ESPE Yearbook of Paediatric Endocrinology

Brief summary: Using a combination of expression studies in human embryos as well as functional studies in zebrafish and genetic sequencing of patient with congenital hypogonadotropic hypogonadism, this study identified a novel role for Jag1/Notch signaling in the development of GnRH neurons.GnRH neurons have a unique characteristic as they start life in the olfactory placode and then migrate into the hypothalamus during embryonic development, thanks to ...

Brief summary: This study evaluated the safety, tolerability and efficacy of Crinecerfont, a CRF1R antagonist in adolescents with classic congenital adrenal hyperplasia (CAH).Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess adrenal androgen secretion. Sufficient suppression of adrenal andogen production in classic CAH may be difficult with current formulations...

Brief summary: In this multicenter, open-label, parallel-group, randomized trial, 97 adolescents (aged 10–16.9 years) were randomized within 21 days after the diagnosis of type 1 diabetes (T1D) to receive either hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. Although closed-loop therapy was associated with better glycemic outcomes, there were no differences in C-peptide between the two groups.The Closed Loop from Ons...

Brief summary: The incidences of T1D and T2D in children and young people increased in the USA over the last 2 decades. For the first time, the incidence of T2D has surpassed that of T1D.Comment: The SEARCH study has served as a national resource to explore the epidemiology and consequences of diabetes in the US. Published over the years, the findings contribute to understanding future trends in other parts of the world. Overall, the current report shows...

In Brief: The authors conducted genome sequencing on 151 mother–father–offspring trios from 68 vertebrate animal species in order to estimate and compare germline mutation rates (GMRs). They found a 40-fold variation in GMR per generation between the species. Higher GMRs were observed in species that have a longer generation time, older age at puberty and fewer offspring per generation.Comment: Mutations in germline DNA during gametogenesis are...

In Brief: The authors created mouse embryos in the laboratory from a combination of multiple stem cell lines. These embryos were developed ex vivo up to the equivalent of day 8.5 post-fertilization. Embryos developed within an extraembryonic yolk sac and were similar to whole natural embryos, with defined forebrain and midbrain regions, a beating heart-like structure, a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and also pr...

Nat Med. 2021 Nov;27(11):1928-1940. doi: 10.1038/s41591-021-01502-7. PMID: 34663987.Brief Summary: This clinical study characterised the spectrum of novel diabetes phenotypes due to mutations in the Transcription factor One Cut Homeobox 1 (ONECUT1)/hepatocyte nuclear factor 6 (HNF6). The study uncovers novel forms of diabetes mellitus due to mutations in ONECUT1.<p cl...

Brief summary: This study identified nitric oxide synthase 1 (NOS1) heterozygous missense variants in 6 patients with hypogonadotropic hypogonadism. Altered minipuberty and puberty as well as cognitive impairment were observed in NOS1 deficient mice.Nitric oxide (NO) is produced under the control of NO synthase in hypothalamic neurons. NO plays a crucial role in regulating gonadotropin-releasing hormone (GnRH) secretion, acting as a strong inhibitory sig...

n.karavitaki@bham.ac.uk Eur J Endocrinol. 2022; 186: P35-P52. PMID: 35319491.Brief Summary: An international panel of experts produced this consensus statement after critical review of the existing evidence on the safety of GH replacement in cancer and intracranial tumour survivors and in patients with increased cancer risk. Current evidence does not support an association betwe...

Cell Rep Med. 2022;3(1):100477. doi: 10.1016/j.xcrm.2021.100477. PubMed ID: 35106505Brief summary: To explore clinical heterogeneity, this study analyzed baseline visit data on 726 adults with newly diagnosed Type 2 diabetes (T2D) adults and identified in 4 distinct profiles (clusters of phenotypes), which predicted differences in subsequent disease progression and anti-diabetic treatments...