Search Results (369)

Background: SET domain-containing 5 (SETD5) is a member of the protein lysine-methyltransferase family. SETD5 gene mutations cause disorders of the epigenetic machinery which determinate phenotypic overlap characterized by several abnormalities. SEDT5 gene variants have been described in patients with KBG and Cornelia de Lange (CdL) syndromes. Case description: A female patient with severe short stature and intellectual disability had been followed since she was 9 years old. Several causes of short stature were ruled out. At the age of 12 years, her height was 114 cm (−5.22 SDS), weight 19 kg (−5.88 SDS), BMI 14.6 kg/m² (−2.26 SDS), and was Tanner stage 1. The target height for the proband was 151.65 cm (−1.80 SDS). The bone age (BA) was delayed by 3 years compared to chronological age. The growth rate was persistently deficient (<<2 SDS). Physical examination revealed dysmorphic features. Genetic analysis documented a de novo SETD5 gene mutation (c.890_891delTT), responsible for phenotypes in the context of an overlap syndrome between the phenotype of MDR23, CdL and KBG syndromes. Recombinant growth hormone therapy (rhGH) was started at the age of 12 years. After both one year (+3.16 SDS) and two years (+2.9 SDS), the growth rate significantly increased compared with the pre-therapy period. Conclusion: This is the first case of a patient with overlap syndrome due to SETD5 mutation treated with rhGH. The review of the scientific literature highlighted the clinical and molecular features of SETD5 gene mutation and the use of rhGH therapy in patients suffering from CdL and KBG syndromes. Full article

Phosphorus deficiency poses a significant challenge to the growth and productivity of crops, particularly in nutrient-poor soils. This study investigates the effects of phosphorus deficiency on the growth, endogenous phytohormones, metabolome, and transcriptome of sweet potato (Ipomoea batatas L.) over a growth period from 30 to 120 days. We found that low phosphorus conditions significantly reduced both above- and below-ground biomass, while tuber number remained unchanged. Endogenous phytohormone analysis revealed altered levels of abscisic acid (ABA), indole-3-acetic acid (IAA), and cytokinins, indicating a complex hormonal response to phosphorus starvation. Transcriptomic analysis identified a total of 6324 differentially expressed genes (DEGs) at 60 days, with significant enrichment in pathways related to stress response and phosphorus utilization (PAPs and PHO1). Metabolomic profiling revealed notable shifts in key metabolites, with consistent downregulation of several phosphorous-related compounds. Our findings highlight the intricate interplay between growth, hormonal regulation, metabolic reprogramming, and gene expression in response to phosphorus deficiency in sweet potato. This research underscores the importance of understanding nutrient stress responses to enhance sweet potato resilience and inform sustainable agricultural practices. Future research should focus on exploring the potential for genetic and agronomic interventions to mitigate the effects of phosphorus deficiency and optimize sweet potato productivity in challenging environments. Full article

The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article

The appearance rate of nutrients into systemic circulation affects hormones like insulin and through that efficiency of growth. This also affects mineral requirements critical for metabolism, notably phosphate (P), magnesium (Mg), and potassium (K). Fasting animals have a downregulated metabolism, upon which P, Mg, and K are exported from their cells into the blood and are subsequently excreted in their urine. Abrupt resumption of feed intake, especially of highly glycemic feeds, creates an acute need for these minerals, which can result in deficiency symptoms, particularly with P deficiency. In human medicine, this is called refeeding syndrome: a large meal after a period of fasting can prove fatal. Young animals seem to be especially sensitive, likely driven by their ability to grow rapidly and thus to drastically upregulate their metabolism in response to insulin. Symptoms of P deficiency are fairly a-specific and, consequently, not often recognized. They include edema, which makes it appear as if piglets are growing well, explaining the high gain/feed rate typically seen immediately after weaning, even when piglets are eating at or below the maintenance requirements. Phosphate deficiency can also result in hypoxia and hypercarbia, which may trigger ear necrosis, Streptococcus suis infections, or even death. Hypophosphatemia can also trigger rhabdomyolysis, which may contribute to tail-biting, but this requires further study. Arguably, when fasting cannot be avoided, diets for newly weaned piglets should be formulated to avoid these problems by lowering their glycemic load and by formulating diets according to the piglets’ actual requirements inspired by their genuine intake and health and not simply by extrapolating from older animals. Full article

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based on serum 25(OH)D concentrations: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Clinical and hormonal parameters were compared across groups. Spearman’s correlation and multiple linear regression analyses were used to explore the relationship between vitamin D levels and peak luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation. Results: No significant differences were observed among the vitamin D groups in terms of age at diagnosis, body mass index (BMI), or other auxological measures. However, serum 25(OH)D levels showed a weak but significant positive correlation with LH peak values (rho = 0.23, p = 0.037). In multivariable regression analysis, vitamin D levels remained an independent predictor of LH peak (β = 0.125, p = 0.036), whereas BMI standard deviations (SDS), growth velocity SDS, and age at diagnosis did not show significant associations. Conclusions: Higher serum vitamin D levels are independently associated with greater LH peak responses in girls with idiopathic CPP. These findings support a potential modulatory role of vitamin D in the neuroendocrine mechanisms underlying pubertal onset and warrant further prospective studies to clarify its clinical relevance. Full article

