rachitic rosary (12/19), and delayed walking (11/19). The radiographic features showed that all children had cupping, splaying, and fraying, twelve children had rachitic rosary, and six exhibited pseudofractures. The biochemical findings showed severe hypocalcemia, normal or mildly low serum phosphate, elevated alkaline phosphatase and parathyroid hormone levels, and normal serum 25-hydroxyvitamin D levels. Genetic analysis identified biallelic CYP27B1 variants, including one known pathogenic frameshift mutation, c.1319_1325dup p.(Phe443Profs*24), one novel likely pathogenic missense variant, c.616C>T p.(Arg206Cys), and one novel pathogenic frameshift mutation, c.96_97del p.(Ala33Thrfs*299). The c.1319_1325dup p.(Phe443Profs*24) variant was the most common, present in 18 out of 19 children. Conclusions: The children with VDDR1A in this study presented with growth failure and skeletal deformities. Key findings included severe hypocalcemia, elevated alkaline phosphatase and parathyroid hormone levels, normal or elevated 25(OH)D, and high RSSs. Predominant frameshift mutations in CYP27B1, especially c.1319_1325dup, highlighted the importance of early genetic diagnosis for optimal management. Additionally, two novel CYP27B1 variants were identified, expanding the known mutation spectrum of VDDR1A. Full article

Background: Among the potential indications for growth hormone (GH) therapy is the presence of mutations in the SHOX (short stature homeobox-containing) gene, located in the telomeric pseudotautosomal region (PAR1) on the short arm of both sex chromosomes. Despite general recommendations supporting GH therapy in these cases, there is a lack of comprehensive evidence specifically evaluating its efficacy and safety in this subgroup of pediatric patients. Aim: The objective of this scoping review was to evaluate the efficacy and safety of growth hormone therapy in patients with SHOX gene variants, providing a narrative synthesis of the included studies. Materials and Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. We summarized information extracted from 22 articles identified by our search strategy. Currently, only one randomized clinical trial has analyzed the efficacy profile of GH in patients with SHOX mutations. Results: Growth hormone is a valuable therapeutic aid for these patients. However, its prescription in children with SHOX gene mutations should consider the specific characteristics of each patient, similar to the approach taken for patients with idiopathic growth hormone deficiency (GHD). Conclusion: Growth hormone therapy in patients with SHOX gene alterations appears to be both safe and effective. However, longitudinal prospective studies and targeted clinical trials are necessary to confirm these findings. Despite this, GH remains one of the preferred hormonal therapies for patients with short stature and confirmed SHOX gene mutations. Full article

Selenium (Se) is a vital trace element for children, playing a crucial role in numerous physiological processes, including antioxidant defense, immune regulation, thyroid function, and bone metabolism. Emerging evidence highlights its potential impact on child development and growth while also underscoring the complexity of its mechanisms and the global variations in Se intake. The aim of this review is to comprehensively elucidate the significance of Se in various biological processes within the human body, with a focus on its role in child development and growth; its biochemical effects on the nervous system, thyroid function, immune system, and bone tissue; and the implications of Se deficiency and toxicity. This review integrates findings from experimental models, epidemiological studies, and clinical trials to explore Se’s role in neurodevelopment, growth regulation, and immune competence in children. Selenoproteins, which regulate oxidative stress and thyroid hormone and bone metabolism, are essential for normal growth and cognitive development in children. Se deficiency and toxicity has been linked to impaired immune function, growth retardation, and decreased immune function. The findings underscore Se’s influence on various biological pathways that are critical for healthy child development and its broader importance for child health. Public health strategies aimed at optimizing selenium intake may play a pivotal role in improving pediatric health outcomes worldwide. Full article

