Journal of pediatric endocrinology & metabolism : JPEM最新文献

{"title":"Permanent congenital hypothyroidism with <i>GBP1</i> p.Leu187Pro: clinical follow-up data and epigenetic insights.","authors":"Dandan Cui, Shuang Liu, Xiang Chen, Qin Zheng, Jingyu Zhao, Leilei Wang","doi":"10.1515/jpem-2026-0478","DOIUrl":"https://doi.org/10.1515/jpem-2026-0478","url":null,"abstract":"<p><strong>Objectives: </strong><i>GBP1</i> variants have recently been identified as a novel cause of congenital hypothyroidism (CH), but the clinical spectrum remains incompletely defined. Longitudinal data on methylation dynamics at cg12054698, an open-sea CpG site within the <i>GBP1</i> 5' untranslated region (5' UTR), and normative methylation levels in euthyroid controls are lacking.</p><p><strong>Methods: </strong>We identified three unrelated CH probands carrying the heterozygous <i>GBP1</i> p.Leu187Pro variant by trio whole-exome sequencing and systematically screened 61 known CH-related genes. Clinical phenotypes and longitudinal outcomes data were collected. For epigenetic analysis, cg12054698 methylation was quantified by pyrosequencing in the three probands, their carrier parents, 30 age-stratified euthyroid controls (newborns, toddlers, and adults), 10 CH patients without <i>GBP1</i> variants, and paired longitudinal samples from two probands.</p><p><strong>Results: </strong>All three probands presented with moderate-to-severe CH at neonatal diagnosis. Thyroid ultrasonography revealed heterogeneous phenotypes, including a normal <i>in situ</i> gland, thyroid agenesis, and a normal-sized gland with diffuse hypoechogenicity. All three cases were confirmed as permanent CH. In euthyroid controls, cg12054698 methylation was significantly higher in newborns than in toddlers and adults (p<0.001). Neonatal methylation levels did not differ significantly among probands with <i>GBP1</i> variants, CH patients without <i>GBP1</i> variants, and euthyroid controls (p=0.260).</p><p><strong>Conclusions: </strong>In this cohort, <i>GBP1</i>-associated CH was permanent and showed a marked phenotypic heterogeneity. cg12054698 was hypermethylated during the neonatal period across study groups, supporting a developmentally regulated, stage-specific epigenetic pattern rather than a disease-specific pathogenic \"second hit.\"</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid decline in smart insulin pen decision-support use in youth with type 1 diabetes: a randomized crossover pilot trial.","authors":"Sarah Murphy, Seema Kumar, Alaa Al Nofal, Roland Hentz, Siobhan T Pittock, Ana L Creo","doi":"10.1515/jpem-2026-0532","DOIUrl":"https://doi.org/10.1515/jpem-2026-0532","url":null,"abstract":"","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum FGF-21 levels and stature in children and adolescents with celiac disease on a gluten-free diet.","authors":"Fırat Kaya, Nafiye Urgancı, Ahmet Uçar, Özge Pelin Akbay, Ayşe Merve Usta, Sedanur Celik, Mustafa Safa Kasım","doi":"10.1515/jpem-2026-0244","DOIUrl":"https://doi.org/10.1515/jpem-2026-0244","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate stature in patients with celiac disease (CD) adherent to a gluten-free diet (GFD), determine the prevalence of growth hormone deficiency (GHD), and assess the associations between stature and serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and FGF 21 levels.</p><p><strong>Methods: </strong>In this prospective cross-sectional study, 141 pediatric patients with CD (79 females) who had adhered to a GFD for at least 2 years were included. Anthropometric and clinical data were obtained from medical records. Serum IGF-1, IGFBP-3, and FGF21 levels were measured in fasting samples. Growth hormone stimulation tests (L-dopa and clonidine) were performed in patients with a height >1.5 SDS below target height (TH).