OBJECTIVES:Hashimoto thyroiditis (HT) is an autoimmune disorder that may be associated with systemic inflammation. Adrenomedullin (ADM) is a peptide known to be elevated in inflammatory conditions, but its role in pediatric HT has not been extensively studied. To investigate serum ADM levels and their relationship with clinical and laboratory parameters in adolescents with HT. METHODS:This cross-sectional study included 46 adolescents with HT and 41 age-, sex-, and BMI-matched healthy controls. Serum ADM, thyroid function tests, anti-thyroid antibodies, IL-6, and CRP levels were measured. Clinical features including goiter and symptom status were recorded. Correlation and multivariate logistic regression analyses were performed to evaluate associations and predictive factors. RESULTS:ADM levels were significantly higher in the HT group than in controls (p=0.016). TSH, anti-TPO, anti-TG, and IL-6 levels were also elevated, while free T4 and CRP did not differ significantly. ADM correlated with TSH and thyroid functional status but not with IL-6 or CRP. Goiter was present in 28 % of patients, with all patients with goiter showing elevated ADM. Multivariate analysis identified TSH, free T4, and ADM as significant predictors of HT. Receiver operating characteristic analysis showed moderate diagnostic performance for ADM (AUC=0.651). CONCLUSIONS:Serum adrenomedullin levels were elevated in adolescents with Hashimoto thyroiditis compared with matched controls and were associated with thyroid dysfunction and local inflammatory activity. Although ADM showed only moderate diagnostic performance, this exploratory first study in pediatric HT suggests a potential role in disease pathophysiology and warrants confirmation in larger prospective cohort studies.

OBJECTIVES:Cryptorchidism is the most prevalent pediatric genital anomaly, yet its clinical significance often extends beyond simple anatomical maldescent. While surgical management is well-established, the necessity for holistic endocrine and genetic evaluation remains underexplored. We aimed to characterize the clinical, hormonal, and genetic landscapes of patients referred for pediatric endocrinological assessment following orchiopexy. METHODS:We retrospectively analyzed 99 boys referred for postoperative evaluation. Clinical findings, basal and dynamic hormonal profiles, and genetic results - including karyotype and targeted DSD gene panels - were evaluated. RESULTS:Preterm birth was recorded in 23.2 % of the cohort, and bilateral involvement was present in 50.5 %. Significant clinical findings included testicular atrophy (34.3 %), scrotal hypoplasia (18.2 %), micropenis (12.1 %), and hypospadias (10.1 %). Hormonal profiling revealed a broad spectrum of FSH (up to 85.7 mIU/mL) and AMH (0.01-71.80 ng/mL) levels. Among patients undergoing hCG stimulation testing, 72.7 % exhibited an insufficient testosterone response. Targeted DSD panel testing in a selected high-risk subgroup yielded a diagnostic rate of 45.4 %, identifying variants in SRD5A2, PTPN11, NR0B1, RAF1, POR, LHX4, and AMHR2. The prevalence of nonisolated cryptorchidism was relatively high, affecting 44.4 % of the cohort. This multisystemic involvement comprised defined syndromic diagnoses (17.2 %) and chronic comorbidities (27.3 %), predominantly endocrine disorders such as congenital hypothyroidism and growth hormone deficiency. CONCLUSIONS:The high frequency of bilateral involvement, testicular atrophy, and genetic mutations suggests that many referred cases represent complex syndromic or endocrine conditions rather than isolated maldescent. Comprehensive endocrinological follow-up and targeted genetic testing are essential for early diagnosis and optimizing long-term fertility management.

