Impact Factor: 1.0

Journal

Journal of Pediatric Endocrinology and Metabolism

Official Journal of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED)

Editor-in-Chief: Clemens Kamrath

Language: English

First published: January 1, 1985

Publication Frequency: 12 issues per year

View latest issue

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

About this journal

Objective
The Journal of Pediatric Endocrinology and Metabolism (JPEM) is a peer-reviewed journal that publishes cutting-edge articles on clinical investigations in pediatric endocrinology, diabetes, inherited metabolic disorders, metabolism and translational research. JPEM is an international journal devoted exclusively to endocrinology in the neonatal, pediatric and adolescent age groups. JPEM is a high-quality journal dedicated to pediatric endocrinology, diabetes and metabolic diseases in its broadest sense, including research on epidemiology, pathophysiology, multidisciplinary management and technology, filling a gap at a time of rapid expansion in the field.
JPEM is a hybrid journal published monthly in print and online. All contributions submitted for publication in JPEM are subject to single-anonymized peer review by at least two experts in the field, selected and invited by the Editor-in-Chief and a dedicated Editorial Team. JPEM publishes only English-language articles.
JPEM is the official journal of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED).

BEST PAPER AWARD
From 2025, the DGPAED and the publisher will jointly award a Best Paper Award for the best paper by a DGPAED member published in the Journal of Pediatric Endocrinology and Metabolism. The prize is endowed with 1000 euros and will be awarded at the 2nd JA-PED. The selection will be made by Prof. Clemens Kamrath, JPEM Editor-in-Chief, Prof. Annette Richter-Unruh and Dr. Sebastian Kummer, JPEM Asociate Editors. Submission deadline is October 1, 2025.
We look forward to receiving your submissions´at https://mc.manuscriptcentral.com/jpem

Topics
Pediatric Endocrinology // Pediatric Diabetes // Pediatric Obesity // Inherited Metabolic Diseases // Neonates/Neonatal Screening // Hormonal Disorders and Therapy // Adrenal Disorders // Pituitary Disorders // Thyroid Disorders // Disorders of Bone, Calcium and Vitamin D Metabolism // Growth Disorders // Endocrine Cancers // Disorders of Gonads and Puberty // Disorders of Sex Differentiation, Gender Dysphoria // Psychosocial Aspects of Chronic Conditions in Pediatric Endocrinology and Diabetology // Multidisciplinary Care for Children and Their Families

Article formats
Original Article, Review Article, Mini Review, Opinion Paper, Perspectives, Editorial, Case Report, Case Report and Review of the Literature, Short Communication, Letter to the Editor and Reply, Guidelines and Recommendations, Congress Abstracts

Your Benefits

Specialized, comprehensive and translational research
High quality peer-review
Rapid online publication of contributions
No submission and publication fee
Listed in major indexing setrvices such as SCIE, PubMed or Scopus
Each article easily discoverable because of Search Engine Optimization (SEO) and comprehensive abstracting and indexing services
Secure archiving by De Gruyter and the independent archiving service Portico
Authors have the option of publishing their articles under the Creative Commons Attribution (CC-BY-4.0) open access license. Open access allows authors to retain copyright and share their findings with the scientific community without restrictions. Authors who belong to an institution that has an agreement with the publisher can publish open access without paying an article processing charge (APC) or at a considerable discount

Requires Authentication Unlicensed
Licensed

45, X/46, XY mosaicism and gender incongruence: ethical, medical, and psychological considerations

September 2, 2025

Charlotte Horrigan, Julie Alderson, Julie Park, Dinesh Giri

Download PDF

Objectives 45, X/46, XY mosaicism is a complex chromosomal difference of sexual development, commonly associated with 45, X/46, XY karyotype. It presents a broad phenotypic spectrum, creating challenges in gender assignment. This report examines the management of a child with 45, X/46, XY mosaicism diagnosed in middle childhood, assigned female at birth but later exhibiting gender incongruence, highlighting dilemmas in pubertal induction after prophylactic gonadectomy. Case presentation An 8-year-old female presented with differences in sexual development (DSD) following maternal concerns regarding genital appearance. Genetic investigations confirmed a 45, X/46, XY karyotype, leading to bilateral gonadectomy due to malignancy risk. By age 11, the child expressed alignment with being a boy while reluctantly being perceived as a girl. The absence of endogenous sex hormones following gonadectomy will complicate pubertal induction as there is incongruency between the child’s gender preference and the sex of rearing. Conclusions Limited guidance exists on managing gender incongruence in DSD, particularly regarding pubertal induction. In the UK, while sex assignment at birth is mandated, there is no specific guidance regarding the revision of sex assignment in childhood. A non-coercive environment is essential to support gender exploration whilst balancing medical, psychological, and ethical considerations in decision-making regarding pubertal induction.
Open Access
Compound heterozygous ROBO1 gene variants in a neonate with congenital hypopituitarism, dysmorphic features and midline abnormalities: a case report and review of the literature

September 1, 2025

Panagiota Markopoulou, Amalia Sertedaki, Eirini Nikaina, Maria Binou, Ioanna Farakla, Tania Siahanidou, Christina Kanaka-Gantenbein

Download PDF

Objectives The majority of congenital hypopituitarism (CH) cases remain genetically unexplained. The transmembrane receptor Roundabout-1 ( ROBO1 ), activated through interaction with SLIT-family proteins, plays crucial role in axonal guidance, branching, targeting, and midline axonal crossing. ROBO1 variants have been associated with pituitary stalk interruption syndrome and highly variable pituitary-phenotypes, ranging from isolated growth hormone deficiency (IGHD) to combined pituitary hormone deficiency (CPHD). This study aimed to investigate the genetic basis of CH in a newborn and to review current evidence linking ROBO1 variants with CH. Case presentation We report the presence of two ROBO1 variants in compound heterozygosity, the NM_002941:c.2914G>A, p.(Ala972Thr) and the novel NM_002941:c.3757G>A, p.(Val1253Met), as well as the identification of the novel NOTCH3 variant NM_000435:c.1505C>T, p.(Ser502Phe) and the novel GPR161 variant NM_001375883.1:c.1117C>T, p.(His373Tyr), in a newborn with CPHD, dysmorphic features and midline abnormalities. Conclusions This case, together with accumulating evidence, supports ROBO1 as a potential causative gene for CH. ROBO1 should be considered during genetic evaluation of patients with CH and midline abnormalities. The co-occurrence of NOTCH3 and GPR161 variants raises the possibility of an oligogenic or multigenic etiology. The cross-talk between ROBO/SLIT and NOTCH signaling pathways may contribute to the complex phenotype observed and warrants further functional investigation.
Requires Authentication Unlicensed
Licensed

Hashimoto’s thyroiditis in children and adolescents: analysis of long-term course

September 1, 2025

Ayşe Yaşar, Heves Kırmızıbekmez, Esma Ebru Altun, Fatma Güliz Atmaca, Şerife Ece Ulu, Gülcan Seymen, Burcu Cüce, Zehra Sucu Saymaz, Fatma Dursun

Download PDF

Objectives This study retrospectively evaluated long-term clinical and biochemical findings in children and adolescents diagnosed with Hashimoto thyroiditis (HT). Methods A total of 233 patients aged 2–18 years, diagnosed with HT and followed for at least three years, were included. Patients were classified into five subgroups based on thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels at diagnosis. Clinical, laboratory, and radiological findings at baseline and during follow-up were analyzed. Results The most common initial thyroid status was subclinical hypothyroidism (SCH) (39.5 %), followed by euthyroidism (36.5 %), overt hypothyroidism (OH) (18.5 %), subclinical hyperthyroidism (3.9 %), and overt hyperthyroidism (1.7 %). Data from 173 patients were available at the third and fifth years. Total of 48.4 % of patients were monitored without treatment, 47.6 % were initiated on levothyroxine and 3 % were initiated on methimazole. Among OH patients, 9 % became euthyroid over time and discontinued treatment. Levothyroxine was initiated in 73.6 % of SCH patients, but only one discontinued treatment due to normalization. Among 63 untreated patients following for five years, no functional deterioration was observed. While autoantibody levels remained stable across all groups at year three, both TPO-Ab and TG-Ab levels significantly decreased by year five (p=0.000). Conclusions Given its dynamic nature, HT requires continuous monitoring through regular clinical assessments and thyroid function testing.
Requires Authentication Unlicensed
Licensed

Identification of pathogenic ACAN variants in healthy children with normal height and advanced bone age

August 28, 2025

María Isabel Hernández, Vivian Gallardo, Nancy Unanue, Hermine van Duyvenvoorde, María Verónica Mericq

Download PDF
Requires Authentication Unlicensed
Licensed

ANKS1B is a potential candidate gene for short stature and failure to thrive in children

