ESPE Yearbook of Paediatric Endocrinology

Brief summary: Steroid analysis using LC-MS/MS in association with clinical parameters may be used to develop a diagnostic score that could successfully differentiate premature pubarche (PP) from non-classic congenital adrenal hyperplasia (NCCAH), thereby obviating the need for ACTH stimulation testing.Late onset, non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency (21-OHD) should be ruled out in children with premature pu...

Brief summary: This retrospective case-control observational study assessed body composition of children with non-classic congenital adrenal hyperplasia (NCCAH) using bioelectrical impedance analysis (BIA). It showed that children with NCCAH have an imbalance between muscle and fat tissues compared with control subjects, which may place them at increased risk for early-onset cardiometabolic morbidity.Non-classic congenital adrenal hyperplasia (NCCAH) is ...

To read the full abstract: Nat Comm 2019; 10(1): 1718Steroid receptor coactivator (SRC)-1 mediates nuclear hormone receptors and transcription factor-dependent transcription (1), and interacts with STAT3 (2) an important mediator of leptin-induced POMC expression and hence satiety (3). Src-1 knockout mice are obese (4), however, the underlying mechanism is unclear. In a...

To read the full abstract: Nature 2017;548:413-419Over recent years, the Yearbook has followed the rapid advances in CRISPR-Cas9 gene editing technology, initially as a widely adopted research tool, but also as an emerging form of gene therapy. Here, Ma et al. report the first use of CRISPR–Cas9 to efficiently and safely correct a pathogenic heterozygous mutation in human embryos. The...

Brief summary: This randomized, multicenter, controlled, phase II study compared the effects of high-dose (HD) once-weekly PEGylated-recombinant human growth hormone (PEG-rhGH) to low-dose (LD) and to an untreated control group of children with idiopathic short stature (ISS) over a period of 52 weeks. PEG-rhGH was effective in increasing height gain in a dose dependent manner with both doses being well tolerated during the observation period.PEG-rhGH is ...

Brief summary: This collaborative study identified 13 monoallelic rare loss-of-function (LoF) variants in the serotonin 2C receptor (HTR2C) gene in 19 unrelated individuals with hyperphagia, severe early-onset obesity, and some degree of maladaptive behaviour. The authors used exome sequencing in 2548 individuals with severe obesity and 1117 control individuals without obesity. They found that HTR2C variants cause monogenic obesity by demonstrating t...

To read the full abstract: Science 2019;365:386–392.By genetically engineering mice, the authors deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets<p c...

Nat Commun. 2021 Jan 11;12(1):256. doi: 10.1038/s41467-020-20511-7. PMID: 33431871.These authors report two Mll4 mutant mouse models that exhibited dwarfism and altered development of GHRH−neurons.Inactivating mutations in KDM6A (aka UTX) or KMT2D (aka MLL4) genes result in Kabuki syndrome (KS), whose hallmarks in...

Diabetologia. 2021 May;64(5):1133-1143. doi: 10.1007/s00125-021-05390-x. PMID: 33558985.In order to gain some insight into the potential mechanism/s of diminished beta cell function over time, this mouse model of CHI was developed with an activating GCK (Glucokinase) mutation. In the short term, the mice developed mild fasting hypoglycaemia (this was very mild with fasting blood glucose...

Lancet Diabetes Endocrinol. 2021;9:94–105. doi: 10.1016/S2213-8587(20)30399-5.This population based nested case-control study integrated registry data from Denmark, Norway, Sweden and Finland over 40 years to investigate the association of maternal, in-utero, and postnatal factors with thyroid cancer risk in offspring. Each patient with thyroid cancer (cases n=...