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Background: Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide. Summary: Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in "developed" countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use. Key Messages: This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited. [ABSTRACT FROM AUTHOR]

Improved local diagnosis of focal hyperinsulinism in the COVID-19 era by interstate radiopharmaceutical transport 2013; 98: E1786 - 9. 7 States LJ, Davis JC, Hamel SM, Becker SA, Zhuang H. 18F-6-Fluoro-l-Dopa PET/CT imaging of congenital hyperinsulinism. Interstate transport of SP 18 sp F-DOPA, rather than the infant, resulted in improved patient safety, reduced cost and shorter time to definitive treatment for an infant with focal congenital hyperinsulinism, but is primarily limited by its 8-h expiry window and requires a close collaborative and multidisciplinary approach. [Extracted from the article]

Phosphate therapy transiently increases phosphate concentrations, lowering ionised calcium concentrations, removing the stimulus to synthesise calcitriol and further reducing calcitriol concentrations. Low levels of phosphate are found in almost all types of rickets and is likely to cause the mineralisation defect, irrespective of the underlying pathophysiology. The tubular reabsorption rate of phosphorus (TRP), the maximal tubular reabsorption of phosphorus per glomerular filtration rate (TmP/GFR) and/or the urinary phosphate/creatinine are critical measurements to distinguish rickets due to insufficient intake (e.g. nutritional rickets), from all causes of rickets associated with renal phosphate wasting. Neurosurgical intervention may be required for craniosynostosis or associated complications.3,7 In summary, HR should be considered in cases of rickets presenting with hypophosphataemia, normal 25OHD levels or where Vitamin D treatment does not resolve the clinical, biochemical or radiological derangements. [Extracted from the article]

For neonates with a suspected congenital hypoglycaemia disorder the recommended goal of treatment is to maintain a plasma blood glucose concentration >3.9 mmol/L. Abnormal neurodevelopment occurs equally in hyperinsulinism that is transient, or persistent. Simultaneous measurement of plasma ACTH and cortisol is helpful, and an ACTH stimulation test may be required.2 4 ¶ I KCNJ11 i homozygous variants are causal variants expected to have resulted in severe diffuse hyperinsulinism in both cases. Following near-total pancreatectomy in both cases, Case 1 had persistent hyperinsulinism postoperatively and Case 2 developed secondary diabetes and pancreatic exocrine insufficiency. [Extracted from the article]

Paediatric thyroid nodules are more likely to be malignant compared with adults. Differentiated thyroid cancer, including papillary thyroid cancer, which accounts for more than 90% of cases, frequently presents as a thyroid nodule with or without cervical lymphadenopathy. The Bethesda System for Reporting Thyroid Cytopathology is well regarded to categorise thyroid nodules; however, false-negative results, particularly in larger nodules (>4 cm) due to sampling errors can occur. [Extracted from the article]

Background: Maturity‐onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort. Methods: MODY variants were assessed using massively parallel sequencing in the population‐based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993). Results: DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody‐negative type 1 diabetes (T1DM), three diagnosed with antibody‐positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls. Conclusions: This is the first comprehensive study of MODY variants in an unselected population‐based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features. [ABSTRACT FROM AUTHOR]

Objective: Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of diabetes, with multiple causative genes. Some MODY subtypes can be treated with sulfonylureas instead of insulin, improving glycemic control, complication rates, quality of life (QoL), and costs. Using massively parallel sequencing (MPS), we recently determined the prevalence of pathogenic/likely pathogenic MODY variants in an Australian pediatric diabetes cohort. Here, these data are used to estimate cost-effectiveness of using MPS for MODY in all pediatric diabetes cases compared with standard practice (sequencing limited to individuals with specific clinical features).Research Design and Methods: A Markov decision model was developed to estimate incremental costs and quality-adjusted life-years (QALYs) of MPS screening, modeled over 30 years. We used our observed prevalence of 2.14% compared with 0.7% for standard practice, based on published data. The probabilities and utility weightings of long-term diabetes complications were based on HbA1c and estimated from published data. A series of one-way sensitivity analyses were performed using the net monetary benefit framework.Results: Routine MPS screening for MODY was more effective and less costly than standard care screening, with 26 QALYs gained and 1,016,000 AUD (782,000 USD) saved per 1,000 patients. Cost of screening was fully offset within 10 years. Routine MPS screening remained dominant until MODY prevalence fell to <1.1%.Conclusions: Routine MPS screening for MODY in the pediatric population with diabetes could reduce health system costs and improve patient QoL. Our results make a compelling argument for routine genetic screening in all children with presumed type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The article discusses the case of a twin boy diagnosed with congenital hyperinsulinism of infancy. Topics discussed include hypoglycemia manifestation of congenital hyperinsulinism of infancy, focal lesion in the pancreas revealed by 18 fluoro-dihydroxy phenylalanine positron emission tomography/computed tomography (PET-CT), and laparoscopic resection of the lesion.

Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2mg/kg divided b.i.d., maximum 200 mg/day) and metformin (1000 mg b.i.d.). Whole body insulin sensitivity index (WBISI) and areaunder- the-curve insulin (AUCins) were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age 15.4 ± 2.9 years, weight 99.7 ± 26.3 kg, BMI 35.5 ± 5.6 kg/m2, and BMI SDS 2.3 ± 0.3. Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy (+1.2 ± 5.9 versus +9.5 ± 2.7 kg, P = .004; -0.3 ± 2.3 versus +2.2 ± 1.5 kg/m2, P = .04; -0.04 ± 0.15 versus +0.11 ± 0.08, P = .021, resp.). AUCins correlated with weight loss (r = 0.82, P = .02) and BMI decrease (r = 0.96, P = .009). Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUCins at study commencement predicted effectiveness of the treatment [ABSTRACT FROM AUTHOR]