August 27, 2025

Pankaj Prasun, Rebecca C. Pulvermacher

Download PDF

Short stature and failure to thrive are among the most common reasons for referral to pediatric endocrinologists. The etiology could be endocrine, genetic, nutritional, psychological, or a systemic disease. Genetic syndromes account for about 5 % of short stature in childhood. However, with increased use of genomic technologies in clinical diagnosis, the number of genes associated with short stature and failure to thrive is increasing. Some of the genetic syndromes such as Silver–Russell syndrome is clinically recognizable, while others may present as isolated short stature. We recently found ANKS1B intragenic deletion in a child with short stature, failure to thrive, and subtle distinct physical features, who was referred to us for evaluation of Silver–Russell or other genetic syndromes associated with short stature. ANKS1B is associated with neurodevelopmental disorders. However, animal study and genetic association studies suggest its role in somatic growth as well. Our observations suggest that ANKS1B is a potential candidate gene for short stature and failure to thrive in children.
Requires Authentication Unlicensed
Licensed

Atypical pediatric presentation of hyperparathyroidism: CDC73 gene mutation and parathyroid carcinoma

August 25, 2025

Emel Hatun Aytaç Kaplan, Mehmet Çakmak, M. Banu Yilmaz Özgüven, Şeyma Tuna Şentürk, Hasan Önal, Serdar Bozlak, Zümrüt Kocabey Sütçü

Download PDF

Objectives Parathyroid carcinoma is the rarest etiological cause of primary hyperparathyroidism and is exceedingly rare in the pediatric population. Clinical manifestations include severe hypercalcemia, pathological fractures, and bone pain. Diagnosis is typically established through surgical intervention and histopathological examination; however, genetic analyses can also support the diagnosis. Case Presentation A 10-year-10-month-old female presented with fatigue, leg pain, and a pathological fracture in her left forearm. Laboratory tests revealed hypercalcemia, hypophosphatemic hypercalcemia, and hyperparathyroidism. Imaging studies identified a 17 mm hypervascular hypoechoic lesion in the left paratracheal area. Surgical intervention included left inferior and superior parathyroidectomy and left thyroidectomy. Histopathology showed atypical parathyroid neoplasia and thyroid hyperplasia. Genetic testing revealed a pathogenic CDC73 mutation (p.E48*, c.142G>T). The patient is under regular follow-up for hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma. Conclusions This case highlights the importance of early genetic testing in pediatric primary hyperparathyroidism (PHP), particularly for detecting CDC73 gene mutations associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT). Early diagnosis allows for timely intervention, surgical planning, and long-term surveillance to manage potential complications such as parathyroid carcinoma and ossifying fibromas.
Requires Authentication Unlicensed
Licensed

Clinical spectrum, imaging characteristics, and treatment outcomes of pediatric adrenocortical tumors: a 24-year experience from Western India

August 25, 2025

Aaditya Daga, Siddhant Dahale, Aditya Phadte, Vijay Sarathi, Saba Memon, Anurag Lila, Chethan Yamichannaiah, Virendra Patil, Manjiri Karlekar, Rohit Barnabas, Nalini Shah, Amey Rojekar, Gwendolyn Fernandez, Pragati Sathe, Padma Badhe, Tushar Bandgar

Download PDF

Objectives This study aims to characterize the clinical spectrum of pediatric adrenocortical tumors (P-ACTs) in individuals aged <20 years and to compare the distinguishing features of pediatric adrenocortical adenomas (P-ACAs) and carcinomas (P-ACCs). Methods This retrospective study consisted of P-ACT patients who presented to our institute over the past 24 years (2001–2024). They were categorized as P-ACC or P-ACA based on Wieneke score. Data on clinical presentation, hormonal evaluation, imaging, management, and outcomes were recorded. Results A total of 30 (22 females) P-ACT patients (7 P-ACA and 23 P-ACC) were identified. The median age at presentation was 7 (range, 1.0–20) years, with a median symptom duration of 6.0 months (range 0.6–42 months). All patients, except one 16-year-old having P-ACC, had hormonal hypersecretion. Cortisol and androgen co-secretion was most common (56.6 %), followed by isolated cortisol (26.6 %) and androgen hypersecretion (13.3 %). On steroid profiling by LCMS/MS, P-ACC patients had raised levels of multiple steroid metabolites (6–9) as compared to P-ACA (2–5). P-ACA patients were relatively older (17.0 vs. 6.0 years, p=0.045), more often had isolated cortisol secretion (57.1 vs. 17.3 %, p=0.060), had smaller tumors (2.8 vs. 8.5 cm, p=0.002), a lower incidence of calcification (0 vs. 80 %) and a lower percentage venous enhancement (PVE 109.6 vs. 187.8 %, p=0.008) and achieved higher disease remission rates (100 vs. 21.4 %, p=0.005). Conclusions CECT features, particularly PVE, may aid in differentiating P-ACT from P-ACC. Serum steroid panels may have a role in preoperative assessment, but their utility remains to be validated.
Open Access
Improving cardiometabolic health in children and adolescents with obesity: a comparison between in-person and virtual supervised training

August 21, 2025

Valeria Calcaterra, Matteo Vandoni, Alessandro Gatti, Vittoria Carnevale Pellino, Virginia Rossi, Caterina Cavallo, Agnese Pirazzi, Daniela Lucini, Gianvincenzo Zuccotti

Download PDF

Objectives Remote physical activity programs have emerged as a promising strategy to improve adherence to exercise guidelines, specifically among pediatric patients with obesity. This study investigated the effectiveness of in-person vs. virtual supervised training in improving cardiometabolic health in children and adolescents with obesity. Methods Forty-six children and adolescents (BMI z-score ≥ 2SD; aged 8–16) were enrolled and assigned to either in-person or virtual supervised combined training. All participants underwent a 12-week, thrice-weekly exercise program (36 sessions total), and the metabolic syndrome (MetS) z-score was used to assess metabolic risk. Results Both virtual and in-person supervised training programs resulted in improvements in the primary outcome, the MetS z-score, within each group. The virtual group showed a mean reduction of −0.26 (p=0.014), while the in-person group showed a greater reduction of −0.44 (p<0.001). Both interventions also improved waist-to-height ratio and blood pressure (p<0.01). Only the in-person group showed significant reductions in fasting glucose (p<0.001), triglycerides (p<0.001), and BMI z-score (p=0.004). The virtual group showed a greater improvement in diastolic blood pressure (p<0.01). Conclusions Both in-person and virtual exercise programs positively impact cardiometabolic health in children with obesity. The research supports the potential of remote exercise programs to enhance adherence to physical activity.
Requires Authentication Unlicensed
Licensed

Hormone-active ovarian steroid cell tumor in a 2-year-old girl

August 21, 2025

Susann Weihrauch-Blüher, Toralf Bernig, Martin Kaiser, Dominik Schneider, Christian Kunze, Katja Ronstedt, Christine Fathke, Amica Müller-Nedebock, Pablo Villavicencio-Lorini, Jessica I. Hoell

Download PDF

Objectives Steroid cell tumors are very rare in children. During the past 25 years, only 3 cases have been reported in Germany. Symptoms may vary from virilization to signs of precocious puberty and increased growth velocity, making it diagnostically challenging. Due to rarity and the wide morphologic as well as differential diagnostic spectrum, initial clinical features may be misleading. Case Presentation We report on a 2-year-old girl, who initially presented with symptoms of virilization and precocious puberty, i.e., pubertal hair growth equivalent to Tanner stage P3. Basal hormone profile yielded 10-fold increased testosterone and androstenedione as well as markedly increased estradiol levels in serum. Diagnostic imaging procedures (ultrasound, MRI of the abdomen) revealed a solid tumor in the left ovary, without any signs of peritoneal dissemination or metastases. After salpingo-oophrectomy of the left ovary (en bloc via laparoscopic surgery, without spillage), the diagnosis of an ovarian steroid cell tumor sized 40 × 25 × 22 mm producing both testosterone and estradiol was confirmed. The increased serum levels of androgens as well as estradiol decreased toward prepubertal values within 1 week after surgery. Conclusions Hormone-active steroid cell tumors of the ovary are extremely rare in infancy. In our patient, the tumor was classified as clinical stage Ia. We thus opted for clinical, biochemical, and sonographical controls without chemotherapy. We herein present follow-up data until 18 months after surgery and discuss them within the context of international literature.
Requires Authentication Unlicensed
Licensed

Concerns for mood disorders in children presenting with early menarche is not an indication for pubertal suppression

August 13, 2025

Kübra Yüksek Acinikli, Ozge Besci, Gözde Akın Kağızmanlı, Nazan Gündoğan, Guldal Unutmaz, Ahmet Berkay Esen, Sevay Alsen Güney, Ece Bober, Korcan Demir, Ayhan Abaci