CONTEXT:Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) poses significant growth challenges, including accelerated bone maturation, precocious puberty, and compromised final height (FH). Data on pubertal growth in large 21-OHD cohorts remain limited. OBJECTIVE:To assess puberty timing, duration, height gain, FH outcomes, and the effects of growth-promoting therapies (GPTs), including GnRH analog, aromatase inhibitors, and cyproterone acetate, in a large cohort with genetically confirmed classical 21-OHD. DESIGN AND SETTING:A multicenter, retrospective, longitudinal analysis of 284 patients (46,XX: 160; 46,XY: 124). METHODS:Data on puberty, growth, and treatments were collected from clinical records. Growth curves were plotted based on GPT use. RESULTS:Median age at diagnosis was 0.1 years (interquartile range [IQR]: 0.03-1.1), and at last visit, 12.1 years (IQR: 7.0-17.0). Median FH was 154.0 cm (IQR: 147.3-158.2) in 46,XX (menarche at 13.0 years) and 167.0 cm (IQR: 160.0-170.0) in 46,XY. In the total cohort, 63.4% were pubertal/postpubertal, and the ratio of GPTs used alone or in combination was 41.1%. GnRH analogs, cyproterone acetate, and aromatase inhibitors were administered in 21.8% (n = 62), 8.1% (n = 23), and 5.3% (n = 15) of the cohort, respectively. The median FH-MPH difference improved from -6.7 cm to -2.3 cm in boys without and with GPT, respectively, whereas in girls it declined from -3.7 cm to -6.6 cm. CONCLUSION:Patients with 21-OHD had diminished FH despite early diagnosis. Puberty in classical 21-OHD had an earlier onset, slower tempo, and prolonged duration, especially in girls, in which GPTs are less effective in promoting height. The management of pubertal growth needs a personalized approach in patients with classical 21-OHD.

BACKGROUND:NGLY1 deficiency is an ultra-rare multisystem disorder characterized by developmental delay, hyperkinetic movement disorder, hypo-/alacrimia, peripheral neuropathy, and elevated transaminases. METHODS:We conducted a multicenter retrospective study including 15 patients from 11 families to evaluate the clinical, biochemical, and molecular features of the disease. A literature review was also performed, and phenotypic data from published patients were evaluated. RESULTS:All patients presented with developmental delay and dysmorphic facial features. Common neurological findings included abnormal EEG (10/15), seizures (9/15), hyperkinetic movement disorder (8/15), reduced deep tendon reflexes (6/15), and peripheral neuropathy (3/5). Frequent non-neurological features included feeding difficulties (9/15), scoliosis (7/13), hypo-/alacrimia (6/15), constipation (6/15), and auditory neuropathy (2/4). Peripheral and auditory neuropathy findings were observed over time. Elevated transaminases were the most common laboratory abnormality (12/14) and were transient in most patients (9/12), followed by low total cholesterol (7/10) and HDL levels (5/10). We identified 10 distinct variants, including two novel variants c.629delA (p.(Lys210SerfsTer14)) and c.1036C > T (p.(Gln346Ter)). Most patients carried homozygous variants, and no clear genotype-phenotype correlation was observed. CONCLUSION:Our findings expand the clinical and molecular spectrum of NGLY1 deficiency and highlight its dynamic and progressive course, supporting the need for long-term clinical follow-up. NGLY1 deficiency may be considered in patients with neurologic findings and dysmorphic features, especially when transient elevated transaminases and hypolipidemia are also present.

This study aimed to explore the developmental outcomes of children with biotinidase deficiency (BD) and the psychological well-being of their parents. The cohort comprised 61 children diagnosed with BD who were followed at the Department of Pediatric Metabolism of Başakşehir Çam and Sakura City Hospital in Istanbul, along with their parents. The control group comprised 49 children who were admitted to the pediatric outpatient clinic during the same period and did not have any chronic physical diseases or previous psychiatric admissions, and their parents. The current findings indicated that children with BD did not show significant developmental delays compared to the control group, with no notable differences in intelligence scores between the groups. Interestingly, parents of children with BD reported lower levels of state anxiety than those of the control group, although no significant differences were observed for other mental health metrics. Conclusion: These findings imply that early diagnosis and intervention through newborn screening could help alleviate developmental and psychological challenges for children and their parents.

