Journal of Clinical Research in Pediatric Endocrinology最新文献

{"title":"Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric Cohort","authors":"Silvia C Martínez Rueda, Maria del Pilar Montilla, Carolina Baquero, Susana Gómez, Maria Victoria Lopera, Nora Alejandra Zuluaga, Adriana Carolina Forero, Gustavo Giraldo, Nicolás Pineda Trujillo, Juan Camilo Martínez, Paola Durán Ventura, Juan Manuel Alfaro","doi":"10.4274/jcrpe.galenos.2026.2025-10-7","DOIUrl":"10.4274/jcrpe.galenos.2026.2025-10-7","url":null,"abstract":"<p><strong>Objective: </strong>Describe the clinical manifestations and genetic variants of Noonan syndrome (NS) in a Colombian pediatric population and to identify the genes most frequently associated with specific phenotypic features.</p><p><strong>Methods: </strong>A retrospective observational study was conducted on patients under 18 years of age diagnosed with NS between 2013 and 2023. Clinical and molecular data were collected from medical records across several hospitals in Colombia. Molecular confirmation was achieved in all included patients through next generation sequencing-based clinical exome sequencing. However, parental samples were not available for segregation analysis in all cases. Descriptive statistical analyses were performed using R version 4.3.1 to evaluate demographic, clinical, and genetic variables.</p><p><strong>Results: </strong>Among the 45 patients included (21 females, 24 males; mean age at diagnosis 7.5±5.2 years), pathogenic variants were identified across 13 genes, with <i>PTPN11</i> being the most frequent (26/45, 57.8%), followed by <i>PPP1CB</i> and several less frequent genes including <i>SOS1, SOS2, LZTR1, RAF1, MAP2K1, KRAS, NRAS, BRAF, CBL, NF1</i>, and <i>SHOC2</i>. The most common phenotypic features were congenital heart defects (80%, 36/45), predominantly pulmonary stenosis (31.1%, 14/45), short stature (66.7%, 30/45), and learning difficulties (51.1%, 23/45). Seven patients developed neoplasms. Juvenile myelomonocytic leukemia was the most frequent neoplasm and occurred mainly in patients with <i>PTPN11</i> variants. Ten patients (22.2%) received growth hormone therapy.</p><p><strong>Conclusion: </strong>This study represents the first genetically characterized Colombian cohort for NS. <i>PTPN11</i> was the predominant gene identified, particularly the p.(Asn308Asp) variant. These findings reiterate the genetic heterogeneity of NS in Colombian children and the importance of early molecular diagnosis to guide clinical management. Multidisciplinary follow-up is essential due to the risks of growth failure, cardiac anomalies, and malignancies.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"385-393"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Cognition in Adolescents with Gender Dysphoria and Congenital Adrenal Hyperplasia: A Preliminary Investigation of Biological vs. Experiential Gender Effects","authors":"Begüm Yuluğ-Taş, Burcu Özbaran, İpek İnal-Kaleli, Nurhak Doğan, Arzu Jalilova, Samim Özen, Sezen Köse, Damla Gökşen, Şükran Darcan, Tezan Bildik","doi":"10.4274/jcrpe.galenos.2025.2025-3-16","DOIUrl":"10.4274/jcrpe.galenos.2025.2025-3-16","url":null,"abstract":"<p><strong>Objective: </strong>To explore hormonal and neurodevelopmental influences on social cognition among individuals with gender dysphoria (GD), congenital adrenal hyperplasia (CAH), and typically developing (TD) controls.</p><p><strong>Methods: </strong>Participants included individuals with GD, CAH, and TD individuals. Social cognition was assessed using the Faces Test (FT), Reading the Mind in the Eyes Test (RMET), and Unexpected Outcomes Test (UOT). Psychiatric comorbidities were evaluated via the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children, depressive symptoms using the Children’s Depression Inventory, autistic traits with the Autism Spectrum Screening Questionnaire, and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms through the ADHD Rating Scale.