Journal of Clinical Research in Pediatric Endocrinology最新文献

Objective: Endocrine-disrupting chemicals may influence the process of puberty including the development of premature thelarche (PT). Our aim was to investigate the relationship between exposure to bisphenol A (BPA) and parabens with PT among a sample of Iranian girls.

Methods: This case-control study was conducted in 2022-2023 on girls with a mean (standard deviation) age of 7.5 (0.6) years in Isfahan, Iran. Participants were 90 newly diagnosed PT cases and 114 healthy controls. Spot urine samples were collected from both groups to measure the levels of BPA and paraben metabolites. Analyses of BPA and paraben metabolites included methyl paraben (MeP), ethyl paraben (EtP), propyl paraben, and butyl paraben and benzyl paraben and were performed by gas chromatography-mass spectrometry. The association between concentrations of creatinine-standardized urinary BPA and parabens and PT was analyzed with multiple logistic regression models, after adjusting for potential confounders.

Results: The results showed that individuals in the highest quartile of MeP [odds ratio (OR)=4.3, 95% confidence interval (CI): 1.2-14.9, p=0.023], EtP (OR=4.7, 95% CI: 1.3-17.2, p=0.018) and BPA (OR=5.03, 95% CI: 1.4-17.9, p=0.013) had a significantly higher odds for PT compared to those in the lowest quartile.

Conclusion: The findings of this study suggest that exposure to BPA, MeP and EtP is related to increased odds of early breast development in girls. Limiting the exposure to these chemicals may help to reduce the risk of PT.

Objective: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease caused by the absence or insufficiency of the survival motor neuron (SMN) protein. Human SMN1 (hSMN1) produces fully functional SMN protein but hSMN2 produces only about 10% functional protein. Deletion or mutation in hSMN1 gene leads to SMA, while the hSMN2 copy number modifies disease severity. Increasing hSMN2 expression has emerged as a potential therapeutic approach. In this study, we investigated the effect of growth hormone (GH) on hSMN2 promoter activity using a reporter in Chinese hamster ovary (CHO) cells.

Methods: Three different hSMN2 promoter regions (588 bp, 1036 bp and 1705 bp) were used to show the effect on gene expression of reporter response to GH in this study. Promoters were amplified by polymerase chain reaction (PCR) and cloned into the pGL3 luciferase reporter vector. The ligation reactions were transformed into DH5α cells and positive colonies containing specific hSMN2 promoter inserts were confirmed by PCR with hSMN2-primers. The plasmids carrying hSMN2 promoters were transfected into CHO cells. After transfection, the cells were treated with GH for 24 hours and luciferase activity was measured to assess promoter activity.

Results: All hSMN2 promoter constructs responded to GH. The 1036 bp promoter construct showed the highest luciferase expression upon GH treatment. However, the 1705 bp promoter construct exhibited reduced gene expression compared to the control vector treated with GH.

Conclusion: These findings suggest that GH can modulate hSMN2 expression in hSMN2 promoter dependent manner. GH may be a candidate hormone for SMA treatment by enhancing hSMN2 expression.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionately short stature, lack of expressive language, and distinctive facial features, including a large nose, long eyelashes, deeply set eyes, and a triangular face. We present a case of an 11-year-old Korean girl who was initially suspected of having Noonan-like syndrome but was later diagnosed with FHS. The patient exhibited short stature, developmental language delay, dysmorphic facial features, and early puberty. Targeted exome sequencing revealed a heterozygous mutation, c.7303C>T (p.Arg2435Ter), in the SRCAP gene, confirming a diagnosis of FHS. She responded well to human recombinant growth hormone and gonadotropin-releasing hormone agonist, effectively suppressing bone maturation and improving her height standard deviation score from -4.6 to -2.4.

Objective: Various methods may be used to estimate target height in patients diagnosed with precocious puberty. These methods include the Bayley-Pinneau (BP) and Roche-Wainer-Thissen (RWT) methods. In addition to these methods, in our clinic, we routinely use a practical approach based on the percentiles in growth charts. In this method, the bone age percentile is projected to the end of the percentile curve (at 18 years of age) to estimate the final adult height. We have named this method Bone Age Percentile Curve Projected Height Estimation (BAPCPHE). The aim of this study was to retrospectively compare the effectiveness of these three methods in predicting target height in patients treated for central precocious puberty and who have reached their final height in our pediatric endocrinology clinic.

Methods: Fifty female patients were included. The predicted adult heights (PAH) were calculated at treatment initiation, at the end of the first, second, and third years of treatment, and at the time of final height attainment using the BP, RWT, and BAPCPHE methods, based on the patients’ heights and bone ages.

Results: When the agreement between the PAH calculated by three methods and the final height was analyzed using intraclass correlation coefficient, significant agreement was found for PAH using the BAPCPHE method in the third year. Among the methods, the strongest agreement with final height and PAH was observed with the BP method at the end of treatment, followed by the BAPCPHE method.

