Volume 39, Issue 1

The prevalence of congenital hypothyroidism (CH) in infants of mothers with hypothyroidism has been described but a comprehensive prevalence estimation is lacking. The comprehensive analyses of subtyping, quantum of excess risk in comparison to those born to euthyroid mothers and association with thyroid antibodies are also lacking. This systematic review and meta-analysis aimed to estimate the pooled prevalence of CH in infants born to mothers with hypothyroidism. PubMed database was searched from inception to February 2025 using the search terms’ ((congenital hypothyroidism) and (maternal hypothyroidism)) or (mothers with hypothyroidism)’. Of 2097 initially identified articles, 18 met inclusion criteria, encompassing 11,242 infants of mothers with hypothyroidism. CH diagnoses were classified as transient (TCH) or permanent (PCH). The overall pooled prevalence of CH among infants of mothers with hypothyroidism was 0.003767 (95 % CI: 0.001796–0.005637). TCH accounted for Prevalence of TCH was 0.001867 (95 % CI: 0.000674–0.003060) whereas that of PCH was 0.001429 (0.000386–0.002473). Infants of hypothyroid mothers exhibited significantly increased risk of CH (OR: 3.48, 95 % CI: 1.25–9.65) than those of euthyroid mothers. Maternal thyroid antibody status (TPOAb positivity) did not significantly influence CH prevalence (OR: 0.97, 95 % CI: 0.19–4.81). In conclusion, infants of mothers with hypothyroidism have a substantially higher prevalence (1 in 265) than that reported in the general population. The risk was also 3.5 times higher in the systematic review. However, no association between maternal thyroid antibodies and CH was observed, emphasizing a need to explore alternative pathogenetic mechanisms.

Objectives Nonclassical congenital adrenal hyperplasia (NCCAH) is a mild form of 21-hydroxylase deficiency that can lead to premature pubarche, rapid growth, and reduced final height. However, data on pubertal progression and final height outcomes remain variable. Methods This retrospective study evaluated 27 patients (20 females, seven males) with genetically confirmed NCCAH, followed until final adult height at a single tertiary center between 2000 and 2020. Clinical, hormonal, and genetic parameters were assessed. Patients were grouped according to CYP21A2 mutation status: Group 1 consisted of patients with the c.844G>T (p.Val282Leu) homozygous mutation, Group 2 consisted of patients with the c.844G>T (p.Val282Leu) compound heterozygous mutation, and Group 3 consisted of patients with other mutations. Final height outcomes and pubertal characteristics were analyzed, and predictors of growth and factors affecting pubertal onset were examined using linear regression. Results The mean age at diagnosis was 8.8 ± 3.2 years. Central precocious puberty (CPP) and rapidly progressive puberty were observed in a total of 9 cases (at presentation and during follow-up). Seven cases used GnRH analogs. Mean final adult height (FAH) SDS was −0.33 ± 0.98, with no significant differences across mutation groups. Pubertal height SDS and height SDS at diagnosis were strongly correlated with FAH SDS (p=0.0001 and p=0.0009, respectively). Although the mean pubertal onset age did not differ significantly across genotypes, menarche was significantly later in the compound heterozygous group (p=0.006). No significant relationship was found between BA/CA, mutation group, and early puberty with either FAH SDS or FAH-predicted adult height (PAH) SDS. Conclusions Final height in NCCAH is primarily influenced by height at diagnosis, pubertal height SDS, and pubertal growth dynamics, rather than genotype or age at presentation. Regular auxological monitoring, timely recognition of pubertal changes, and individualized treatment decisions are critical for optimizing adult height outcomes.