</p><p><strong>Results: </strong>Participants included 34 GD, 29 CAH, and 35 TD. Psychiatric diagnoses were significantly more prevalent in the GD group, with major depressive disorder (64.7%) and ADHD (50%) being the most common (p<0.001). TD participants showed moderately better performance on RMET (p=0.003) and UOT (p<0.001) compared to GD and CAH, while CAH individuals scored lower on FT (p=0.046). Regression analyses revealed depressive symptoms (B=-0.105, p=0.004) and CAH status (B=-2.221, p=0.003) predicted RMET scores, while GD (B=-3.232, p=0.022) and CAH (B=-7.974, p<0.001) predicted lower UOT performance. FT regressions were nonsignificant.</p><p><strong>Conclusion: </strong>Findings highlight the interplay of hormonal and psychosocial factors in social cognition, reiterating the need for nuanced, contextsensitive approaches to supporting social functioning and well-being in gender-diverse youth.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"467-478"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Gastrointestinal Symptoms and Sleep Habits in Children with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study","authors":"Behzat Özkan, İshak Abdurrahman Işık, Atike Atalay, Nazlı Sivil, Memduha Sarı, Arzu Aras, Coşkun Fırat Özkeçeci, Hicran Altın, Mehmet Özen, İsmail Topal, Ulaş Emre Akbulut","doi":"10.4274/jcrpe.galenos.2026.2025-11-6","DOIUrl":"10.4274/jcrpe.galenos.2026.2025-11-6","url":null,"abstract":"<p><strong>Objective: </strong>Reduced sleep quality in children has been associated with obesity and fatty liver disease. However, there are no studies evaluating the impact of gastrointestinal symptoms on sleep quality in children with metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this cross-sectional study was to investigate the prevalence of gastrointestinal symptoms and sleep disturbances in children with MASLD and to examine the association of gastrointestinal symptoms with sleep disturbances.</p><p><strong>Methods: </strong>Anthropometric and biochemical examinations were performed on children aged 8-18 years, including children with MASLD and matched healthy controls for comparison. The Hepatic Steatosis Index (HSI) and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated for children with MASLD. Sleep disturbances were assessed using the Child Sleep Habits Questionnaire (CSHQ), and gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Logistic regressions were used to examine factors associated with sleep quality.</p><p><strong>Results: </strong>A total of 176 children, consisting of 84 (47.7%) with MASLD and 92 healthy controls were included. Of these 123 (69.9%) had sleep disturbances. In unadjusted analysis, sleep disturbances were significantly more common in the MASLD group (89% vs 57%, p<0.001). However, in the final multivariate regression model adjusting for metabolic confounders, the independent predictors of sleep disturbances were low family income [odds ratio (OR)=9.56, 95% confidence interval (CI)=2.80-32.57], total GSRS score (OR=1.15, 95% CI=1.06-1.24), and Homeostatic Model Assessment of Insulin Resistance (OR=1.51, 95% CI=1.01-2.27). The presence of MASLD lost statistical significance after adjustment (p=0.554). NFS, a marker of fibrosis risk, was associated with both sleep disturbances and gastrointestinal symptoms.</p><p><strong>Conclusion: </strong>This study showed that sleep disturbances and gastrointestinal symptoms are more common in children with MASLD, and that gastrointestinal disturbances are significantly associated with sleep disturbances. Furthermore, the results suggest that sleep disturbances may be more common in children with MASLD who have a higher estimated risk of liver fibrosis. Children with MASLD should be evaluated not only for liver health but also for extrahepatic conditions, including sleep and gastrointestinal disorders.