Adenylate cyclase 3 (ADCY3) gene alterations have been found to be associated with obesity. However, few patients with homozygous mutations have been reported so far, and the follow-up procedure and treatment options have not been clarified. A 10-month-old female presented with increased appetite and weight gain. She was born from a consanguineous marriage. Weight, height, head circumference measurements and standard deviation scores (SDS) were 19 kg (+6.98 SDS), 82 cm (+3.53 SDS), and 49 cm (+3.07 SDS), respectively. Laboratory tests revealed a fasting glucose level of 103 mg/dL (5.7 mmol/L), insulin level of 25.39 µIU/mL, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value of 6.43. Whole-exome sequencing revealed a novel, homozygous c.1102G>A(p.Asp368Asn) variant in ADCY3. Her parents and healthy sister were heterozygous for the variant. At the age of 2.5 years, neurodevelopmental delay was observed. At the age of 3.5 years, the patient's weight, height, and body mass index values were 49.5 kg (+8.16 SDS), 111 cm (+2.59 SDS), and 40.18 kg/m2 (+6.48 SDS), respectively. Signs of Blount's disease and acanthosis nigricans were distinctive, and she had hyperphagia. She was undergoing speech therapy. Homozygous ADCY3 variants may present with early onset, severe obesity, insulin resistance, and neurodevelopmental delay in children. Severe complications may occur even at young ages. More data regarding the follow-up process and treatment of these patients are needed.

Hyperprolactinemia (HPRL) is a rare endocrinopathy in childhood caused by tumors, pituitary stalk interruption, and systemic diseases. In this retrospective study, we examined the clinical characteristics of pediatric patients with prolactin (PRL) elevation. The study examined 70 pediatric and adolescent patients with elevated PRL. The patients (52 female, 18 male; age range, 0.03-18) were divided into two groups: Physiological (n=46, 65.7%) and pathological (iatrogenic+sellar mass) (n=24, 34.3%) HPRL. Six patients (8.6%) were included in the pathological group due to iatrogenic causes and 18 patients (25.7%) due to a sellar mass. Subdiagnostic groups were found in the pathological group: 14 patients with prolactinoma (10 microadenomas; 4 macroadenomas), 6 patients with drug-induced HPRL, 2 patients with craniopharyngioma, 1 patient with dysgerminoma, and 1 patient with tuberculoma. Symptoms such as headache (p=0.004), galactorrhea (p=0.000), amenorrhea (p=0.037), and menstrual irregularity (p=0.037) were more common in the pathological group. Short stature and early thelarche complaints were more common in the physiological group (p=0.004, p=0.045, respectively). The presence of galactorrhea was significant in predicting pathological PRL elevation (p=0.002) (odds ratio=56.1%, 95% confidence interval=4.33-728.1). Twenty-seven point one percent (n=19) received cabergoline treatment, and 8.5% (n=6) received levothyroxine treatment. Three patients underwent surgical treatment for dysgerminoma and craniopharyngioma, respectively. The probability of detecting HPRL is high in the presence of galactorrhea. In prolactinoma, if there are significant pituitary compression symptoms, the disease can be controlled with medical treatment.

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.

Aim: This study aimed to evaluate coagulation disorders in patients with argininemia associated with arginase 1 gene mutations and the control of these disorders with sodium benzoate treatment. Materials and Methods: Five argininemia patients followed up in the Pediatric Metabolism Clinic in University of Health Sciences T & uuml;rkiye, Ba & scedil;ak & scedil;ehir & Ccedil;am and Sakura City Hospital, were included in this study. The patients initially received protein-restricted diet treatment, while their ammonia, platelet count, liver enzymes and coagulation parameters were measured regularly. Later, sodium benzoate was added to the treatment and the same parameters were measured at 1-month intervals. Results: In the coagulation parameters measured after sodium benzoate treatment, one out ofthe five patients showed complete improvement, three had partial improvement, and one had no change. In the patients with coagulation disorders, factor VII and IX levels were low, while arginine levels remained above 250 mu mol/L. Conclusion: The pathophysiology of coagulation disorders in patients with argininemia has not yet been fully elucidated, but it is thought that high arginine levels may affect the synthesis of short-lived coagulation factors. Adding sodium benzoate to dietary therapy may contribute to both the control of arginine levels and an improvement in coagulation parameters. This study demonstrates the importance of coagulation monitoring in those patients with argininemia and the potential therapeutic role of sodium benzoate.