Objectives α-Klotho is an anti-aging protein involved in insulin-like growth factor 1 (IGF-1) signaling and reproductive function. Studies in girls with central precocious puberty (CPP) reported elevated α-Klotho levels that declined with treatment, suggesting a potential biomarker role. Whether boys with CPP exhibit similar patterns remains unclear. Methods This study included 36 boys with CPP and 34 age-matched healthy controls. α-Klotho, gonadotropins, testosterone, IGF-1, and other biochemical parameters were measured at baseline. In 15 patients, measurements were repeated after 6 months of gonadotropin-releasing hormone (GnRH) agonist therapy. Results Boys with CPP showed advanced bone age, higher body mass index standard deviation score (SDS), and elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and IGF-1 SDS compared with controls. Baseline α-Klotho levels did not differ. Serum α-Klotho correlated strongly with testosterone (r=0.755, p<0.001) and moderately with IGF-1 SDS (r=0.570, p<0.001), but not with gonadotropins. In multiple regression, testosterone (β=0.612, p=0.004) and IGF-1 SDS (β=0.317, p=0.033) were independent predictors of α-Klotho. After 6 months of GnRH agonist therapy, testosterone and gonadotropins decreased significantly, while α-Klotho showed a non-significant decline. Conclusions Unlike girls with CPP, boys did not show elevated or treatment-responsive α-Klotho levels. The correlation with testosterone suggests α-Klotho may reflect androgenic activity in boys rather than serve as a dynamic biomarker. These findings should be considered exploratory, and larger studies with longer follow-up are needed to clarify its role in puberty and potential sex-specific regulation.

Objectives Gynecomastia is common during adolescence, yet its relationship with body composition remains unclear. This study investigates differences in body composition, fat distribution, and hormonal profiles between adolescents with gynecomastia and healthy controls. Methods This case–control study included 70 adolescents diagnosed with gynecomastia and 67 healthy controls matched for age and Tanner stage. Anthropometric measurements, bioelectrical impedance analysis (BIA), and serum hormonal profiles were assessed. Body composition parameters, including fat mass (FM), fat-free mass (FFM), muscle mass (MM), bone mass (BM), total body water (TBW), muscle-to-fat mass ratio (MFR), and basal metabolic rate (BMR), were measured using the Tanita MC-780 MA device. Results Adolescents with gynecomastia exhibited significantly higher trunk fat mass (trunk fat mass: 20.60 ± 9.48 % vs. 17.64 ± 6.61 %, p=0.0462) and hormonal alterations, including reduced follicle-stimulating hormone (FSH) and free thyroxine (fT4) levels (FSH: 2.7 ± 1.4 vs. 3.5 ± 2.0 IU/L, p=0.0164; fT4 12.4 ± 1.9 vs. 13.1 ± 2.5 p=0.0193). Conclusions These findings highlight the interplay between adiposity and endocrine changes in gynecomastia, warranting further exploration of underlying causative factors.

Objectives There has been a growing rate of obesity among children and adolescents in recent years. Understanding the molecular mechanisms is crucial for grasping the onset and progression. Adipose tissue is recognized for its role in endocrine functions, releasing adipokines that play a vital role in the metabolic disruptions linked to obesity. Given the involvement of adipokines such as FSTL-1 (follistatin related protein 1), FAM19A5 (family with sequence similarity to 19 member A5), and CTRP-6 (C1q/tumor necrosis factor related protein 6) in this condition, the primary goal of our study was to explore the connection between these adipokines, metabolic parameters, anthropometric data, and obesity. Methods Seventy-nine children aged 0–10 years with exogenous obesity and 88 healthy children were included in the study. Adipokine levels were measured using ELISA. The relationship between biochemical parameters and anthropometric data was also evaluated. Results CTRP6 was 6.11 (4.95–8.13) ng/mL in the obese group and 2.79 (1.73–4.58) ng/mL in the healthy control group (p<0.0001); FSLT1 was 157.7 (130.5–216.5) ng/mL in the obese group and 187.4 (151.8–289.6) ng/mL in the healthy control group (p=0.0003), FAM19A5 was 590.8 (476.4–703.9) ng/L in the obese group and 736.8 (491.8–1,719.0) ng/L in the healthy control group (p=0.0003). Conclusions CTRP6 levels were found to be higher in obese children than in the healthy control group, while FSLT1 and FAM19A5 levels were found to be lower. Changes in the levels of these adipokines may play important roles in obesity and related conditions.