Conclusion: The BAPCPHE method allows estimation of PAH quickly, making it a valuable tool in the outpatient setting. Given its simplicity and accuracy, we find the BAPCPHE method preferable.

Objective: Progranulin (PGRN), a growth factor, modulates cell proliferation, wound repair, and inflammation. It is also involved in glucose metabolism and is associated with insulin resistance and diabetes mellitus (DM). In the present study, PGRN levels were measured at admission and during follow-up in children with newly diagnosed type 1 DM (T1DM) and compared to healthy controls.

Methods: Children with T1DM and healthy controls were included. The age, weight, height, body mass index (BMI), severity of acidosis, glucose, insulin, C-peptide, and diabetes-specific autoantibodies of children with newly diagnosed T1DM were collected. PGRN was measured in children with T1DM at admission, at first week of follow-up, and in healthy controls.

Results: A total of 49 children were included; 25 with T1DM [12 Female/13 Male (12F/13M)] and 24 healthy controls (10F/14M). There was no differences in age (11±3.9 years vs 12.1±3.1 years, p=0.269) and BMI standard deviation (SD) score (-0.11±1.49 SD vs. 0.10±0.82 SD, p=0.540) of children with T1DM and healthy controls. The mean basal PGRN level of children with newly diagnosed T1DM was higher than in controls (90.8±17.3 ng/mL vs. 30±11.5 ng/mL, p<0.001). In children with T1DM, mean basal PGRN at admission had declined significantly (58.4±16.9 ng/mL; p<0.001) in the first week after glycemic regulation was achieved but remained significantly higher than in controls (p<0.001).

Conclusion: These findings suggest that elevated PGRN levels in children with newly diagnosed T1DM may reflect either an acute inflammatory response to diabetic ketoacidosis or a persistent alteration in metabolic regulation, or both of these, highlighting the potential role of PGRN as a biomarker in the early course of T1DM.

Objective: Artificial intelligence (AI) is increasingly used in medicine, including pediatric endocrinology. AI models have the potential to support clinical decision-making, patient education, and guidance. However, their accuracy, reliability, and effectiveness in providing medical information and recommendations remain unclear. The aim was to evaluate and compare the performance of four AI models, ChatGPT, Bard, Microsoft Copilot, and Pi, in answering frequently asked questions related to pediatric endocrinology.

Methods: Nine questions commonly asked by parents regarding short stature in pediatric endocrinology were selected, based on literature reviews and expert opinions. These questions were posed to four AI models in both Turkish and English. The AI-generated responses were evaluated by 10 pediatric endocrinologists using a 12-item Likert-scale questionnaire assessing medical accuracy, completeness, guidance, and informativeness. Statistical analyses, including Kruskal-Wallis and post-hoc tests, were conducted to determine significant differences between AI models.

Results: Bard outperformed other models in guidance and recommendation categories, excelling in directing users to medical consultation. Microsoft Copilot demonstrated strong medical accuracy but lacked guidance capacity. ChatGPT showed consistent performance in knowledge dissemination, making it effective for patient education. Pi scored the lowest in guidance and recommendations, indicating limited applicability in clinical settings. Significant differences were observed between AI models (p<0.05), particularly in completeness and guidance-related categories.

Conclusion: The present study highlights the varying strengths and weaknesses of AI models in an area of pediatric endocrinology. While Bard was effective in guidance, Microsoft Copilot excelled at accuracy, and ChatGPT was informative. Future AI improvements should focus on balancing accuracy and guidance to enhance clinical decision-support and patient education. Tailored AI applications may optimize the role of AI in specialized medical fields.

Objective: Nutrition may affect visceral adipose tissue, but the effect of dietary diversity on visceral adiposity is unknown. Our aim was to investigate the relationship between dietary diversity and visceral adiposity indices and biochemical parameters in obese adolescent.

Methods: Subjects were obese adolescents. Participants’ biochemical parameters, anthropometric measurements, and blood pressures were measured. Two days of retrospective food intake records were collected, and dietary diversity scores (DDS) were calculated and divided into tertiles. A DDS score of <4.09 was classified as tertile 1 (low); 4.09-4.96 as tertile 2 (medium); and >4.96 as tertile 3 (high). Visceral adiposity, triglyceride/glucose, lipid accumulation product, and body shape indexes were calculated according to previously published formulas.

Results: The study included 141 obese adolescents (70 males, 49.6%) aged between 12 and 18 years. Insulin and Homeostasis Model assessment for Insulin Resistance (HOMA-IR) values were higher in individuals in Tertile 1 compared to those in other tertiles (p<0.001). The triglyceride/glucose index was lower in individuals in Tertile 3 compared to those in Tertile 1 (p=0.028). In individuals in Tertile 3, fibre (p=0.002), vegetable p<0.001), and whole grain (p<0.001) intake were higher than in other tertiles, while refined grain (p<0.001) and meat consumption (p=0.013) were lower than in other tertiles. A negative correlation was found between the DDS and fasting blood glucose (rho=-0.177; p=0.036), insulin (rho=-0.633; p<0.001), triglycerides (rho=-0.223; p=0.008), HOMA-IR (rho=-0.656; p<0.001), visceral adiposity index (rho=-0.228; p=0.007), triglyceride/glucose index (rho=-0.251; p=0.003), and lipid accumulation product index (rho=-0.200; p=0.018). When confounding factors were controlled for, fasting blood glucose emerged as a significant factor affecting DDS.