</p><p><strong>Results: </strong>Twelve patients (8.5 %) had persistent short stature despite long-term adherence to a GFD. Growth hormone deficiency was diagnosed in three patients (2.1 % of the entire cohort; 25 % of patients with persistent short stature). Patients with persistent short stature without GHD had significantly lower serum IGF-1 and IGFBP-3 standard deviation scores than those with normal stature, whereas serum FGF21 concentrations did not differ significantly between the groups. Serum FGF21 concentrations were not significantly correlated with height SDS, IGF-1, IGFBP-3, or other anthropometric variables.</p><p><strong>Conclusions: </strong>Persistent short stature may occur despite long-term adherence to a GFD in a small proportion of children and adolescents with CD. GHD was identified in 2.1 % of patients, emphasizing the importance of growth monitoring. Lower IGF-1 and IGFBP-3 SDS in patients with persistent short stature without GHD suggest alterations within the GH-IGF axis. Serum FGF21 concentrations were not associated with stature, suggesting that persistent growth impairment in treated CD is likely multifactorial and is not explained by circulating FGF21 alone.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: A case report of Xp21 contiguous gene deletion syndrome with adrenal crisis and sensorineural hearing loss: clinical highlights and management pitfalls.","authors":"Rungroj Thangpong, Samkhwan Thongsukkaeo, Kulpatra Paisansukanant, Nattakarn Numsriskulrat","doi":"10.1515/jpem-2026-0733","DOIUrl":"https://doi.org/10.1515/jpem-2026-0733","url":null,"abstract":"","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular makeup of differentiated thyroid carcinoma in a free-standing children's hospital with a predominantly Hispanic population.","authors":"Andrea G Martinez Sanchez, Daniela Baboun, Erick Delgado, Natalia Solano, Fuad Alkhoury, Ricardo Restrepo, Carole D Brathwaite, Adriana Carrillo","doi":"10.1515/jpem-2026-0083","DOIUrl":"https://doi.org/10.1515/jpem-2026-0083","url":null,"abstract":"<p><strong>Objectives: </strong>Molecular testing is commonly used to guide thyroid cancer management in adults, but its role in adolescents remains unclear. This study examines the molecular profile of differentiated thyroid carcinoma (DTC) in a predominantly Hispanic pediatric population, aiming to correlate genetic variations with clinical behavior and improve treatment outcomes.</p><p><strong>Methods: </strong>A single-center retrospective study included 59 patients aged 8-20 years with DTC. Data on demographics, pathology, and molecular testing from surgical specimens were analyzed using analysis of variance (ANOVA) and chi-squared tests.</p><p><strong>Results: </strong>Among the 59 patients, the average age was 14 years, with 76.2 % female and 88.1 % Hispanic. Autoimmune thyroiditis was present in nearly half the cohort. Tumor sizes mainly ranged between 1 and 4 cm, and the classical subtype of DTC was the most common subtype. Molecular testing identified mutations in 37 out of 41 samples, the most prevalent being <i>BRAF V600E</i> and <i>RET</i>/PTC rearrangements. Extrathyroidal invasion and angioinvasion were especially notable among <i>RET</i>/PTC rearrangements. Lymph node metastases were more frequently observed in patients with <i>BRAF V600E</i> and <i>RET</i>/PTC rearrangements. This suggests a possible association between mutation type and metastatic behavior despite the lack of a statistically significant difference between groups.</p><p><strong>Conclusions: </strong>In this Hispanic pediatric cohort, <i>BRAF V600E</i> and <i>RET</i>/PTC rearrangements were the most observed mutations. <i>BRAF V600E</i> was associated with lymph node metastases and the classical papillary thyroid carcinoma subtype, whereas <i>RET</i>/PTC rearrangements exhibited more aggressive features like distant metastases. This study highlights the role of molecular profiling in understanding the unique molecular features of pediatric DTC across ethnically diverse populations.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term thyroid outcomes and thiol-disulfide homeostasis in childhood Hodgkin lymphoma survivors treated with neck radiotherapy.","authors":"Mustafa Safa Kasım, Dildar Bahar Genç, Süheyla Ocak, Şevval Kaplan Kılıç, Halil İbrahim Ada, Salim Neşelioğlu, Funda Eren, Hediye Çiğdem Şimşek, Ahmet Uçar","doi":"10.1515/jpem-2026-0544","DOIUrl":"https://doi.org/10.1515/jpem-2026-0544","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate long-term thyroid outcomes and thiol-disulfide homeostasis (TDH) in childhood Hodgkin lymphoma (HL) survivors treated with neck radiotherapy (RT).