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Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists. Adrenocortical cell therapy and gene therapy may obviate many of the shortcomings of adrenal hormone replacement. Physiological cortisol secretion regulated by pituitary adrenocorticotropin could be achieved through allogeneic adrenocortical cell transplantation, production of adrenal-like steroidogenic cells from either stem cells or lineage conversion of differentiated cells, or for CAH, gene therapy to replace or repair a defective gene. The adrenal cortex is a high-turnover organ and thus failure to incorporate progenitor cells within a transplant will ultimately result in graft exhaustion. Identification of adrenocortical progenitor cells is equally important in gene therapy, for which new genetic material must be specifically integrated into the genome of progenitors to ensure a durable effect. Delivery of gene-editing machinery and a donor template, allowing targeted correction of the 21-hydroxylase gene, has the potential to achieve this. This review describes advances in adrenal cell transplants and gene therapy that may allow physiological cortisol production for children and adults with PAI. [ABSTRACT FROM AUTHOR]

Aim: To determine if the timing of manuscript submissions to The Journal of Paediatrics and Child Health (JPCH) changed following the onset of the COVID‐19 pandemic and to determine if the timing of manuscript submissions influenced editorial decisions. Methods: A retrospective observational study of submissions to JPCH from 1 January 2015 to 1 August 2022 was performed. Regression models were used to explore the change over time. Editorial decisions were examined using a multinomial regression model with the three‐category ordinal outcome of reject, revise and accept. All statistical models were fitted using a Bayesian approach and show 95% credible intervals (CI). Results: The analyses included 11 499 manuscript submissions between 2015 and 2022. The mean number of manuscript submissions increased by 17 papers per month (CI 15–19), with a larger 4‐month long increase after the COVID‐19 pandemic was declared of 86 submissions per month (CI 67–103). There was no clear effect of the pandemic on weekend submissions, mean difference in probability 0.003 (CI –0.021 to 0.026). Throughout the study period, the peak submission time was later in the day and was shifted +37 min later post‐March 2020 (CI +22 to +52 min). Throughout the study period, submissions out‐of‐hours and on weekends were less likely to get an editorial decision of 'accept' or 'revise': odds ratio weekend versus weekday 0.87 (CI 0.78–0.97). Conclusion: The COVID‐19 pandemic had a limited effect on the timing of manuscript submissions to JPCH. However, the timing of manuscript submission impacted the likelihood of a more positive editorial decision. While the time of manuscript submission is only one part of the research process, it is postulated that it may be associated with research quality. [ABSTRACT FROM AUTHOR]

In adults, there has been a decline in the incidence of diabetic retinopathy (DR) associated with improvements in diabetes management. Data on incident severe DR in adolescents are sparse. In our established diabetes complications assessment service, we recorded nine cases of sight‐threatening retinopathy in youth aged 15–17.9 years from 2017 to 2021. Proliferative retinopathy and clinically significant macular oedema were identified. The subjects were diagnosed with type 1 diabetes before the age of 10 years and had a history of poor glycaemic control (HbA1c 86‐130 mmol/mol, 10%–15%). Five cases of retinopathy developed rapidly within 2.5 years of a previously normal retinal examination on seven‐field stereoscopic retinal photography. Three adolescents required laser photocoagulation therapy. Two adolescents were diagnosed with retinopathy following improvement in diabetes control after being lost to medical follow‐up and their retinopathy improved with improved glycaemic control. Thus, we support repeated retinal screening in adolescents with diabetes duration >10 years with suboptimal glycaemic control, even when initial retinal examination is normal, as retinopathy can progress rapidly during adolescence. [ABSTRACT FROM AUTHOR]

Aim: Paediatric hypoglycaemia often requires specific investigations to determine aetiology. Samples from the time of hypoglycaemia may not be available and a diagnostic fasting test may be required. Additionally, fasting studies can determine safe fasting intervals and prolonged oral glucose challenges can assess hypoglycaemia due to abnormal post‐prandial glucose handling. This audit reviewed the current utility and yield of fasting studies, prolonged oral glucose challenges and starch loads. Methods: Retrospective audit of clinical record to determine purpose and outcome of tests performed at a Tertiary Paediatric Endocrine/Metabolic Testing Unit in Sydney, Australia, from 2013 to 2018 inclusive. Results: One hundred and thirty‐eight children (aged 3 weeks–17 years) underwent 170 tests: 122 fasting studies, 20 five‐hour OGTTs, 22 uncooked corn starch loads and six modified waxy maize starch (Glycosade) loads. The majority were for diagnostic purposes (n = 113, 66%), with 57 (34%) to guide management in patients with known diagnoses. Following diagnostic studies, 35 (31%) patients received a pathological diagnosis, the most common of which (n = 19, 17%) was accelerated starvation. Hypoglycaemia developed in n = 15/113 (13%) during the diagnostic studies. Management studies helped determine length of safe fast, adjustment of medication or diet and document resolution of pathology. Conclusion: Fasting studies remain a safe and effective method to assist with diagnoses, confirm or exclude pathological causes of childhood hypoglycaemia and to guide management of known diagnoses in the paediatric population. [ABSTRACT FROM AUTHOR]

Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder characterised by adrenocorticotropic hormone (ACTH) deficiency, red hair and hyperphagic obesity. Two unrelated cases presented with hypoglycaemia due to isolated ACTH deficiency in the neonatal period. POMC deficiency was suspected at age 2 years (c.133‐2A>C) and at age 9 months (c.64del) due to infantile hyperphagic obesity. Neither patient had a convincing red hair phenotype at the time of diagnostic suspicion, illustrating the importance of suspecting POMC deficiency in isolated ACTH deficiency. Both patients have normal psychomotor development, whereas the only other reported case of c.64del had significant delay. This suggests, if ACTH deficiency is treated early in the neonatal period, that psychomotor retardation is not a part of the phenotype. We review 24 reported cases of POMC deficiency published to date. Although there is no current specific treatment for obesity in POMC deficiency, we anticipate that setmelanotide may be a useful future treatment option. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in COL1A1 or COL1A2 that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected individuals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in COL1A2 c.3356C>T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is becoming more prevalent and even with new advancements which improve glycaemic control, complications of diabetes are common. Vascular complications of diabetes include the microvascular complications: retinopathy, nephropathy, and peripheral and autonomic neuropathy. Macrovascular complications are also common in patients with diabetes and arguably more concerning as they confer a high mortality risk yet are sometimes under-treated. Risk factors for diabetes complications start to occur in childhood and adolescents and some youths may be diagnosed with complications before transition to adult care. This article discusses the prevalence, risk factors, screening, and treatment recommendations for vascular complications in children and adolescents with diabetes. [ABSTRACT FROM AUTHOR]