Objectives This study examines the roles of hyperandrogenism (HA) and insulin resistance (IR) in eating behaviors among adolescents with polycystic ovary syndrome (PCOS). Methods Fifty adolescents with PCOS (mean age 16.04 ± 1.46 years, BMI 27.55 ± 6.34) were assessed. IR was evaluated using HOMA-IR, and eating behaviors were measured with the Eating Attitudes Test (EAT) and the Eating Disorders Examination Questionnaire (EDE-Q). Results IR was present in 46 % of participants, with obesity affecting 71 % of those with IR. While EAT scores showed no significant association with BMI, HA, or IR, the IR group had higher EDE-Q Total scores (p=0.05), particularly in Shape Concern (SC, p=0.003) and Weight Concern (WC, p=0.03). HA primarily influenced WC (p=0.04). BMI correlated more strongly with WC (r=0.579, p<0.001) than IR. ROC analysis indicated BMI>27.5 (AUC=0.967) and HOMA-IR>3.1 (AUC=0.961) as strong predictors of disordered eating. Conclusions BMI and HOMA-IR are more reliable than HA for identifying disordered eating behaviors in PCOS adolescents. The EDE-Q is recommended for effective screening, emphasizing the need to monitor BMI and HOMA-IR in this population.

Objectives This study aimed to evaluate the relationship between epicardial adipose tissue (EAT) thickness and hepatic steatosis in pediatric patients with obesity, exploring EAT as a potential biomarker for cardiovascular risk. Methods A retrospective analysis was conducted on children with obesity aged 10–18, including 48 patients with non-alcoholic fatty liver disease (NAFLD) and 50 age- and sex-matched controls with no liver steatosis. EAT thickness was measured using echocardiography, and liver fat was assessed via ultrasound. Correlations between EAT, metabolic parameters, and anthropometric measurements were examined. Results EAT thickness was significantly more excellent in the NAFLD group than in controls (p<0.001), with an optimal cutoff of >1.6 mm predicting hepatic steatosis with 98 % sensitivity and specificity. Positive correlations were found between EAT thickness, body mass index (BMI) Z-scores, and liver steatosis stages. Additionally, structural cardiac changes, such as increased right ventricular diastolic diameter (RVDD) and interventricular septal thickness in diastole (IVSd), were observed in the NAFLD group, suggesting early signs of cardiac remodeling. Conclusions EAT thickness may be a non-invasive biomarker for identifying cardiovascular risk in pediatric patients with obesity and NAFLD. Early detection of elevated EAT could guide interventions to reduce obesity-related cardiovascular risk in this population.

Objectives In youth with type 2 diabetes (YT2D), glucagon-like peptide 1 receptor agonists (GLP1) are recommended as adjuncts to metformin (Met) when glycemic targets are not achieved. Early GLP1 use may improve weight and glycemic control, but its efficacy as monotherapy in treatment-naïve YT2D remains unstudied. This exploratory study compares GLP1 and Met monotherapy for glycemic and weight outcomes in newly diagnosed YT2D. Methods This retrospective study analyzed patients<21 diagnosed with T2D between January 2022 and March 2024 at a single center. Data were collected for up to 1 year following diagnosis for patients prescribed GLP1 or Met alone. Records were excluded if additional diabetes medication or bariatric surgery was introduced. A mixed effects linear regression model adjusted for baseline BMI, HbA 1c , age, and gender. Results The cohort included 12 GLP1 and 113 Met patients. About 83 % GLP1 patients were female (vs. Met 51 %). All were publicly insured. Median age at diagnosis was 14.8 years. Baseline and final HbA 1c were similar: GLP1 (52–36 mmol/mol) and Met (52–44 mmol/mol), with 83 % GLP1 and 67 % Met patients achieving HbA 1c ≤48 mmol/mol (6.5 %) (p=0.253). Baseline BMI was higher in GLP1 (46.37 vs. Met 35.06 kg/m 2 ). Percentage BMI reduction favored GLP1 (−5.10 %) over Met (−0.59 %). Regression analysis showed GLP1 was associated with greater monthly percentage BMI reduction (β= −1.08 %, p=0.001) but not with HbA 1c change (β= −1.1, p=0.308). Conclusions GLP1 led to greater BMI reduction with comparable glycemic control relative to Met in newly diagnosed YT2D.