To evaluate the clinical characteristics, surgical outcomes, and endocrinological follow-up findings of pediatric patients who underwent surgical treatment for sellar and parasellar masses. Forty-seven patients who underwent surgical treatment for sellar and parasellar masses between January 2021 and January 2025 were retrospectively analyzed. All patients were followed up in the pediatric endocrinology clinic. Demographic characteristics, clinical findings, surgical approaches, histopathological diagnoses, and postoperative outcomes were evaluated. Endocrinological assessments were performed using standardized hormone assays with age- and sex-specific reference ranges. Twenty-eight (59.6

Aim: Familial hypercholesterolemia leads to the buildup of atherosclerotic plaques in the arteries, greatly elevating the risk of early-onset coronary heart disease. The objective of this study was to examine the clinical, laboratory, and genetic profiles of patients affected by familial hypercholesterolemia. Methods: A retrospective review was performed on the demographic, clinical, biochemical and genotypic profiles of 124 individuals diagnosed with familial hypercholesterolemia. Results: These cases from 6 centres comprised 50.8% males and 49.2% females. There was a history of hypercholesterolemia in the mothers of 43.5% of the cases and in the fathers of 53.2%. At the time of diagnosis, 81.5% of the cases had no complaints, 3.2% had skin lesions and 3.2% had weight gain complaints. Mutations were detected in the LDLR gene in 95.2% of the cases, in the APOE gene in 3.2% and in the APOB gene in 1.6%. Conclusion: Familial hypercholesterolemia cases are still under-detected both in Türkiye and worldwide. Consequently, the prevention of coronary artery diseases caused by hypercholesterolemia is not feasible, underscoring the need for implementing more robust and widespread screening protocols.

Abstract Background Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely recognition and treatment of CAN are crucial in averting the onset of cardiovascular complications. Both clinically apparent autonomic neuropathy and subclinical autonomic neuropathy, particularly CAN pose a significant risk of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). Notably, CAN can progress silently before manifesting clinically. In our study, we assessed patients with poor metabolic control, without symptoms, following the ISPAD 2022 guideline. The objective is is to determine which parameters we can use to diagnose CAN in the subclinical period. Methods Our study is a cross-sectional case–control study that includes 30 children diagnosed with T1DM exhibiting poor metabolic control (average HbA1c > 8.5% for at least 1 year) according to the ISPAD 2022 Consensus Guide. These patients, who are under the care of the pediatric diabetes clinic, underwent evaluation through four noninvasive autonomic tests: echocardiography, 24-h Holter ECG for heart rate variability (HRV), cardiopulmonary exercise test, and tilt table test. Results The average age of the patients was 13.73 ± 1.96 years, the average diabetes duration was 8 ± 3.66 years, and the 1-year average HbA1c value was 11.34 ± 21%. In our asymptomatic and poorly metabolically controlled patient group, we found a decrease in HRV values, the presence of postural hypotension with the tilt table test, and a decrease in ventricular diastolic functions that are consistent with the presence of CAN. Despite CAN, the systolic functions of the ventricles were preserved, and the dimensions of the cardiac chambers and cardiopulmonary exercise test were normal. Conclusions CAN is a common complication of T1DM, often associated with the patient’s age and poor glycemic control. HRV, active orthostatic tests, and the evaluation of diastolic dysfunctions play significant roles in the comprehensive assessment of CAN. These diagnostic measures are valuable tools in identifying autonomic dysfunction at an early stage, allowing for timely intervention and management to mitigate the impact of cardiovascular complications associated with T1DM.

This study aims to evaluate the etiology, clinical presentation, and management of pediatric hypoparathyroidism in a tertiary center. A retrospective review was conducted on pediatric patients diagnosed with hypoparathyroidism at the Pediatric Endocrinology Clinic from March 2021 to June 2023. Data on demographic characteristics, presenting symptoms, laboratory findings, genetic analyses, and treatment outcomes were collected. A total of 56 patients (31 females) were included. The median age at diagnosis of the patients was 5.5 years (range 0.04–17 years), and the median age of symptom onset was 5 years (range 0.04–16.5 years). The etiology was genetic and idiopathic in 39 patients (70.9

