ESPE Yearbook of Paediatric Endocrinology

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 significantly advances our understanding of the genetic underpinnings of congenital hypopituitarism (CH) by utilizing whole exome sequencing (WES) in a large cohort of patients from Argentina.CH is a complex and highly heterogeneous disorder that is associated with highly variable clinical phenotypes that range in severity (1). The aetiology of CH may extend beyond monogenic causes, involving oligogenic, polygenic, or multifacto...

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...

To read the full abstract: N Engl J Med. 2020;382(22):2117–2128. doi: https://pubmed.ncbi.nlm.nih.gov/32233338/Kelly et al. randomly assigned (1:1) n =251 obese adolescents (age 12 to <18 years) to receive either liraglutide (3.0 mg), a long-acting glucagon-like peptide-1 agonist, or placebo subcutaneously once daily in addition to lifestyle therapy. Liraglutide w...

To read the full abstract: Lancet Child Adolesc Health. 2020;4(3):210–19. PMID 31978372.In this non-randomized matched-control study, 81 obese adolescents undergoing Roux-en-Y gastric bypass surgery (RYGB) who participated in the Adolescent Morbid Obesity Surgery (AMOS) study (11) were compared with 80 obese controls from the Swedish Childhood Obesity Treatment Register (BORIS) who rec...

Brief summary: Using human induced pluripotent stem cells as well as transgenic mouse models, this paper shows that MKRN3 could initiate pubertal onset by regulating hypothalamic development and plasticity.The reactivation of GnRH secretion at puberty is thought to result from a loss in inhibitory input together with an increase in transactivation onto GnRH neurons. The main component of this inhibitory tone was incompletely understood until the discover...

Brief summary: This study summarises the involvement of specific miRNAs in diabetes mellitus, thyroid diseases, osteoporosis, pituitary tumours, Cushing’s disease, adrenal insufficiency and multiple endocrine neoplasia’s. Furthermore, the potential of miRNA as candidates for developing novel diagnostic and therapeutic tools is also discussed.Endocrine disorders are common worldwide and represent a considerable public health problem due to long ...

Brief summary: In this experimental study, a transdermal polymeric microneedle (MN) patch for glucose-responsive closed-loop insulin and glucagon delivery was developed. In chemically-induced type 1 diabetes (T1D) mouse and minipig models, this glucose-responsive dual-hormone MN patch demonstrated tight regulation in blood glucose.The interplay between insulin and glucagon is essential for blood glucose regulation in individuals with or without diabetes....

Brief Summary: This study describes the clinical characteristics of pathogenic variants in the ACAN gene and the response to rhGH treatment over three years in children with a heterozygous ACAN variant. The results indicate that rhGH therapy may be considered to reduce the height deficit in these patients, particularly in prepubertal children with ACAN deficiency.Aggrecan is the major proteoglycan of the cartilage growth plate. Homozygo...

Elife. 2021 Jun 15;10:e67714. doi: 10.7554/eLife.67714. PMID: 34128468https://elifesciences.org/articles/67714Brief Summary: This histological and transcriptomic study evaluates the presence and the potential role of extra-hypothalamic GnRH neurons in humans and identifies cholinergic GnRH-synthesizing cells in the human basal...