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"448-458"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary Hypophosphatemic Rickets with Hypercalciuria-Importance of Further Evaluation when Clinical Suspicion is Strong","authors":"Chathupani Anuradha Wettasinghe, Ishara Minuri Kumarasiri, Mahendralingam Vidushajini, Thabitha Jebaseeli Hoole, Manimel Wadu Akila Nimanthi, Imalka Jayasundara, Reha Balasubramaniam, Navoda Atapattu","doi":"10.4274/jcrpe.galenos.2025.2025-1-15","DOIUrl":"10.4274/jcrpe.galenos.2025.2025-1-15","url":null,"abstract":"<p><p>Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic condition with autosomal recessive inheritance and a prevalence of 1 in 250000. It is due to mutation of the SLC4A3 gene. Correct diagnosis of this condition is important as treatment with active vitamin D metabolites is contraindicated. Evolution of the disease despite initial completely normal biochemistry has been observed, potentially creating diagnostic confusion. The first child presented at the age of 5.5 years with features of rickets. He had an abnormal bone profile with normal vitamin D levels. Urinary phosphate studies were compatible with HHRH. He was treated with phosphate supplementation and potassium citrate. He has well responded well to treatment. The second child initially presented at 1.5 years of age with leg bowing and a family history of hypercalciuria. All investigation findings, including urinary phosphate studies, were within normal limits. At the age of 2.5 years, he again presented with worsening of bowing. Biochemical and urinary investigations were repeated and laboratory findings were now compatible with HHRH. These cases highlight the importance of repeated investigations despite initial normal parameters, if the initial clinical suspicion is strong. Clinical- and investigation-based diagnosis of this rare genetic disease, HHRH, is feasible in resource limited setting.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"549-553"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Role of <i>LRG1</i> in Hepatosteatosis and Insulin Resistance in Obese Children","authors":"Berna Singin, Zeynep Donbaloğlu, Ebru Barsal Çetiner, Bilge Aydın Behram, Aynur Bedel, Sebahat Özdem, İkbal Özen Küçükçetin, Mesut Parlak, Hale Ünver Tuhan","doi":"10.4274/jcrpe.galenos.2026.2025-11-5","DOIUrl":"10.4274/jcrpe.galenos.2026.2025-11-5","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between <i>leucine-rich alpha-2-glycoprotein 1</i> (<i>LRG1</i>), hepatosteatosis, and insulin resistance (IR) in obese children, and to evaluate the potential role of <i>LRG1</i> as a biomarker in these metabolic conditions.</p><p><strong>Methods: </strong>A cohort of obese and non-obese children were enrolled. Obese subjects were further grouped by hepatosteatosis and IR status. Anthropometric measurements, biochemical parameters, and inflammatory markers including <i>LRG1</i>, adiponectin, and tumor necrosis factor-α (TNF-α) were evaluated. Associations between these markers and metabolic parameters were analyzed.</p><p><strong>Results: </strong>The cohort consisted of 172 children, of whom 100 (58.1%) were obese and 72 were non-obese. Obese children had significantly higher body mass index (BMI), BMI standard deviation scores, waist and upper arm circumferences, triceps skinfold thickness, total and percentage body of fat (PBF), and elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p<0.001). Laboratory findings revealed elevated glucose, insulin, homeostatic model assessment of IR (HOMA-IR), alanine aminotransferase, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein cholesterol (HDL-C) in the obese group (p<0.05). <i>LRG1</i> levels did not differ by obesity or hepatosteatosis status but were significantly lower in those with IR (p=0.03). <i>LRG1</i> was negatively correlated with waist circumference, DBP, insulin, HOMA-IR, TG, TC, and LDL-C, and positively with HDL-C (p<0.05). Adiponectin showed inverse correlations with waist circumference, SBP, insulin, HOMA-IR, TC, LDL-C, TG, and a positive correlation with HDL-C (p<0.05).</p><p><strong>Conclusion: </strong>Findings suggest <i>LRG1</i> may not serve as a direct biomarker for hepatosteatosis in obese children but was negatively associated with IR and dyslipidemia. These results highlight a complex role for <i>LRG1</i> in obesity-related metabolic dysfunction and support further longitudinal and pathophysiological studies.