It is hypothesized that growth hormone deficiency (GHD) is associated with increased oxidative stress (OS), contributing to elevated cardiovascular risk. This preliminary study evaluates changes in OS markers and cardiovascular biomarkers in 15 adult patients with severe GHD undergoing 12 months of recombinant human growth hormone (rhGH) therapy. IGF-1 concentrations increased significantly following 6 and 12 months of therapy (p = 0.0003 and p = 0.0001, respectively). These changes were accompanied by a significant decrease in endothelin-1 (ET-1) levels at 12 months (p = 0.007), as well as reductions in asymmetric dimethylarginine (ADMA) levels at both 6 and 12 months (p = 0.01 for each timepoint). Total oxidative capacity (TOC) decreased significantly after 6 months of therapy (p = 0.02), followed by a significant increase at 12 months (p = 0.04), whereas total antioxidant capacity (TAC) showed a significant increase at 12 months (p = 0.02). Tissue fat % showed significant reductions at 6 months (p = 0.006), suggesting early improvements in body composition. Correlation analyses indicated negative associations between IGF-1 and TOC (p < 0.006; R = −0.73), and positive associations with TAC (p < 0.001; R = 0.83). These findings suggest that rhGH therapy in adult patients with severe GHD reduces OS and cardiovascular risk through the modulation of biomarkers and improved body composition. This study explores the role of rhGH therapy in reducing cardiovascular risks in GHD, emphasizing the importance of individualized treatment approaches. Full article

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

Nitrogen is an important nutrient required for plant growth and development, but most of the time plants face nitrogen deficiency, all it is important to study the mechanism of low nitrogen tolerance in plants. This study addresses this gap by investigating the role of the StDWF1 gene through the generation and analysis of transgenic potato lines overexpressing StDWF1 (OE1, OE2, OE3). Exogenous BL treatment showed that the StDWF1 gene responded to oleuropein lactone. Phenotypic assessments under normal nitrogen (NN) and low nitrogen (LN) conditions demonstrated that OE2 consistently outperformed WT, showing a 43% increase in root vitality and a 23% retention of chlorophyll under LN. Additionally, OE2 transgenics accumulated significantly higher levels of nitrate nitrogen (64.1% increase) and ammonium nitrogen (53% increase) compared to WT. Enzymatic assays further confirmed elevated activities of glutamine synthetase and nitrate reductase in both OE1 and OE2 lines. Hormone analyses showed that BL content of StDWF1 overexpression lines was significantly increased under LN conditions, higher Oleandrin lactone (BL) content of OE2 improved plant stress tolerance, and WT was more affected by low nitrogen stress than OE2, resulting in higher levels of stress hormones than OE2. Temporal gene expression analysis showed significant upregulation of key nitrogen metabolism-related genes (NR, NiR, AT, NRT2.1) in OE2, with StDWF1 expression reaching 79% higher than WT at 3 h. Protein–protein interaction assays, including yeast two-hybrid and BiLC assays, verified the interaction between StDWF1 and StGRP1, suggesting the existence of a functional network to enhance low-nitrogen tolerance in potato plants. In conclusion, these findings suggest that overexpression of StDWF1 significantly enhances low-nitrogen tolerance in transgenic potato lines, providing a promising strategy for improving crop performance under nitrogen-limited conditions. Full article

Sub-optimal light environments in controlled agricultural settings often limit the productivity of plants. While LED supplementary lighting has been widely adopted to mitigate light deficiencies, the spatial arrangement of LED light sources remains a critical but under-explored factor affecting plant physiological responses. In this study, we used the affiliation function method to comprehensively analyze the effects of four spatial LED supplementary lighting configurations—top-down lighting (T1), mid-canopy upward lighting (T2), mid-canopy downward lighting (T3), and bottom-up lighting (T4)—on the growth and photosynthetic performance of tomato plants. Our findings reveal that the T1 treatment significantly increased light absorption in the upper and middle leaves, enhanced photosynthetic efficiency, promoted the CO₂ assimilation rate, and elevated the activities of key Calvin cycle enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), fructose-1,6-bisphosphatase (FBPase), transketolase (TK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and fructose-1,6-bisphosphate aldolase (FBA). These changes led to improved carbohydrate metabolism and biomass accumulation. Additionally, the T4 treatment markedly enhanced photosynthetic activity in the lower leaves, increasing sugar metabolism-related enzyme activities, such as sucrose synthase (SS), sucrose phosphate synthase (SPS), acid invertase (AI), and neutral invertase (NI). Consequently, compared with the CK treatment, the T4 treatment significantly increased the accumulation of glucose, fructose, and sucrose, with increases of 47.36%, 27.61%, and 87.21%, respectively. Furthermore, LED supplementation regulated endogenous hormone levels, thereby promoting overall plant growth. This study highlights the importance of the spatial arrangement of LEDs in optimizing light distribution and enhancing plant productivity, providing valuable theoretical and practical insights for improving agricultural practices in controlled environments. Full article