Background/Objectives: the aim of the current cross-sectional study is to explore and compare the emotional and behavioural conditions of children and adolescents with short stature (i.e., familial short stature and constitutional delay of growth), idiopathic growth hormone deficiency (GHD), and normal height. Methods: Twenty-nine participants (15 males, 14 females; mean age ± standard deviation (SD) = 11.2 ± 1.96 years) with short stature (height standard deviation score (SDS): −2.10 ± 0.57), 10 age-matched participants (4 males, 6 females; mean age ± SD = 10.9 ± 2.35 years) with growth hormone deficiency (GHD; height SDS: −2.44 ± 0.29), and 36 age-matched participants (19 males, 17 females; mean age ± SD = 11.3 ± 1.93 years) with normal stature (height SDS: 0.56 ± 0.78) were admitted to this study. Psychological distress was evaluated using the Depression Anxiety and Stress Scale (DASS-21), and emotional and behavioural problems using the Child Behaviour Checklist for Children (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Results: Participants with GHD exhibited higher levels of the “withdrawn/depressed subscale” score of CBCL (H = 7.794, df = 2, p = 0.020), compared to their peers with normal height, while no significant differences were observed between participants with short stature and those with normal stature. Normal-statured participants reported higher levels of the “conduct problems” subscale score (H = 10.421, df = 2, p = 0.005) and the “rule-breaking behaviour” subscale score of CBCL (H = 10.358, df = 2, p = 0.006) compared to both short-statured groups. No significant differences among the three subgroups were found in the DASS-21 and SDQ scores questionnaires, suggesting the lack of short stature-dependent effects on psychological distress and emotional and behavioural adjustment. Conclusions: Although participants with GHD exhibited higher levels of the “withdrawn/depressed subscale” score of CBCL (H = 7.794, df = 2, p = 0.020) compared to their peers with normal height, participants with short stature did not experience the same problems. Although short-statured participants had lower levels of “conduct problems” and “rule-breaking behaviours” scores than their normal-statured peers, the psychological distress and emotional and behavioural adjustment were not affected by short stature, being comparable to those recorded in normal-statured participants. Full article

Before 1985, growth hormone (GH) was extracted from human pituitaries, and its therapeutic use was limited to children with severe GH deficiency (GHD). The availability of an unlimited amount of recombinant GH (rhGH) allowed for investigating the efficacy of its therapeutic use in a number of conditions other than GHD. Nowadays, patients with Turner syndrome, SHOX deficiency, Noonan syndrome, Prader–Willi syndrome, idiopathic short stature, chronic kidney disease, and children born small for gestational age can be treated with rhGH in order to improve adult height. In patients with Prader–Willi syndrome, rhGH therapy also improves body composition and cognitive function. Large post-marketing multinational studies in a large number of pediatric patients demonstrated a good safety profile for rhGH. Recently, long-acting formulations of rhGH have been approved and licensed for GHD, and clinical trials are ongoing for other conditions. In this paper, we review the rhGH therapy in children with conditions other than GHD. Full article

Background/Objectives: Hypothyroidism can profoundly affect growth, particularly if it insidiously arises during early childhood. Congenital hypothyroidism is now detected through newborn screening, significantly improving the overall growth outcomes of these children. Conversely, acquired hypothyroidism often results in delayed somatic growth and shorter stature, with many affected children initially remaining non-symptomatic. The main objective of this review is to summarize the current knowledge about the impacts of acquired hypothyroidism on children’s growth outcomes. Methods: We performed a literature review to analyze growth and final height in children with acquired hypothyroidism, matching the following keywords: “hypothyroidism & growth”, “hypothyroidism & height”, “hypothyroidism & stature”, “hypothyroidism & development”, “hypothyroidism & auxological parameters”. We reviewed each article that met the eligibility criteria, and after a thorough selection, we included 16 studies. Results: Growth arrest is frequently noted as a symptom in hypothyroidic children, with substantial portions of affected children presenting below the third percentile for height. The timing of diagnosis significantly influences growth outcomes: those diagnosed during puberty tend to experience less catch-up growth due to accelerated skeletal maturation. Even if thyroxine replacement can induce rapid catch-up growth, it may be incomplete if treatment begins during puberty or if there is a markedly prolonged deficiency of thyroid hormones. While levothyroxine therapy typically results in some degree of catch-up growth, many children do not reach their expected genetic height. Conclusions: This review highlights the necessity of both early diagnosis and treatment of acquired hypothyroidism. Even if many children show improvements in height velocity post-treatment, the complete normalization of growth may remain elusive. Full article

Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease globally. NAFLD is a complex pathology, considered to be the hepatic expression of metabolic syndrome (MetS). It is supposed to become the main indication for liver transplantation in the coming years and is estimated to affect 57.5–74.0% of obese people, 22.5% of children and 52.8% of obese children, with 50% of individuals with type 2 diabetes being diagnosed with NAFLD. Recent research has proved that an increase in adipose tissue insulin resistance index is an important marker of liver injury in patients with NAFLD. Despite being the main underlying cause of incidental liver damage and a growing worldwide health problem, NAFLD is mostly under-appreciated. Currently, NAFLD is considered a multifactorial disease, with various factors contributing to its pathogenesis, associated with insulin resistance and diabetes mellitus, but also with cardiovascular, kidney and endocrine disorders (polycystic ovary syndrome, hypothyroidism, growth hormone deficiency). Hepatitis B and hepatitis C, sleep apnea, inflammatory bowel diseases, cystic fibrosis, viral infections, autoimmune liver diseases and malnutrition are some other conditions in which NAFLD can be found. The aim of this review is to emphasize that, from the clinician’s perspective, NAFLD is an actual and valuable key diagnosis factor for multiple conditions; thus, efforts need to be made in order to increase recognition of the disease and its consequences. Although there is no global consensus, physicians should consider screening people who are at risk of NAFLD. A large dissemination of current concepts on NAFLD and an extensive collaboration between physicians, such as gastroenterologists, internists, cardiologists, diabetologists, nutritionists and endocrinologists, is equally needed to ensure we have the knowledge and resources to address this public health challenge. Full article

Background: Hypophosphatemia is a known side-effect of parenteral iron administration, especially after intravenous ferric carboxymaltose (FCM). Fibroblast growth factor 23 (FGF23) is thought to play an important role in the pathophysiology of serum phosphate homeostasis. This study aimed to investigate the effects of FCM on FGF23 serum levels in FCM-treated pediatric patients with iron deficiency (ID)/iron deficiency anemia (IDA) caused by gastrointestinal diseases. Methods: Over 30 months, FGF23 serum levels were assessed prospectively in children with ID/IDA due to gastrointestinal diseases and treated with FCM infusion. Serum levels of intact FGF23 (iFGF23) were assessed and correlated to phosphate serum levels and factors of bone metabolism. Blood sampling was performed in three phases: before FCM infusion, 7–10 days after FCM infusion, and 6–8 weeks after FCM infusion. Results: A total of 42 FCM infusions were given to 35 children (20 girls) with a mean age (±SD) of 12.2 (±4.03) years (range: 2–16 years). The median levels of iFGF23 did not show a significant difference across the three phases (p = 0.56). No significant correlation was found between iFGF23 levels and 25-hydroxyvitamin D/parathyroid hormone/serum phosphate/serum calcium/alkaline phosphatase. No significant change was noted between pre- and post-treatment serum phosphate levels. However, four children (11.42%) developed asymptomatic and transient hypophosphatemia. Conclusions: No significant difference was found between pre-and post-FCM infusion serum iFGF23 levels and bone metabolism parameters. An increase of iFGF23 serum levels 7–10 days after FCM infusion was noted in patients with hypophosphatemia. Full article

