ESPE Yearbook of Paediatric Endocrinology

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 experimental study, pancreas-derived mesenchymal stem cells (PMSCs) were implanted into the kidney capsule of mice with streptozotocin (STZ)-induced diabetes. PMSCs led to increased levels of IL-6 in T-helper 1 and T-helper 17 cells, which transiently activated tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), which in turn decreased levels of interleukin-17. This was associated with exocrine pancreas regeneration and rescue of ...

Brief summary: In this experimental study, immunomodulatory microparticles, consisting of encapsulating self-antigens with rapamycin, were injected into mouse lymph nodes to protect against type 1 diabetes (T1D) and islet graft rejection. Antigens and rapamycin were both required for maximal efficacy and they induced durable tolerance, accompanied by expansion of antigen-specific regulatory T cells (Treg) in both treated and untreated lymph nodes.Antigen...

Brief summary: This paper describes 18 patients with bi-allelic leptin deficiency (LEP, n=11) or leptin receptor deficiency (LEPR, n=7), including 10 new cases and two novel variants. In addition, in a review of the literature (until July 2022), the authors identified n=75 patients living with LEP deficiency and n=90 with LEPR deficiency (n=152 included for comparison between groups).<p class=...

Brief summary: This basic science study in mice shows how melanocortin neurons integrate reproductive signaling with energy homeostasis. In melanocortin neurons, estradiol (E2) enhances the anorectic action of leptin. Cited1 is enriched in these neurons and its loss exacerbates diet-induced obesity in female mice. Using several specific mouse models it is demonstrated how hypothalamic Cited1, via ERα and Stat3 interactions, link the effects of E2 and leptin on food intake...

Brief summary: This observational study in three different cohorts found an increased risk for atherothrombotic disease associated with the commonly used sugar substitute erythritol. Untargeted metabolomics (in cohort 1, n=1157) and targeted metabolomics (in cohorts 2 and 3, n=2149 USA and n=833 Europe, respectively) investigations revealed an increased risk for major adverse cardiovascular events (MACE) including death, myocardial infarction and str...

In Brief: This manuscript was prepared from presentations given at the ESPE New Inroads for Child Health (NICHe) conference held in May 2009 in Marstrand, Sweden. It reviewed the concept of plasticity in developmental programming and evidence for the role of epigenetic mechanisms. It became widely accepted as a leading reference on this topic with currently >750 citations in Google Scholar.Comment: Ze’ev Hochberg had a brilliant, creative mind. ...

J Clin Invest. 2020 Dec 1;130(12):6338–6353. doi: 10.1172/JCI141455. PMID: 33164986.This manuscript describes a novel disorder due to homozygous mutations in the YIPF5 gene which cause a complex syndrome of neonatal/early onset diabetes mellitus, epilepsy and microcephaly. The underlying mechanism of the diabetes involves the accumulation of proinsulin (unable to be transported to the Golgi...

Nat Commun. 2021 Apr 1;12(1):2028. doi: 10.1038/s41467-021-21712-4. PMID: 33795686.The authors describe 5 patients with Cardio-Facio-Cutaneous (CFC) syndrome with features of septo−optic dysplasia (SOD), and GH/IGF−1 deficiency of variable degree. All were identified to carry a gain−of−function mutation in BRAF.RASopathies encompass Noonan ...

Nat Med. 2020 Oct;26(10):1583–1592 Abstract: https://pubmed.ncbi.nlm.nih.gov/32807933/In brief: Improved treatments for osteoarthritis and other degenerative joint diseases are urgently needed. This study demonstrates, for the first time, that the synovial microenvironment can be modified to allow resident skeletal stem cells to form hyaline articular cartilage and thereby reg...