Background/Objectives: Growth hormone deficiency (GHD) is a rare endocrine disorder characterized by inadequate secretion of growth hormone, which affects growth, cellular processes, and physiological functions. In addition to growth impairment, GHD is associated with a range of otorhinolaryngological (ENT) symptoms, such as sensorineural hearing loss, dizziness, and voice alterations. These symptoms may be underrecognized due to a lack of routine ENT evaluations in GHD management. Methods: This systematic review, conducted in accordance with PRISMA guidelines, assessed the prevalence of ENT symptoms in patients with GHD by analyzing studies from the PubMed, Embase, and Scopus databases. Results: Based on the analysis of eleven studies that met the inclusion criteria, more than half of patients with GHD experience ENT symptoms (61.4%). Symptom variability appeared to correlate with treatment access, age of onset, and the presence of comorbidities. The study underscores the importance of routine ENT assessments as part of the multidisciplinary management of patients with GHD. Conclusions: Early detection and management of ENT symptoms may significantly improve quality of life, reduce social and educational challenges, and support long-term health outcomes. Further research is needed to clarify the role of recombinant human growth hormone therapy in mitigating ENT manifestations in this patient population. Full article

Background and Clinical Significance: Joubert syndrome (OMIM #213300) is a rare predominantly autosomal recessive inherited condition characterized by the classic cerebellar vermis hypoplasia and brainstem anomalies (also known as the “molar tooth sign”), hypotonia, and developmental delays. Joubert syndrome is a ciliopathy that affects multiple systems including the central nervous system, eyes, kidneys, liver, respiratory, musculoskeletal system, cardiovascular system, and endocrine system. Endocrine abnormalities are not uncommon in Joubert syndrome, such as growth hormone deficiency, thyroid hormone deficiency, central diabetes insipidus, hypopituitarism, micropenis, and obesity. However, a new-onset type 1 diabetes in childhood is not common in Joubert syndrome. Case Presentation: Herein, we report a case of a 7-year-old male with a history of Joubert syndrome presenting with polydipsia, polyuria, weight loss, and hyperglycemia who was diagnosed with type 1 diabetes. Conclusions: While diabetes has been reported as a rare complication in Joubert syndrome, this is the first case report of Joubert syndrome to accentuate new-onset type 1 diabetes as an endocrine complication. Full article

Turner syndrome (TS) is a genetic disorder caused by abnormalities in one of the X chromosomes. Individuals with TS have a higher incidence of autoimmune thyroid disorders, particularly Hashimoto’s disease, leading to thyroid dysfunction, most commonly hypothyroidism. Hormonal imbalance, growth hormone deficiency, and reduced physical activity contribute to muscle weakness in TS patients, and thyroid dysfunction can exacerbate these effects. The purpose of this study was to evaluate whether thyroid factors affect muscle strength in female patients with TS. The study included 70 women with TS and 88 age- and weight-matched controls. TS diagnoses were genetically confirmed (mosaic karyotypes: n = 20; monosomy X: n = 37; structural abnormalities: n = 7). The main criterion for exclusion from the study was unbalanced thyroid function. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid antibodies (anti-thyroid peroxidase antibodies (aTPO), anti-thyroglobulin antibodies (aTG)) were measured, and muscle strength was assessed using hand-held dynamometry. In TS patients, higher TSH levels were positively correlated, and higher fT4 levels were negatively correlated with muscle strength. No such correlations were found in controls. Thyroid compensation may impact musculoskeletal health in TS. Lower-normal TSH levels are associated with reduced muscle strength, and autoimmune thyroid changes like aTPO and aTG may contribute to muscle deterioration. Further research is needed to confirm these findings. Full article

Recombinant human growth hormone (rhGH) is utilized in pediatric patients with short stature for a variety of indications, including those in which the primary growth defect is not related to growth hormone deficiency (GHD). However, due to the instability of the hormone in the gastrointestinal tract and its short half-life, an alternative route of administration is being sought, which may be the skin. One strategy to extend the half-life of proteins involves the use of biodegradable polymeric matrices for transdermal drug delivery systems. While hydrogels are recognized for their high stability, the transport of proteins through the skin may be hindered. To address this, the use of active carriers is being investigated to enhance the efficiency of protein permeation through the skin. In this study, an effort was made to optimize the concentration of phosphitin (PV) as a carrier for somatotropin (STH). PV is a protein that possesses a distinctive cation chelating capability and amphiphilic character. As the concentration of PV increased, the rate of its emulsifying activity increased concomitantly. Methylcellulose (MC) was used as the hydrogel matrix. The study investigated three distinct concentrations of PV to ascertain the most optimal concentration to enhance STH availability. Following the formulation of hydrogel compositions containing STH and PV, the permeation process through porcine skin was examined using Franz’s chambers. The findings revealed that the incorporation of PV significantly impacted both the penetration time of STH and the extent of STH penetration. Subsequently, an extensive evaluation of the physicochemical parameters of the formulations, encompassing pH, rheological, and textural properties, was conducted to assess their suitability for skin application. This evaluation aimed to ensure not only adequate persistence time of the formulation on the skin surface but also formulation stability and persistence of the active substance (STH). 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