Conclusion: High DDS in obese adolescents are associated with lower visceral adiposity, and lower triglyceride/glucose and lipid accumulation product indexes, indices associated with visceral obesity. As DDSs increased, fasting blood sugar, insulin, triglyceride, and HOMA-IR levels decreased.

Objective: Nailfold capillaroscopy (NC) is a non-invasive tool that can detect microvascular changes in the early stages of vascular disease. To assess capillary microarchitecture in children with type 1 diabetes mellitus (T1DM) and its relationship with clinical characteristics, laboratory findings, and glycemic control.

Methods: We included children and adolescents with T1DM, aged 6-18 years, and diagnosed for at least one year and an equal number of age- and sex-matched healthy controls. For all patients with T1DM, data on diabetes duration were collected, and the average annual HbA1c value was calculated for the four measurements made at routine follow-up in the preceeding year. In patients using 24-hour continuous glucose monitoring (CGM) devices, glycemic data from the previous three months were analyzed. The capillaroscopic findings were evaluated by two different researchers with experience in the field of pediatric rheumatology. Capillaroscopic parameters were compared based on glycemic control (HbA1c ≥7.5% vs. <7.5%), disease duration (<5 vs. ≥5 years), time in range (TIR≥70% vs. <70%), and glucose variability (CV≤36% vs. >36%).

Results: The median age of the 55 patients with T1DM was 14.5 (11.3-17.2) years, with a median disease duration of 3.8 (2.3-6.7) years. Compared to controls, patients with T1DM had significantly lower capillary density and more frequent dilated, tortuous, cross-linked, and abnormal capillaries (p<0.001, p<0.001, p<0.001, p=0.01, and p=0.03, respectively). Capillary density was significantly lower in patients with poor glycemic control (p<0.001) and those with longer disease duration (p=0.02). A negative correlation was observed between capillary density and disease duration (r=-0.3, p=0.02). After adjusting for age, gender, body mass index, and diabetes duration, capillary density remained negatively correlated with average HbA1c (r=-0.4, p=0.004). Among CGM users (n=22), capillary density showed a positive correlation with TIR (r=0.5, p=0.04), even after adjustment for confounders.

Conclusion: Children with T1DM exhibited significantly higher microvascular changes, mostly associated with poor glycemic control, compared to healthy controls. NC may be a useful technique for detecting early alterations in the capillary structures of children with T1DM, even in the absence of overt clinical microvascular complications.

Diabetic peripheral neuropathy (DPN) is the most common form of acquired neuropathy. In children with type 1 diabetes, the reported prevalence of DPN varies widely, ranging from 3% to 62%, mainly due to differences in screening methodologies and patient population characteristics. While intraepidermal nerve fiber density assessment via skin biopsy remains the gold standard for detecting small fiber neuropathy, nerve conduction studies are the established diagnostic tool for large fiber involvement. However, several novel and non-invasive diagnostic tools have emerged recently, offering improved screening options for early-stage and subclinical DPN. The frequent presence of asymptomatic neuropathy in pediatric populations, combined with its limited treatment options, underscores the importance of early identification of modifiable risk factors thus reducing the risk of developing clinically significant DPN. This review provides a comprehensive overview of the current evidence on the prevalence, risk factors, and modern diagnostic approaches for DPN in children with diabetes.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare genetic disease mainly associated with Carney complex (CNC), which is caused by germline mutations of the regulatory subunit type I-alpha of the cAMP-dependent protein kinase (PRKAR1A) gene. We report three cases suffering from CNC with unique features in diagnosis and follow-up. All cases had obesity and a cushingoid appearance and exhibited laboratory characteristics of hypercortisolism. However biochemical and radiological examinations initially suggested Cushing’s disease in one case. All of the cases were treated surgically; two of them underwent bilateral adrenalectomy at once, one of them had unilateral adrenalectomy at first but required contralateral adrenalectomy after nine months. Contrary to what is usually known regarding PPNAD, the adrenal glands of two cases (Case 2 and 3) had a macronodular morphology. Genetic analyses revealed pathogenic variants in PRKAR1A (Case 1: c.440+5 G>A, not reported in the literature; cases 2 and 3: c.349G>T, p.V117F). One case developed Hodgkin lymphoma five year after adrenalectomy, this association was not previously reported with CNC. The findings of these families provides important information for a better understanding of the genetic pathogenesis, diagnosis, and clinical management of CNC. Hodgkin lymphoma may be a component of CNC.