</p><p><strong>Methods: </strong>Forty consecutive childhood HL survivors and 40 healthy controls were included. Thyroid function, autoimmunity markers, and ultrasonographic findings were evaluated in survivors. Native thiol, total thiol, disulfide, and related ratios were assessed in both groups. Factors associated with subclinical hypothyroidism and thyroid nodules were analyzed.</p><p><strong>Results: </strong>Survivors had a median age of 16.8 years (range, 5.1-33.2) and a median interval since RT of 4.6 years (range, 1.3-20.2). Seventeen survivors (42.5 %) had received >25 Gy neck RT. Subclinical hypothyroidism was identified in 18 survivors (45.0 %); 13 of these 18 (72.2 %) were receiving levothyroxine. Thyroid nodules were identified in seven survivors (17.5 %), with no thyroid malignancy detected. TDH parameters did not differ significantly between survivors and controls. In survivors, native thiol/total thiol and disulfide/total thiol ratios correlated significantly with free T4 and free T3 concentrations. Thyroid nodule presence was associated with longer time since RT (OR=1.354 per year).</p><p><strong>Conclusions: </strong>Functional and structural thyroid abnormalities were frequent in childhood HL survivors treated with neck RT, supporting continued thyroid surveillance. Associations between TDH ratios and thyroid hormones in survivors remain exploratory and warrant evaluation in longitudinal studies.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of metformin-associated lactic acidosis without hemodialysis.","authors":"Praewa Sophark, Somchit Jaruratanasirikul, Pornsak Dissaneewate, Prayong Vachvanichsanong","doi":"10.1515/jpem-2026-0161","DOIUrl":"https://doi.org/10.1515/jpem-2026-0161","url":null,"abstract":"<p><strong>Objectives: </strong>Metformin-associated lactic acidosis (MALA) is a rare but potentially life-threatening condition. Hemodialysis is often recommended, but evidence of successful nondialytic management in children is limited. We report a girl with MALA successfully treated with supportive medical management without dialysis.</p><p><strong>Case presentation: </strong>We report a girl with nondialyzed chronic kidney disease (CKD) and non-insulin-dependent diabetes mellitus (NIDDM), and dyslipidemia who developed MALA after 18 months of metformin, insulin, and sodium bicarbonate therapy. She presented with dyspnea, palpitations, and vomiting. She was lethargic, afebrile, tachypneic, tachycardic, hypertensive, and had Kussmaul breathing. Laboratory results showed blood glucose 55 mg/dL, potassium 6.7 mEq/L, arterial pH 7.038, pCO₂ <5 mmHg, and lactate 19.55 (0.56-1.39) mmol/L. She was diagnosed with CKD and NIDDM complicated by acute kidney injury and MALA. She was treated with intravenous glucose, sodium bicarbonate, respiratory support, and rectal calcium polystyrene sulfonate and then referred to our hospital, arriving 9 h after the initial presentation. For MALA, hemodialysis (HD) or continuous renal replacement therapy (CRRT) was considered, but predialysis COVID-19 testing requirements delayed immediate initiation. Intravenous fluids were maintained at 100-150 cc/h with urine output of 200-220 cc/h. Seven hours after arrival, laboratory results improved (pH 7.361, lactate 11.7 mmol/L), so HD/CRRT was deferred. Serum bicarbonate and lactate normalized at 25 and 29 h, respectively.</p><p><strong>Conclusions: </strong>This report supports that pediatric MALA can be successfully treated without renal replacement therapy, using liberal hydration, alkali therapy, and measures to ensure adequate urine output.