ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this in vivo study, Xia et al. demonstrate that AAV-mediated gene therapy recovers testosterone levels, restarts sexual development, restores spermatogenesis, and produces fertile offspring in a mouse model of Leydig cell failure (LCF).A null mutation in the gene encoding luteinizing hormone/choriogonadotrophin receptor (Lhcgr) causes a hereditary LCF in mice which is characterized by a reduction in testosterone levels...

Brief summary: In this double-blind, randomized clinical trial conducted in 6 US centres, 88 children and adolescents (aged 7–17 years) with newly diagnosed type 1 diabetes (T1D) were randomized to either once-daily oral verapamil or placebo, within 1 month from diagnosis. Treatment with verapamil led to better stimulated C-peptide secretion at 52 weeks post-diagnosis, with levels 30% higher compared to placebo.Verapamil is a calcium channel blocker...

Brief summary: This international multicentre study collected data from 104 290 children and adolescents (6 months-18 years-old), to compare prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) before and during the COVID-19 pandemic. Prevalence of DKA at T1D diagnosis increased from 27.3% pre-pandemic to 39.4% during the pandemic, and the increased trends were associated with the pandemic containment measures.DKA is a life-thr...

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...

Eur J Endocrinol, 2021. 185(5): p. 691-705. PMID: 34516402Brief Summary: This study evaluated the prevalence of genetic variants in children with idiopathic short stature (ISS) using next-generation sequencing (NGS). Heterozygous variants in known genes involved in skeletal physiology were identified in almost 20% of children. The use of advanced genetic analysis techniques will lead to an increased identification of new genetic variants, expand...

Science. 2021;373(6557):871-6. doi: 10.1126/science.abj8754 PubMed ID: 34282049Brief summary: This study reveals a Deep Learning method, ‘RoseTTA fold’, based on DeepMind’s Alphafold2 framework, to predict 3-dimensional protein structures from 1-dimensional sequence information and generate models of protein–protein complexes with high accuracy.Previ...

Front Endocrinol (Lausanne). 2020 Oct 27;11:545638. doi: 10.3389/fendo.2020.545638. PMID: 33193079.Using human islets from CHI patients and islets from ABCC8 (SUR1) knockout mice, the authors tested several novel compounds to inhibit insulin over-secretion. These novel compounds targeted KATP channels as well as KATP indepe...

Nat Commun. 2021 Jun 7;12(1):3355. doi: 10.1038/s41467-021-23661-4.This study describes the interaction of individual genetic variation for autoimmune thyroid disease with risk of thyroid immune related adverse events (irAE) during or after immune checkpoint inhibitor (ICI) treatment for advanced cancer.ICIs are monoclonal antibodies blocking T-cell exhaustion and...

Nat Commun. 2020;11:4807. doi: 10.1038/s41467-020-18497-3.This interesting paper illustrates the potential of machine learning to improve the sensitivity and specificity of routine techniques in clinical practice if large cohorts for training and validation of models are used. Yu et al. present a transfer learning model (machine learning approach to solve research problems by r...

J Clin Endocrinol Metab. 2020;105:3203–3214. doi: 10.1210/clinem/dgaa443. PMID: 32652002The authors performed a large genome-wide association study (GWAS) to assess the role of common genetic variants in the response to GH therapy. A total of 614 children treated with GH were included: 276 with idiopathic GHD, 297 with ISS, and 41 born SGA. The findings implicate some novel mechanisms...