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"431-439"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel <i>IGF1R</i> Variants in Short Stature: Lessons from Two Patients and Outcome of Growth Hormone Therapy","authors":"Mehmet Eltan, Hilal Sekizkardeş, Sezin Canbek, Murat Hakkı Yarar, Saygın Abalı, Zehra Yavaş Abalı","doi":"10.4274/jcrpe.galenos.2025.2024-12-7","DOIUrl":"10.4274/jcrpe.galenos.2025.2024-12-7","url":null,"abstract":"<p><p>The growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis is essential for the regulation of growth. IGF1 exerts its effects through the IGF1 receptor type 1 (IGF1R) that plays a pivotal role in fetal and postnatal growth. Pathogenic monoallelic <i>IGF1R</i> variants are known to cause pre-and postnatal growth restriction, often accompanied by normal or elevated serum IGF1 levels. Herein, the clinical and genetic characteristics of two cases with <i>IGF1R</i> novel variants, describing their growth patterns, endocrinological findings, and response to recombinant human GH (rhGH) therapy are presented. Case 1 was a 6.3-year-old boy, with birth weight of 2,500 g [-2.5 standard deviation score (SDS)] and a height of 101.5 cm (-3.2 SDS). Laboratory investigations revealed IGF1 and IGFBP3 levels of 117.8 ng/mL (0.9 SDS) and 4.55 μg/mL (1.3 SDS), respectively. Clinical exome sequencing (CES) identified a novel heterozygous c.3722+1G>A/p.(?) variant in the <i>IGF1R</i> (NM_000875.5) inherited from the mother. At 6.9 years of age, rhGH treatment was initiated at a dose of 0.035 mg/kg/day. The patient has been receiving rhGH for two years, achieving a height gain of +0.3 SDS per year, with an uneventful follow-up. Case 2 was a 3-year-old male with short stature and a history of being born small for gestational age (SGA) (-2.6 SDS). His height and weight were 70.0 cm (-2.1 SDS) and 8.8 kg (-1.1 SDS), respectively. He had a history of frequent respiratory infections. Pituitary hormone levels were normal, and he had no evidence of GH deficiency. CES revealed a novel heterozygous variant c.2275_2278 dup/p.(Ala760Glyfs*21) in the <i>IGF1R</i>. Identifying genetic causes of idiopathic short stature in SGA babies is important, as it facilitates more precise diagnoses, reduces unnecessary testing, and potentially enables targeted therapies. Our experience with rhGH therapy in one patient suggests a modest growth response, consistent with previous studies. However, elevated IGF1 levels during treatment highlight the importance of balancing therapeutic doses to optimize height gains without causing side effects.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"519-526"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Identity and Preferences in Children with Variations in Sex Development","authors":"Canice E. Crerand, Natalie M. Gallagher, Margaret P. Adam, Maria G. Vogiatzi, Elizabeth McCauley, Jennifer Hansen-Moore, Margarett Shnorhavorian, Patricia Y. Fechner, Anne-Marie E. Amies Oelschlager, Justin A. Indyk, V. Rama Jayanthi, Hailey M. Umbaugh, Rachel Horton, Shira Kahn-Samuelson, Grace Raber, Madeline McClinchie, Kristina R. Olson","doi":"10.4274/jcrpe.galenos.2025.2025-2-2","DOIUrl":"10.4274/jcrpe.galenos.2025.2025-2-2","url":null,"abstract":"<p><strong>Objective: </strong>To assess gender-typed preferences and gender identity in children with and without variations in sex developments (VSDs).</p><p><strong>Methods: </strong>In this cross-sectional study, 78 children with VSDs (ages 3-12; mean age=7 years; 55% White, non-Hispanic) recruited through specialty clinics in the United States and 78 children without VSDs (ages 3-13; mean age=7 years; 55% White, non-Hispanic) recruited through university-based community databases completed assessments of gender-typed toy, clothing and peer preferences, continuous and categorical measures of gender identity, and perceived similarity to boys and to girls.