Intrauterine onset syndromic short stature constitutes a group of diseases that pose challenges in differential diagnosis due to their rarity and clinical as well as molecular heterogeneity. The aim of this study was to investigate the presence of (epi)genetic causes in children born small for gestational age (SGA) and manifesting clinically undiagnosed syndromic short stature. The study group comprised twenty-nine cases selected from the syndromic SGA cohort. Various analyses were performed, including chromosomal microarray (CMA), methylation-specific-multiple ligation probe amplification for chromosomes 6,14 and 20, and whole exome sequencing (WES). Pathogenic copy number variants (CNVs) on chromosomes 2q13, 22q11.3, Xp22.33, 17q21.31, 19p13.13 and 4p16.31 causing syndromic growth disturbance were detected in six patients. Maternal uniparental disomy 14 was identified in a patient. WES was performed in the remaining 22 patients, revealing pathogenic variants in nine cases; six were monoallelic (ACAN, ARID2, NIPBL, PIK3R1, SMAD4, BRIP1), two were biallelic (BRCA2, RFWD3) and one was hemizygous (HUWE1). Seven of these were novel. Craniofacial dysmorphism, which is an important clue for the diagnosis of syndromes, was very mild in all patients. This study unveiled, for the first time, that ARID2 mutatios can cause syndromic SGA. In conclusion, a high (55.2%) diagnosis rate was achieved through the utilization of CMA, epigenetic and WES analyzes; 15 rare syndromes were defined, who were born with SGA and had atypical and/or mild dysmorphic findings. This study not only drew attention to the association of some rare syndromes with SGA, but also introduced novel genes and CNVs as potential contributors to syndromic SGA.

Amaç: Çalışmanın amacı obezlerde 25(OH)D3’ün yağ dokusunda akümüle olup olmadığını incelemek ve böylece obez bireylerde genel populasyona göre daha sık olan D vitamini eksikliğinin sebebine ışık tutmaya çalışmaktır Yöntem: Çalışmaya İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi çocuk endokrinoloji polikliniğine obezite nedeni ile aralık ayında başvuran ve çalışma şartlarını sağlayan 67 çocuk dahil edildi. 3 aylık diyet ve egzersiz sonrası hastalarda ağırlık, VKİ ve serum 25(OH)D3 düzeylerindeki değişim incelendi. Hastalar anlamlı kilo kaybı olanlar (Grup1) ve olmayanlar (Grup2) şeklinde iki gruba ayrıldı. Bulgular: Kilo kaybı olan (Grup 1) hastalarda başlangıçtaki serum 25(OH)D3 değeri (12,59 ± 5,69 ng/ml) ile 3 ay sonrasındaki 25(OH)D3 değeri (16,87 ± 10,08 ng/ml) arasında istatistiksel olarak anlamlı fark vardı (P=0,004). Kilo kaybı olmayan (Grup 2) hastalarda diyet-egzersiz öncesi ortalama 25(OH)D3 değeri (14,58 ± 6,6 ng/ml) ile sonrasındaki 25(OH)D3 değeri (13,99 ± 6,69 ng/ml) arasında istatistiksel olarak anlamlı fark yoktu. Her iki grupta insülin ve HOMA-IR değişimleri arasında anlamlı fark yoktu. Sonuç: Obez hastalarda serum D vitamin düzeyinde yetersizlik sıktır ve bu hastalar gelişebilecek metabolik komplikasyonlar açısından risk altındadır. Çalışmamızda obez hastalarda kilo kaybı sonrasında serum D vitamini düzeyinde artış görülmüştür. Sonuçlarımız obezlerde D vitamininin yağda toplandığı ve dolaşımdaki efektif miktarın düşük olduğu görüşünü desteklemektedir. Bu hastalara diyet ve egzersiz ile birlikte vitamin D takviyesi sağlamanın yerinde olduğunu düşünmekteyiz.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a well-known mitochondrial depletion syndrome. Since Van Goethem et al. described MNGIE syndrome with pathogenic POLG1 mutations in 2003, POLG1 gene became a target for MNGIE patients. Cases with POLG1 mutations strikingly differ from classic MNGIE patients due to a lack of leukoencephalopathy. Here we present a female patient with very early onset disease and leukoencephalopathy compatible with classic MNGIE disease who turned out to have homozygous POLG1 mutation compatible with MNGIE-like syndrome, mitochondrial depletion syndrome type 4b.