Download PDF

Objectives The aim of this research was to assess the psychological problems of pubertal girls who presented with early menarche. To the best of our knowledge, there is no similar prospective cross-sectional research in the medical literature. Methods Group I included patients under 10 years old, who presented with menarche. Peripheral causes of puberty were excluded. Group II included 9–10-year-old prepubertal healthy girls. Four mental tests were employed to both groups. Children in Group I was recalled for re-evaluation after 6 months. Results A total of 49 girls (Group I, n=28; Group II, n=21) were included. Median ages of the groups were similar [9.7 (0.4) years vs. 9.3 (0.6) years, p=0.06, respectively]. Median bone age and the time between first signs of puberty and menarche in girls in Group I were 11.4 (1) years and 12 (0.1) months, respectively. Height age, height, weight, and BMI SD scores were significantly higher in Group 1 (p<0.01). Mental test scores and the frequency of mood disorders were similar among the groups [Group I, n=2, 7 % vs. Group II, n=2 (9 %), p=0.76)]. Re-evaluation of 17 patients (60.7 %) in Group 1 revealed no significant differences in test scores and no new cases of psychiatric conditions. Conclusions There was no significant difference in psychological and behavioral problem scores between the early menarche and control groups. GnRH analogue therapy should not be based on the assumption that premature pubertal development will cause psychosocial effects and should only be considered after a thorough psychiatric evaluation.
Requires Authentication Unlicensed
Licensed

First evaluation of fibroblast growth factor 21 levels in patients diagnosed with glycogen storage diseases with liver involvement

August 12, 2025

Abdullah Bozkurt, Esra Kara, Fatma Derya Bulut, İrem Kaplan, Ezgi Burgac, Burcu Köseci, Nazmiye Tüzel Gündüz, Gülçin Dağlıoğlu, Gülşah Seydaoğlu, Halise Neslihan Önenli Mungan, Deniz Kor

Download PDF

Objectives Glycogen storage diseases (GSDs) are inherited metabolic disorders caused by deficiencies in the enzymes responsible for glycogen synthesis and breakdown. GSD subtypes involving the liver are commonly associated with symptoms such as fasting hypoglycemia and hepatomegaly, and medical nutrition therapy remains the gold standard of treatment. Fibroblast growth factor 21 (FGF21), a hormone primarily secreted by the liver, plays a key role in regulating lipid, glucose, and energy metabolism. This study measured FGF21 levels in patients with hepatic forms of GSD at Çukurova University, evaluating differences among GSD subtypes and their correlations with biochemical parameters. Methods The study included 50 patients with hepatic GSD who were categorized by subtypes: 10 with type Ia, 2 with type Ib, 16 with type III, 3 with type VI, 8 with type IXa, 4 with type IXb, and 7 with type IXc. Serum FGF21 levels were measured, and their associations with biochemical findings, abdominal imaging results, and growth parameters were evaluated. Results Of the 50 patients, 52 % were female and 48 % male. The mean age at admission was 142.26 ± 76.19 months (range: 23–360 months). Common reasons for admission included abdominal distension, hepatomegaly, hypoglycemia, and growth retardation. The average FGF21 level across all patients was 318.3 ± 126.9 pg/mL, with the highest levels observed in patients with GSD type IXc (464.31 ± 112.88 pg/mL), followed by those with type IXa (343.35 ± 137.18 pg/mL) and type III (323.80 ± 116.04 pg/mL). Patients with GSD type IXc had significantly higher FGF21 levels than those with other subtypes (p=0.001). Conclusions This is the first study to evaluate FGF21 levels in patients with GSD. FGF21 levels in this cohort were comparable to those observed in patients with acute fatty liver disease and hepatosteatosis. Although no statistically significant differences were observed across most GSD subtypes, patients with GSD type IXc exhibited notably higher FGF21 levels, indicating that FGF21 may serve as a biomarker for identifying more severe phenotypes of GSD.
Requires Authentication Unlicensed
Licensed

Rare pediatric insulinoma case diagnosed by endoscopic ultrasonography: insights into endogenous hyperinsulinemic hypoglycemia

August 11, 2025

Meliha Esra Bilici, Yücel Ustundağ

Download PDF

Objectives In childhood, endogenous hyperinsulinemic hypoglycemia is most commonly associated with congenital hyperinsulinism due to genetic mutations. Pancreatic neuroendocrine tumors, which have an incidence of approximately four cases per million per year, are rare in children. Detecting small lesions is challenging, and clinical suspicion is crucial for early diagnosis. This report aims to emphasize the importance of endoscopic ultrasonography (EUS) in the clinical approach to endogenous hyperinsulinism. Additionally, a focused literature review was conducted to support the diagnostic and therapeutic aspects discussed in the case. Case presentation A 16-year-9-month-old male with no prior medical history was admitted to the emergency department with excessive sweating, speech difficulties, and an inability to wake up, occurring 8 h after a post-training meal. His blood glucose was 35 mg/dL. He had experienced similar episodes previously, resolving with food intake. An extended fasting test revealed hyperinsulinemic hypoglycemia (glucose: 45 mg/dL, insulin: 15.9 µU/mL, ketone: 0.1). Imaging studies (USG, MRI, CT) failed to detect a lesion. EUS identified a 12  ×  9 mm pancreatic body lesion, confirmed as a well-differentiated grade 2 neuroendocrine tumor via fine-needle aspiration biopsy. Laparoscopic enucleation verified the insulinoma diagnosis, with no metastasis or MEN-1 findings. Following surgery, the patient remained asymptomatic with no recurrence of hypoglycemia during a 2-year follow-up. Conclusions Insulinoma should be considered in cases of hypoglycemia triggered by fasting or exercise due to its intermittent insulin secretion. Given the small size of the pancreas and the anatomical differences in children, EUS is a highly sensitive diagnostic tool for detecting small pancreatic tumors, such as insulinoma.
Requires Authentication Unlicensed
Licensed

Observations of the effect of gonadotropin-releasing hormone analog treatment on psychosocial well-being in transgender youth and their caregivers – a pilot study

August 8, 2025

Anisha Gohil, Kelly Donahue, Erica A. Eugster

Download PDF

Objectives We investigated indices of mental health in transgender youth and their primary caregiver during 12 months of GnRHa therapy. Methods Psychological measures were completed at baseline, 6 months, and 12 months by patients and caregivers using validated questionnaires from the Patient Reported Outcomes Measurement Information System and National Institutes of Health Toolbox. One-way repeated-measures ANOVAs were performed to evaluate differences in psychological measures across time. One-sample t-tests compared the sample mean of each measure to the population mean at each time point. Results Of 28 patients enrolled, 16 were treated with a GnRHa alone for 12 months. No significant main effect of time on any measure of psychological functioning in patients or caregivers was found (all ps>0.05). Compared to the general population, transgender youth reported higher levels of psychological stress and lower levels of life satisfaction at all time points, and higher levels of depression and anger at later time points, while caregivers perceived decreased well-being in their child on all measures at all time points. Caregivers reported higher levels of self-reported anxiety at all time points and higher levels of self-reported depression at baseline. Conclusions Transgender youth and their caregivers in the early stages of medical transition experience more challenges related to psychological well-being compared to the general population. However, all measures of psychological well-being remained stable throughout the study.
Requires Authentication Unlicensed
Licensed

Stress hyperglycemia in pediatric patients as a risk factor for type 1 diabetes – a single center experience

August 8, 2025

Giora Weiser, Yitshak Yaniv, Saar Hashavya, Adi Auerbach, Carmit Avnon-Ziv, Floris Levy-Khademi

Download PDF

Objectives Stress hyperglycemia is relatively common in the pediatric emergency department. It is usually associated with severe illnesses such as infections, seizures, and trauma. The association between stress hyperglycemia and future development of type 1 diabetes mellitus is unclear. Different reports have shown controversial results. Methods This was a retrospective follow-up cohort of children admitted to the pediatric emergency department at the Shaare Zedek Medical Center in Jerusalem, Israel during the years 2010–2014 with stress hyperglycemia. The study group was then evaluated over a 10-year period for developing type 1 diabetes mellitus. The study group incidence was then compared to the general population. Results During the study period, there were 1,184 admissions with stress hyperglycemia. The most common diagnoses were infectious (36.5 %) and respiratory (24.3 %) diseases. There were two cases that later developed type 1 diabetes. This resulted in an odds ratio of 14.95 for developing type 1 diabetes in the study cohort (with fatalities removed) compared to the known incidence in Israel at that time (95 % CI, (p<0.01)). Conclusions Children presenting with stress hyperglycemia may be at greater risk for developing type 1 diabetes and should warrant close follow-up and possibly advanced testing to offer early diagnosis.
Open Access
The diagnostic value of stimulated androgen ratios in 5-alpha reductase type 2 (SRD5A2) deficiency: a case series and review of the literature

August 7, 2025

Chamila Balagamage, Rebecca Igbokwe, Trevor Cole, Elizabeth S. Baranowski, Liam McCarthy, Harish Chandran, Elmarie Van Der Merwe, Piers Fulton, Caroline Godber, Jeremy Kirk, Zainaba Mohamed, Jan Idkowiak