</p><p><strong>Results: </strong>Generally, children with and without VSDs did not differ in their gender development on 5 of 7 measures for each gender group. Children raised as girls who had VSDs had more masculine toy preferences, t(84.89)=3.421; p=0.001; d=0.698, and viewed themselves as more similar to boys, t(67.43)=2.994; p=0.004; d=0.648, than comparison children raised as girls. Boys with VSDs selected more masculine toys [t(55.17)=2.413; p=0.019; d=0.623], and responded in a more-masculine way on the continuous gender identity measure [t(38.40)=2.364; p=0.023; d=0.621], than did boys in the community comparison sample, though these effects, unlike the effects amongst girls, were not robust against corrections for multiple comparisons.</p><p><strong>Conclusion: </strong>During early and mid-childhood, VSDs were not strongly associated with differences in gender development. Future longitudinal research on the gender development of youth with VSDs is necessary, particularly as they mature into adolescence.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"410-421"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucocutaneous Findings and Endocrinopathies in Children with Turner Syndrome: A Cross-Sectional Study","authors":"Selami Aykut Temiz, Filiz Cebeci, Aslıhan Çiçekli, Begüm Işık, Sevil Savaş Erdoğan, Selma Emre, Hilal Kaya Erdoğan, İsa An, Sezgi Sarıkaya Solak, Sevilay Kılıç, Eda Öksüm Solak, Arzu Ataseven, Beray Selver Eklioğlu, Suna Kılınç, Mehmet Boyraz, Enver Şimşek, Tuğba Çetin Kontbay, Filiz Tütüncüler, Durmuş Doğan, Ülkü Gül Şiraz, Güllü Eren","doi":"10.4274/jcrpe.galenos.2026.2025-12-10","DOIUrl":"10.4274/jcrpe.galenos.2026.2025-12-10","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the frequency of skin, hair, nail, and mucosal findings in children with Turner syndrome (TS) and their associations with coexisting endocrinopathies.</p><p><strong>Methods: </strong>A cross-sectional study was conducted with TS patients who were followed up by pediatric endocrinology and referred to the dermatology outpatient clinic. Data were collected using standardized dermatological examination forms, including demographic information, clinical features, presence of endocrinopathies, and medication usage. Statistical analysis was used to evaluate differences between groups and to analyze relationships between variables.</p><p><strong>Results: </strong>The cohort consisted of 112 girls with TS. Skin and hair findings were detected in 86.6% of the patients, with melanocytic nevi (44.6%) and xerosis (41.1%) being the most commonly observed. Oral mucosal findings were observed less frequently (17.0%). Nail findings were detected in 63.4% of the cases, with leukonychia (15.2%) and subungual hyperkeratosis (14.3%) being the most prevalent. Older age, delayed diagnosis, longer follow-up duration, and lower body mass index were associated with an increased frequency of skin and hair findings (p<0.05). Moreover, the presence of coexisting endocrinopathies was significantly associated with skin and hair findings. Nail findings were significantly associated with longer follow-up duration (p=0.002), the presence of endocrinopathies (p<0.001), and comorbidities (p=0.004).</p><p><strong>Conclusion: </strong>This study confirmed that skin, hair, and nail abnormalities are commonly observed in TS. The association of these findings with endocrinopathies suggests that systemic factors influence dermatological problems in TS. It is recommended to integrate dermatological evaluations into the routine endocrine and cardiological follow-up of children with TS.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":"459-466"},"PeriodicalIF":1.