Objectives Monogenic diabetes (MD) is a group of diabetes subtypes caused by defects in single genes. We report phenotypes and genotypes of MD among Sudanese children. Methods Referred patients (from birth to 18 years of age) with diabetes and a clinical diagnosis of MD to Gaafar Ibnauf Pediatric Tertiary Hospital or the Sudan Childhood Diabetes Center between January 2006 and April 2023 were included. Patients were divided into two groups based on onset of diabetes before six months of age (Group 1, or neonatal diabetes mellitus) or after (Group 2, or non-neonatal diabetes mellitus). Genetic testing was performed for 87 patients at the Exeter Genomics laboratory and for one patient at the University of Cambridge, Metabolic Research Laboratories, UK. Results Out of 88 patients, 50 were from Group 1 and 38 from Group 2. We reported consanguinity in 63.6 % of the cohort and identified disease-causing variants for 18 genes in 43.2 % (Group 1) and 37.5 % (Group 2) of patients from the total cohort. The commonest causes in Group 1 and Group 2 were pathogenic variants in the EIF2AK3 and WFS1 genes, respectively. Pathogenic variants in recently reported novel genes ZNF808 , NARS2 , and FICD were detected in 8.5 %, 4.2%, and 1.4 % of patients, respectively. Patients with a disrupted WFS1 gene were found to have deafness (92.8 %) and optic atrophy (64 %). While skeletal deformities and liver disease were both seen in 28.6 % of patients with pathogenic variants in the ElF2AK3 gene. Hepatomegaly and hypophosphatemic rickets were uniformly seen in patients with pathogenic variants in the SLC2A2 gene. Generalized subcutaneous tissue loss and acanthosis nigricans were main features in AGPAT2 and INSR variants, respectively. Conclusions Characterization of MD in Sudan showed a predominance of syndromic forms. Genetic studies conducted on consanguineous populations may raise higher probabilities in identifying rare genes.

Objectives Nutrition education is important for managing type 2 diabetes (T2D), and how much knowledge is retained after nutrition education for new onset diabetes is challenging to assess. We hypothesize that deployment of a nutrition assessment will reinforce nutrition knowledge in newly diagnosed youth with T2D. Methods An exploratory quality improvement project was conducted to evaluate nutrition knowledge retained following new diagnosis of T2D. We implemented an 18-item nutrition assessment (at the first or second outpatient visit) evaluating nutrition label reading, hypoglycemia/hyperglycemia management, insulin management, and physical activity. Data was collected from the medical record, and descriptive and summary statistics were performed. Results Quizzes were administered to 19 patients and their caregivers, mean patient age 14.9 ± 2.1 years, 68 % female, 68 % NH Black, 79 % publicly insured, with mean HbA 1c 11.3 % at diagnosis, and 8.2 % at time of assessment. Mean overall nutrition assessment score was 14/18 (76 %). Patients scored well on questions about insulin (87 % correct) and physical activity (90 % correct) but needed additional reinforcement on questions about general nutrition (61 % correct) and acute and chronic complications of diabetes (64 % correct). Patients who had a lower HbA 1c at follow-up scored higher on the quiz (p=0.037). Dietitians commented that the assessments allowed them to gain “quick insight” into patients’ baseline knowledge, which enabled more tailored nutrition education with each patient. Conclusions Implementation of nutrition assessments during comprehensive diabetes visits is feasible and facilitates nutrition education with the patient and/or caregiver in an engaging manner. Reinforcement of nutrition education is critical for type 2 diabetes management and outcomes.

Objectives Noonan syndrome (NS) is a genetic disease characterized by dysregulation in the RAS/MAPK pathway. Affected individuals present peculiar physical features, short stature, and congenital cardiovascular defects. Autoimmune hepatitis is a chronic immunoinflammatory liver disease. Case presentation A 17-year-old boy with NS due to PTPN11 gene variation and type 1 autoimmune hepatitis (AIH-1; biopsy proven) is described. A literature search on the association between NS and AIH1 showed additional two cases. Conclusions This report highlights the importance of monitoring patients with NS for signs of autoimmune diseases, mainly liver dysfunction. Precise mechanisms linking NS and AIH-1 remain unclear. Anyway, the dysregulation of the RAS/MAPK pathway may be involved. Periodic monitoring of transaminases and prompt evaluation with liver biopsy should be done to optimize diagnosis and treatment of people with NS.

Objectives This report presents a rare pediatric functional AO causing CS and androgen excess. It aims to discuss the diagnostic challenges of cortisol and DHEAS co-secretion, which may mimic adenomas or carcinomas. It also emphasizes the role of clinical, biochemical, and imaging assessments, as well as histological classification using LWB criteria, and the need for long-term follow-up. Case presentation A 17-year-old female presented with weight gain, moon facies, cushingoid striae, oligomenorrhea, and acne over six months. Examination showed hypertension, grade I obesity, cushingoid stigmata without virilization. Endocrine evaluation was confirmed ACTH independent CS due to right AO. Conclusions This case illustrates functional AO as a rare cause of adolescent CS with androgen excess. Co-secretion patterns complicate diagnosis, imaging may not be definitive, and long-term follow-up is vital due to uncertain prognosis.