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth plate senescence, chondrocyte biology, and the growth hormone-insulin-like growth factor 1 axis in childhood growth.","authors":"Ashraf T Soliman, Fawzia Alyafei, Nada Alaaraj, Noor Hamed, Shayma Ahmed","doi":"10.1515/jpem-2026-0485","DOIUrl":"https://doi.org/10.1515/jpem-2026-0485","url":null,"abstract":"<p><p>Longitudinal bone growth in children depends on endochondral ossification within the epiphyseal growth plate, a process long viewed as a passive readout of systemic hormones but now recognized as an actively regulated, self-limiting process. This mini-review synthesizes recent evidence on chondrocyte biology, growth plate senescence, and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis. Local paracrine networks establish precise antagonistic and synergistic interactions: fibroblast growth factor receptor 3 (FGFR3) suppresses chondrocyte proliferation via MAPK/STAT signaling, while the C-type natriuretic peptide/NPR2 pathway counters this via cGMP-mediated stimulation; the Indian hedgehog-parathyroid hormone-related protein feedback loop, the <i>SHOX</i> gene, and mechanical loading provide additional structural control. Growth plate senescence follows a proposed localized, cell-counting mechanism reflecting cumulative chondrocyte division that current evidence supports but that has not been established as the sole explanation for chronological variation in physeal closure. Estrogen is a key accelerant of this senescent process during puberty. Pathogenic variants in these local regulators underlie conditions such as achondroplasia and a minority of cases classified as idiopathic short stature, and mechanism-targeted therapies - including vosoritide, a C-type natriuretic peptide analog, together with the FGFR3-directed tyrosine kinase inhibitor infigratinib and the once-weekly CNP prodrug navepegritide - illustrate, for achondroplasia specifically, how targeting a defined paracrine lesion can produce growth responses that systemic hormone stimulation alone does not achieve in that disorder. For a limited group of monogenic growth-plate disorders, resolving these molecular networks is beginning to complement uniform systemic intervention with precision, mechanism-based therapy, although this paradigm remains investigational for the great majority of children with short stature.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune adrenalitis in adolescents in Germany: a series of 4 cases.","authors":"Luise Pudig, Lorenz Greifoner, Marlene Dieke, Constanze Vilser, Simone Hettmer, Susann Weihrauch-Blüher","doi":"10.1515/jpem-2026-0187","DOIUrl":"https://doi.org/10.1515/jpem-2026-0187","url":null,"abstract":"<p><strong>Objectives: </strong>This case report summarises clinical findings in four adolescents (aged 14-17 years) diagnosed with autoimmune adrenalitis at a German University Children's Hospital between 2019 and 2025.</p><p><strong>Case presentation: </strong>Clinical presentation varied and included fatigue, arterial hypotension, depressive symptoms, hyperpigmentation of the skin, and in one case acute kidney failure associated with acute viral infection. All patients showed hyponatraemia, reduced cortisol levels in serum and elevated adrenocorticotropic hormone concentrations at diagnosis. Autoimmune adrenalitis was confirmed in all patients by the presence of autoantibodies against the adrenal cortex. Interestingly, three of the four cases were diagnosed within a period of only 18 months.</p><p><strong>Conclusions: </strong>Our case series of autoimmune adrenalitis may suggest a potential increase  in the annual incidence among adolescents. The clinical diversity of symptoms at diagnosis ranging from depression to acute kidney failure was striking. Since delayed diagnosis may lead to life-threatening complications, awareness of clinical variability is essential for physicians to achieve timely diagnosis. Cortisol levels should be routinely measured in patients with unclear fatigue and hyponatraemia.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam Bruno Weber.","authors":"Olga Kordonouri, Thomas Danne","doi":"10.1515/jpem-2026-0675","DOIUrl":"https://doi.org/10.1515/jpem-2026-0675","url":null,"abstract":"","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}