The utilization of recombinant human growth hormone therapy in pediatric populations, originally approved to treat diseases of growth hormone deficiency, has expanded to encompass a broader range of indications, leading to a threefold increase in its utilization in the last two decades. However, concerns regarding its safety, particularly those that are orthopedic in nature, have grown alongside its increasing popularity. Growth hormone usage has been reported to predispose patients to a multitude of common orthopedic conditions, including carpal tunnel syndrome, Legg–Calve–Perthes disease, little league shoulder, Osgood–Schlatter disease, osteochondritis dissecans, scoliosis, Sever’s disease, and slipped femoral capital epiphysis. The pathways by which growth hormone therapy can precipitate orthopedic pathology has been shown to be multifactorial, involving mechanisms such as hormonal changes, growth plate instability, rapid growth, and increased susceptibility to overuse injury. This review examines the orthopedic consequences of growth hormone therapy in pediatric patients by discussing these potential pathophysiologic mechanisms of injury and analyzing subsequent clinical manifestations. By examining processes underlying these complications, we highlight the need for orthopedic surveillance and management in children receiving GHT, particularly those with pre-existing musculoskeletal comorbidities or high levels of physical activity. Our findings underscore the importance of a multidisciplinary approach involving co-management by pediatricians, endocrinologists, and orthopedic surgeons to optimize safety and outcomes for these patients. Directions for future research include correlating pathophysiologic mechanisms to injury patterns, investigating long-term complications in recently approved growth hormone therapy indications, and informing clinical guidelines on the management of orthopedic injuries in this patient population. Full article

Recombinant human growth hormone therapy (rhGH) has been widely accepted as the safe treatment for short stature in children with such genetic syndromes as Prader–Willi syndrome and Turner or Noonan syndrome. Some patients with short stature and rare genetic syndromes are treated with rhGH as growth hormone-deficient individuals or as children born small for their gestational age. After years of experience with this therapy in syndromic short stature, it has been proved that there are some aspects of long-term rhGH treatment beyond growth promotion, which can justify rhGH use in these individuals. This paper summarizes the data of a literature review of the effects of rhGH treatment beyond growth promotion in selected genetic syndromes. We chose three of the most common syndromes, Prader–Willi, Turner, and Noonan, in which rhGH treatment is indicated, and three rarer syndromes, Silver–Russel, Kabuki, and Duchenne muscular dystrophy, in which rhGH treatment is not widely indicated. Many studies have shown a significant impact of rhGH therapy on body composition, resting energy expenditure, insulin sensitivity, muscle tonus, motor function, and mental and behavioral development. Growth promotion is undoubtedly the primary benefit of rhGH therapy; nevertheless, especially with genetic syndromes, the additional effects should also be considered as important indications for this treatment. Full article

We intend to evaluate the association of intact Fibroblast Growth Factor 23 (i-FGF23), a phosphaturic hormone that contributes to anemia of inflammation, with markers of iron homeostasis, inflammation, and bone mineral metabolism in acute pediatric infections. Seventy-nine children, aged 1 month–13 years, out of which forty-two were males and thirty-seven females, participated in this study. Children with diseases and nutrient deficiencies causing anemia were excluded. Twenty-six patients had bacterial infections, twenty-six had viral infections, and twenty-seven children served as healthy controls. Complete blood count, markers of inflammation, iron and mineral metabolism, serum hepcidin, and i-FGF23 were compared between the groups. Thirty-nine percent of patients with bacterial infection and twelve percent of patients with viral infection presented characteristics of anemia of inflammation (p < 0.001). Ninety-two percent of patients with bacterial infection and eighty-one percent of patients with viral infection had functional iron deficiency (p < 0.001). Hepcidin was significantly positively correlated with the duration of fever, markers of inflammation, and negatively with iron, mineral metabolism parameters, and i-FGF23. i-FGF23 was positively correlated with iron metabolism parameters and negatively with the duration of fever, markers of inflammation, and hepcidin. Hepcidin levels increase, whereas i-FGF23 levels decrease in acute pediatric infections. Further research is required to understand the role of FGF23 in the hepcidin–ferroportin axis and for hepcidin in the diagnosis of bacterial infections and mineral metabolism. Full article

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m² per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice. Full article

Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles. Full article