Download PDF

Objectives Precise and timely diagnosis is essential in the management of children born with atypical genitalia/differences or disorders of sex development (DSD) to provide optimal personalised care. Establishing the diagnosis can be challenging and time-consuming. The human chorionic gonadotrophin (hCG) stimulation test is useful in assessing male gonadal function, and stimulated testosterone: 5α-dihydrotestosterone (T:DHT)>10 suggests 5-alpha reductase type 2 (SRD5A2) deficiency. Methods We report the clinical, hormonal and genetic data of patients with 46, XY DSD with genetically confirmed SRD5A2 deficiency to assess the value of the hCG-stimulated T:DHT ratio in the diagnostic work-up. Additionally, we reviewed the literature on the usefulness of hCG-stimulated androgen ratios in determining DSD aetiology. Results Of 14 patients with genetically confirmed SRD5A2 deficiency, including one novel variant, nine underwent hCG stimulation test: seven in infancy, one at 4 years and one at puberty. A T:DHT ratio above 10 was observed in seven patients (median: 15; range: 10.7–66.5). Two patients, aged one month and 4 years, had ratios of 8.3 and 4.4, respectively. Urinary steroid profiling (GC/MS) suggested SRD5A2 deficiency in all patients who had the testing (n=13). No association was found between T:DHT ratios and age at presentation or external masculinisation score (EMS). Conclusion The hCG stimulation test appears less sensitive than urinary steroid profiling in establishing the diagnosis of SRD5A2 deficiency.
Requires Authentication Unlicensed
Licensed

Differentiating transient and permanent congenital hypothyroidism: predictive clues from Istanbul, Türkiye

August 7, 2025

Ceren Ulusoy, Heves Kırmızıbekmez, Fatma Dursun

Download PDF

Objectives Congenital hypothyroidism (CH) requires early diagnosis to prevent irreversible neurodevelopmental impairments. This study aimed to determine cutoff values for initial capillary thyroid-stimulating hormone (TSH), first venous TSH, and levothyroxine (LT4) dose at 6 months to differentiate between transient and permanent CH. Methods A retrospective analysis was conducted on 289 patients diagnosed with CH at the Pediatric Endocrinology Clinic of the University of Health Sciences, Umraniye Training and Research Hospital, from January 2014 to September 2021. Patients received treatment and were followed for at least 6 months after treatment discontinuation or remained under therapy. Patients were divided into two groups: permanent CH and transient CH. Initial capillary TSH, first venous TSH, and LT4 dose at 6 months were recorded, and cutoff values were determined using ROC analysis. Results Of the 289 patients, 179 (62 %) had transient CH and 110 (38 %) had permanent CH. The permanent CH group had significantly higher levels of capillary TSH, first venous TSH, and LT4 dose at 6 months (p<0.001). The cutoff values for predicting transient CH were <23.1 mIU/L for capillary TSH, <64.5 mIU/L for first venous TSH, and <3.6 mcg/kg/day for LT4 dose at 6 months, all statistically significant. Conclusions Initial capillary TSH, first venous TSH, and LT4 dose at 6 months are reliable predictors for distinguishing between transient and permanent CH. These cutoff values provide clinical guidance, especially for early treatment discontinuation in patients with LT4 doses below 3.6 mcg/kg/day, indicating a higher likelihood of transient CH.
Open Access
Pseudohypertriglyceridemia as a clue: clinical and genetic spectrum of glycerol kinase deficiency in three pediatric cases

August 1, 2025

Cemre Kara, Pınar Kılıçdağı Çanakcı, Engin Köse, Şule Haskoloğlu, Fatma Tuba Eminoğlu

Download PDF

Objectives Glycerol kinase deficiency (GKD) is a rare X-linked metabolic disorder caused by pathogenic variants in the GK gene. It can be present in either isolated or complex forms and often mimics primary hyperlipidemia, leading to diagnostic challenges and unnecessary treatment. This study aims to highlight the phenotypic variability and diagnostic features of GKD through a case series. Case Presentation We describe three pediatric patients diagnosed with GKD. Two siblings with isolated GKD presented with persistent, asymptomatic hypertriglyceridemia, confirmed by glyceroluria and genetic testing revealing a hemizygous c.213_214delAT (p.Cys72Ter) mutation. The third patient, diagnosed with complex GKD, presented in infancy with multisystem involvement, including immunodeficiency, hypotonia, splenic abscesses, and elevated and creatine kinase levels. Genetic analysis revealed a 6.9 Mb contiguous deletion spanning Xp21.2–Xp11.4. In all cases, elevated triglyceride levels were unresponsive to therapy, and serum samples lacked lipemic appearance. Lipid-lowering treatments were discontinued following diagnosis, with no adverse outcomes. Conclusions This case series underscores the clinical and genetic heterogeneity of GKD. Urinary glycerol analysis and the absence of serum lipemia are key diagnostic clues. Early recognition is essential to prevent misdiagnosis and guide appropriate management, particularly in treatment-resistant hypertriglyceridemia.
Requires Authentication Unlicensed
Licensed

Impact of high-dose vitamin D supplementation initiated shortly after diagnosis on residual beta cell function and partial remission rates in children with type 1 diabetes

August 1, 2025

Chandan Nallapu, Devi Dayal, Naresh Sachdeva, Mohit Kumar, Savita Verma Attri

Download PDF

Objectives We aimed to determine the effect of high-dose cholecalciferol supplementation starting soon after diagnosis on residual β-cell function (RBCF) and partial remission (PR) rates in children with type 1 diabetes (T1D). Methods A prospective, randomized, open-label study was conducted in children aged 2–12 years with newly-diagnosed T1D. Cases received additional cholecalciferol (60,000 IU every fortnight) for six months, while age-matched controls received standard care. Primary outcome variables included change in RBCF (measured by stimulated C-peptide, SCP) and the proportion of patients with PR (insulin dose-adjusted HbA1c, IDAA1c ≤9.0 %) at study endpoint. Secondary outcomes included change in mean daily insulin dose (DID) and mean HbA1c levels. Results The mean serum vitamin D concentrations achieved in cases (n=32, mean age 7.2 ± 2.8 years) were higher at 6 months (44.91 ± 5.36 vs. 24.87 ± 4.10 ng/mL, p<0.001). Compared to controls (n=31, mean age 6.6 ± 2.5 years), children receiving vitamin D exhibited a slower decline in SCP levels (mean decrease −0.28 ± 0.10 vs. −0.50 ± 0.10 ng/mL, p<0.001). The mean decrease in IDAA1c was higher in cases (−11.1 ± 0.56 %) compared to controls (−10.1 ± 0.52 %), but the difference in mean decrease (−1.1 ± 0.61) did not attain statistical significance (p=0.08). At 6 months, PR rates were significantly higher in cases compared to controls (19, 59.4 % vs. 6, 19.4 %, p<0.001). Regression analysis revealed baseline SCP as strong predictor of SCP at the study endpoint (r=0.92, p<0.001). Conclusions High-dose vitamin D supplementation may preserve RBCF and prolong PR in children with newly diagnosed T1D. Large-scale randomized controlled trials are warranted.
Requires Authentication Unlicensed
Licensed

Lipoatrophy following weekly growth hormone therapy: a case report

August 1, 2025

Ilhan Hazer, Veysel Nijat Bas

Download PDF

Objectives Traditional daily recombinant human growth hormone injections can be burdensome for patients and caregivers, leading to compliance issues. Long-acting growth hormone formulations have been developed to overcome these challenges. Case presentation We report a 7-year-old girl who developed severe lipoatrophy secondary to repeated somatrogon injections at the same anatomical site during the third month of therapy, with complete resolution after 10 weeks of treatment discontinuation. Conclusions To our knowledge, this is only the second reported case of somatrogon-induced lipoatrophy in the literature. This case also showed that lipoatrophy developing as a result of somatogron treatment is a reversible side effect.
Requires Authentication Unlicensed
Licensed

Phenotypic variation among four members in a family with DAX1 deficiency

July 29, 2025

Yuko Seki, Haruna Kakimoto, Izumi Tamada, Shozo Oku, Satoshi Morita, Minako Tokunaga, Michiyo Mizota, Naoko Amano, Noboru Uchida, Tomonobu Hasegawa, Yasuhiro Okamoto

Download PDF

Objectives To describe four members of a family with DAX1 deficiency caused by a novel NR0B1 variant. Case presentation All family members carried a novel hemizygous NR0B1 variant, p.Gln318Alafs*71. The elder brother, aged 13 years, developed an adrenal crisis at the age of 3 years. The third brother, aged 4 years, showed a relatively low cortisol response to the short Synacthen test, but exhibited no clinical signs of adrenal insufficiency. The youngest brother developed an adrenal crisis at the age of 16 days. Additionally, their 14-year-old cousin was diagnosed with DAX1 deficiency based on skin pigmentation and family history. Conclusions Despite carrying the same NR0B1 variant, the initial symptoms and age of adrenal insufficiency onset varied among the four members of this family. Male members with a family history of DAX1 deficiency should be confirmed genetically as possible.
Requires Authentication Unlicensed
Licensed