Objectives To highlight the diagnostic value of the T3/T4 ratio in Allan–Herndon–Dudley syndrome (AHDS) through a case report of a novel SLC16A2 mutation. Case presentation We report a 36-month-old boy with severe neurodevelopmental delay and axial hypotonia. Initial thyroid function tests at 10 months showed TSH at 4.77 μIU/mL and T3 at 8.9 pmol/L. Brain MRI was normal. At 28 months, genetic analysis identified a novel hemizygous c.1343_1344dup mutation in the SLC16A2 gene. Follow-up thyroid profiling at 36 months revealed the characteristic AHDS pattern: elevated free T3 (10.20 pmol/L), low free T4 (7.80 pmol/L), and borderline high TSH (5.20 μIU/mL), with a T3/T4 ratio of 1.31 pmol/pmol. Conclusions This case highlights the diagnostic value of the T3/T4 ratio (>0.75 pmol/pmol) as an essential biochemical marker of AHDS in any male infant presenting with unexplained developmental delay and hypotonia. A systematic diagnostic approach including early T3 measurement and T3/T4 ratio calculation should be applied in the initial evaluation of severe developmental delays, even in the presence of normal brain MRI findings, to avoid diagnostic delays in AHDS.

Objectives Congenital isolated adrenocorticotropic hormone deficiency (IAD) is a rare condition often caused by variants in the TBX19 gene, leading to significant adrenal insufficiency and metabolic disturbances in neonates. Early recognition and treatment are significant for improving outcomes. Although the c.856 C>T (p.Arg286Ter) variant in TBX19 has been identified as pathogenic, little is known about the genotype–phenotype correlation due to the limited number of cases. Case presentation We present a male infant diagnosed with neonatal IAD, presenting with hypoglycemic seizures, hypokalemia, and cholestasis within the first 10 h postnatally. There was notable facial dysmorphism, including long philtrum, depressed nasal root, epicanthus, prominent low ears, and mild hypertelorism. A homozygous c.856 C>T (p.Arg286Ter) variant in TBX19 was identified by genetic analysis. After receiving hydrocortisone treatment, the patient showed normal growth and neurodevelopment by the age of 3.2, free from hypoglycemia or recurrent seizures. Conclusions Variants in TBX19 , especially the c.856 C>T mutation, are a predominant cause of neonatal-onset adrenal insufficiency disorder (IAD). Prompt assessment of adrenal function in neonates presenting with hypoglycemia and cholestasis is essential for accurate diagnosis and timely initiation of hydrocortisone replacement therapy. Genetic assessment is essential for improving patient outcomes and advancing our comprehension of the relationship between genotype and phenotype.

Objectives To report an unusual case of Wolcott–Rallison syndrome (WRS) due to a novel homozygous missense mutation c.1805G>T (p.Gly602Val) in the Exon 11 of eukaryotic translation initiation factor 2 alpha kinase 3 ( EIF2AK3 ) gene. Case presentation A 2-month-old infant, born to a consanguineous marriage presented to PICU with the manifestation of severe diabetic ketoacidosis (severe hyperglycemia, pH 6.984 + ketones in urine). Genomic sequencing analyses detected a novel homozygous missense variation in the Exon 11 of the EIF2AK3 gene that resulted in the amino acid substitution of valine for glycine at codon 602 (p.Gly602Val). A diagnosis of Wolcott–Rallison syndrome was confirmed. He was treated with fluid therapy and regular insulin infusion. The purpose of this case report is to highlight the novel mutation in the Exon 11 of the EIF2AK3 gene and to raise awareness for screening of pathogenic genetic variants in the EIF2AK3 gene in all patients with neonatal diabetes mellitus. Conclusions In the evaluation of infants with diabetic ketoacidosis, genomic DNA sequencing analyses should be performed in all cases of neonatal diabetes mellitus for early diagnosis of Wolcott–Rallison syndrome.