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Context: Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse., Objectives: To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes., Design: Multicenter cross-sectional retrospective chart review., Setting: Nine pediatric endocrine units throughout Israel., Patients: Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset., Results: CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis., Conclusions: Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Diagnosing hypoglycemia in infants and children presents significant challenges. Our objective was to elucidate the diagnoses and clinical features of children with hypoglycemia referred to a pediatric endocrine tertiary clinic., Methods: Retrospective study of 154 children (0-18 years old) presenting with hypoglycemia, during 1992-2018., Results: The cohort was divided by clinical diagnosis into six groups: ketotic hypoglycemia (n=45, 29.2%), congenital hyperinsulinemic hypoglycemia (n=35, 22.7%), transient hyperinsulinemic hypoglycemia (n=28, 18.2%), metabolic disorder (n=14, 9.1%), systemic disease/syndrome (n=15, 9.7%), and hormone deficiencies (n=8, 5.2%). Two patients had insulinoma and in 7 (4.5%) no diagnosis was elucidated. At diagnosis, 58 (37.7%) were <1 month old, 23 (14.9%) aged 1-12 months, 58 (37.7%) aged 1-6 years, and 15 (9.7%) aged 6-18 years. Hypoglycemia etiology varied among neonates, infants, and children. In eight patients hypoglycemia was asymptomatic. Of 47 patients who completed a diagnostic fast, 31 became hypoglycemic, yet a significant added value for diagnosis was only found in 14 (29.8%) patients., Conclusions: Hypoglycemia etiology in children is heterogeneous and varies by age. Any hypoglycemia measured in a child should be seriously evaluated as 7% are asymptomatic. Work-up should be tailored based on age, and clinical, biochemical, and imaging findings. Despite extensive work-up, in a significant number of patients the mechanism underlying pediatric hypoglycemia remains an enigma. This emphasizes the unmet needs and challenges in studying pediatric hypoglycemia., (The Author(s). Published by S. Karger AG, Basel.)

Background: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1., Methods: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated., Results: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence., Conclusions: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments., Impact: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: Arterial catheters may serve as an additional source for blood cultures in children when peripheral venipuncture is challenging. The aim of the study was to evaluate the accuracy of cultures obtained through indwelling arterial catheters for the diagnosis of bloodstream infections in critically ill pediatric patients., Design: Observational and comparative., Setting: General and cardiac ICUs of a tertiary, university-affiliated pediatric medical center., Patients: The study group consisted of 138 patients admitted to the general or cardiac PICU in 2014-2015 who met the following criteria: presence of an indwelling arterial catheter and indication for blood culture., Interventions: Blood was drawn by peripheral venipuncture and through the arterial catheter for each patient and sent for culture (total 276 culture pairs)., Measurements and Main Results: Two specialists blinded to the blood source evaluated each positive culture to determine if the result represented true bloodstream infection or contamination. The sensitivity, specificity, and positive and negative predictive values of the arterial catheter and peripheral cultures for the diagnosis of bloodstream infection were calculated. Of the 56 positive cultures, 41 (15% of total samples) were considered diagnostic of true bloodstream infection. In the other 15 (5%), the results were attributed to contamination. The rate of false-positive results was higher for arterial catheter than for peripheral venipuncture cultures (4% vs 1.5%) but did not lead to prolonged unnecessary antibiotic treatment. On statistical analysis, arterial catheter blood cultures had high sensitivity (85%) and specificity (95%) for the diagnosis of true bloodstream infection, with comparable performance to peripheral blood cultures., Conclusion: Cultures of arterial catheter-drawn blood are reliable for the detection of bloodstream infection in PICUs.

Introduction: Bi-allelic mutations in the TRMU gene cause reversible infantile liver failure. Little is known about extra-hepatic manifestations in these patients., Background: Two infants, aged 4 and 5 months, presented with progressive life threatening liver failure, characterized by lactic acidosis, highly elevated alpha-fetoprotein and recurrent hypoglycemia. Both showed significant extra-hepatic findings, including: hypothyroidism, macrocytic anemia and microcephaly. Both were of Jewish Yemenite descent and homozygous for Y77H mutation in the TRMU gene., Conclusions: TRMU bi-allelic mutations cause severe life-threatening liver failure. Extra-hepatic involvement is common and should be evaluated. Spontaneous resolution and recovery occurs in most patients with a remarkably good long-term prognosis. Liver failure in a Jewish-Yemenite infant should prompt early genetic testing for TRMU Y77H mutation. Pediatricians should be aware of this disease and the common mutation in Israel., Discussion: Nineteen additional patients were described in the literature, of whom 13 were from Israel; 6/19 (31%) manifested extra-hepatic involvement, namely: myopathic weakness, cardiomyopathy, renomegaly and proteinuria, bulbar dysfunction, cerebral white matter changes and abnormal growth including microcephaly. Mortality was 24% (5/21). Survivors (16/21, 76%) showed complete recovery and resolution of clinical, laboratory and histologic abnormalities. Most Israeli patients (10/15) were of Jewish-Yemenite ancestry. Homozygous Y77H genotype was exclusive to this patient subgroup and was associated with a 100% survival and recovery rate.