Surgical treatment and somatostatin experience in growth hormone-secreting pituitary macroadenoma due to novel AIP mutation

July 23, 2025

Kıymet Karagöz, Emine Şeyma Eken, Gülin Karacan Küçükali, Muhammed Erkan Emrahoğlu, Duygu Düzcan Kilimci, Melikşah Keskin, Erdal Kurnaz, Keziban Aslı Bala, Şule Yeşil, Şükriye Yılmaz, Abdullah Sezer, Şenay Savaş Erdeve

Download PDF

Objectives Somatotropinomas are extremely rare in children and frequently associated with genetic causes. Among pituitary gigantism, approximately 30 % are attributed to the aryl hydrocarbon receptor-interacting protein ( AIP ) gene mutations, whereas other genetic causes are less common. These mutations cause more aggressive tumors that are challenging to control with a single intervention and often exhibit resistance to somatostatin analogs (SSAs). Our aim is to present a pediatric patient with a somatotropinoma due to a novel AIP variant who responded positively to SSA therapy following a single surgical intervention. Case presentation A 15-year and 8-month-old male patient presented with complaints of excessive height and enlargement of the hands and feet over the past 2 years. Laboratory investigations revealed a random growth hormone level of 50 μg/L (normal range [NR]: 0.077–10.8) and insulin-like growth factor-1(IGF-1) level of 1,107 ng/mL (age-adjusted NR: 224–978/>+2 standardised deviation scores). Magnetic resonance imaging demonstrated a pituitary macroadenoma extending into the suprasellar region. A craniotomy was performed, and the majority of the tumor was resected. Due to the presence of residual tumor, SSA therapy (octreotide-LAR) was initiated. After 1 year of follow-up, IGF-1 levels returned to the normal range, and tumor growth was controlled. Genetic analysis identified a heterozygous frameshift novel variant (c.25delC, p.(Arg9Glyfs*9)) in the AIP gene. Conclusions Although AIP mutation-positive cases are typically resistant to SSAs, our patient carrying a novel AIP variant demonstrated a favorable response to SSA treatment.
Requires Authentication Unlicensed
Licensed

Evaluation of thyrotrophic and lactotrophic reserves in patients with pituitary dwarfism with and without empty sella turcica

July 21, 2025

César Geremia, Felipe Geremia

Download PDF

Objectives Empty sella turcica (ES) is commonly observed in idiopathic growth hormone deficiency (GHD) in children. This study aims to determine the frequency of ES in children with GHD, assess their pituitary thyroid-stimulating hormone (TSH) and prolactin (PR) reserves using the thyrotropin-releasing hormone (TRH) stimulation test, and investigate whether ES is associated with a higher prevalence of combined pituitary hormonal deficiencies. Methods TSH and PRL pituitary reserves were assessed through the TRH stimulation test in 22 patients with ES and 31 without this finding (non-ES). All participants had childhood-onset GHD and underwent pituitary imaging, primarily by computed tomography (CT) Anti-thyroid peroxidase (anti-TPO) antibodies were measured in all patients with elevated basal TSH. Results Among 125 children diagnosed with GHD between 1988 and 1996, ES was identified in 29 cases (23 %). Fifty-three patients agreed to participate (86.8 % male), with ES present in 43.5 % of males and 28.6 % of females. No significant differences in TSH and PRL responses to TRH were observed between the ES and non-ES groups. Mildly elevated basal TSH was observed in 50 % of patients with ES and 55 % without ES, most of who tested negative for anti-TPO antibodies. Among patients with elevated basal TSH and hypothyroidism, the majority exhibited exaggerated or delayed TSH responses to TRH and elevated basal PRL, findings suggestive of hypothalamic dysfunction. Four patients presented combined GH, TSH, and PRL deficiencies. Conclusions ES is common in children with GHD but presents distinct features compared to adults. Central hypothyroidism (CeH) was observed in 45.6 % of patients with ES and 54.8 % without ES. Mild TSH elevation was frequent and rarely associated with anti-TPO antibodies, supporting the exclusion of primary hypothyroidism and suggesting underlying hypothalamic dysfunction. Subclinical hormonal abnormalities were also frequent among euthyroid patients. The TRH stimulation test proved valuable in distinguishing hypothalamic dysfunction from pituitary or primary hypothyroidism. Genetic testing for POU1F1 and PROP1 mutations may be warranted in selected cases with combined deficiencies.
Requires Authentication Unlicensed
Licensed

A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency

July 21, 2025

Céline De Cuyper, Willem Staels, Siel Daelemans, Jesse Vanbesien, Elise Nauwynck, Inge Gies

Download PDF

Objectives To describe the case of a young girl with severe congenital neutropenia caused by a homozygous variant in the Jagunal homolog 1 ( JAGN1 ) gene, who later developed atypical diabetes. Case presentation JAGN1 deficiency disrupts neutrophil maturation, resulting in immunodeficiency and recurrent infections. Our patient also exhibited impaired humoral immunity, requiring immunoglobulin replacement therapy, which reduced infection frequency. Several years after the identification of her JAGN1 mutation, she developed atypical insulin-dependent diabetes mellitus – a condition not previously associated with JAGN1 mutations. This novel finding suggests a potential role for JAGN1 in pancreatic β-cell function. Conclusions This case expands the spectrum of JAGN 1 -related immune dysfunction and introduces a potential link between JAGN1 deficiency and diabetes. We explore possible mechanisms underlying this association, highlighting the need for further research. Clinicians should consider JAGN1 mutations in the differential diagnosis of combined immune and metabolic disorders.
Requires Authentication Unlicensed
Licensed

Understanding rickets in osteopetrosis via a case: mechanisms and treatment implications

July 17, 2025

Meliha Esra Bilici, Zeynep Şıklar, Elif Özsu, Serdar Ceylaner, Zehra Aycan, Rukiye Uyanık, Merih Berberoğlu

Download PDF

Objective Osteopetrorickets is a rare autosomal recessive disease that affects many systems and is characterized by dense bone mass and paradoxical rickets due to insufficient resorption of calcified cartilage. Its rarity and presentation with nonspecific symptoms may cause delays in diagnosis. Early diagnosis and improvement of rickets accompanying bone marrow transplantation as a curative treatment option before the development of any irreversible complications are essential for prognosis. However, the etiopathogenesis and management of rickets treatment strategies are still controversial. Case presentation A 4-month-old female patient, whose loss of vision had been followed for 1.5 months, was admitted to our clinic with the request for a disability report. Clinical and laboratory findings were consistent with osteopetrorickets. Molecular analysis revealed a homozygous variant in the TCIRG1 gene. She was normocalcemic and hypophosphatemic, and the 25-OH vitamin D level was normal, while 1.25-dihydroxyvitamin D levels were quite high. Treatment was started with low-dose calcium replacement and calcitriol. The dose of calcitriol was gradually increased to 300 ng/kg/d, and a significant clinical response was achieved. Bone marrow transplantation was conducted at 8 months postnatally from an HLA-compatible non-related donor; nonetheless, the patient succumbed to respiratory problems on the 71st day following the procedure. Conclusion Nonspecific symptoms of osteopetrorickets should be considered for early diagnosis, as a timely intervention in the first months of life can be life-saving. The pathophysiology of rickets remains unclear, but low calcium-phosphorus product and resistance to 1.25-dihydroxyvitamin D appear to play key roles. High-dose calcitriol and cautious calcium supplementation may improve outcomes, though further research is needed to optimize treatment strategies.
Requires Authentication Unlicensed
Licensed

Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye

July 15, 2025

Ayşenur Engin Erdal, Sümeyra Zeynep Özbey, Gülten Burcu Civelek Ürey, Aynur Küçükçongar Yavaş, Berrak Bilginer Gürbüz, Mehmet Gündüz, Esra Kiliç, Avni Merter Keçeli, Aydan Değerliyurt, Çiğdem Seher Kasapkara