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late Recognition of Aromatase Deficiency Following 16 Years of Misdiagnosis as Congenital Adrenal Hyperplasia: A Case with Coexisting Gonadoblastoma and Dysgerminoma.","authors":"Eman Alfadhli, Abdulaziz Turkistani","doi":"10.4274/jcrpe.galenos.2026.2026-6-8","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2026.2026-6-8","url":null,"abstract":"<p><p>Aromatase deficiency (AD) is a rare autosomal recessive disorder caused by pathogenic variants in the CYP19A1 gene, resulting in impaired conversion of androgens to estrogens. Clinical manifestations in 46, XX individuals include ambiguous genitalia, delayed puberty, and reproductive dysfunction. Both sexes may develop metabolic abnormalities, delayed epiphyseal closure, eunuchoid body proportions, and low bone mass. Because of its rarity and overlap with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), diagnosis may be delayed or missed. Gonadal tumors have not been reported in association with AD. We describe a 20-year-old female with ambiguous genitalia at birth who was diagnosed in infancy with 21OHD and treated with hydrocortisone and fludrocortisone. Despite poor treatment adherence, she never developed adrenal insufficiency. At 16 years of age, she was referred for evaluation of primary amenorrhea and absent puberty. Assessment revealed hypergonadotropic hypogonadism with markedly low estradiol levels, normal basal and ACTH-stimulated 17-hydroxyprogesterone levels (17-OHP), and a 46, XX karyotype, findings that were inconsistent with CAH. Additional features included metabolic abnormalities and low bone mass. Whole-genome sequencing identified a homozygous pathogenic CYP19A1 splice-site variant (c.1263+1G>T), confirming AD. Imaging and surgery demonstrated an enlarged right adnexal mass and a hypoplastic left ovary. Histopathology revealed bilateral gonadoblastoma with dysgerminoma arising in the right ovary. This case highlights the diagnostic challenges of AD and emphasizes the importance of reconsidering a diagnosis of CAH when biochemical findings are discordant with the clinical picture. To our knowledge, this is the first reported case of genetically confirmed aromatase deficiency with coexisting gonadoblastoma and dysgerminoma. Whether this coexistence represents a causal association or a coincidental finding remains uncertain.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Sex Steroids, Sex Hormone-binding Globulin and Leptin in the Development of Pubertal Gynecomastia and its Persistence into Adulthood.","authors":"Zdravka Petrova Todorova, Blagomir Nikolaev Zdravkov","doi":"10.4274/jcrpe.galenos.2026.2025-12-20","DOIUrl":"https://doi.org/10.4274/jcrpe.galenos.2026.2025-12-20","url":null,"abstract":"<p><strong>Objective: </strong>Pubertal gynecomastia (PG) is a benign condition considered to be caused by imbalance between estrogen and testosterone, though this is not frequently evident from serum analysis. This study aimed to determine possible alteration in sex hormone levels, as well as to investigate the role of sex hormone-binding globulin (SHBG) and leptin in PG development and persistence.</p><p><strong>Methods: </strong>A total of 95 boys with PG were included. They were divided into 3 groups considering stage. Anthropometric measurements, hormonal investigations, SHBG and leptin were collected and compared group of 64 controls without PG matched in pubertal status and anthropometrics.</p><p><strong>Results: </strong>Investigations of patients with gonadal Tanner stage 2 proved statistically significant estradiol [120.0 pmol/l (73.4-240.0) vs.77.80 (23.2-120), p=0.023] and decrease in testosterone/estradiol ratio compared to control group. The same is not found in PG groups with Tanner stage 3, 4 5. Difference of the levels of testosterone and Free Androgen Index (FAI) were not found in Tanner stage 2, but significantly lower FAI was determined in mid-pubertal boys with gynecomastia compared to controls [36.0(6.8-197.0) vs.64.0(1.79-140.1), p=0.017]. Additionally, a lack of decrease of SHBG in the PG group with pubertal advancement was observed, which might explain the lower FAI in that cohort. No statistically significant difference leptin level was found.</p><p><strong>Conclusion: </strong>The early rise of estradiol at the beginning of puberty might be responsible for PG, while lack of SHBG reduction with advancement of puberty and lower FAI might have an impact on its development and/or persistence in mid-pubertal boys.</p>","PeriodicalId":48805,"journal":{"name":"Journal of Clinical Research in Pediatric Endocrinology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}