Download PDF

Objectives L-2-hydroxyglutaric aciduria (L2HGA) is a hereditary metabolic disorder characterized by the accumulation of L-2-hydroxyglutaric acid in body fluids, particularly in cerebrospinal fluid, which disrupts neuron function in the central nervous system and triggers oxidative stress. It can cause seizures, developmental disorders, and behavioral abnormalities. Methods The study retrospectively evaluated the demographic information, initial symptoms, clinical characteristics, cranial magnetic resonance imaging (MRI) findings, and post-treatment biochemical changes of 10 cases diagnosed with L2HGA. Results The study included five paediatric and five adult cases with a molecular diagnosis of L2HGA. The mean age at diagnosis was 10.1 years. Convulsion was identified as the primary presenting symptom in 70 % of cases. We identified intellectual disability in 80 % of our cases. In addition to the classic cranial MRI findings of subcortical white matter involvement, basal ganglia involvement was detected in 60 % of cases. We found that 2-hydroxyglutaric acid levels in urine organic acid analysis were significantly decreased riboflavin and carnitine post-treatment, with a mean decrease of 133.89 ± 101.43 mmol/mol creatinine (p=0.017). The most common missense variant identified in the L2HGDH gene was c.905C>T (p.Pro302Leu), occurring at a frequency of 50 % (5/10). The cases did not report significant improvement in their symptoms with treatment. Conclusions L2HGA is a rare metabolic disorder that is more common in communities where consanguineous marriages are prevalent. Early diagnosis enables early treatment and protection of the brain from oxidative stress. As more cases are reported publicly, studies on genotype–phenotype relationships will yield more significant findings.
Requires Authentication Unlicensed
Licensed

GNB1 haploinsufficiency presents as monogenic obesity syndrome

July 10, 2025

Pankaj Prasun, Katelyn J. Watkin

Download PDF
Requires Authentication Unlicensed
Licensed

Performance of adult height prediction methods in 6 to 8-year-old girls with GnRH-dependent precocious puberty

July 10, 2025

Anni Erkko, Matti Hero, Tero Varimo, Taneli Raivio

Download PDF

Objectives In girls with precocious puberty (PP), adult height prediction (PAH) is crucial in treatment planning, yet the estimations may be prone to inaccuracies. This study aimed to compare the accuracy of two commonly used PAH methods in 6–8-year-old girls diagnosed with idiopathic GnRH-dependent PP. Methods This retrospective study included data on 60 six- to eight-year-old girls diagnosed with PP. Data was collected from medical records. Forty-eight (82 %) girls were treated with GnRH analogues, and 18 (30 %) had data on AH. Bone ages (BA) were assessed with Greulich–Pyle and BoneXpert. PAHs were estimated with Bayley-Pinneau and BoneXpert. Results In girls treated with GnRH-analogue, AH did not significantly differ from the mean PAH calculated by Bayley-Pinneau (mean difference, −0.1 cm ± 6.6 cm (SD); p=0.93). Predicted adult height estimated by BoneXpert was higher than the actual AH (−3.6 cm ± 4.6 cm, p=0.01), but it showed lower variability in individual prediction errors and less bias related to the degree of BA advancement than Bayley-Pinneau. All subjects reached their mid-parental target height range. Conclusions In 6- to 8-year-old girls with signs of idiopathic GnRH-dependent precocious puberty, the potential to reach their growth target remains, and overestimation of residual height growth at diagnosis should be carefully considered before initiating treatment.
Requires Authentication Unlicensed
Licensed

Exploring the impact of androgen levels on depression and anxiety in adolescent females: a clinical perspective

July 2, 2025

Emel Hatun Aytaç Kaplan, Yasin Çalişkan, Zümrüt Kocabey Sütçü

Download PDF

Objectives Depression and anxiety are rare disorders that can be seen in childhood. Anxiety disorders are more common. The underlying causes of these mental disorders are generally unknown. Changes in the body caused by hyperandrogenism may lead to mental disorders. In this study, we investigated the association of androgen excess with depression and anxiety in adolescent girls. Methods Adolescent girls with elevated androgen levels were evaluated using the DSC and SCARED scales and underwent a child psychiatric evaluation. Physical examination and the relationship between scale scores and anxiety and depression were investigated. Results Fifty-three girls aged 10–18 (mean 15.09 ± 1.26) with androgen elevation participated in the study. In our study, the frequency of panic disorder, separation anxiety, and eating disorders was shallow, but the frequency of generalized anxiety, social anxiety, and depression was high (21 %, 29%, 23 %). None of our patients had school phobia, bipolar disorder, suicidality, obsessive-compulsive disorder, enuresis, or encopresis. No significant change was observed in scale scores with any androgen elevation. Conclusions In our study, we found that androgen elevation did not change the frequency of mental disorders in adolescent girls. Despite the large number of studies, it is still controversial whether hyperandrogenemia increases mental disorders due to conflicting results between studies.
Requires Authentication Unlicensed
Licensed

Prolonged symptom duration and the potential for gradual progression in pediatric adrenocortical tumors: observations from the MET studies

June 30, 2025

Michaela Kuhlen, Stefan A. Wudy, Clara Baumann, Christian Vokuhl, Michaela F. Hartmann, Marina Kunstreich, Rainer Claus, Antje Redlich

Download PDF

Objectives To explore the clinical spectrum and symptom duration in pediatric adrenocortical tumors (pACTs), with a focus on identifying cases that may reflect gradual tumor progression. Methods We retrospectively analyzed data from 110 pediatric patients with pACTs enrolled in the German Pediatric Oncology Hematology-Malignant Endocrine Tumor (GPOH-MET) studies (1997–2022). Endocrine symptom duration, histopathological classification, and clinical outcomes were assessed. Patients with symptom durations ≥2 standard deviations (SDs) from the mean were defined as outliers and evaluated for potential progression. Results The cohort included 31 patients with adrenocortical adenomas (ACAs), 12 with tumors of uncertain malignant potential (ACx), and 67 with adrenocortical carcinomas (ACCs). Seven patients (6.4 %) showed markedly prolonged symptom duration, including four with ACC. One representative case demonstrated a nearly 5-year course from initial androgen excess to metastatic ACC, with evolving biochemical features and a diagnostic urinary steroid profile indicative of adrenal tumor activity. Conclusions A small subset of pACTs may present with prolonged endocrine symptoms, possibly reflecting gradual tumor evolution. While molecular validation is lacking, these findings support the need for early recognition and further research into the natural history of pACTs.
Requires Authentication Unlicensed
Licensed

Transient worsening of thyrotoxic myopathy following methimazole and metoprolol initiation in a 12-year-old girl: a case report and literature review

June 25, 2025

Yuto Onishi, Shinji Higuchi, Kohei Iwata, Yoh Watanabe, Yuki Yamada, Jun Mori

Download PDF

Objectives Thyrotoxic myopathy (TM) is a muscle disorder associated with hyperthyroidism. Although TM is common in adults, its incidence in children is unknown due to the limited number of reports. TM usually improves with the treatment of hyperthyroidism. This is the first report of a patient with TM who experienced transient worsening of muscle weakness shortly after administration of methimazole (MMI) and metoprolol tartrate. Case Presentation A 12-year-old Japanese girl with Graves’ disease was administered MMI and metoprolol tartrate. Within 12 h of treatment initiation, the patient experienced difficulty in standing from a chair. Examination revealed proximal lower-limb weakness and reduced grip strength. Based on the patient’s clinical course and blood test results, thyrotoxic periodic paralysis, myasthenia gravis, or polymyositis were considered unlikely. While the side effects of MMI and metoprolol tartrate were also considered as differential diagnoses, her history revealed mild pre-existing lower limb muscle weakness for 2 months before treatment, suggesting that the side effects of the medication were unlikely. Given the clinical course, the worsening of TM was the most probable cause, and treatment was continued cautiously. Muscle weakness gradually improved over 3 months as her thyroid hormone levels normalized. Magnetic resonance imaging taken 1 month later revealed gluteus muscle atrophy, which resolved within 10 months. Conclusions TM may show transient worsening after MMI and metoprolol tartrate administration, requiring the evaluation of TM, drug side effects, and other possible causes before continuing treatment. This case highlights the importance of recognizing TM in pediatric patients.
Requires Authentication Unlicensed
Licensed

Height velocity in the detection of growth disorders reconsidered: a retrospective analysis of the DONALD study

June 20, 2025

Ibrahim Duran, Maja Zimmermann, Jonathan Buggisch, Heike Hoyer-Kuhn, Ute Alexy, Eckhard Schoenau

Download PDF

Objectives To generate current reference values for height velocity (HV, cm/year) in German children and adolescents and to evaluate the sensitivity of auxological parameters in the evaluation of short stature (referral criteria). Methods The study population consisted of healthy German participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study (1985–2022). In total, data was available from n=453 girls (mean age 9.1 ± 2.4 years) and n=473 boys (mean age of 9.6 ± 2.5 years). As the participants were measured repeatedly, 4,557 HV assessments for girls and 5,224 HV assessments for boys were analyzed (median number of observations in female was nine and in male 11). The reference percentiles were created using the LMS method. The referral criteria of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED) and of the Growth Hormone Research Society (GHRS) for further endocrinological evaluation were evaluated in a subsample. Results The specificity of the referral criteria “HV<25th centile for 1 year” (DGPAED) was 10.4 % in girls and 4.3 % in boys. When this criterion was changed to “HV<3rd centile for 1 year” the specificity increased to 75.5 % in girls and 76.1 % in boys. With omission of the 5th criterion (“height> −2.0 SD AND HV< −2.0 over 1 year”) of the six referral criteria of the GHRS, the specificity of the remaining five referral criteria was 91.4 % in girls and 90.5 % in boys. Conclusions New reference centiles for HV are presented. With modification of the already proposed GHRS criteria, the specificity of the assessment of HV in the evaluation of short stature could be increased significantly.
Requires Authentication Unlicensed
Licensed

Caudal epidural steroid injection as a novel therapy for treatment-induced neuropathy of diabetes in children: report of two cases

June 20, 2025

Anju Bala, Babita Ghai, Arun George, Sayan Banerjee, Mohit Kumar, Devi Dayal

Download PDF

Objectives Treatment-induced neuropathy of diabetes (TIND) is a rare complication of rapid glycemic improvement, characterized by severe shooting pain, predominantly in the lower extremities. This report aims to highlight the clinical presentation of TIND and evaluate the effectiveness of caudal epidural steroid injections (CESI) in managing refractory pain in pediatric cases. Case Presentation We describe two pediatric cases of TIND following rapid improvement in glycemic control for type 1 diabetes. Both patients presented with debilitating pain and sleep disturbances that severely impacted their daily activities. Initial management with a combination of analgesics, pregabalin, gabapentin, and duloxetine failed to provide adequate relief. Subsequently, both patients received CESI with bupivacaine and methylprednisolone. Significant symptomatic improvement in pain and sleep was observed within 4–6 weeks post-intervention. At the 6-month follow-up, the pain relief was sustained, and no adverse effects were reported. Conclusions These cases underscore the importance of recognizing TIND as a potential complication of rapid glycemic control and the challenges in its management. CESI appears to be a promising therapeutic option for children with refractory TIND, offering durable pain relief and improved quality of life. Further studies are needed to validate its efficacy and safety in larger cohorts.
Requires Authentication Unlicensed
Licensed

Endocrinopathies associated with pediatric common variable immunodeficiency

June 20, 2025

Jan Neneman, Marek Niedziela, Kamil Dyrka, Magdalena Banaszak-Ziemska, Cezary Miedziarek, Monika Obara-Moszynska, Aleksandra Szczawinska-Popłonyk

Download PDF

Objectives The pediatric common variable immunodeficiency (CVID) is the most prevalent symptomatic antibody deficiency characterized by a marked heterogeneity of genetic underpinnings, immune system dysfunctions, and clinical manifestations encompassing susceptibility to infections and immune dysregulation disorders, thus increasing autoimmunity. Endocrinopathies associated with CVID have multifactorial etiology and usually lead to hypofunction of the affected organs. The aim of the study was to evaluate the parameters of endocrine homeostasis in children with CVID and to ascertain whether endocrinopathies are components belonging to the spectrum of organ-specific immunopathologies associated with this condition. Methods The study cohort comprised 22 children (aged 5–17 years) with a confirmed diagnosis of common variable immunodeficiency (CVID) who were undergoing immunoglobulin replacement therapy. A range of anthropometric and hormonal parameters related to growth, thyroid, parathyroid, adrenal glands function, and calcium-phosphate metabolism were assessed. Results Antithyroid peroxidase antibodies were identified in 81.81 % of children, while antipancreatic islet (GAD-Ab) antibodies were present in 59.09 %. Among those without preexisting diabetes, 50 % exhibited low C-peptide levels, while 35 % demonstrated both positive GAD-Ab and low C-peptide, with one case displaying elevated HbA1c. Vitamin D3 deficiency was identified in 50 % of patients, and 40.91 % exhibited elevated parathormone levels, suggestive of secondary hyperparathyroidism. Conclusions Endocrinopathies, particularly autoimmune thyroiditis, are prevalent in pediatric CVID, reflecting the condition’s immune dysregulation. Regular monitoring of clinical and hormonal parameters is essential for the provision of multidisciplinary care and the enhancement of patient outcomes.
Requires Authentication Unlicensed
Licensed

A novel homozygous missense DNAJC3 variant in syndromic juvenile-onset diabetes

June 20, 2025

Eda Mengen, Deniz Kor, Fatma Derya Bulut, Leman Damla Kotan, İhsan Turan, Bilgin Yüksel, Neslihan Önenli Mungan

Download PDF

Objectives The DNAJC3 gene encodes a protein that acts as a cochaperone of binding immunoglobulin protein (BiP), a major member of the heat shock protein 70 (HSP70) family, which is found in the endoplasmic reticulum (ER) and promotes normal protein folding. Loss-of-function mutations in DNAJC3 lead to early-onset diabetes and multisystemic neurodegeneration. In this article, we report a case of monogenic syndromic diabetes caused by a previously undescribed DNAJC3 variant. Case presentation A 15-year-old 5-month-old girl with polyuria and polydipsia for the last 2–3 months was diagnosed and treated as diabetic ketoacidosis at the center where she was admitted with complaints of general condition disorder and frequent breathing. Her laboratory findings were HbA1c 15.1 %, serum insulin 7.83 m U/L, C-peptide 0.78 μg/L. Tests for autoimmune diabetes markers were negative. Physical examination revealed severe short stature 141.4 cm (−3.62 SDS). Sensorineural hearing loss developed 5 months after the diagnosis of diabetes and intellectual functions were impaired. Neurologic examination revealed marked ataxia. Monogenic syndromic diabetes mellitus with multisystemic neurodegeneration including juvenile onset diabetes mellitus, ataxia, short stature and sensorineural hearing loss was considered. Exome sequencing and CNV (Copy Number Variation) analysis revealed a novel homozygous c.1244G>C (p.Arg415Pro) variant in DNAJC3 gene. Conclusions This case supports the wide phenotypic spectrum and multisystem involvement potential of DNAJC3 variants and demonstrates the need to increase awareness in the diagnostic process of these rare genetic disorders..
Requires Authentication Unlicensed
Licensed

Distinguishing organic from idiopathic central precocious puberty: clinical characteristics and predictive factors for organic etiology in a multicenter Italian cohort study

June 17, 2025

Giorgio Sodero, Marilea Lezzi, Luigi Antonio Moscogiuri, Elena Malavolta, Federica Arzilli, Aniello Meoli, Anna Camporeale, Francesco Gallo, Donato Rigante, Clelia Cipolla

Download PDF

Objectives Central Precocious Puberty (CPP) is characterized by the early onset of secondary sexual characteristics before the age of 8 in girls and 9 in boys. While rapid progression of sexual development may indicate an underlying organic cause, such as the presence of anatomical abnormalities of the hypothalamic-pituitary axis, no definitive diagnostic standard exists. Therefore, diagnosis requires a comprehensive assessment incorporating clinical, biochemical, and radiological evaluations. The aim of this study is to identify clinical, hormonal, and radiological factors that differentiate idiopathic from organic CPP, in order to establish predictive criteria for the identification of organic etiology. Methods A multicenter retrospective study was conducted on female patients diagnosed with CPP at two major Italian hospitals between January 2015 and February 2025. Clinical, hormonal, and radiological data were analyzed to differentiate between idiopathic and organic CPP. A total of 134 patients were included, all of whom underwent a GnRH stimulation test for diagnosis. Results Among the 134 patients, 12 (9 %) were diagnosed with organic CPP. Patients with organic CPP were diagnosed at a younger age, exhibited higher growth velocity, and showed elevated basal and stimulated gonadotropin levels. Multivariate analysis identified several significant predictors of organic CPP, including age at diagnosis, LH peak, LH/FSH ratio, height SD, and growth velocity. ROC curve analysis demonstrated that an LH peak >9.1 mIU/mL and growth velocity >1.75 standard deviations (SD) were highly sensitive (80 %) and specific (85 %) indicators of organic CPP. Conclusion Organic CPP is characterized by a younger age at diagnosis, faster progression of puberty, and higher gonadotropin levels compared to idiopathic CPP. An LH peak >9.1 mIU/mL and a growth velocity >1.75 SD should be considered key diagnostic markers for identifying organic causes of CPP and guiding further investigation and treatment.
Requires Authentication Unlicensed
Licensed

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: case report of a child with rare HMGCL gene variants

June 13, 2025

Milena Bjelica, Aleksandra Stojadinović, Marija Knežević Pogančev, Katarina Koprivšek, Jӧrn Oliver Sass, Sarah C. Grünert, Falko Wünsche, Raina Yamamoto

Download PDF

Objectives 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessive organic aciduria. Most patients present within the first year of life with metabolic decompensation, which can cause neurological damage or death if untreated. Case presentation A 20-month-old previously healthy boy was admitted to the hospital after a nocturnal seizure. Upon admission, the child was unconscious and laboratory analysis revealed severe hypoglycemia and metabolic acidosis without ketonuria. Hypoglycemia was corrected with a bolus of 10 % glucose followed by continuous glucose-electrolyte infusion. Status epilepticus was treated with midazolam and phenobarbital. Magnetic resonance imaging (MRI) performed on the second hospital day, revealed bilateral and symmetric T2 hyperintense lesions in the cortex, supratentorial white matter, basal ganglia and central pons, along with slight white matter volume reduction. Urinary organic acids indicated HMGCLD. HMG-CoA lyase activity in immortalized lymphocytes was significantly decreased. Sanger sequencing of the HMGCL gene identified a heterozygous sequence variant, c.796T>C, p.(Cys266Arg). MLPA analysis showed a reduced gene dosage for exons 3 and 4 of HMGCL , consistent with a heterozygous deletion. Upon diagnosis, a low-protein diet was recommended, as well as oral l -carnitine therapy with a high-calorie supplement drink at night. Initially, the child had slightly impaired psychomotor development, which normalized by age 3.5. He was without metabolic crises or seizures since diagnosis. Conclusions In any child presenting with hypoketotic hypoglycemia and metabolic acidosis of unknown etiology, HMGCLD should be considered. Given the rarity of HMGCLD and its sporadic cases across Europe, management should involve a well-experienced multidisciplinary team.
Requires Authentication Unlicensed
Licensed

Comparison study of the correlation between free and total 25(OH)D in maternal and umbilical blood and early-life physical development parameters

June 13, 2025

Zhihong Tian, Xiaoyan Xu, Xiaohui Gong, Suimin Zeng, Shibo Fu, Yumin Chen, Yide Yang, Guoying Sun, Mei Tian, Jian Li

Download PDF

Objectives To investigate the association between free and total 25(OH)D levels and fetal growth during pregnancy, and to evaluate whether free 25(OH)D is a better indicator of vitamin D status compared to total 25(OH)D. Methods A total of 160 pregnant women and their newborns were consecutively recruited from a Jiangsu hospital (March–May 2019). Maternal blood was collected before delivery, and cord blood was collected after umbilical cord disconnection. Serum free and total 25(OH)D were measured by ELISA. Clinical data, including pregnancy records, neonatal assessments, and 6-month follow-ups, were extracted from electronic medical records. Associations between vitamin D levels and developmental outcomes were analyzed using univariate correlation analysis and multivariable linear regression in SPSS 20.0 (p<0.05). Results Maternal-umbilical free 25(OH)D correlation was stronger than total (rho=0.699 vs. 0.475; both p<0.001). Maternal free 25(OH)D showed stronger associations with early pregnancy femur length (11.37 ± 3.39 mm; β=2.053), late pregnancy biparietal diameter (82.65 ± 4.60 mm; β=−0.273), and femur length growth efficiency (0.89 ± 0.15 mm/week; β=−0.289) than total 25(OH)D (all p<0.05). Umbilical free 25(OH)D correlated with mid-pregnancy transverse cerebellar diameter (22.0[21.0–23.0] mm; β=−0.231) and femur length growth efficiency (0.92[0.78–1.05] mm/week; β=−0.224) (p<0.05 and p<0.01). Maternal free 25(OH)D negatively associated with late pregnancy head circumference (330.11 ± 7.89 mm; β=−9.050, p<0.01). Conclusions Compared to total 25(OH)D, free 25(OH)D in maternal and umbilical blood may be more strongly associated with early-life physical growth parameters.
Requires Authentication Unlicensed
Licensed

MMP13-related metaphyseal dysplasia: a differential diagnosis of rickets

June 13, 2025

Abdulkerim Kolkiran, Tuğba Daşar, Abdullah Sezer

Download PDF

Objectives MMP13 -related metaphyseal dysplasia Spahr type, is an extremely rare skeletal disorder, and only a dozen patients with a confirmed molecular diagnosis have been reported. It is characterized by mild short stature, genu varum, and metaphyseal irregularities including fraying, splaying, and cupping of the long bones. The disorder is in the differential diagnosis of rickets, a relatively common disorder in childhood that shares similar clinical and radiological features with metaphyseal dysplasia. Case presentation Herein, we present a 39-month-old girl patient who was initially evaluated for rickets due to mild short stature, bowing of the lower extremities, and metaphyseal changes. Biochemical tests including calcium, phosphate, alkaline phosphatase, and vitamin D levels were all within normal ranges. Radiographies revealed advanced bone age, mildly enlarged epiphyses, wide and irregular metaphyses of the long tubular bones, mildly thickened long tubular bones, and coxa vara. Clinical exome sequencing identified a homozygous variant in the MMP13 gene, confirming the diagnosis of metaphyseal dysplasia Spahr type. Conclusions We emphasize that metaphyseal dysplasias mimic the clinical and radiographic features of rickets and play a significant role in the differential diagnoses, particularly in patients presenting with short stature, genu varum, and metaphyseal irregularities, despite the absence of biochemical abnormalities. In accordance with the Nosology of Genetic Skeletal Disorders: 2023 Revision, we reinforce the dyadic naming system for the two groups of MMP13 -related metaphyseal dysplasia, differentiated solely by their inheritance patterns, which also exhibit consistency with the location of the variants.
Requires Authentication Unlicensed
Licensed

Transition of care from childhood/adolescence to adulthood in familial hypercholesterolemia

May 6, 2025

Ariana Maia, Liliana Fonseca, Isabel Palma

Download PDF

Familial hypercholesterolemia (FH) is a common genetic disorder with a co-dominant inheritance pattern, characterized by persistently elevated levels of atherogenic low-density lipoprotein cholesterol (LDL-C) and a significantly increased risk of premature atherosclerotic cardiovascular disease. Given that the cardiovascular risk associated with elevated LDL-C begins in early childhood and progresses over time, early identification and long-term management are crucial. Implementing effective screening programs, genetic testing, and timely initiation of lipid-lowering therapy are essential strategies to mitigate future coronary events, improve quality of life, and reduce morbidity and mortality. This document outlines strategies and recommendations to improve early detection, genetic screening, and holistic management of individuals affected by FH, with particular emphasis on facilitating a structured transition from pediatric to adult healthcare services to ensure continuity of care and sustained treatment adherence.
Requires Authentication Unlicensed
Licensed

The association between hydration status and body composition in healthy children and adolescents

May 1, 2023

Priscilla Clayton, María Angélica Trak-Fellermeier, Alison Macchi, Rodolfo Galván, Zoran Bursac, Fatma Huffman-Ercanli, Juan Liuzzi, Cristina Palacios

Download PDF

Objectives Children 10–20 years old in the US are currently obese, showing suboptimal hydration as 60% fail to meet the US Dietary Reference Intakes for water. Studies have shown a significant inverse association between hydration status and body composition in children, although most failed to use the Dual-X-Ray Absorptiometry Scan (DEXA), the gold standard for body composition. Limited studies used an objective marker to measure hydration, such as urine specific gravity (USG) from a 24-h urine collection. Therefore, this study aimed to examine the association between hydration status (measured from USG in a 24-h urine sample and assessed from three 24-h dietary recalls) and body fat % and lean mass (assessed from a DEXA scan) in children (10–13 years, n=34) and adolescents (18–20 years, n=34). Methods Body composition was measured using DEXA, total water intake (mL/d) was assessed from three 24-h dietary recalls and analyzed using the Nutrition Data System for Research (NDSR). Hydration status was objectively measured using USG via 24-h urine collection. Results Overall body fat % was 31.7 ± 7.31, total water intake was 1746 ± 762.0 mL/d, and USG score was 1.020 ± 0.011 uG. Linear regressions showed significance between total water intake and lean mass (B=12.2, p<0.05). Logistic regressions showed no significant association between body composition and USG and total water intake. Conclusions Findings showed total water intake was significantly associated with lean mass. Future research should be conducted to explore other objective markers of hydration and with a larger sample.
Publicly Available
Corrigendum to: Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience

September 13, 2019

Saba Samad Memon, Kunal Thakkar, Virendra Patil, Swati Jadhav, Anurag R. Lila, Gwendolyn Fernandes, Tushar R. Bandgar, Nalini S. Shah

Article number: 20198888

Download PDF

Issue 0

Issue 8

Journal Impact Factor	1.0	2024, Journal Citation Reports (Clarivate, 2025)
5-year Journal Impact Factor	1.4	2024, Journal Citation Reports (Clarivate, 2025)
Journal Citation Indicator	0.44	2024, Journal Citation Reports (Clarivate, 2025)
CiteScore	2.6	2024, Scopus (Elsevier B.V., 2025)
SCImago Journal Rank	0.445	2024, SJR (Scimago Lab, 2025; Data Source: Scopus)
Source Normalized Impact per Paper	0.580	2024, CWTS Journal Indicators (CWTS B.V., 2025; Data Source: Scopus)

Journal of Pediatric Endocrinology and Metabolism

Overview

About this journal

Your Benefits

Ahead of Publication / Just Accepted

Issues

Special issues

Ranking

Submit

Editorial

Abstracting and Indexing

Supplementary Materials

Supplementary Materials

Topics

Topics

External Links

Bibliographic data